StemCell Therapy

Abstract

Functional coating materials have found broad technological applications in diverse fields. Despite recent advances, few coating materials simultaneously achieve robustness and substrate independence while still retaining the capacity for genetically encodable functionalities. Here, we report Escherichia coli biofilm-inspired protein nanofiber coatings that simultaneously exhibit substrate independence, resistance to organic solvents, and programmable functionalities. The intrinsic surface adherence of CsgA amyloid proteins, along with a benign solution-based fabrication approach, facilitates forming nanofiber coatings on virtually any surface with varied compositions, sizes, shapes, and structures. In addition, the typical amyloid structures endow the nanofiber coatings with outstanding robustness. On the basis of their genetically engineerable functionality, our nanofiber coatings can also seamlessly participate in functionalization processes, including gold enhancement, diverse protein conjugations, and DNA binding, thus enabling a variety of proof-of-concept applications, including electronic devices, enzyme immobilization, and microfluidic bacterial sensors. We envision that our coatings can drive advances in electronics, biocatalysis, particle engineering, and biomedicine.

Surface modification of materials is an essential aspect of engineering and technology fields including electronics, biomedicine, catalysis, textiles, and industrial equipment (16). The application of diverse coatings is one of the major methods through which either surface properties of a substrate are changed or completely new properties to a finished product are imparted. Some advanced coating materials that have recently been developed include polyelectrolytes, proteins, polydopamine, and polyphenols (2, 714); however, certain limitations have prevented the widespread adoption and practical use of these materials. For example, although polydopamine and polyphenol coatings are substrate independent, both coating types are unstable in certain application environments: Polydopamine coatings suffer from easy detachment in polar solvents, whereas polyphenol coatings exhibit pH-dependent disassembly (7, 15).

Protein-based coating materials (e.g., bovine serum albumin, hydrophobins, and mussel foot proteins) have attracted considerable attention because of their outstanding biocompatibility, biodegradability, and environmental friendliness (11, 12, 16, 17). Amyloid proteins are particularly appealing as a potential source of bioinspired coatings, as their characteristic -sheet structures exhibit high tolerance toward high temperature, organic solvents, and harsh pH conditions (18, 19). Recent work demonstrated that phase transition lysozyme (PTL), an amyloid protein coating material, could coat the surface of virtually any substrates and have outstanding robustness; however, it is notable that the applications reported for PTL to date have mainly exploited its intrinsic chemical properties (i.e., the aforementioned -sheet structures) rather than its potentially genetically engineerable functionalities (10, 20, 21).

In nature, bacteria use biofilms to robustly coat an enormous number of surfaces, and these coatings promote cellular survival in harsh environments (22, 23). Fundamental studies have revealed that biofilms produced by Escherichia coli contain amyloid nanofibers, which are self-assembled by secreted monomers of the CsgA protein (the major protein component within the biofilms); these nanofibers provide mechanical strength and structural integrity to biofilms (Fig. 1A) (2426). In addition, a molecular dynamics study recently suggested that CsgA, owing to its unique protein sequence and structural features, should strongly adhere to both polar and nonpolar surfaces (27). For practical applications, multiple studies have shown that genetically engineered CsgA fusion proteins can be used as underwater adhesives, nanoparticle (NP) assembly scaffolds, patternable materials, biomimetic mineralization, and medical hydrogels (2832). In light of their intrinsic adherence toward diverse substrates as well as the fact that a variety of functional peptides and protein domains could be rationally inserted in the CsgA protein through a modular genetic strategy without disrupting their self-assembly into -sheet structures, we rationalized that engineered CsgA fusion proteins could be used as a coating platform to endow materials with diverse functionalities. Conceivably, such genetically engineered CsgA-based coatings would likely achieve precise performance for myriad applications, likely far surpassing the scope of existing protein coating materials such as PTL and bovine serum albumin. However, exploiting the genetically programmable functionality of CsgA amyloid proteins as a coating material have not been widely explored.

(A) Illustration of natural E. coli biofilms, in which self-assembled CsgA nanofibers constitute the major protein component. (B) Modular genetic design of genetically engineered CsgA proteins enabled by rationally fusing desired fusion domains at the C terminus of CsgA. (C) Illustrations of producing diverse protein coatings via a solution-based fabrication approach for various applications based on genetically engineered functionalities such as electronic devices, enzyme immobilization, and microfluidic sensor (from top to bottom).

Here, we report a proteinaceous coating material platform based on genetically programmable CsgA fusion amyloid nanofibers. We successfully used a simple, aqueous solutionbased fabrication method based on the amyloid protein self-assembly to generate thin-film materials that can conformably coat substrates with highly diverse compositions (e.g., polymeric, metal oxide, inorganic, and metal) and varied shapes (flat, round, pyramid, the interior of a microfluidic device, and even irregular or asymmetric structures). We demonstrate that these coating materials can be further decorated with various molecules and nano-objects such as fluorescent proteins, enzymes, DNA probes, and NPs. The robust coating materials maintained their integrity and functionality, even after exposure to various common organic solvents such as acetone and hexane or after high-temperature challenge. Last, we exploited the process simplicity, flexibility, and functional customization of our coating materials in proof-of-concept demonstrations for electronic devices including a touch switch and a pressure sensor, immobilized multienzyme systems for bioconversion production applications, as well as a hybrid amyloid/DNAzyme microfluidic sensor (Fig. 1, B and C). We anticipate that our genetically engineered CsgA coating materials, which are substrate independent, ultrastable, and afforded precisely with tailor-made and tunable functionality, will find broad application in electronics, biocatalysis, particle engineering, and biomedicine.

Leveraging a modular genetic design, we constructed four genetically engineered CsgA variants: CsgAHis-tag, CsgASpyTag, CsgASnoopTag, and CsgADNA binding domain (DBD) (Fig. 1B). We expressed our engineered CsgA proteins as inclusion bodies using E. coli BL21(DE3) as a host and purified the proteins following a typical guanidine denaturation protocol for amyloid proteins (28, 30); this approach markedly reduced batch-to-batch variation and impurities. To produce coating materials, we dissolved the purified proteins in an aqueous solution and directly immersed diverse substrates into this protein solution overnight. We first conducted detailed characterization to confirm the coating-forming ability of the CsgA fusion proteins. We chose plates made of unmodified poly(tetrafluoroethylene) (PTFE)a classical adhesion-resistant materialas the test substrate. After immersion of the substrate in fresh-made CsgAHis-tag monomer (His-tag fused at the C terminal of the CsgA protein) solution overnight, water contact angle tests showed that the contact angle of CsgAHis-tag nanofibercoated PTFE was 72.7 2.7, whereas that of bare PTFE was 110.2 3.2 (Fig. 2A). To test the coating effect, we first incubated the bare and coated PTFE in the presence of solution containing nickelnitrilotriacetic acid (Ni-NTA)decorated red-emitting quantum dots (QDs) (allowing thorough interactions between Ni-NTAdecorated QDs and CsgAHis-tag nanofibers) and subjected them to copious amount of water to remove nonspecific binding (33).

(A) Top: Digital images and water contact angles (inset) of bare and CsgAHis-tagcoated PTFE; bottom: digital images of bare and coated PTFE substrates after incubation with QD solution and illumination under UV light. Photo credit: Yingfeng Li, ShanghaiTech University. (B) AFM height image of CsgAHis-tagcoated PTFE. (C) XPS spectra of bare and CsgAHis-tagcoated PTFE, CPS representing counts per second. (D) Schematic showing stability tests consisting of a water contact angle test and a QD binding test. (E) Water contact angle comparison of CsgAHis-tag coatings on PTFE substrates after organic solvent exposure. (F) Digital image of challenged CsgAHis-tagcoated PTFE substrates after incubation with QD solution and illumination under UV light. Photo credit: Yingfeng Li, ShanghaiTech University. (G) Water contact angles of bare and CsgAHis-tagcoated diverse polymer substrates. (H) Water contact angles of bare and CsgAHis-tagcoated various inorganic substrates.

The coated sample displayed bright and uniform red fluorescence under ultraviolet (UV) illumination, whereas the bare PTFE sample showed almost no fluorescence (Fig. 2A). This vast difference in fluorescence intensity was also verified quantitatively through photoluminescence spectroscopy (fig. S1A). Moreover, as revealed by atomic force microscopy (AFM) imaging, CsgAHis-tag nanofiber coatings were formed on the PTFE substrate (Fig. 2B and fig. S1B). X-ray photoelectron spectroscopy (XPS) was also performed to further analyze the surface composition after nanofiber coating, revealing newly appeared N 1s and O 1s peaks at 399 and 531 eV, respectively, thereby confirming the coating of CsgAHis-tag proteins on the PTFE substrate (Fig. 2C). Collectively, these results validate the nanofiber coatingforming ability of the genetically engineered CsgA proteins.

To demonstrate the stability of CsgAHis-tag nanofiber coatings in organic solvents, we conducted two kinds of tests: contact angle and QD binding (Fig. 2D). We first measured the contact angles of coated PTFE substrates before and after contact with common organic solvents including hexane, acetone, and dimethyl sulfoxide (DMSO). After immersion in these solvents for 24 hours, the contact angles of the substrates underwent almost no changes, indicating that our coatings had outstanding chemical endurance in these harsh solvents (Fig. 2E). Furthermore, digital images showed that CsgAHis-tagcoated PTFE substrates anchored with Ni-NTA QDs still displayed red fluorescence after contact with the aforementioned common organic solvents, again highlighting the organic solvent tolerance of our nanofiber coatings (Fig. 2F). The CsgAHis-tag proteins also have outstanding environmental tolerance even after long-term exposure to both acidic and basic aqueous solutions as described in a previous study (30).

We next assessed the thermal stability of CsgAHis-tag nanofiber coatings. To such ends, we first used NanoDSF (differential scanning fluorimetry) to determine melting temperatures of proteins using their intrinsic fluorescence change during a programmed temperature gradient increase (34). The fluorescence intensity change of a protein sample is directly correlated to the structural change (e.g., unfolding) of the protein over the heating process. Briefly, our NanoDSF analysis of CsgAHis-tag nanofibers and control bovine serum albumin proteins in solution revealed that whereas the serum albumin proteins began to unfold at ~65C, the CsgAHis-tag nanofibers had impressive thermal stability, as indicated by the steady fluorescence intensity even at 95C (fig. S2A). Moreover, the attenuated total reflectionFourier transform infrared (ATR-FTIR) spectrum of the challenged CsgAHis-tag nanofiber sample showed that the typical -sheet structures (absorption peak at ~1625 cm1) were still retained in the nanofiber structures after heating in a 90C oven for 24 hours (fig. S2B). In addition, water contact angle analysis and QD binding test indicated that CsgAHis-tag nanofibers were still completely coated over on the PTFE substrates even after challenge at 90C for 24 hours (fig. S2C). These data thus reveal that our CsgAHis-tag protein coatings have outstanding thermal stability.

Biodegradability under appropriate protease conditions is considered as one of the attractive material attributes for protein-based coatings (17). To assess whether our CsgAHis-tag protein coatings have such on-demand biodegradability, we chose two enzymes, trypsin from bovine pancreas and fungal protease from Aspergillus oryzae (protease AO), in our studies. Thioflavin T (ThT; an amyloid specific dye) assay was used to monitor the digestion process of CsgAHis-tag nanofibers. As illustrated in fig. S2 (D and E), the decreasing fluorescence intensities indicate the gradual disappearance of the -sheet structures over time, suggesting the structural instability of CsgAHis-tag nanofibers under trypsin or protease AO digestion conditions. We next challenged the stability of CsgAHis-tag nanofiber coatings by incubating the CsgAHis-tag nanofibercoated PTFE plate in the two enzyme solutions (trypsin, 2.5 mg/ml; fungal protease, 55 U/g) for 24 hours and assessed the morphological and physicochemical properties with scanning electron microscopy (SEM) and water contact angle analysis, respectively. SEM images showed that very little amount of nanofibers was found on the substrate surface and water contact angle analysis revealed that the enzyme-treated substrates restored their hydrophobicity after nanofiber coating digestions (fig. S2, F to H). These data convincingly demonstrate that our CsgAHis-tag nanofiber coatings can be degraded in the presence of proteases. Collectively, our coating materials have strong environmental robustness while retaining their on-demand biodegradability, and thus can broaden the application scope of existing protein-based coating materials.

To establish that our CsgAHis-tag nanofiber coatings can be applied to other substrates, we coated several typical material substrates, including common organic polymers [polydimethylsiloxane (PDMS), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET)] and inorganics [indium tin oxide (ITO), Si, Au, stainless steel 304, fluorine-doped tin oxide (FTO), and glass]. Our results from water contact angle analysis revealed that CsgAHis-tag nanofibers were successfully coated on each of these substrates (Fig. 2, G and H). These applications convincingly demonstrate the substrate-independent nature of the genetically engineered CsgA protein coatings.

The apparently very broad substrate scope for our coatings raises interesting questions about the molecular interactions that occur between nanofibers and substrates. Previous molecular simulation research has demonstrated that the unique structural features as well as its unique amino acid sequence and diversity of the CsgA protein enable its strong adhesion capacity for both polar and nonpolar substrates (27). Therefore, on the basis of the above contact angle test results, we speculated that the hydrophobic residues within the CsgA protein such as alanine, proline, and valine could provide adhesion to hydrophobic surfaces such as PTFE and PDMS through hydrophobic interactions; that aromatic amino acids such as tyrosine, phenylalanine, and histidine may contribute to adhesion to PS and PET surfaces through - stacking interactions; and that charged and polar amino acids such as arginine, lysine, and glutamine could form strong interactions with oxides through electrostatic interactions (35).

Having illustrated the coating formation capacity as well as their basic physicochemical properties of genetically engineered CsgA coatings, we next focused on establishing proof of concept for multiple programmable functions for the CsgA fusion protein coatings.

Flexible and wearable electronics play critical roles in our daily lives, and the introduction of metal NPbased conductive coatings within such devices is definitely a key step (36, 37). Existing conventional top-down approaches to obtain metal NP coatings often require high temperature and sometimes suffer from low interfacial adhesion (36, 37). Gold enhancement is a promising bottom-up process for fabricating Au-based conductive coatings (38, 39). However, this process preliminarily requires the ability to anchor Au NPs to the targeted substrates (38, 39). Such NPs can then be used to heterogeneously catalyze further Au deposition and form NP-structured coatings in an aqueous AuCl4 and hydroxylamine solution. In the previous section, we confirmed that CsgAHis-tag coatings could anchor Ni-NTAcapped QDs on substrates. Transmission electron microscopy (TEM) images confirmed that CsgAHis-tag nanofibers could firmly bind Ni-NTAcapped Au NPs (fig. S3A). We thus reasoned that our Au NPbound CsgA nanofiber coatings could theoretically lead to a gold enhancement process on the surface of a substrate, potentially forming Au coatings consisting of closely packed NPs.

To test the feasibility of our concept, we first incubated a CsgAHis-tagcoated three-dimensional (3D)printed pyramid with Ni-NTAcapped Au NPs. After assembly for 30 min, we transferred this pyramid into a gold enhancement solution (AuCl4 and hydroxylamine), allowing chemical reduction (Fig. 3A). Photographic images showed that the surface color of the pyramid was successfully changed from pristine white to typical tan (Fig. 3B). The above experimental results thus showed the feasibility of our fabrication process. The simple Au coating technique could be easily applied to various substrates, including polyimide (PI), PDMS, PET, PTFE, and PP, highlighting the substrate independence and conformability features of our nanofiber coatings (fig. S3B).

