StemCell Therapy

An article on the spread of the novel coronavirus in Iceland was published by the The New England Journal of Medicine yesterday. The authors are scientist at deCode Genetics and their colleagues at the Directorate of Health and at Landsptali National University Hospital, mbl.is reports.

At the website of deCode, the aim of the study is explained:

The aim of the study was to provide as comprehensive a view as possible of how the virus spreads in a population, in this case one of 360,000 and implementing early and aggressive testing, tracking and isolation measures to contain the epidemic.

The results show that roughly 0.8 percent of the population at large is infected with several strains or clades of the virus supporting the concern that silent carriers spread the disease.

This suggests that while the efforts of the public health system have been effective so far in mitigating the spread to date, more data, including massive population screening, will be key to informing efforts to contain the virus in Iceland in the long run.

In attempting to carefully map the molecular epidemiology of COVID-19 in Iceland we hope to provide the entire world with data to use in the collective global effort to curb the spread of the disease, Kri Stefnsson, CEO of deCode Genetics is quoted as saying.

Kri states that widespread screening (ten percent of the nation has already been tested for the virus) and measures taken by the Directorate of Health to slow the spread of the virus give a good example of how this dangerous pandemic can be fought.

General screening in Iceland by deCode began March 13, where anyone who wanted could sign up for screening. By March 31, 10,797 individuals had been tested, 87 of whom tested positive for the virus. Subsequently, 2,283 peoople, randomly chosen, were tested, with a similar result.

After that, a sequence analysis of 643 positive tests was done, showing that the first cases originated in Italy and Austria, but later on, transmissions were traced to other countries.

Currently, 291 mutations of the virus have been found in the country that have not been identified elsewhere, according to decode.com.

See the rest here:
Article on COVID-19 in Iceland in New England Journal of Medicine - Iceland Monitor

When a patient with puzzling neurological symptoms enrolled in the Undiagnosed Diseases Network, researchers led by Dr. Hugo J. Bellen were set on solving the mystery. The patient presented with an unidentified late-onset neurodegenerative disorder. The team named this new syndrome "Mitchell disease" in reference to the first patient to be diagnosed with this disorder and looked to identify its genetic basis."On comparing the patient's and his parents' DNA, the team identified a mutation in the patient that resulted in a single amino acid substitution (N237S) in the ACOX1 protein. This change was seen only in the patient and was not present in either of his parents' DNA, indicating that the patient had a de novo, or new, mutation on this gene,' said Bellen, professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and also a Howard Hughes Medical Institute investigator. "With the help of the online gene-matching tool GeneMatcher, we found two more patients who had the same new mutation in the ACOX1 gene."

All three patients, who ranged from 3 to 12 years old at the time of disease onset, had remarkably similar clinical features, including degeneration of peripheral nerves that caused a progressive loss of mobility and hearing. The three individuals had identical gene variants, a clear indication that ACOX1 dysfunction likely was the cause of the symptoms.

"The brain has large amounts of lipids, which are critical for the proper functioning of the nervous system. Abnormal breakdown of lipids in the brain and peripheral nervous system is associated with several neurodegenerative diseases," Bellen said.

The gene ACOX1 is involved in lipid breakdown. It produces an enzyme called Acyl-CoA oxidase 1 that initiates a series of reactions that break down very-long-chain-fatty acids in small intracellular organelles called peroxisomes.

To understand how ACOX1 variants affect the function of glia, they generated two mutant fly lines, the first one lacked both the copies of ACOX1 gene and the second, carried the substitution mutation (N237S) found in one of the ACOX1 genes in the Mitchell disease patients.

"Flies lacking ACOX1 mimicked the symptoms of ACOX1 deficiency in humans, including elevated levels of very-long-chain-fatty acids along with dramatic loss of glia and neurons and progressively impaired neuronal function. When we reduced the synthesis of very-long-chain-fatty acids in these flies by administering the drug bezafibrate, we observed significant improvement in lifespan, vision, motor coordination and neuronal function, implicating elevated levels of these lipids and their excessive accumulation in glia as an important contributor," said Chung, postdoctoral fellow in the Bellen lab.