(A) Schematic showing the fabrication of Au coatings based on CsgAHis-tag coatings. (B) Digital images of pristine and Au-coated CsgAHis-tagmodified 3D printed pyramids. Photo credit: Yingfeng Li, ShanghaiTech University. (C) Digital (left) and SEM (right) images of an Au interdigital electrode fabricated by a CsgAHis-tag coatingenabled gold enhancement process assisted by a patterned waterproof sticker. Photo credit: Yingfeng Li, ShanghaiTech University. (D) XPS spectrum of the Au interdigital electrode. (E) Capacitance change of the Au interdigital electrode with different distances between the electrode and a finger; the inset digital images indicate different distances. Photo credit: Yingfeng Li, ShanghaiTech University. (F) Digital images of the Au interdigital electrode as the sensing element in a touch switch. Photo credit: Yingfeng Li, ShanghaiTech University. (G) Digital (left) and SEM (right) images of pristine (top) and Au-coated textiles (bottom). Photo credit: Yingfeng Li, ShanghaiTech University. (H) Schematic diagram of a pressure sensor fabricated by Au-coated textiles along with an Au interdigital electrode (inset) and the corresponding current variation (I/I0) under different pressures. (I) Current variation as a function of time at two pressures (the inset digital images indicate the two different types of pressure applied). Photo credit: Yingfeng Li, ShanghaiTech University.

Having demonstrated the feasibility of conformable Au coating technique using the CsgAHis-tag protein as functional coating proteins, we next explored the fabrication of diverse electronic devices with increasingly complex functionalities. We first generated patterned Au coatings by first fabricating CsgAHis-tag coatings with commercially available patterned waterproof stickers, then incubating the substrates in an Au NP solution followed by an Au enhancement process (see the Supplementary Materials). Accordingly, we fabricated an interdigital electrode consisting of patterned Au coatings on a PDMS substrate that conformably stuck to the outer surface of a 50-ml centrifugation tube (Fig. 3C). As expected, SEM and AFM images indicated that the coating was composed of NPs, and further XPS analysis confirmed the appearance of Au element on the surface (Fig. 3, C and D, and fig. S3C). To demonstrate the potential application of this interdigital electrode, we carefully tested the capacitance change of the electrode when a finger approached and then moved away from the electrode. As illustrated in Fig. 3E, as a finger gradually began touching the electrode, the capacitance correspondingly decreased. Likewise, when the finger was removed, the capacitance was restored to the original value.

This behavior is attributed to the higher dielectric constant of the human body as compared to air: a higher dielectric constant reflects lower capacitance. In this way, such an electrode could be used as the sensing unit of a touch switch (40). We therefore linked this electrode to a circuit including a power source, a commercially available signal processing chip, and a light-emitting diode (LED). As shown in Fig. 3F, when no finger was in contact with the electrode, the LED was off; however, when a finger touched the electrode, the circuit was connected and the LED was on.

To assess the mechanical stability of the conductive Au coatings, we applied an abrasion test for our CsgAHis-tagenabled Au conductive coatings following a previous approach for coating structures (37, 41). Specifically, we first attached a soft PET fabric on the Au-coated PET plate, followed by placing a 2-kg counterweight on the fabric. We then moved the fabric against the conductive surface of PET plates. As illustrated in fig. S4A, the sheet resistance had almost no change (~23 ohms/sq) even after 500 cycles of abrasion. In addition, although SEM images showed the abrasion traces on the surfaces, the morphology of the conductive layers consisting of highly packed irregular Au NPs remained unchanged (fig. S4, B to D). These findings highlight the mechanical robustness of our conductive coatings on the PET plates. Because CsgAHis-tag coatings are vulnerable to enzymatic digestions, we next used trypsin and protease AO to challenge the Au conductive coatings. The sheet resistance and the microstructures of conductive coatings had negligible changes after incubation with the enzyme solutions for 24 hours, indicating the strong resistance of Au coatings to proteolytic digestion (fig. S5, A and B). It is likely that the extremely compact Au coatings above the nanofiber coatings could hinder the direct contact of enzymes with CsgAHis-tag nanofiber coatings and thus protected the nanofiber layers from enzymatic digestion.

Motivated by the impressive durability of CsgAHis-tag nanofiberenabled Au conductive coatings, we next turned to explore more exciting applications based on such coatings. We first coated PET textiles with CsgAHis-tag nanofibers and then fabricated Au-coated conductive textiles (fig. S6A). Photographic and SEM images indicated the vast differences between textiles in apparent color and micromorphology after the formation of Au coatings (Fig. 3G). Furthermore, energy-dispersive spectroscopy (EDS) result implied the uniform distribution of Au on the textile surface, and electron backscatter diffraction (EBSD) analysis showed that the in situ generated Au NPs were closely anchored on the entire PET textile (fig. S6, B and C). We next constructed a pressure sensor based on our Au-coated PET textiles (Fig. 3H, inset). Briefly, we first used the Au-coated PET textile to cover the aforementioned PDMS-based Au interdigital electrode and sealed it with 3M VHB tape. The constructed pressure sensor worked as designed following a specific working principle as follows: When a certain pressure that led to the compression of the hierarchical porous textile was applied, the contact area between the textile and electrode was increased, so the contact electric current increased correspondingly under a constant voltage. When the external pressure was removed, the textile recovered from the deformation because of its inert elasticity, and the current returned to the initial state (42). The large surface area and sufficient surface roughness of the Au-coated textile, as revealed by SEM and EBSD images (Fig. 3H and fig. S6C), reliably reflect the changes in contact resistance resulting from an external stimulus.

We next carefully conducted several critical tests on the prepared pressure sensor. The sensitivity of the pressure sensor is defined as S = (I/I0) /P, where I is the relative current change, I0 is the current without external pressure, and P is the applied pressure (42). In the range from 1.25 to 17.50 kPa, the relation between the change in current and the applied pressure was linear, and the sensitivity S was 8.3 kPa1 (Fig. 3H). Figure 3I shows two representative current profiles (I/I0) under two different pressures (5 kPa and finger press). After 300 cycles of bending (1-cm bending radius) or 500 cycles of repeated 5-kPa presses, the values of I/I0 under various external pressures had negligible changes, emphasizing the stable performance of the pressure sensor (tables S1 and S2). In general, our pressure sensor has high sensitivity (8.3 kPa1), mechanical flexibility (300 bends), and cycle stability (500 cycles).

Functional protein-immobilized particles have a broad spectrum of applications in biosensor, biocatalysis, and drug delivery (4345). However, existing approaches for protein-based conjugation of microparticles are largely based on nonspecific interactions (e.g., electrostatic interactions in enzyme immobilization on silica) (46). Accordingly, these systems typically lack specificity and functional tunability. Note that CsgA is a genetically engineerable protein, so it can be appended with a variety of functional tags. We next explored the functional flexibility of CsgA coatings for diverse applications ranging from fluorescent coating materials to enzymatic immobilization on spherical particles for optimized bioconversion reactions. To this end, we first developed CsgASpyTag (SpyTag fused at the C terminus of CsgA)/CsgASnoopTag (SnoopTag fused at the C terminus of CsgA)coated SiO2 microparticles as a platform to enable easy and flexible conjugation reaction systems (Fig. 4A). SpyTag and SnoopTag can covalently conjugate with their partners, SpyCatcher and SnoopCatcher, respectively (47, 48). Therefore, our CsgASpyTag/CsgASnoopTag coatings should be suitable for ligation of corresponding SpyCatcher- and SnoopCatcher-fused proteins.

(A) Illustration of CsgASpyTag/CsgASnoopTag (1:1, weight ratio)coated microparticles. (B) SEM images of a CsgASpyTag/CsgASnoopTag-coated SiO2 microparticle. (C) Schematic showing fluorescent proteins conjugated on CsgASpyTag/CsgASnoopTag nanofiber (top) and fluorescence microscopy images of corresponding fluorescent proteinconjugated CsgASpyTag/CsgASnoopTag-coated microparticles. (D) Schematic showing the immobilization of LDHSpyCatcher and GOXSnoopCatcher on a CsgASpyTag/CsgASnoopTag-coated microparticle. (E) Illustration of a dual-enzyme reaction system enabled by LDHSpyCatcher and GOXSnoopCatcher co-conjugated microparticles. (F) Conversion ratio of l-tert-leucine in two different microparticle systems (LDHSpyCatcher and GOXSnoopCatcher co-conjugated together on CsgASpyTag/CsgASnoopTag coatings versus LDHSpyCatcher-conjugated CsgASpyTag coatings along with GOXSnoopCatcher-conjugated CsgASnoopTag coatings) during a 3-hour reaction period. (G) Conversion ratio of l-tert-leucine in the CsgASpyTag/CsgASnoopTag coating system over five cycles of 3-hour reactions.

SEM images showed that the SiO2 microparticle surface was successfully covered with CsgASpyTag/CsgASnoopTag nanofibers (Fig. 4B). Furthermore, the fluorescence spectra revealed that, compared to pristine particles, CsgASpyTag/CsgASnoopTag-coated microparticles exhibited an obvious enhancement in fluorescence intensity at 480 nm induced by the specific interaction between ThT molecules and -sheet structures (fig. S7A). ATR-FTIR analysis of CsgASpyTag/CsgASnoopTag-coated microparticles showed an obvious absorption peak at ~1625 cm1 corresponding to a -sheet structure (fig. S7B) (49). In addition, XPS analysis of CsgASpyTag/CsgASnoopTag-coated microparticles revealed characteristic peaks of amide bonds originating from the coated proteins (fig. S7C). All the above results highlighted that the surface of SiO2 microparticles could be modified by our CsgASpyTag/CsgASnoopTag nanofiber coatings. Subsequent fluorescence microscopy images showed that these nanofiber-coated SiO2 microparticles displayed uniform bright red, green, and merged yellow fluorescence, confirming that SpyCatcher-fused mCherry (mCherrySpyCatcher) and SnoopCatcher-fused GFP (GFPSnoopCatcher) were successfully conjugated on the particle surfaces (Fig. 4C). Note that the microspheres stacking to each other displayed heterogeneous fluorescence strength in the image, which was likely due to their different focal planes under the fluorescence microscopy. Collectively, these results illustrate an alternative way of using nanofiber-coated microparticles to realize diverse applications.

We next applied a similar strategy to achieve multienzyme immobilization coupling with coenzyme regeneration. To this end, we first constructed SpyCatcher domainfused leucine dehydrogenase (LDH; EC1.4.1.9; LDHSpyCatcher) and SnoopCatcher domainfused glucose oxidase (GOX; EC1.1.3.4; GOXSnoopCatcher) and coimmobilized on the CsgASpyTag/CsgASnoopTag-coated SiO2 microparticle (Fig. 4D). In this proof-of-concept reaction system, trimethylpyruvic (TMP) acid was converted into the high-value chemical l-tert-leucine by LDH from the soil bacterium Lysinibacillus sphaericus, a reaction that requires NADH [reduced form of nicotinamide adenine dinucleotide (NAD+)] as a coenzyme. Moreover, GOX from Bacillus subtilis can regenerate NADH by oxidizing low-value glucose into gluconic acid (Fig. 4E) Therefore, these two enzymes could assemble into an NADH-recycling system (Fig. 4E). We chose LDHSpyCatcher and GOXSnoopCatcher conjugated onto CsgASpyTag- and CsgASnoopTag-coated microparticles, respectively, as a control group. We used high-performance liquid chromatography (HPLC) to analyze the conversion ratio of l-tert-leucine.

As shown in Fig. 4F, in the first 3-hour reaction, the conversion ratio of l-tert-leucine in the CsgASpyTag/CsgASnoopTag coating system was about 50%, whereas there was only 30% conversion in the control system. We speculate that the substantial disparity may lie in substrate channeling (50). That is, in the CsgASpyTag/CsgASnoopTag coating system, the generated NADH could be immediately consumed by adjacent LDHSpyCatcher on the same particle surface. However, in the control system, the produced NADH would not be used until it arrived at the surface of LDHSpyCatcher-conjugated particles, thereby resulting in a slower reaction rate.

To demonstrate the recyclable use of these immobilized enzymes, we recollected the enzyme-conjugated CsgASpyTag/CsgASnoopTag-coated microparticles via simple centrifugation. We then transferred these particles into a new reaction solution and again assessed the conversion ratio of l-tert-leucine. We found that the ratio did not significantly change over a series of five reaction cycles of 3 hours each (Fig. 4G). These experimental results demonstrate that our genetically engineered protein coatings are highly suitable for biocatalytic applications.

RNA-cleaving fluorogenic DNAzyme (RFD) is a well-established technology for detecting bacteria, and the ability to immobilize RFD probes on material surfaces such as the interiors of microfluidic devices is highly demanded because it could enable substantial improvements in the efficiency and speed of detection (5153). Our genetically engineered CsgA fusion coatings represent a potentially alternative approach. We produced CsgADBD proteins with a C-terminally fused DNA-binding domain (DBD) originally from Vibrio fischeri (fig. S8A) (54). We aimed to use this tailored protein to modify the surface of a microfluidic channel and bind E. colispecific RFD probes. We expected that upon interaction with target molecule(s) present in the supernatants of E. coli bacteria, these bound RFD probes would be converted into an active state that can catalyze the cleavage of the fluorogenic substrate, thereby producing a detectable fluorescent signal on the interiors of the microfluidic channel (Fig. 5A) (52).

(A) Schematic diagram of a DNAzyme-bound CsgADBD-coated microfluidic sensor device and an illustration of the DNAzyme detection mechanism. (B) Digital image of the microfluidic device. Photo credit: Yingfeng Li, ShanghaiTech University. (C) Fluorescence intensity of RFD-functionalized CsgADBD- and CsgAHis-tagcoated interiors of microfluidic channels upon exposure to supernatants from E. coli cultures of various cell densities. (D) 3D image of the RFD-functionalized CsgADBD coatings activated by E. coli culture (OD600 = 1) supernatants on the microfluidic channel.

To demonstrate the feasibility of our general design, we first incubated CsgADBD nanofibers with RFD probes. Agarose gel electrophoresis analysis indicated that CsgADBD nanofibers were able to bind these probes (fig. S8B). A standard PDMS microfluidic device was used for this experiment (Fig. 5B). We first coated the interior of a microfluidic channel and then conducted a Ni-NTAcapped QD binding test (the His-tag used for purification of CsgADBD protein can also be used to bind these QDs). The fluorescence microscopy image indicated that the channel interiors were homogeneously modified by CsgADBD proteins (fig. S8C). We next tested the detection performance by injecting a filtered supernatant from an E. coli culture into the channel and found that the CsgADBD-coated channel generated a strong fluorescent signal, whereas a control channel with a CsgA coating did not (Fig. 5C). Moreover, the fluorescence intensity increased linearly with the number of E. coli cells present in the samples [measured as OD600 (optical density at 600 nm); Fig. 5C]. In addition, 3D reconstructed images from fluorescence microscopy further confirmed that the resulting fluorescence was on the channel surface (Fig. 5D). These results establish proof of concept for the use of our genetically engineered protein coatings in diagnostic devices to monitor specific infectious pathogens.

In summary, we demonstrate that genetically engineered CsgA fusion proteins can be used as a functional coating system. These coatings have substrate universality, ultrastability, and genetically programmable functions. We also confirm that genetically engineered CsgA fusion protein nanofibers can modify various substrates with different compositions, sizes, shapes, and structures and show that these coatings exhibit outstanding chemical robustness. Moreover, these protein coatings offer flexible genetically programmable functionalization (e.g., NP anchoring, protein conjugation, and DNA binding). By combining the coatings with various fabrication processes, we established multiple proof-of-concept applications, including touch switching, pressure sensing, enzyme immobilization, and microfluidic sensors for bacterial detection. Given these unique coating features and the development of protein conjugation technologies, our genetically engineered CsgA fusion protein nanofiber coatings should serve as a versatile surface functionalization platform for electronics, biocatalysis, textiles, biomedicine, and other application areas.

All genes were synthesized by GENEWIZ and then amplified by polymerase chain reaction. The DNA fragment was cloned into pet-22b vectors (Nde I and Xho I sites) using one-step isothermal Gibson assembly. All constructs were sequence-verified by GENEWIZ.

For CsgAHis-tag, CsgASpyTag, CsgASnoopTag, or CsgADBD protein, the corresponding plasmid was transformed into BL21(DE3) E. coli competent cell. The bacterial seed was grown for 16 hours at 37C in shaking flasks (220 rpm/min) containing 20 ml of LB medium supplemented with carbenicillin (50 g/ml). The culture was then added into 1 liter of LB and grown to OD600 ~1.0. Protein expression was induced with 0.5 mM isopropyl--D-thiogalactopyranoside (IPTG) at 37C for 45 min. Cells were collected by centrifugation for 10 min at 4000g at 4C. The cell pellet was then lysed in 50 ml of GdnHCl [8 M, 300 mM NaCl, 50 mM K2HPO4/KH2PO4 (pH 8)] for 12 hours at room temperature. Supernatants of the lysates were collected at 12,000g for 30 min before loading in a His-Select Ni-NTA column. The column was washed with KPI [300 mM NaCl, 50 mM K2HPO4/KH2PO4 (pH 8)] buffer and 40 mM imidazole KPI buffer and then eluted with 300 mM imidazole KPI buffer.

For mCherrySpyCatcher, GFPSnoopCatcher, LDHSpyCatcher, or GOXSnoopCatcher protein, the corresponding plasmid was transformed into BL21(DE3) E. coli competent cell. Cell seeds were cultured for 16 hours at 37C in LB broth containing carbenicillin (50 g/ml). The culture solution was then added into 1 liter of LB and grown to OD600 ~0.6. Protein expression was induced with 0.5 mM IPTG for 12 hours at 16C. Cells were collected by centrifugation for 10 min at 4000g at 4C. The collected cell pellets were then resuspended in KPI solution (50 ml) containing lysozyme (1 mg/ml) and incubated on ice for 30 min before ultrasound disruption. The purification follows the same procedure used for purification of the genetically engineered CsgA proteins. The purified proteins were stored at 4C for later use.

To enable coating formation, given substrates (plates, pyramids, or textiles) were directly immersed in fresh eluted CsgAHis-tag monomer (1 mg/ml) solution. After 16 hours of incubation at room temperature (~25C), proteins could form nanofiber coatings on substrates. The coated substrates were then washed by deionized H2O and dried by clean N2 and finally stored in a desiccative cabinet (~25C) for further use.

To coat microparticles with functional proteins, 1 ml of CsgASpyTag, CsgASnoopTag, or CsgASpyTag/CsgASnoopTag (1:1, weight ratio) monomer solution (1 mg/ml) was added into 2-ml tube containing 100 l of SiO2 aqueous solution (25 mg/ml). After 16 hours of incubation at room temperature (~25C), microparticles were collected by centrifugation for 5 min at 1000g and washed by deionized H2O followed by further centrifugation. This process was repeated for three times to remove the loosely bound proteins. The coated microparticles were then stored in a 4C refrigerator for further use.

PDMS channel was first fabricated by replica molding of a glass model and then pressed on the surface of a clean glass slide. To coat the PDMS microfluidic device channel, fresh eluted CsgADBD monomer solution was directly injected into the channel using a syringe and incubated for 16 hours at room temperature (~25C). The microfluidic channel was then washed by deionized H2O through injection. The microfluidic device was stored in the refrigerator (4C) for further use.

Synthesis of Ni-NTAcapped QDs was performed following a previous report (33). To ensure thorough QD binding on protein-coated flat substrates, the substrates were immersed in the aqueous QD solution (ca. 500 nmol/ml) at room temperature (~25C) and incubated for 30 min. The substrates were then washed by deionized H2O and dried by high-pressure N2 for further characterization. To ensure QD binding in a microfluidic device, QD solution was injected into the channel using a 1-ml syringe. After incubation for 30 min at room temperature (~25C), the channel was washed by deionized H2O for further characterization.

For the stability test of CsgAHis-tag coatings in organic solvents, 30 ml of acetone, hexane, or DMSO was poured into a 9-cm glass culture dish containing the CsgAHis-tagcoated PTFE substrates. After challenge at room temperature (~25C) for 24 hours, the PTFE substrates were washed by deionized H2O and dried by high pressure N2 for further characterization. For the high temperature challenge, CsgAHis-tagcoated PTFE substrates were directly placed in an oven (90C) for 24 hours and then taken out for further characterization.

CsgAHis-tagcoated PTFE substrates or Au-coated PET substrates were placed in 9-cm culture dishes containing 30 ml of solution of trypsin (2.5 mg/ml) from bovin pancreas or fungal protease (55 U/g) from A. oryzae (protease AO). After incubation at 37C for 24 hours, substrates were washed by deionized H2O and dried by high-pressure N2 for further characterization. For ThT assay, 100 l of enzyme solution (trypsin, 2.5 mg/ml or fungal protease, 55 U/g) was added into the 96-well microplate containing 100 l of CsgAHis-tag nanofiber protein solution (0.5 mg/ml). ThT was then added to a concentration of 20 M. Fluorescence was measured every 0.5 min after shaking 5 s with a BioTek Synergy H1 microplate reader (excitation at 438 nm, emission at 495 nm, and cutoff at 475 nm) at 37C.

Preparation of Ni-NTAcapped Au NPs was based on a previous report (33). To perform a gold enhancement process, CsgAHis-tag nanofibercoated pyramid or textile substrates were first immersed into Ni-NTAcapped Au NP solution. After incubation at room temperature (~25C) for 30 min, the substrates were washed with deionized H2O and dried by high-pressure N2. The substrates were then transferred into a 50-ml gold enhancement solution containing AuCl4 (50 mg/ml) and hydroxylamine (100 mg/ml). After reaction for 10 min at room temperature (~25C), substrates were washed by deionized H2O and dried by high-pressure N2.

To prepare patterned Au coatings including interdigital electrode, substrates were first covered by waterproof stickers followed by producing patterned CsgAHis-tag nanofiber coatings through protein solution incubation. The patterned CsgAHis-tag nanofiber coatings were then bound with Ni-NTAcapped Au NPs, followed by a standard gold enhancement procedure described above. After drying, the stickers were carefully peeled off using a tweezer to produce the patterned CsgAHis-tag nanofiberenabled Au coatings.

Bare PET fabric was attached on the Au conductive coatings formed on a PET plate, followed by placing a 2-kg counterweight on the fabric. The abrasion test was achieved by moving the bare PET fabric. Sheet resistance of PET-based conductive coatings was measured with a four-probe ohmmeter (HPS 2523).

The capacitance of the interdigital electrode was measured with an LCR (inductance, capacitance, and resistance) meter (HG2817A) at a voltage of 1 V and a frequency of 100 kHz at room temperature (~25C). To fabricate the pressure sensor, Au-coated PET textile was covered on the PDMS-based Au interdigital electrode. Then, the textile and bottom Au electrode were sealed with a 3M VHB tape. Functional performances of the pressure sensor including current change under different pressures were assessed with an electrochemical work station (CHI 660E) at room temperature (~25C).

For fluorescent protein conjugation, 1 ml of mCherrySpyCatcher/GFPSnoopCather (1:1, weight ration) aqueous solution (1 mg/ml) was added into a 2-ml tube containing the CsgASpyTag/CsgASnoopTag-coated SiO2 microparticles. After incubation for 1 hour at room temperature (~25C), fluorescent proteinconjugated microparticles were collected by centrifugation for 5 min at 1000g and washed by KPI solution followed by further centrifugation. This process was repeated for three times to remove those unreacted loosely bound fluorescent proteins.

For enzyme immobilization, 1 ml of LDHSpyCatcher, GOXSnoopCather, or LDHSpyCatcher/GOXSnoopCather (1:1, weight ration) aqueous solution (1 mg/ml) was added into a 2-ml tube containing the CsgASpyTag-, CsgASnoopTag-, or CsgASpyTag/CsgASnoopTag-coated SiO2 microparticles, respectively. After incubation for 1 hour at room temperature (~25C), the enzyme-immobilized microparticles were collected by centrifugation for 5 min at 1000g and washed by 100 mM phosphate buffer followed by further centrifugation. This process was repeated for three times to remove those unreacted loosely bound enzymatic proteins.

The enzyme-immobilized microparticles were resuspended in 100 l of 100 mM phosphate buffer, 50 l of LDHSpyCatcher immobilized microparticles, and 50 l of GOXSnoopCatcher immobilized microparticles added into the reaction solution, or 100 l of LDHSpyCatcher/GOXSnoopCatcher immobilized microparticles was directly pipetted into the reaction solution. The reaction mixture containing 50 mM glucose, 0.1 mM NAD+, 50 mM ammonium chloride, 50 mM TMP acid, and 100 mM phosphate buffer (pH 8.0) was fixed with a final volume of 1 ml. The reaction was then conducted at 37C under continuous shaking in a microplate reader.

To analyze the yield of l-tert-leucine, a 20-l sample was filtered with a 220-nm syringe filter and analyzed by reversed-phase HPLC using a 1200 Series chromatograph and ZORBAX SB-C18 column (4.6 mm 150 mm, 5 m) at 35C. The mobile phase composed of 2 mM CuSO4 was set with a flow rate of 1.0 ml/min. Quantitative analysis of the l-tert-leucine was monitored with a UV spectra detector at 210 nm (55).

The yield of l-tert-leucine was determined using the following equation=Practical concentration of L-tert-leucineTheoretical concentration of L-tert-leucine(50mM)100%

For recyclable usage of the enzymes, the LDHSpyCatcher/GOXSnoopCatcher immobilized microparticles were collected by centrifugation for 5 min at 1000g after each round of reaction. The microparticles were then resuspended in 100 l of 100 mM phosphate buffer and pipetted into a new reaction solution for another new round of reaction. The yield of l-tert-leucine in the new reaction system was determined following the same equation.

The synthesis of RFD probes was based on a protocol described in a previously published study (52). The microfluidic channel was then homogeneously coated with CsgADBD proteins following a typical fabrication protocol described in the coating fabrication process.

To ensure thorough binding of RFD probes onto the protein coatings on the microfluidic channel, DNAzyme in 100 mM tris-HCl (pH 8.0) and 0.2 mM EDTA binding buffer was injected into the microfluidic channel. After incubation for 2 hours at room temperature (~25C), the channel was washed with 1 ml of injected 100 mM tris-HCl to remove loosely bound RFD probes.

E. coli K12 (MG1655) cell culture with different cell densities (OD600) was injected into the channels after filtration using a 220-nm PTFE filter. The channel was monitored by fluorescence microscopy, and the relative fluorescence intensity was calculated using the imaging software of the fluorescence microscopy.

Samples were tested with Asylum MFP-3D-Bio using the tapping mode with AC160TS-R3 cantilevers (Olympus, k 26 N/m, 300 kHz). The data are presented in Fig. 2B and figs. S1B, S2C, and S8A.

The water contact angle of samples was tested with a contact angle goniometer (SL200KS). The substrate was placed on the stage, and 1-l droplet of water was dropped onto the surface of the substrate. The data are presented in Fig. 2 (A, F, G, and H) and fig. S2 (C, G, and H).

XPS spectrum was obtained with Thermo Fisher Scientific ESCALAB 250 Xi. The data are presented in Figs. 2C and 3D and fig. S7C.

NanoDSF curve was obtained with NanoTemper Prometheus NT.48. The data are presented in fig. S2A.

Samples were coated with Au for 30 s with an SBC-12 sputter coater. SEM images including EBSD and EDS images were acquired with JEOL 7800 Prime or JSM-6010. The data are presented in Figs. 3 (C and G) and 4B and figs. S2 (F to H), S4 (B to D), S5B, and S6 (A to C).

TEM images were obtained on an FEI T12 transmission electron microscope operated at 120-kV accelerating voltage. The data are presented in fig. S3A.

Protein-coated microparticles, bare microparticles, or protein nanofibers were put on the ATR crystal directly. Spectra were recorded from 1700 to 1600 cm1 using a nominal resolution of 2 cm1 with Spectrum Two (PerkinElmer). The data are presented in figs. S2B and S7B.

Fluorescence imaging was performed on an Olympus IX83, Leica DMi8, or LSM 710 fluorescence microscope. Cy5 channel of Leica DMi8 was used to image RFD. The data are presented in Figs. 4C and 5D and fig. S8C.

Photoluminescence spectra were collected using HORIBA FL-3 with excitation at 350 nm. The data are presented in figs. S1A and S7A.

Acknowledgments: We thank X. Wang for AFM training. AFM characterization was executed at the Analytical Instrumentation Center (AIC), and SEM and TEM characterization were performed at the Electron Microscopy Center (EMC) at School of Physical Science and Technology (SPST), ShanghaiTech University. Funding: This work was partially sponsored by the Commission for Science and Technology of Shanghai Municipality (grant no. 17JC1403900), the Joint Funds of the National Natural Science Foundation of China (Key Program No. U1932204), and the National Science and Technology Major Project of the Ministry of Science and Technology of China (grant no. 2018YFA0902804). C.Z. also acknowledges start-up funding support from ShanghaiTech University and 1000 Youth Talents Program, granted by the Chinese Central Government. Author contributions: C.Z. conceived the concept and directed the research. C.Z., Y.L., and K.L. designed and conducted the experiments and data analysis. X.W. synthesized QDs and performed TEM. M.C. participated in coating fabrication process. P.G. and J.Z. fabricated microfluidic devices. F.Q. participated in protein purification. C.Z., Y.L., and K.L. wrote the manuscript with help from all authors. Competing interests: The authors have filed a provisional patent based on this work with the China Intellectual Property Office (PCT/CN2018/085988). The authors declare no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Conformable self-assembling amyloid protein coatings with genetically programmable functionality - Science Advances

There is no silver bullet to the ability to feed a global population of more than 9 billion people by 2050. There is a menu of solutions across many sectors of the food economy, according to Jack Bobo, CEO of food consultancy firm Futurity, who spoke May 21 during Alltechs ONE Virtual Experience.

When it comes to sustainability, the ideas of local sustainability vs. global sustainability are often very different from each other, Bobo said.

When we think about local sustainability, thats really how most consumers think about sustainability, because theyre thinking about farmers using less fertilizer and less insecticide and producing things in a way that doesnt have runoff into the local environment, he said. They want to have less of an impact of agriculture on the land.

But, he pointed out, methods such as organic agriculture result in 20-30% less food for a given amount of land.

Imagine for a moment that the entire world were organic: What would that mean? he asked. Well, the main thing it would mean is that we just wouldnt have any forest anymore, because we would need 20% to 30% more land in order to produce the food we have. And 40% of all the land on earth is already used for agriculture. So that would have a devastating impact.

For this reason, the concept of global sustainability is the opposite of local sustainability.

Its about prioritizing intensive agriculture in one place in order to protect the environment somewhere else, he said. That could mean more intensive livestock production through contained animal feeding where you see the environmental impact locally of that intensive agricultural production. But what you dont see is that you dont need to have more animals going out into in Brazil, where they have to cut down forests in order to make way for expanded livestock production. So, you dont see the land protected; you only see the local impact. This comparison between local and global sustainability is part of the different story that were telling.

But, Bobo said we need local and global sustainability; neither one is right or wrong.

Its really about choices and consequences, he said. But there are consequences to the choices we make.

Those choices the menu of solutions will be different across various regions or sectors, and they will all work together to create a better food production system to feed the world.

Rather than thinking about sustainability as farming is the problem, I like to think that Im just happy that consumers and conservationists are now joining farmers on this journey of sustainability, because we could use their help, he said. And instead of framing it as agriculture is the problem to be solved, we need to help them to understand that agriculture is the solution to the problem.

Some of the solutions Bobo discussed include:

Shifting diets: For many, if we would all just become vegan or vegetarian, we wouldnt have any problems, he said.

But, while there is a need for a healthier diet in the developed world, in low-income regions, people eat more protein as their income increases.

So, even if we do shift diets in the United States and Europe and places like that, people are going to be shifting their diets in a way that increases the impact of agriculture in most places around the world, he said.

Food waste: One-third of all the food produced is lost to food waste, Bobo said. The good news is that people are much more focused on this issue than they were 20 years ago. But, in the developed world, that waste is post-consumer whereas in the developing world, the waste happens along the supply chain.

Addressing food waste is hard, because food waste is not one problem. Food waste is a thousand problems, he said. Food waste doesnt just occur in the field. It doesnt just occur in storage. It doesnt just occur during distribution. It occurs at all of these different points along the supply chain.

Cover crops: While organic farmers have advocated for cover crops for decades, big data has shown a return on investment that has larger farmers also adopting this low-tech solution.

Cover crops are adding some nutrients theyre reducing soil erosion, he said.

Gene editing and genetic engineering: These are more high-tech solutions to increasing crop production and lowering environmental impact. Plants can be genetically engineered to be resistant to insect damage or be more tolerant to drought, for example.

There are all sorts of solutions to the problems of agriculture. And they occur, whether its organic, high tech, or otherwise, he said.

Alternative proteins: Whether its companies that create alternative proteins through fermentation, cellular technology or plant-based products, they are all competing for market share instead of working together toward a solution.

When we think about trying to feed the world in 2050, the market opportunity is $1 trillion dollars just in the protein space, he said. Who really believes that plant-based meat is going to become a trillion-dollar industry in just 30 years? And even if, somehow, they did become a trillion-dollar industry, so what? We wouldnt lose a single cow, we wouldnt lose any cattle. Wed still be producing all of that food in the same way that we did, and hopefully, in a much, much more environmentally friendly way.

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Menu of solutions, no silver bullet, to feed the world - FeedStrategy.com

Walking towards the school gate, as I adjusted the N-99 face mask on my four-year-old, I felt deeply disturbed. The AQI numbers in our city had soared to hazardous levels and the air pollution was causing worrisome adverse effects on the tiny lungs of our children.

Pollution was not the only cause for anxiety. The extreme weather conditions, the rise of vector-borne diseases like dengue and chikungunya, the continuing emergence of novel viruses, the increasing resistance of infectious agents to medication: everything was pointing towards an extremely grim future in the world of health. The thought of our children being the bearers of such a future perplexed me, both as a mother and as a pulmonologist.

Thus started my exploration of the obvious, yet oft-ignored, changes taking place in our ecosystems and led me to my research on climate change.

The AQI numbers in our city had soared to hazardous levels and the air pollution was causing worrisome adverse effects on the tiny lungs of our children. (Photo: Reuters)

The direct effects of climate change on our health are easy to guess. The average global temperature of the earth, which has increased by 1C since the pre-industrial era, is rising at a rate of 0.2C per decade. It may soon reach a level that is irreversible (2.5C above the pre-industrial average). 95 per cent of this global warming is being caused by greenhouse gases, the atmospheric levels of which are increasing alarmingly due to human activities. This global warming is causing melting of ice masses, the rise of sea levels and major alterations in regional precipitation patterns, resulting in unprecedented and extreme weather conditions heatwaves, wildfires, earthquakes, floods, tsunamis and snow-storms. These natural calamities are leading to deaths, diseases, malnutritionand mental health issues. Extreme temperatures are causing heat strokes, respiratory and cardiovascular diseases. Greenhouse effects are leading to diseases because of air pollution.

But what is more important and less obvious is the gradual and persistent damage that is being caused by climate change to the natural habitats and ecosystems of the world, and its quietyet devastating effects on our health.Think about it why are we having newer and frequent viral infections to deal with? Why are our children falling sick so often? Why is every simple viral cough leading to bronchitis? Why is the prescription of anti-inflammatory inhalers, medicines that were reserved for asthmatics, increasing rampantly?

Climate change, human behaviour and emerging infections

75 per cent of emerging infectious diseases, like Influenza, HIV/AIDS, Ebola, SARSand MERS are zoonotic. It means that they exist in animals but can be transmitted to humans.Most of them are caused by viruses predominantly RNA viruses.

Loss of Biodiversity: Climate change and land loss cause loss of habitat, leading to extinction or relocation of native species, with growing predominance of invasive, resilient species. These become likely to harbour and transmit pathogens (so-called reservoir hosts). In a healthy ecosystem, where biodiversity is high, multiple species dilute the effect of the reservoir species, the so-called dilution effect. Studies on hantavirus, West Nile virus etc. have shown strong links between low biodiversity and high rates of viral transmission.

The average global temperature of the earth, which has increased by 1C since the pre-industrial era, is rising at a rate of 0.2C per decade. (Photo: Reuters)

Migration of species: Global warming causes many species to migrate away from the equator and toward higher altitudes, bringing them in contact with new pathogens, to which they have not evolved resistance. These animals are also stressed and immunosuppressed, hence more susceptible to infection.

Contact with humans: Disruption of pristine forests by anthropogenic activities like mining,road building, urbanisation and livestock ranching brings people into closer contact with forest species, increasing the interaction between them. Ebola fever has had several outbreaks in Africa since 1970 because of increased interaction of local population with fruit bats due to population growth and encroachment into forest areas. Kyasanur forest disease, once limited to Karnataka, has spread to adjacent states over the last five years, because of conversion of forests into plantations and paddy fields, that has brought the locals nearer to monkeys.

Intermediate hosts and inter-species transmission: Although most of the novel viruses, including SARS-CoV-2, are generalist viruses that infect many different hosts, jumping into human species from wildlife species is not easy because of significant biological barriers. Transmission from mammalian species which are genetically closer to humans (the intermediate hosts), like pigs, is easier. Pig farming around forests facilitated the transmission of Nipah virus from bats in Malaysia, and civet cats sold in wet markets transmitted SARS-CoV from bats in China.

The market connection: In informal wet markets, animals are slaughtered, cut up and sold on the spot. The Wuhan wet market soldnumerous wild animals - live pangolins, wolf pups, crocodiles, foxes, civets. Wet markets in Africa sell monkeys, bats, birds, etc. They are a perfect platform for cross-species transmission of pathogens as novel interactions with a range of species occur in one place. 39per cent of the early cases in the SARS outbreak were wildlife food handlers, likely connected to the wet market of Guangdong, China.

The Wuhan wet market sold numerous wild animals, making it a perfect platform for cross-species transmission of pathogens.

Human transmission: Once inside new hosts, most viruses, fortunately, adapt, replicate and transmit inefficiently. Out of the 1,399 recognised human pathogens, 500 are transmissible between humans, and only 100to 150 are sufficiently transmissible to cause epidemics or pandemics. Restrictions occur at many cellular levels like entry into host cells by receptor binding, trafficking within cell, genome replication and gene expression. Each barrier requires a corresponding genetic change or mutation in the virus. RNA viruses, especially single-stranded RNA viruses like coronavirus, replicate rapidly and are prone to mutations due to lack of a proofreading mechanism. Only after extensive replications and re-assortments in the genome of H3N2 influenza A virus, was it capable of causing the 1968 pandemic.

Human behavioural changes: Factors like international travel, international trade of wildlife, urbanisation, and increase in population density further facilitate transmission.

Covid-19: What do we know?

In late December 2019, Wuhan Centre for Disease Control and Prevention detected a novel coronavirus in two hospital patients with atypical pneumonia. It sent the samples to the Wuhan Institute of Virology for further investigation. The genomic sequence of the virus, eventually named SARS-CoV-2, was 96 per cent identical to that of a coronavirus identified in horseshoe bats in a bat-cave in Yunnan during virus-hunting expeditions. It belonged to the SARS group of coronaviruses.

The expeditions were carried out by the Director of the Centre for Emerging Infectious Diseases at the Wuhan Laboratory, Shi Zhengli (nicknamed Chinas Bat-woman) and her team, from 2004 for over 16 years, in an attempt to isolate the SARS coronavirus. They discovered hundreds of bat-borne coronaviruses with incredible genetic diversity in bat-caves deep inside forests. In bat dwellings, constant mixing of different viruses creates a great opportunity for dangerous new pathogens to emerge and the bats turn into flying factories of new viruses.

But bats were not present at the Wuhan wet market. The wild pangolin, sold for its exotic meat and medicinal scales, became suspect as an intermediate host when a SARS-CoV-2 like coronavirus was discovered in pangolins that were seized in illegal trade markets in southern China.

Whether or not the SARS-CoV-2 was accidentally or deliberately released from the Wuhan Laboratory is a debate not proven. None of the coronaviruses that were under study in this laboratory were identical to the SARS-CoV-2 virus. Also, researchers believe that the spike proteins present on the viral surface, that target the ACE2 receptors on human cells, are so effective in binding the virus to the cells, that they could have developed only by natural selection and not by genetic engineering. When computer simulations were carried out, the mutations in the SARS-CoV-2 genome did not work well in binding the virus to human cells, leading to the argument that if scientists were to deliberately engineer the virus, they would not choose mutations that computer models suggested did not work.

A recent analysis done in China estimates that there are now more than 30 strains of the virus spread across the globe.(Photo: Reuters)

Whatever the origin of the virus, the response to develop what is needed to control the present outbreak remains the same, as do the policies needed to prevent such outbreaks in the future.

A recent analysis done in China estimates that there are now more than 30 strains of the virus spread across the globe. This means that it has already mutated 30 times, which filters down to roughly one mutation every two weeks. More studies are needed to determine the effects of these mutations on the virulence and transmissibility of the virus. But going by the rapidity with which Covid is taking over the world, it should be an easy guess.

So really, is the Covid-19 pandemic a surprise? Not at all. It was coming, and so will others.

Covid-19 has thrown us into a world of turmoil and uncertainty. The impacts on health and economy have been devastating. The only thing that is flourishing is nature! Maybe nature will make us see what innumerable climate-related world conferences could not. It is there for us to appreciate in its full glory the blue skies, the clean air, the blooming flowers, the variety of birds and the wild creatures returning to claim the land that was once theirs. Nature is sending us a message. It would do us good to heed to it.

Also read| I don't believe you: Donald Trump, world's biggest climate change denier

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Climate change and coronavirus: Is the Covid-19 pandemic really a surprise? - DailyO

Global RNA and DNA Extraction Kit Market: Overview

RNA and DNA extraction plays a crucial role in cancer genetic studies, which involves mutation analysis, comparative genomic hybridization, and microsatellite analysis. The rising incidences of cancer globally are creating a need for the advanced RNA and DNA extraction kit and are expected to drive market growth in the coming years.

Based on the product, the market is expected to segregate into RNA extraction kit and DNA extraction kit. Of these, the DNA extraction kit segment is expected to account for the leading share in the overall RNA and DNA extraction kit market. Additionally, the applications of DNA extraction kits mainly in the genetic engineering of animals and plants in pharmaceutical manufacturing. This is expected to fuel growth of RNA and DNA extraction kit market.

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Global RNA and DNA Extraction Kit Market: Notable Developments

Some of the key players in the global RNA and DNA extraction kit market include Agilent Technologies Inc., Merck KGaA, Bio-Rad Laboratories Inc., Thermo Fisher Scientific Inc., and QIAGEN. Introduction of new products is benefiting growth of the global RNA and DNA extraction kit market.

Global RNA and DNA Extraction Kit Market: Drivers and Restraints

The rise and progress in customized drug have helped social insurance experts create exact sub-atomic focused on treatment dependent on a persons hereditary cosmetics and prescient information explicit to patients. The advancement of customized medication requires genome-mapping investigations of separated cells, which can be completed with the assistance of DNA and RNA extraction kits. DNA extraction kits are utilized to recognize quality polymorphisms identified with sickness or medication digestion though RNA extraction kits are utilized to break down RNA combination in separated cells. With the expanding appropriation of customized prescription, the demand for RNA and DNA extraction kits will likewise develop.

There is a developing rate of malignant growth over the globe. The inside and out understanding of tumor hereditary qualities given by trend-setting innovations in malignant growth research has empowered the advancement of novel treatments to battle disease-causing qualities. The virtue, amount, and nature of separated RNA assume a huge job in the accomplishment of RNA examination and examination and consequent capacity of specific quality articulation. RNA extraction likewise helps in recognizing circulating tumor cells (CTCs) and non-intrusive observing of cutting edge malignant growths.

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Global RNA and DNA Extraction Kit Market: Regional Outlook

On the basis of region, the RNA and DNA extraction kit market is segmented into North America, Europe, Latin America, Asia Pacific, and the Middle East & Africa. Of these, North America is expected to dominate the global RNA and DNA extraction kit market owing to robust innovation procedures running in the region. This factor is expected to offer robust growth opportunities to key players in RNA and DNA extraction kit market. Additionally, increasing demand for the automated systems coupled with the rising need for the RNA and DNA extraction kit across the extraction kits especially in the medical diagnosis is expected to drive growth of the market in coming years.

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RNA and DNA Extraction Kit Market Supply and Demand with Size (Value and Volume) by 2028 - Cole of Duty

The report on the CRISPR And CRISPR-Associated (Cas) Genes market provides a birds eye view of the current proceeding within the CRISPR And CRISPR-Associated (Cas) Genes market. Further, the report also takes into account the impact of the novel COVID-19 pandemic on the CRISPR And CRISPR-Associated (Cas) Genes market and offers a clear assessment of the projected market fluctuations during the forecast period. The different factors that are likely to impact the overall dynamics of the CRISPR And CRISPR-Associated (Cas) Genes market over the forecast period (2019-2029) including the current trends, growth opportunities, restraining factors, and more are discussed in detail in the market study.

CRISPR And CRISPR-Associated (Cas) Genes market reports deliver insight and expert analysis into key consumer trends and behaviour in marketplace, in addition to an overview of the market data and key brands. CRISPR And CRISPR-Associated (Cas) Genes market reports provides all data with easily digestible information to guide every businessmans future innovation and move business forward.

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The worldwide CRISPR And CRISPR-Associated (Cas) Genes market is an enlarging field for top market players,

Sales and Pricing AnalysesReaders are provided with deeper sales analysis and pricing analysis for the global CRISPR And CRISPR-Associated (Cas) Genes market. As part of sales analysis, the report offers accurate statistics and figures for sales and revenue by region, by each type segment for the period 2015-2026.In the pricing analysis section of the report, readers are provided with validated statistics and figures for the price by players and price by region for the period 2015-2020 and price by each type segment for the period 2015-2020.Regional and Country-level AnalysisThe report offers an exhaustive geographical analysis of the global CRISPR And CRISPR-Associated (Cas) Genes market, covering important regions, viz, North America, Europe, China and Japan. It also covers key countries (regions), viz, U.S., Canada, Germany, France, U.K., Italy, Russia, China, Japan, South Korea, India, Australia, Taiwan, Indonesia, Thailand, Malaysia, Philippines, Vietnam, Mexico, Brazil, Turkey, Saudi Arabia, UAE, etc.The report includes country-wise and region-wise market size for the period 2015-2026. It also includes market size and forecast by each application segment in terms of sales for the period 2015-2026.Competition AnalysisIn the competitive analysis section of the report, leading as well as prominent players of the global CRISPR And CRISPR-Associated (Cas) Genes market are broadly studied on the basis of key factors. The report offers comprehensive analysis and accurate statistics on sales by the player for the period 2015-2020. It also offers detailed analysis supported by reliable statistics on price and revenue (global level) by player for the period 2015-2020.On the whole, the report proves to be an effective tool that players can use to gain a competitive edge over their competitors and ensure lasting success in the global CRISPR And CRISPR-Associated (Cas) Genes market. All of the findings, data, and information provided in the report are validated and revalidated with the help of trustworthy sources. The analysts who have authored the report took a unique and industry-best research and analysis approach for an in-depth study of the global CRISPR And CRISPR-Associated (Cas) Genes market.The following manufacturers are covered in this report:Caribou BiosciencesAddgeneCRISPR THERAPEUTICSMerck KGaAMirus Bio LLCEditas MedicineTakara Bio USAThermo Fisher ScientificHorizon Discovery GroupIntellia TherapeuticsGE Healthcare DharmaconCRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by TypeGenome EditingGenetic engineeringgRNA Database/Gene LibrarCRISPR PlasmidHuman Stem CellsGenetically Modified Organisms/CropsCell Line EngineeringCRISPR And CRISPR-Associated (Cas) Genes Breakdown Data by ApplicationBiotechnology CompaniesPharmaceutical CompaniesAcademic InstitutesResearch and Development Institutes

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This CRISPR And CRISPR-Associated (Cas) Genes report begins with a basic overview of the market. The analysis highlights the opportunity and CRISPR And CRISPR-Associated (Cas) Genes industry trends that are impacted the market that is global. Players around various regions and analysis of each industry dimensions are covered under this report. The analysis also contains a crucial CRISPR And CRISPR-Associated (Cas) Genes insight regarding the things which are driving and affecting the earnings of the market. The CRISPR And CRISPR-Associated (Cas) Genes report comprises sections together side landscape which clarifies actions such as venture and acquisitions and mergers.

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COVID-19 impact: CRISPR And CRISPR-Associated (Cas) Genes Market Key Players, Product and Production Information analysis and forecast to 2027 -...

From a purely chemical standpoint, a cannabinoid is a cannabinoid and a THC molecule is a THC molecule, no matter how its produced, whether in a lab or grown on a farm. From a legal perspective, a cannabinoid is a cannabinoidat least in Canada. Production and distribution of CBD is held to the same standards as the psychoactive compounds in cannabis.

However, in the US, THC and CBD are legally distinct. After the 2018 Farm Bill passed, hemp and cannabis with extremely low percentages of THCless than 0.3%became federally legal. So while non-psychoactive cannabinoids may act, look, and quack like ducks, they might turn out to be swans.

This possibility has researchers and companies salivating at the medical possibilities and potential profits of the less common cannabinoids contained in cannabis plants. These rarer cannabinoids appear at such low levels that its impractical to extract large quantities from marijuana plants. But a little genetic engineering, a lot of research, and a few metal tanks full of yeast bacteria could make mass-production possible.

Yeast fermentation is an age-old process, familiar to most as a source of beer or bread. But in the scientific community, its known as one of the primary bacteria used to produce biopharmaceuticals (the other is E. coli).

Today, the scientific race is on to study specific cannabinoids other than THC or CBD as treatments for illnesses such as epilepsy. And the commercial race is on to provide those cannabinoids to research institutions.

From a researchers perspective, it doesnt matter how the cannabinoid is produced. Consistency and reliability of supply are required, not sunlight and dirt. While yeast has to be genetically modified to produce a cannabinoid, the end product is genetically identical to its plant-produced counterpart.

While there is no safety or efficacy concern, from a consumer perspective, substance origin can matterif you know about it. But once cannabinoids have been harvested and refined into an oil, its impossible to tell whether they came from a plant or a test tube. They all quack like ducks.

Theres so much territory to explore. Were just taking the first steps, said Cynthia Bryant, the Chief Business Officer at Demetrix, a US company focusing on the potential medical benefits of non-psychoactive cannabinoids for the US pharmaceutical market.

Based out of California, Demetrix is working toward large-scale, non-farming cannabinoid production. And they think yeast fermentation will take them there.

The technology works very well to produce a rare cannabinoid, said Bryant. Once they are up and running, they will be able to quickly and regularly produce large amounts of specific cannabinoids, setting up a supply chain thats reliable enough for pharmaceutical research and medicines. Sales could include oils and crystalized powders for research, clinical trials, and eventually, as active ingredients in medications.

Over a hundred different cannabinoids can be extracted from cannabis plants, but many exist at such low levels that they have never been studied as isolated medical ingredients.

Demetrix has identified the first so-called rare cannabinoid that they want to bring to market. Bryant wouldnt name the specific cannabinoid the company plans to release to market next year, citing trade secrets, and said only that theyve discovered some useful effects.

Insulin, the first biopharmaceutical, was once extracted from pig pancreases. In the late 1970s scientists cloned the gene that makes the human body produce insulin, cut out a piece of DNA from a yeast cell, and inserted the engineered gene into its place. Instead of producing alcohol, the yeast cells became tiny factories that produced insulin.

Suddenly, it was exponentially easier and cheaper to manufacture insulin. The new method was fast, consistent, and scalable, allowing it to be replicated at commercial levels. It is also completely safe. Todays yeast fermentation process is similar, if significantly advanced.

Demetrix mail orders synthetically produced DNA sequences of the enzymes in cannabis that have been identified as instigators of natural cannabinoid production. Scientists then insert the DNA sequence into yeast cells, reprogramming their purpose. The specific methods used to do this vary from company to company and are considered trade secrets. But the general tack of using a microorganism to produce a specific molecule is common across the field.

The modified yeast cultures are then left to ferment and grow in tanks, multiplying and producing large amounts of the desired cannabinoid. Workers then extract the cannabinoids from the yeast slurry, isolate, and purify them.

I think theres going to be a huge need for these cannabinoids, said Bryant. The more cannabinoids are studied, the more medical solutions might be found. So its a good thing that the fermentation field is crowdedand that cannabinoid plant extraction is also plowing forward, Bryant explained. Competition will bring down prices and increase availability, she said. We need all of the various sources.

Far north of Demetrixs Berkeley, CA, base, Canadian company Hyasynth is just about ready for full-scale production of fermented cannabinoids, said Kevin Chen, Hyasynths CEO.

Hyasynth also mail orders DNA sequences, slots them into yeast genomes, and extracts the desired compounds from the slurry to produce medical grade cannabinoids for sale to pharmaceutical companies.

Its the modern way, said Chen, who extolled the same virtues of fermentation over farming as Demetrix does: scale, consistency, speed, and, most especially, specificity. We have full control over which cannabinoid we produce and which we dont.

Fermentation is a process that takes five days, instead of the three months it would take to plant and grow marijuana to use for enzyme extraction, he said. Farming can be difficult. Once you nail down your specific splicing method, fermentation is easy.

Engineered cannabinoids may be superior for pharmaceutical purposes, but not everyone will want cannabis grown in tanks or tubes, Chen acknowledges.

Were not too worried about people rejecting our product, said Chen. Were using yeast to manufacture things, but the yeast isnt what were selling.

From the standpoint of personal preference, not all cannabinoids are equal. Some consumers might prefer a holistic, whole-plant product. Some might only care about results.

Do people care that it comes from a different place? Absolutely, said Chen. But different methods of cannabinoid production are suited to different purposes, and fermentation seems poised to win in a pharmaceutical ingredient contest. It is differentin many ways its better.

Celia Gorman is a science journalist and video editor based out of New York. She holds a master's in digital journalism from the CUNY Graduate School of Journalism and previously worked as an Associate Editor at tech magazine IEEE Spectrum, where she developed and ran an award-winning video section.

Link:
Yeast fermentation may be the answer to creating rare cannabinoids - Leafly

SILVER SPRING, Md., May 20, 2020 /PRNewswire/ -- You have probably heard of GMOs or genetically modified organisms, but how much do you know about them? GMO is a common term used by consumers to describe foods that have been created through genetic engineering. While GMOs have been available to consumers since the early 1990s and are a common part of today's food supply, research shows consumers have limited knowledge and understanding about what GMOs are, why they are used, and how they are made.

The U.S. Food and Drug Administration (FDA), with the U.S. Department of Agriculture (USDA) and U.S. Environmental Protection Agency (EPA), launched Feed Your Mind, a new Agricultural Biotechnology Education and Outreach Initiative. The Initiative aims to increase consumer awareness and understanding of genetically engineered foods or GMOs.Find answers to your questions and help educate others with Feed Your Mind's science-based educational resources, like web pages, fact sheets, infographics, and videos.

What are GMOs?"GMO" is a common term used to describe a plant, animal, or microorganism that has had its DNA changed through a process scientists call genetic engineering. Most of the GMO crops grown today were developed to help farmers prevent crop loss. There are ten GMO cropscurrently grown and sold in the U.S.: alfalfa, apples, corn, cotton, papayas, potatoes, soybeans, summer squash, and sugar beets.

Are GMOs safe to eat?Many federal agencies play an important role in ensuring the safety of GMOs. FDA, USDA, and EPA work together to ensure that crops produced through genetic engineering are safe for people, animals, and the environment. Collaboration and coordination among these agencies help make sure food developers understand the importance of a safe food supply and the rules they need to follow when creating new plants through genetic engineering.

Look for "Bioengineered food" on food labels Soon, you may see the term "bioengineered food" on certain food packaging. Congress used "bioengineered food" to describe certain types of GMOs when it passed the National Bioengineered Food Disclosure Standard. The Standard establishes requirements for labeling foods people eat that are bioengineered or may have bioengineered ingredients. It also defines bioengineered foods as those that contain detectable genetic material that has been modified through certain lab techniques and cannot be created through conventional breeding or found in nature.

To learn more about the Feed Your MindInitiative, visit http://www.fda.gov/feedyourmind.

Contact: Media: 1-301-796-4540 Consumers: 1-888-SAFEFOOD (toll free)

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Feed Your Mind with FDA's New Education Initiative on Genetically Engineered Foods - Herald-Mail Media

If humanity is ever going to settle down on Mars, we may need to become a little less human.

Crewed missions to Mars, which NASA wants to start flying in the 2030s, will be tough on astronauts, exposing them to high radiation loads, bone-wasting microgravity and other hazards for several years at a time. But these pioneers should still be able to make it back to Earth in relatively good nick, agency officials have said.

It might be a different story for those who choose not to come home, however. If we want to stay safe and healthy while living permanently on Mars, or any other world beyond our home planet, we may need to make some tweaks to our species' basic blueprint, experts say.

Related: Space radiation threat to astronauts explained (infographic)

Genetic engineering and other advanced technologies "may need to come into play if people want to live and work and thrive, and establish their family, and stay on Mars," Kennda Lynch, an astrobiologist and geomicrobiologist at the Lunar and Planetary Institute in Houston, said on May 12 during a webinar hosted by the New York Academy of Sciences called "Alienating Mars: Challenges of Space Colonization."

"That's when these kinds of technologies might be critical or necessary," she said.

Genetic enhancement may not be restricted to the pages of sci-fi novels for much longer. For example, scientists have already inserted genes from tardigrades tiny, adorable and famously tough animals that can survive the vacuum of space into human cells in the laboratory. The engineered cells exhibited a greater resistance to radiation than their normal counterparts, said fellow webinar participant Christopher Mason, a geneticist at Weill Cornell Medicine, the medical school of Cornell University in New York City.

NASA and other space agencies already take measures to protect their astronauts physically, via spacecraft shielding, and pharmacologically via a variety of medicines. So, it's not a huge conceptual leap to consider protecting them genetically as well, provided that these measures are proven to be safe, Mason said.

"And are we maybe ethically bound to do so?" he said during the webinar. "I think if it's a long enough mission, you might have to do something, assuming it's safe, which we can't say yet."

Tardigrades and "extremophile" microbes, such as the radiation-resistant bacterium Deinococcus radiodurans, "are a great, basically natural reservoir of amazing traits and talents in biology," added Mason, who has been studying the effects of long-term spaceflight on NASA astronaut Scott Kelly. (Kelly spent nearly a year aboard the International Space Station in 2015 and 2016.) "Maybe we use some of them."

Harnessing these traits might also someday allow astronauts to journey farther than Mars, out to some even more exotic and dangerous cosmic locales. For instance, a crewed journey to the Jupiter moon Europa, which harbors a huge ocean beneath its icy shell, is out of the question at the moment. In addition to being very cold, Europa lies in the heart of Jupiter's powerful radiation belts.

"If we ever get there, those are the cases where the human body would be almost completely fried by the amount of radiation," Mason said. "There, it would be certain death unless you did something, including every kind of shielding you could possibly provide."

Genetic engineering at least lets us consider the possibility of sending astronauts to Europa, which is widely regarded as one of the solar system's best bets to harbor alien life. (The Jovian satellite is a high priority for NASA's robotic program of planetary exploration. In the mid-2020s, the agency will launch a mission called Europa Clipper, which will assess the moon's habitability during dozens of flybys. And Congress has ordered NASA to develop a robotic Europa lander as well, though this remains a concept mission at the moment.)

Related: The 6 most likely places to find alien life

Genetic engineering almost certainly won't be restricted to pioneering astronauts and colonists. Recent advances in synthetic biology herald a future in which "designer microbes" help colonists establish a foothold on the Red Planet, Lynch said.

"These are some of the things that we can actually do to help us make things we need, help us make materials to build our habitats," she said. "And these are a lot of things that scientists are researching right now to create these kinds of things for our trip to Mars."

Some researchers and exploration advocates have even suggested using designer microbes to terraform Mars, turning it into a world much more comfortable for humans. This possibility obviously raises big ethical questions, especially considering that Mars may have hosted life in the ancient past and might still host it today, in subsurface lakes or aquifers. (Permanently changing our own genomes for radiation protection or any other reason may also strike some folks as ethically dubious, of course.)

Most astrobiologists argue against terraforming Mars, stressing that we don't want to snuff out or fundamentally alter a native ecosystem that may have arisen on the Red Planet. That would be both unethical and unscientific, Lynch said.

After all, she said, one of the main reasons we're exploring Mars is to determine if Earth is the only world to host life.

"And how can we do that if we go and change the planet before we go and find out if life actually was living there?" Lynch said.

Mike Wall is the author of "Out There" (Grand Central Publishing, 2018; illustrated by Karl Tate), a book about the search for alien life. Follow him on Twitter @michaeldwall. Follow us on Twitter @Spacedotcom or Facebook.

Link:
Colonizing Mars may require humanity to tweak its DNA - Space.com

On May 18, 2020, the U.S. Department of Agricultures (USDA) Animal and Plant Health Inspection Service (APHIS) issued the much-anticipated final Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient (SECURE) rule. 85 Fed. Reg. 29790. The rule is intended to update and modernize USDAs biotechnology regulations under the Plant Protection Act. The final rule amends the regulations regarding the movement (importation, interstate movement, and environmental release) of certain genetically engineered (GE) organisms in response to advances in genetic engineering and APHISs understanding of the plant pest risk posed by GE organisms, thereby reducing the regulatory burden for developers of organisms that are unlikely to pose plant pest risks. APHIS states that the final rule marks the first comprehensive revision of the regulations since they were established in 1987, providing a clear, predictable, and efficient regulatory pathway for innovators, facilitating the development of genetically engineered organisms that are unlikely to pose plant pest risks.

SECURE Regulatory Changes

According to APHIS, the SECURE rule differs from the previous regulatory framework by focusing on an organisms properties and not on the method used to produce it. APHIS states that this approach enables it to regulate organisms developed using genetic engineering for plant pest risk with greater precision than the previous approach. This method will reduce regulatory burden for developers of organisms that are unlikely to pose plant pest risks and will continue to provide oversight of organisms developed using genetic engineering that pose a plant pest risk.

Under the new rule, no person shall move any GE organism, except under permit, that:

The new regulatory process for organisms developed using genetic engineering consists of the following steps:

Exemptions from Regulation

Under the SECURE rule, certain categories of modified plants are exempt from the regulations because they could otherwise have been developed through conventional breeding techniques and thus are unlikely to pose an increased plant pest risk compared to conventionally bred plants. APHIS notes that it has historically not regulated conventionally bred plants under 7 C.F.R. Part 340. These exemptions apply only to plants because the long history of plant breeding gives APHIS extensive experience in safely managing associated plant pest risks.

The revised regulations also exempt plants developed using genetic engineering that contain a plant-trait-MOA combination that APHIS has already evaluated under the previous or new regulations and found to be unlikely to pose a plant pest risk. The results of all completed regulatory reviews will be publicly accessible on the APHIS website.

Determining Regulatory Status for GE Plants/Organisms

Under the previous regulations, APHIS assessed the plant pest risk of each plant transformation event (also sometimes referred to as the individual transformed line, transgenic line, or GE line) separately, even though the inserted genetic material may have been identical or very similar to transformation events already assessed. This part has been referred to as an event-by-event approach.

APHIS states that under the revised regulations, developers have the option of requesting a permit or an RSR of a plant developed using genetic engineering that has not been previously evaluated and determined to be nonregulated. This process replaces the petition process in the previous regulations. The revised regulations evaluate whether a plant requires oversight based on the characteristics of the plant itself and not on the method by which the plant was genetically engineered. Once APHIS determines that the plant is not regulated, subsequent transformation events using the same plant-trait-MOA combination would not be regulated.

Decisions on regulatory status are based on APHISs assessment of plant pest risk. If movement or release of a plant developed using genetic engineering is found to be unlikely to pose a plant pest risk, APHIS will not require regulation under 7 C.F.R. Part 340. If APHIS is unable to reach such a finding, it will regulate the plant and the plant will be allowed to move only under permit.

Permitting GE Plants and Organisms That Pose a Plausible Plant Pest Risk

Permits are required for the importation, interstate movement, or environmental release of any plant or organism developed using genetic engineering that may post a plant pest risk to plant health. For plants, developers must apply for a permit if the plant does not qualify for an exemption or if the RSR process determines that the plant poses a plausible plant pest risk. APHIS will approve or deny an application for an importation or movement permit within 45 days, and an application for a permit for an environmental release in 120 days. Developers may also choose to request a permit rather than an RSR, or they may elect to obtain a permit and request an RSR. Applicants will still apply for a permit using the same methods as before -- a paper application, ePermits, or APHIS eFile.

Under the previous regulations, APHIS also offered an option for notifications for certain plants as an administratively streamlined alternative to a permit. Under the SECURE rule, the notification process has been eliminated and replaced by the RSR and permitting process.

SECURE Implementation Time Line

The SECURE rules provisions will take effect on key dates over the next 18 months. According to APHIS, the biotechnology community will have to learn some new processes and meet new requirements in accordance with the implementation schedule. APHIS states that it is available to support stakeholders through this process. The key dates include:

Commentary

The final rule is a welcome change for biotechnology enthusiasts. The Biotechnology Industry Organization (BIO) praised the final rule, welcoming the diminished barriers to innovation as sensible and efficient. The Center for Food Safety condemned the final rule, noting that under it, the overwhelming majority of GE plant trials would not have to be reported to USDA, or have their risks analyzed before being allowed to go to market.

Most would agree that the previous regulations, first drafted in 1987, were in dire need of modernizing. Whether the dramatic shift away from the method of production to focus on the properties of the plant will invite consumer concern with too little regulatory oversight and thus erode public confidence remains to be seen.

Additional Resources

SECURE Biotechnology Website;

Questions and Answers on the final SECURE Rule;

Final Programmatic Environmental Impact Statement;

Documents Associated with the Proposed Rule

[View source.]

Excerpt from:
Final SECURE Rule Will Update and Modernize USDAs Biotechnology Regulations - JD Supra

Octant, a company backed by Andreessen Horowitz just now unveiling itself publicly to the world, is using the tools of synthetic biology to buck the latest trends in drug discovery.

As the pharmaceuticals industry turns its attention to precision medicine the search for ever more tailored treatments for specific diseases using genetic engineering Octant is using the same technologies to engage in drug discovery and diagnostics on a mass scale.

The companys technology genetically engineers DNA to act as an identifier for the most common drug receptors inside the human genome. Basically, its creating QR codes that can flag and identify how different protein receptors in cells respond to chemicals. These are the biological sensors which help control everything from immune responses to the senses of sight and smell, the firing of neurons; even the release of hormones and communications between cells in the body are regulated.

Our discovery platform was designed to map and measure the interconnected relationships between chemicals, multiple drug receptor pathways and diseases, enabling us to engineer multi-targeted drugs in a more rational way, across a wide spectrum of targets, said Sri Kosuri, Octants co-founder and chief executive officer, in a statement.

Octants work is based on a technology first developed at the University of California Los Angeles by Kosuri and a team of researchers, which slashed the cost of making genetic sequences to $2 per gene from $50 to $100 per gene.

Our method gives any lab that wants the power to build its own DNA sequences, Kosuri said in a 2018 statement. This is the first time that, without a million dollars, an average lab can make 10,000 genes from scratch.

Joining Kosuri in launching Octant is Ramsey Homsany, a longtime friend of Kosuris, and a former executive at Google and Dropbox . Homsany happened to have a background in molecular biology from school, and when Kosuri would talk about the implications of the technology he developed, the two men knew they needed to for a company.

We use these new tools to know which bar code is going with which construct or genetic variant or pathway that were working with [and] all of that fits into a single well, said Kosuri. What you can do on top of that is small molecule screening we can do that with thousands of different wells at a time. So we can build these maps between chemicals and targets and pathways that are essential to drug development.

Before coming to UCLA, Kosuri had a long history with companies developing products based on synthetic biology on both the coasts. Through some initial work that hed done in the early days of the biofuel boom in 2007, Kosuri was connected with Flagship Ventures, and the imminent Harvard-based synthetic biologist George Church . He also served as a scientific advisor to Gen9, a company acquired by the multi-billion dollar synthetic biology powerhouse, Ginkgo Bioworks.

Some of the most valuable drugs in history work on complex sets of drug targets, which is why Octants focus on polypharmacology is so compelling, said Jason Kelly, the co-founder and CEO of Gingko Bioworks, and a member of the Octant board, in a statement. Octant is engineering a lot of luck and cost out of the drug discovery equation with its novel platform and unique big data biology insights, which will drive the companys internal development programs as well as potential partnerships.

The new technology arrives at a unique moment in the industry where pharmaceutical companies are moving to target treatments for diseases that are tied to specific mutations, rather than look at treatments for more common disease problems, said Homsany.

People are dropping common disease problems, he said. The biggest players are dropping these cases and it seems like that just didnt make sense to us. So we thought about how would a company take these new technologies and apply them in a way that could solve some of this.

One reason for the industrys turn away from the big diseases that affect large swaths of the population is that new therapies are emerging to treat these conditions which dont rely on drugs. While they wouldnt get into specifics, Octant co-founders are pursuing treatments for what Kosuri said were conditions in the metabolic space and in the neuropsychiatric space.

Helping them pursue those targets, since Octant is very much a drug development company, is $30 million in financing from investors led by Andreessen Horowitz .

Drug discovery remains a process of trial and error. Using its deep expertise in synthetic biology, the Octant team has engineered human cells that provide real-time, precise and complete readouts of the complex interactions and effects that drug molecules have within living cells, said Jorge Conde, general partner at Andreessen Horowitz, and member of the Octant board of directors. By querying biology at this unprecedented scale, Octant has the potential to systematically create exhaustive maps of drug targets and corresponding, novel treatments for our most intractable diseases.

View original post here:
Emerging from stealth, Octant is bringing the tools of synthetic biology to large scale drug discovery - TechCrunch

UC Riverside engineers are transforming yeast, both the domesticated kind used to make bread and beer and lesser-known wild species, so it can be used in a variety of new ways including fighting cancer.

Yanran Li, a UC Riverside assistant professor of chemical and environmental engineering, is working with the yeast species Saccharomyces cerevisiae in an effort to turn it into a bioproduction platform for hormones, such as plant steroids, or phytosteroids, with anticancer properties.

Her approach, known as synthetic biology, involves transferring the biosynthetic machinery responsible for producing the desired steroids in plants to the engineered yeast strains so the yeast will robustly produce them, too. Plants cannot produce enough of these steroids for pharmaceutical use because doing so would interfere with their own growth.

S. cerevisiae has been used to make beer for about 13,000 years, and its what you still get today, in dried, purified form, when you open a packet of yeast if you can find one at the store as hordes of amateur bakers have turned to making loaves of crusty sourdough bread to pass the time while sheltering at home.

Of the manywild yeast species present in ancient breweries, the best alcohol producer was Saccharomyces cerevisiae. Though that wouldnt be known until the 1800s, people around the world nonetheless understood its power and cultivated it for use in baking and brewing, making S. cerevisiae one of the oldest domesticated organisms.

S. cerevisiae and its close relatives have, through careful breeding or genetic editing, been made into industrial-scale producers of ethanol fuel, flavorings, vitamins, proteins, and drugs such as insulin and interferon.

Lisaid she expects that one day her research group will know enough about how phytosteroids fight cancer to build a custom phytosteroid that delivers maximum tumor inhibiting or killing properties without hurting normal cells along the way.

Its a pity we cant get enough of these natural products from the original sources, she said. We are using yeast as a cell factory to produce these valuable compounds.

As any baker knows, S. cerevisiae thrives best in environments that are warm but not too hot. Keeping industrial facilities cool enough, especially in hot or tropical climates, has high environmental and financial costs. This makes it unsuitable and less sustainable for some industrial processes and limits what it can produce even with genetic manipulation.

We have fancy genetic engineering techniques for S. cerevisiae and can make it do a lot. But when were looking at industrial uses at a higher temperature we cant use it, said Ian Wheeldon, an associate professor of chemical and environmental engineering at UC Riverside, who uses synthetic biology to modify the genomes of wild yeasts. We take yeast that already grows in heat and tune it to produce more of what we want.

Wheeldon is working on ways to make Kluyveromyces marxianus, a heat tolerant wild yeast that reproduces more quickly than domesticated yeast, produce fruity esters for scents and flavorings. Hes also developing new multipurpose tools to rapidly make new strains of Yarrowia lipolytica, a wild yeast that consumes hydrocarbons, such as petroleum, and produces fats.

Because less is known about wild yeasts, engineering them is more difficult than S. cerevisiae, whose genome was first sequenced 24 years ago.

Theres huge variation between wild and domesticated yeasts, and the wild ones are often unpredictable, said Justin Chartron, a UC Riverside assistant professor of bioengineering, who studies how proteins are made in yeast. Theres a lot to making proteins. They need to be moved around, folded up, and modified. Theres a whole network of cellular machines to do this, but were trying to get them to produce more than they normally would so we hit a bottleneck.

Chartrons group uses high throughput sequencing to find what machines, or parts of the organisms metabolism, are in use at any given time in order to locate the proteins that take up the most space and remove them. This makes it easier for the yeast to produce the desired proteins.

If we ask the cell to make something it doesnt usually make, it destroys it. So we have to turn off those pathways, but we need to be clever about how we do it because the cell needs it to grow, Chartron said. Shining a blue light a technique known as optogenetics on an especially engineered cell is one way we can switch those pathways off.

The researchers said their work isnt that different from what amateur sourdough bakers are doing at home.

Were looking at nature to find properties of microbes and finding tools to develop those properties, Wheeldon said. These sourdoughs are exactly the kind of process were talking about you find an organism that produces acids and cultivate it to give your bread that sour taste.

Chartron, who also bakes sourdough bread, noted the baking process involves some of the same things as their own work: temperature, feeding the yeast, and fine-tuning the breads flavor.

We just use different instruments, he said.

Header photo: Stan Lim/UC Riverside

Original post:
Coveting yeast? It's much more than a loaf of bread - UC Riverside

A desperately needed tool to curb the COVID-19 pandemic is an inexpensive home-based rapid testing kit that can detect the coronavirus without needing to go to the hospital.

The Food and Drug Administration has approved a few home sample collection kits but a number of researchers, including myself, are using the gene-editing technique known as CRISPR to make home tests. If they work, these tests could be very accurate and give people an answer in about an hour.

I am a biomolecular scientist with training in pharmaceutical sciences and biomedical engineering and my lab focuses on developing next-generation of technologies for detecting and treating cancer, genetic and infectious diseases.

The COVID-19 disease is caused by a coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unlike humans which carry their genetic material encoded in DNA, the coronavirus encodes theirs in a related molecule called RNA.

My research group recently engineered a sensitive CRISPR-based technology, that we named CRISPR-ENHANCE, and used it to create a rapid test for SARS-CoV-2 RNA. Our assay works like a pregnancy test and shows two purple colored lines if the sample is positive for the virus. Using our technology, I envision developing a test kit that would allow rapid detection of SARS-CoV-2 RNA in saliva within 45-60 minutes at home without needing any expensive equipment.

The FDA recently gave a green light to a couple of sample collection kits from LabCorp and Everywell under the Emergency Use Authorization (EUA) that would allow people to ship out the nasal swab samples for analysis. Patients can take a swab of their nose, ship the samples to a lab, and wait for a few days to get the results back.

Although not an at-home testing kit, the test allows the samples to be shipped directly to a lab for detecting SARS-CoV-2 RNA. There they use a technique called reverse transcription-polymerase chain reaction (RT-PCR), which converts the viral RNA into DNA so that it can be easily multiplied and detected.

Although most FDA-approved tests are based on detecting SARS-CoV-2 RNA at an early stage, before symptoms even appear, such tests can only be performed in a laboratory setting with expensive equipment and can take multiple days to get the results.

Several antibody testing kits have been approved by the FDA that use a paper-based lateral flow strip, also similar to an at-home pregnancy testing strip, for detecting antibodies called IgM and IgG. Almost all SARS-CoV-2 infected patients make antibodies within 19 days of onset of symptoms and then the body continues to make detectable antibodies for several weeks to months even after symptoms fades away. Therefore, the Centers for Disease Control and Prevention recommends using antibody tests for detecting past infections.

However, the coronavirus is usually very active and contagious in the first week of infection and peaks on the day of onset of symptoms. Therefore, to prevent the spread of coronavirus, it is extremely important to detect coronavirus early to block the spread.

The antibody testing can be great for detecting past infections but they cannot reliably detect current or early infections. The delayed appearance and patient-to-patient variability of antibodies in a blood test further complicates the COVID-19 diagnosis with antibody testing kits.

In addition, the variability between different antibody testing methods have raised doubts about the reliability of these test kits.

Therefore, the National Institutes of Health recently announced a Rapid Acceleration of Diagnostics (RADx) which offers up to US$500 million in funding for ramping up the technologies that detect the SARS-CoV-2 virus.

Most people know of CRISPR/Cas systems as a famous gene-editing technology that can precisely edit DNA. Researchers engineer a guide RNA molecule with a target genetic sequence that serves like a GPS and zooms in on a location on the DNA where a Cas protein, a pair of molecular scissors, can cut at the desired location.

Scientists in the labs of Feng Zhang at MIT, Jennifer Doudna at UC Berkeley and others discovered several newer versions of CRISPR/Cas systems, including ones using the proteins Cas12a and Cas13a-d, which get crazy cutting once they find their match.

My colleagues and I have used this Cas12a-based CRISPR technique to detect the coronavirus.

The coronavirus RNA activates CRISPR/Cas, transforming a pair of controlled molecular scissors into an unstoppable chainsaw. When the the CRISPR/Cas enzyme activates, we know that the genetic sequence of the coronavirus is present in the saliva sample. To make the signal of the coronavirus stronger in the testing kit, we add millions of synthetic reporter molecules which are also chopped up by the CRISPR/Cas mechanism. This means that within minutes we can detect detect the presence of coronavirus.

Under EAU, the FDA recently approved the first CRISPR-based SARS-CoV-2 RNA testing kit from Sherlock Biosciences for testing nasal swabs in a lab. Although not yet approved for at-home testing, this is a big leap toward the development of CRISPR-based diagnostics.

While similar CRISPR-based test kits are in development including one from Mammoth Biosciences and others, our CRISPR-ENHANCE technology relies on engineered CRISPR RNAs that increases the speed of Cas12a chainsaw by between three- and four-fold.

This technique dramatically enhances the sensitivity of detection. Our system can detect fewer virus in a clinical sample faster with a clear visual readout. We are in the process of clinically validating the CRISPR-ENHANCE technology for SARS-CoV-2 RNA detection.

Standard collection method for detecting respiratory viruses in the clinic is the nasal swab. However, coronaviruses have been detected at comparable levels in saliva so some researchers are now turning to saliva for diagnostic testing.

Collecting saliva is not only less invasive than the nasal swabs but also contains more virus, which makes it easier to detect with RT-PCR. In fact, an at-home saliva collection kit just received a green light by the FDA on May 8, 2020. In our validation study we will be internally comparing our test between the nasal swabs and saliva for FDA approval.

We are developing a six-step procedure for home-based testing for saliva along with the nasal swabs. Here is how it would work with saliva.

Spit into a sample collection tube that contains dry chemical reagents that will begin to react with your saliva when you drop the closed tube into the warm water for 30 minutes.

The heat helps the chemicals break up the virus particle and expose the viruss genetic material RNA. The RT-PCR reagents basically multiply the viral RNA creating billions of copies, which are more easily detected.

After 30 minutes, transfer the contents of the collection tube to a second tube containing dried CRISPR components and leave it at room temperature for 10-15 minutes.

Only if CRISPR/Cas finds the specific coronavirus RNA, will it become active and chop up the synthetic reporter molecules that are engineered and added to this second tube. This part happens in just six minutes.

We then drop a paper strip into the second tube. Within 30 seconds one or two purple bands reveal the results.

The health care provider can then direct the individual to either quarantine, isolate and/or recommend further testing such as antibody-based tests. In our study, currently under peer review, we demonstrated that the ENHANCE technology itself is versatile and can also be adopted for detecting a range of targets including HIV, HCV and prostate cancer.

While there are several labs and companies are rushing to develop similar CRISPR-based coronavirus detection kits for saliva testing, we believe our approach offers the fastest detection. We hope to bring the cost of the kit down to between $1 and $2 so that developing countries can also afford a rapid and reliable coronavirus testing kit.

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Rapid home-based coronavirus tests are coming together in research labs were working on analyzing spit using advanced CRISPR gene editing techniques...

New Delhi | Updated: May 20, 2020 8:24:50 pm

Written by Dr R L Raina

With the Indian government keen on promoting India as a medical tourist destination for patients seeking affordable treatment, there is going to be a demand for healthcare professionals. To meet this demand, a new course on healthcare engineering has emerged for students. It is a multi-disciplinary specialty that focuses on advancing this sector through engineering approaches involving both healthcare and engineering professionals.

In this course, candidates will not only need to know their subject, but also possess entrepreneurial skills, along with business and technology acumen. Researchers work with clinicians, collaborators and patients to identify and solve problems that are relevant today. They use scientific, engineering methodology to create solutions to complex health care problems and improve quality of life.

Read| Emerging courses to pursue:Virology|Actuarial science| Pharma Marketing|FinTech | Coronavirus | Robotics |

As a healthcare engineer, one needs to have the knowledge of engineering principles that will enable him/her to come up with solutions for healthcare. At times, it is also concerned with the development and design of a medical product. Some of the major skills that an aspirant requires:

Analytical skills Good eye for design Vast knowledge about various diseases Attention to detailing Communication

To pursue a Bachelors degree in healthcare engineering, a candidate must have cleared class 12 exams, with science subjects like biology, mathematics, physics, and chemistry. The course curriculum will be around the application of engineering tools in the healthcare industry and developing new cutting edge equipment to protect people from illness and injury, and property from damage.

Read |Colleges offering AI-powered exams from home: All you need to know about proctoring

Engineers are always in demand in healthcare. It is a misconception that only people who have studied biomedical and clinical engineering can become healthcare engineers. Even students pursuing chemical, civil, computer, electrical, environmental, industrial, information, materials, mechanical, software and systems engineering can pursue this field.

Biomechanics: It is the study of the structure, function and motion of the mechanical aspects of biological systems by using the methods of mechanics.

Medical devices: Under this, a student should have knowledge about devices that benefit patients by helping healthcare providers diagnose and treat patients and helping them overcome sickness or disease, improving their quality of life.

Genetic engineering: It is the knowledge of a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms.

Read |IIT-Gandhinagar launches PG courses, direct admission for students affected by coronavirus

Health Informatics: This is the study of a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms.

Emergency Management: According to the World Health Organisation (WHO), emergency is a state in which normal procedures are interrupted, and immediate measures need to be taken to prevent that state from turning into a disaster. Thus, emergency management is crucial to avoid the disruption transforming into a disaster, which is even harder to recover from.

If you are interested in public health challenges, this is the perfect time to pursue a career in healthcare engineering. It is in high demand as they have a crucial role to play in terms of designing and validating models in the context of public health, predictive modelling, epidemiological studies, machine learning and data visualisation. These skills are already some of the most sought after across a wide variety of sectors, and healthcare has also caught up during the current crisis.

Healthcare engineering covers the following two major fields:

Engineering for Healthcare Intervention: This comes into play when there are chances of any treatment, preventive care, or test that a person could take or undergo to improve health or to help with a particular health problem.

Read | How will colleges function post lockdown

Engineering for Healthcare Systems: Engineering involved in the complete network of organisations, agencies, facilities, information systems, management systems, financing mechanisms, logistics, and all trained personnel engaged in delivering healthcare within a geographical area.

Universities offering this course

Since it is a relatively new course in India, none of the Indian universities offer this course yet, but some international universities do, such as Texas Tech University, Cambridge University, and John Hopkins University.

The author is vice-chancellor, JK Lakshmipat University

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Emerging courses: How to become a healthcare engineer - The Indian Express

SIDAMA, Ethiopia For Lidya Ashango and 14 million other Ethiopians, the false banana plant widely known as enset is a staple food and, on many occasions, a supplementary source of income. But its no longer easy to grow this crop in the southern part of the country, where land is scarce and plant disease is inevitable.

A mother of seven living in this southern town of Sidama, Ashango and her family have been growing, harvesting and processing enset as long as she can remember.

Men plant the crop, but the women do the time-consuming and laborious work of producing food from the crop. By the time a well-tended crop is ready to harvest, three to four years after planting, the woman goes to the farm with a machete and cuts the false stem to scrape and separate it into a starchy pulp and a fiber.

The pulp is covered with enset leaves and left in a pit to ferment for months before being used to make various bread and porridge dishes. Kocho,the fermented product to turn into bread, and bulla,the flour to be cooked into porridge, are among the dishes prepared by the women from the plant. The leaves are used for livestock feed and packaging.

Although enset varieties are known to be found in other countries in Africa such as Uganda, this cultivation and fermentation process is largely known only to Ethiopians with traditional indigenous knowledge. Gurage, Sidama, Gedeo and Hadiya are a few of the ethnic groups that grow and depend on this perennial crop.

Ensets label as a tree against hunger was adopted in 1984, when the northern part of Ethiopia thats mainly dependent upon cereals like teff was severely hit by drought and famine. Researchers note that the south, which relies on enset, saw no such tragedy; and also that the tree is relatively resistant to climate change and exists in hundreds of varieties.

Unlike other cereals, it can also be intercropped with coffee or other fruit-bearing trees, still providing a higher yield per unit area.

However, despite ensets popularity, rapid population growth in Ethiopia has put pressure on available land, and farmers seeking more income are turning toward cash crops like khat, a stimulant, and maize.

Less land means less livestock and less manure for the plant, said Beyene Teklu in an interview. Teklu has been researching farming systems in Ethiopia, especially enset, for the past six years.

According to a study he did on 240 farms in Sidama and Gedeo, khat-based farms grew by 21% between 1991 and 2013, whereas enset-based farming showed a decline of 13% during this period.

But the intensive production of cash crops like khat and maize can only be good for the first three or four years. After that, land that was left empty for several months after harvesting will be eroded and the nutrients gone, resulting in a very low yield the next harvest.

Teklu says this will in turn force youths to abandon the farms and leave for cities, which are growing increasingly crowded with jobseekers.

Beyond land scarcity, the other threat to enset is its high vulnerability to mealy bugs and diseases like bacteria wilt, which dry up its leaves and eventually kill the whole plant.

Recent reports by the U.S. Department of Agriculture show that Ethiopian researchers, in collaboration with the International Institute of Tropical Agriculture (IITA), have used genetic engineering to produce a modified enset thats resistant to bacteria wilt.

However, scholars like Teshome Hunduma, a Ph.D. research fellow at the Norwegian University of Life Sciences, looks at the initiative with a critical eye.

In an article for the local news site Addis Standard in April, Hunduma said there are no independent studies that show improved yield, disease-resistance or socioeconomic benefits for smallholder farmers from the use of genetically modified crops. An attempt to genetically modify and release enset for commercialization requires a high-level of precaution, he wrote.

An orphan crop thats been neglected by the government for several years, ensets future lies in long-term strategies that apply beyond five or 10 years, according to experts like Tekle.

Banner image: Ashangos brother-in-law, Dilke Didamo, 38, is portrayed at the familys enset farm in Sidama, Ethiopia. Photo by Maheder Haileselassie Tadese.

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Land scarcity and disease threaten a multifaceted indigenous crop in Ethiopia - Mongabay.com

December 31, 2019 is a day that will live in infamy. On this day, a pneumonia of unknown origin in the Hubei province of China was reported to the World Health Organization (WHO). We did not know it then, but this would be the day that the world would change. At the time of writing this article, there have been more than 4 million confirmed cases and nearly 300,000 confirmed deaths worldwide.

This global enemy, which we have learned to call COVID-19, has ravaged lives, regardless of age, creed or socioeconomic status. It has caused economic turmoil and has disrupted the lives of almost every human across the globe.

The impact that an entity approximately 120 nanometers in diameter -- approximately 1/100th the diameter of a human hair -- can have on the world is remarkable. But as indelible a mark as the virus has had, so too has been the call to arms by the scientific community. Every generation tends to be called to rise to a great challenge, and the response of this generation of scientists, technologists, engineers and mathematicians will shape the future of humanity and health more than SARS-CoV-2 itself.

As mentioned in a recent article on Forbes, the mobilization of biotechnology is similar to the allies storming the beaches on D-Day. Just like that fateful day, the attack on coronavirus is multipronged. There are new-generation vaccine methods, such as synthetic peptide-based vaccines and nucleic acid-based vaccines, that are genetically engineered. Retrovirals, diabetic medications, immunologic drugs, antibiotics and even anticoagulants have all been proposed to combat the pandemic. By the last count, over 250 medications are being evaluated at various stages.

Before the Defense Research Advanced Projects Agency's (DARPA) support of this work in 2011, the concept of engineering vaccines into DNA strands was at the edge of science. This allows the immune system to generate proteins directly. Prior to this, conventional vaccines were created by inducing an immune response by introducing antigens into the body. Now, many of the vaccines that are being evaluated are using the more novel approach, including Modernas vaccine, the first to enter phase one human trials, and Inovios vaccine, scheduled to enter trials this summer.

But newer, even more audacious biotechnological solutions are currently underway by DARPA in a project they're calling COVID-19 Shield, as part of the Pandemic Protection Platform. The cutting-edge concept is to harvest B cells from survivors of the disease and replicate and mass produce them via genetic engineering. This concept, if successful, could potentially mitigate any future potential pandemic in a matter of weeks and allow time for a vaccine to be developed while maintaining a flat infection curve.

However, DARPA is not the only group actively seeking solutions. There are myriad others, including the Biomedical Advanced Research and Development Authority (BARDA), which is seeking both low and high technology readiness level (TRL) solutions through a broad agency announcement (BAA). This includes a large vaccine contract with J&J worth over $1 billion andfast-tracking an IL-6 inhibitor by Actemra that could mitigate the lung manifestations of COVID-19.

This joins several other immune-mediated drug therapies to attempt to ameliorate the suspect cytokine storm cascade that occurs in more severe cases. BARDA is also reviewing advances from the pinnacle of bioengineering by exploring the use of extremophiles for drug therapies.

Biologic countermeasures are, however, not the only weapons being developed in this new viral war. Artificial intelligence (AI) is also playing a role to combat the novel coronavirus. AI is helping to mitigate the spread of disease, find therapies and aid in treatment strategies. BlueDot was the first to use its AI application to identify a novel pneumonia outbreak in China.

Then there is the COVID-19 Open Research Dataset (CORD-19),a multi-institutional initiative that includes The White House Office of Science and Technology Policy, Allen Institute for AI, Chan Zuckerberg Initiative (CZI), Georgetown Universitys Center for Security and Emerging Technology (CSET), Microsoft, and the National Library of Medicine (NLM) at the National Institutes of Health (NIH).

The goal of this initiative is to create new natural language processing and machine learning algorithms to scour scientific and medical literature to help researchers prioritize potential therapies to evaluate for further study. AI is also being used to automate screening at checkpoints by evaluating temperature via thermal cameras, as well as modulations in sweat and skin discoloration. What's more, AI-powered robots have even been used to monitor and treat patients. In Wuhan, the original epicenter of the pandemic, an entire field hospital was transitioned into a smart hospital fully staffed by AI robotics.

Any time of great challenge is a time of great change. The waves of technological innovation that are occurring now will echo throughout eternity. Science, technology, engineering and mathematics are experiencing a call to mobilization that will forever alter the fabric of discovery in the fields of bioengineering, biomimicry and artificial intelligence. The promise of tomorrow will be perpetuated by the pangs of today. It is the symbiosis of all these fields that will power future innovations.

December 31, 2019 is a day that will always be remembered. Currently, the day is known as the beginning of a disruption to our lives that few -- if any -- have ever experienced, but none shall ever forget. However, as time passes and life begins anew, I believe it will be remembered for a different reason. It will be remembered as the day science and technology went to war. A day in which humanity united to unleash the full capacity of scientific innovation on an enemy that was indiscriminate to race, religion or creed. And on that fateful day, in our darkest hour, science shined brightest. And in science we trust.

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Technology In A Time Of Crisis: How DARPA And AI Are Shaping The Future - Forbes

Biohacking Market (Type - Inside Biohacking, and Outside Biohacking; Product - Smart Drugs, Strains, Sensors, and Other Products; Application - Genetic Engineering, Forensic Science, Diagnosis and Treatment, Synthetic Biology, Drug Testing, and Other Applications; End-user - Forensic Laboratories, Pharmaceutical and Biotechnological Companies, and Other End-users): Global Industry Analysis, Trends, Size, Share and Forecasts to 2025. The global biohacking market is projected to grow at a CAGR of 19.2% over the forecast period of 2019-2025.

This press release was orginally distributed by SBWire

Pune, India -- (SBWIRE) -- 05/20/2020 -- Infinium Global Research has recently published a global report on "Biohacking Market (Type - Inside Biohacking, and Outside Biohacking; Product - Smart Drugs, Strains, Sensors, and Other Products; Application - Genetic Engineering, Forensic Science, Diagnosis and Treatment, Synthetic Biology, Drug Testing, and Other Applications; End-user - Forensic Laboratories, Pharmaceutical and Biotechnological Companies, and Other End-users): Global Industry Analysis, Trends, Size, Share and Forecasts to 2025." According to the report, the global biohacking market is projected to grow at a CAGR of 19.2% over the forecast period of 2019-2025.

To Know More Request Sample of this Report@ https://www.infiniumglobalresearch.com/reports/sample-request/18407

Increasing Demand for Smart Devices and Effective Drugs

The increasing demand for smart devices and effective drugs contributes to the growth of the biohacking market. Biohacking is a new frontier in the development of drugs and therapeutics due to the emerging healthcare industry and social movement. The rising prevalence of chronic diseases led to the surge in demand for biohacking. As per the World Health Organization, it is projected that by 2020, chronic diseases account for almost three-quarters of all deaths globally.

Growing Awareness About Biohacking

The growing geriatric population boosts the expansion of the biohacking market. A study estimated that around 8.5 percent of people globally are aged 65 and over and it is projected to reach around 17 percent of the world's population by 2050. The geriatric population is prone to chronic diseases escalating the demand for biohacking. Further, growing awareness about biohacking stimulates the growth of the market. Biohacking labs are set up in garages, warehouses, with second-hand equipment bought online.

Thus, anyone interested in science can perform experiments and learn by doing. The rise in the use of radiofrequency identification technology in medical devices aligned with the penetration of the internet of things in healthcare promotes the expansion of the biohacking market. Additionally, increasing the inclusion of fitness and consumer electronics leverages the growth of the market.

Advancement in Technologies Creates Several Opportunities

The rise in demand for biohacking devices in key application areas such as forensic science, genetic engineering, drug testing, synthetic biology, and others leverages the growth of the biohacking market. On the flip side, lack of funds required for research, lack of expertise hinders the growth of the biohacking market. Moreover, advancement in technologies creates several opportunities for the growth of the biohacking market.

"We are Now Including the Impact Analysis of the COVID-19 on this Premium Report and the Forecast Period of this Report Shall be Revised to 2020-2026. The Section on the Impact of COVID-19 on Biohacking Market is Included in the Report for Free."

North America is Anticipated to Have the Largest Share

Geographically, the global biohacking market is divided into North America, Asia-Pacific, Europe, and the Rest of the World. North America is anticipated to have the largest share in the global biohacking market. The presence of key market players in the United States drives the growth of the biohacking market in North America. The increasing awareness about biohacking among the younger generation in North America led to the development of the market in the region. Asia-Pacific region is expected to grow in the global biohacking market with a healthy CAGR over the forecast period. The revamping healthcare sector with increasing investments in it contributes to the growth of biohacking market in Asia-Pacific. Europe has significant growth opportunities in the global biohacking market. The rising research and development in Europe drive the growth of the biohacking market in Europe.

Get this Section as a Free Customization in the Report Along With a 30% Discount on the Study. https://www.infiniumglobalresearch.com/reports/customization/18407

"We Have Decided to Extend Our Support to the Industry on Account of Corona Outbreak by Offering Flat Discount 30% on All Our Studies and Evaluation of the Market Dynamics in Biohacking Amidst COVID-19"

Biohacking Market Coverage

Chapter - 1 Preface

=> Report Description

=> Research Methods

=> Research Approaches

Chapter - 2 Executive Summary

=> Biohacking Market Highlights

=> Biohacking Market Projection

=> Biohacking Market Regional Highlights

Chapter - 3 Global Biohacking Market Overview

=> Introduction

=> Market Dynamics

=> Porter's Five Forces Analysis

=> IGR-Growth Matrix Analysis

=> Value Chain Analysis of Biohacking Market

Chapter - 4 Biohacking Market Macro Indicator Analysis

Chapter - 5 Global Biohacking Market by Type

=> Inside Biohacking

=> Outside Biohacking

Chapter - 6 Global Biohacking Market by Product

=> Smart Drugs

=> Strains

=> Sensors

=> Other Products

Chapter - 7 Global Biohacking Market by Application

=> Genetic Engineering

=> Forensic Science

=> Diagnosis and Treatment

=> Synthetic Biology

=> Drug Testing

=> Other Applications

Chapter - 8 Global Biohacking Market by End-user

=> Forensic Laboratories

=> Pharmaceutical and Biotechnological Companies

=> Other End-users

Chapter - 9 Global Biohacking Market by Region 2019-2025

=> North America

=> Europe

=> Asia-Pacific

=> RoW

Chapter - 10 Company Profiles and Competitive Landscape

=>Thync Global Inc.

=> Moodmetric

=> InteraXon Inc.

=> Behavioral Tech.

=> Fitbit, Inc.

=> Apple Inc.

=> Synbiota Inc.

=> The ODIN

=> HVMN Inc.

=> Modern AlkaMe

=> Other companies

Chapter - 11 Appendix

=> Primary Research Findings and Questionnaire

Browse Complete Report@ https://www.infiniumglobalresearch.com/ict-semiconductor/global-biohacking-market

About Infinium Global ResearchInfinium Global Research is a business consulting and market research firm; a group of experts that caters to fulfilling business and market research needs of leading companies in various industry verticals and business segments. The company also serves government bodies, institutes and non-profit/non-government organizations to meet their knowledge and information needs.

Through our information services and solutions, we assist our clients to improve their performance and assess the market conditions to achieve their organizational goals. Our team of experts and analysts are engaged in continuously monitoring and assessing the market conditions to provide knowledge support to our clients. To help our clients and to stay updated with the advances and inventions in technology, business processes, regulations and environment, Infinium often conducts regular meets with industry experts and opinion leaders. Our key opinion leaders are involved in monitoring and assessing the progress in the business environment, so as to offer the best opinion to our clients.

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How Covid-19 Is Transforming the Biohacking Industry? Major Key Players: Thync Global Inc., Moodmetric, InteraXon Inc., Behavioral Tech., Fitbit,...

Phase 1 Clinical Study to Evaluate Multiple Doses of FT538 as Monotherapy for Acute Myeloid Leukemia and in Combination with Anti-CD38 Monoclonal Antibody Therapy for Multiple Myeloma

Off-the-shelf NK Cell Product Candidate Derived from Clonal Master iPSC Line Engineered with Three Functional Components to Enhance Innate Immunity

SAN DIEGO, May 20, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Companys Investigational New Drug (IND) application for FT538, the first CRISPR-edited, iPSC-derived cell therapy. FT538 is an off-the-shelf natural killer (NK) cell cancer immunotherapy that is derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components to enhance innate immunity: a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor; an IL-15/IL-15 receptor fusion (IL-15RF); and the elimination of CD38 expression. The Company plans to initiateclinical investigation of three once-weekly doses of FT538as a monotherapy in acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-directed monoclonal antibody therapy, for the treatment of multiple myeloma.

We are very pleased to expand the clinical application of our proprietary iPSC product platform to multiple myeloma, where rates of relapse remain high, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Clinical data suggest that deficiencies in NK cell-mediated immunity, which are evident even at the earliest stages of myeloma, continue to accumulate through disease progression. We believe administration of FT538 to patients can restore innate immunity, and that the anti-cancer effect of certain standard of care treatments, such as monoclonal antibodies, can be more effective when combined with the engineered functionality of FT538.

The three functional components of FT538 are designed to boost the innate immune response in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to endogenous NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action including:

The first-in-human, multi-center, dose-escalation Phase 1 clinical trial of FT538 is designed to determine the maximum tolerated dose (MTD) of three once-weekly doses of FT538 in up to 105 adult patients across four dose cohorts (100M cells per dose; 300M cells per dose; 900M cells per dose; and 1.5B cells per dose). The study will assess two treatment regimens: Regimen A as a monotherapy in patients with relapsed / refractory AML; and Regimen B in combination with daratumumab, an FDA-approved anti-CD38 monoclonal antibody, in patients with relapsed / refractory multiple myeloma who have failed at least two lines of therapy. In addition, the Company may initiate a third treatment regimen in combination with elotuzumab, an FDA-approved anti-SLAMF7 monoclonal antibody, in patients with relapsed / refractory multiple myeloma who have failed at least two lines of therapy starting at one dose level below the MTD of Regimen B. For all regimens, multiple indication- or dose-specific dose-expansion cohorts of up to 15 patients per cohort may be enrolled to further evaluate the clinical activity of FT538.

FT538 is the fourth off-the-shelf, iPSC-derived NK cell product candidate from the Companys proprietary iPSC product platform cleared for clinical investigation by the FDA. The Company has initiated clinical manufacture of FT538 at its GMP facility in San Diego, CA.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of and plans related to the Company's product candidates and clinical studies, the Companys progress, plans and timelines for the clinical investigation of its product candidates, the therapeutic potential of the Companys product candidates including FT538, and the Companys clinical development strategy for FT538. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk of difficulties or delay in the initiation of any planned clinical studies, or in the enrollment or evaluation of subjects in any ongoing or future clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of FT538 may not be replicated in ongoing or future clinical trials or studies, and the risk that FT538 may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

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Fate Therapeutics Announces FDA Clearance of IND Application for FT538, First CRISPR-edited, iPSC-derived Cell Therapy - GlobeNewswire

There is "no evidence" supporting conspiracy theories that the coronavirus originated in a laboratory in Wuhan, an expert has told parliament.

Claims that COVID-19 was created in a lab were amplified by Donald Trump earlier this month, although the president refused to offer any evidence or give specific details.

The coronavirus outbreak first emerged in the Chinese city of Wuhan last year and international blame around the pandemic has incited conspiracy theories about its origin.

Rumours linking the virus to the Wuhan Institute of Virology - based on geographic proximity, and without any endorsement from qualified epidemiologists - have circulated.

But speaking to the House of Lords science and technology committee on Tuesday, Professor David Robertson dismissed the conspiracy theory as "unlikely".

Following the president's comments, the US Secretary of State Mike Pompeo claimed there was a "significant amount of evidence" supporting the theory but, just two days later, admitted: "We don't have certainty."

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Scientists have discovered that the coronavirus was 96% identical to coronavirus found in bats, one of the many animals sold at a Wuhan seafood market where it is suspected the virus jumped to humans.

British authorities believe it is highly likely the global pandemic is unconnected to the laboratory in Wuhan and was passed from animals to humans naturally.

"You have a virus that you think comes from an exotic species and then you have a wildlife market - that seems the most parsimonious explanation," Professor Robertson said.

He was asked whether a sample of the virus found at the Wuhan Institute of Virology - and thought to be about 40 to 50 years old - could have been behind the initial outbreak.

Professor Robertson, who is the head of viral genomics and bioinformatics at the University of Glasgow, firmly responded: "No, absolutely not.

"That's partly what has driven some of these conspiracy theories, is what is the chance they would have this virus in the labs that is close? And actually, even though it is close in sequence, it is not close in time."

"There is really no evidence for this. We can all enjoy a conspiracy theory but you need to have evidence," he added.

Scientists have analysed the entirety of the novel coronavirus' genomic sequence to assess claims that it may have been made in a laboratory or been otherwise engineered.

The value of the genomic sequence could prove vital for those developing a vaccine, but it also contains key details revealing how the virus evolved.

Researchers at the Scripps Research Institute in the US, UK and Australia discovered that the virus has proved so infectious because it developed a near-perfect mechanism to bind to human cells.

This mechanism is so sophisticated in its adaptions that the researchers say that it must have evolved and not been genetically engineered in their paper, titled "COVID-19 coronavirus epidemic has a natural origin", published in the journal Nature Medicine.

Dr Josie Golding, the epidemics lead at the Wellcome Trust in the UK, described the paper as "crucially important to bring an evidence-based view to the rumours that have been circulating about the origins of the virus causing COVID-19".

"They conclude that the virus is the product of natural evolution, ending any speculation about deliberate genetic engineering," Dr Golding added.

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Coronavirus: Parliament told there is 'no evidence' virus came from Wuhan laboratory - Sky News

In a bid to protect wheat and other crops from the Brome Mosaic virus, scientists from UC Riverside set out to better understand how the virus particles interact with each other when infecting crops.

Brome Mosaic virus

University of California, Riverside scientists have announced that they have solved a 20-year-old genetics puzzle that could result in ways to protect wheat, barley, and other crops from a devastating infection.

Ayala Rao, professor of plant pathology and microbiology, has been studying Brome Mosaic virus for decades. Unlike some viruses, the genetic material of this virus is divided into three particles that until now were reportedly impossible to tell apart.

Brome Mosaic virus primarily affects grasses such as wheat and barley, and occasionally affects soybeans as well. According to Rao, it is nearly identical to Cucumber Mosaic virus, which infects cucumbers as well as tomatoes and other crops that are important to California agriculture.

Without a more definitive picture of the differences between these particles, we couldnt fully understand how they work together to initiate an infection that destroys food crops, Rao said. Our approach to this problem has brought an important part of this picture into very clear focus.

Inside each of the particles is a strand of RNA, the genetic material that controls the production of proteins. The proteins perform different tasks, Rao explained, some of which cause stunted growth, lesions and ultimately death of infected host plants.

Two decades ago, scientists used the average of all three particles to create a basic description of their structure. In order to differentiate them, Rao first needed to separate them, and get them into their most pure form.

Using a genetic engineering technique, Raos team disabled the pathogenic aspects of the virus and infused the viral genes with a host plant.

This bacterium inserts its genome into the plants cells, similar to the way HIV inserts itself into human cells, Rao said. We were then able to isolate the viral particles in the plants and determine their structure using electron microscopes and computer-based technology.

Now that one of the particles is fully mapped, it was said to be clear that the first two particles are more stable than the third.

Once we alter the stability, we can manipulate how RNA gets released into the plants, Rao said. We can make the third particle more stable, so it doesnt release RNA and the infection gets delayed.

Moving forward, Rao hopes to bring the other two viral particles into sharper focus with the expertise of scientists at UCLA and UC San Diego.

Not only could this research lead to the protection of multiple kinds of crops, it could advance the understanding of any virus, Rao added.

It is much easier to work with plant viruses because theyre easier and less expensive to grow and isolate. But what we learn about the principles of replication are applicable to human and animal viruses too.

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Particle research could save wheat and other crops from deadly virus - New Food

DUBLIN, May 18, 2020 /PRNewswire/ -- The "Global Infectious Vaccines Partnering Terms and Agreements 2014 to 2020: Deal trends, players and financials" report has been added to ResearchAndMarkets.com's offering.

This report provides a detailed understanding and analysis of how and why companies enter infectious vaccines partnering deals.

The majority of deals are development stage whereby the licensee obtains a right or an option right to license the licensors vaccine technology. These deals tend to be multicomponent, starting with collaborative R&D, and commercialization of outcomes. The report also includes adjuvant deals and alliances.

This report provides details of the latest infectious vaccines agreements announced in the healthcare sectors.

Understanding the flexibility of a prospective partner's negotiated deals terms provides critical insight into the negotiation process in terms of what you can expect to achieve during the negotiation of terms. Whilst many smaller companies will be seeking details of the payments clauses, the devil is in the detail in terms of how payments are triggered - contract documents provide this insight where press releases and databases do not.

This report contains a comprehensive listing of all infectious vaccines partnering deals announced since January 2014, including financial terms where available, including over 350 links to online deal records of actual infectious vaccines partnering deals as disclosed by the deal parties. In addition, where available, records include contract documents as submitted to the Securities Exchange Commission by companies and their partners.

The initial chapters of this report provide an orientation of Infectious Vaccines dealmaking and business activities.

In addition, a comprehensive appendix is provided organized by Infectious Vaccines partnering company A-Z, deal type definitions and Infectious Vaccines partnering agreements example. Each deal title links via Weblink to an online version of the deal record and where available, the contract document, providing easy access to each contract document on demand. The report also includes numerous tables and figures that illustrate the trends and activities in Infectious Vaccines partnering and dealmaking since Jan 2014.

In conclusion, this report provides everything a prospective dealmaker needs to know about partnering in the research, development and commercialization of Infectious Vaccines technologies and products.

Analyzing actual contract agreements allows assessment of the following:

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/8txhqv

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Research and Markets Laura Wood, Senior Manager [emailprotected]

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Infectious Vaccines Partnering 2014 to 2020: Deal Trends, Players and Financials - PRNewswire