"It is remarkable how well bezafibrate suppressed the symptoms of ACOX1 deficiency, suggesting a new therapeutic avenue for patients with this condition," Bellen said.

In contrast to the loss of ACOX1, the introduction of the single amino acid substitution (N237S) in ACOX1 gene resulted in a hyperactive ACOX1 protein. Typically, breakdown of very-long-chain-fatty acids by the enzymatic action of ACOX1 produces small amounts of highly reactive oxygen species, but glial cells quickly neutralize them. However, in Mitchell's disease, hyperactive ACOX1 produces copious amounts of toxic reactive oxygen species, leading to the destruction of glia and their neighboring neurons.

The harmful effects due to hyperactive ACOX1 were potently reversed with the antioxidant N-acetyl cysteine amide (NACA). However, NACA did not suppress the lethality or toxic effects in flies that lacked ACOX1, a clear indication that the two diseases act via entirely different pathways and would need to be treated with two distinct therapeutic strategies.

"This study is a prime example of how combining UDN's unique team science approach with power of fruit fly genetics is facilitating rapid and phenomenal progress in rare diseases research. We take on cases of patients with conditions never described before, uncover new diseases and find definitive molecular diagnosis for them. We make significant progress in unraveling the causes of these novel diseases and rapidly identify and test promising new treatment options," Bellen said. "We have successfully identified more than 25 disease-causing genes within the past three years - a task that typically takes many years."ReferenceChung et al. (2020) Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron. DOI: https://doi.org/10.1016/j.neuron.2020.02.021

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Solving the Puzzle of Mitchell Disease - Technology Networks

Universityof Toronto researcherSachdev Sidhuand his collaborators are engineering antibody molecules that can neutralize the novel coronavirus in the body before it invades cells.

Sidhu (left) already leads a differentteam that received supportin the first round of federal funding. The goal of that project is to design antiviral medicines that block viral replication.

With our two funded projects, we are working to develop molecules that can target the virus both inside human cells and on the outside to prevent it from getting in, says Sidhu, who is a professor of molecular genetics in the Faculty of Medicine.

Rini has previously helped to determine how antibodies bind to and inactivate the SARS virus, the coronavirus that caused the outbreak in Asia more than 15 years ago. Also on the team isAlan Cochrane, a professor in the department of molecular genetics and an HIV virologist with expertise in viral RNA processing.

The antibodies will be engineered to block the so-called S-protein that forms spikes on the virus's surface. The spikes lock on to a protein called ACE2 on the surface of human cells to gain entry. Coating viral particles with synthetic antibodies should prevent the spikes from binding to ACE2.

Sidhu and Rini will also engineer antibodies that bind ACE2 to make it inaccessible to the virus. This type of engineered immunity surpasses the capacity of the bodys natural immune system since antibodies that react against self-proteins have been filtered out. If successful, the approach may obviate worries about viral mutations that can render drugs ineffective to new emerging viral strains becausethe host protein ACE2 does not change over time.

Sidhus team has advanced a technology called phage display to rapidly create and select human antibodies with desired biological properties, including blocking the virussspike protein. Over the last decade, his team has created hundreds of antibodies with therapeutic potential some of which are in clinical development through spin-off companiesand large pharmaceutical firms.

The group has demonstrated success with both approaches for inhibiting viral entry, having developed neutralizing antibodies that target the Ebola virus as well as antibodies that target the human host receptor of hantavirus or hepatitis C. Moreover, other research has shown that antibodies targeting SARS, a related virus whose genetic material is over 80 per cent identical to the one causing COVID-19, can clear infection in cells and mice.

Using phage display, in which tiny bacterial viruses called phages are instructed to create vast libraries of diverse antibodies, the team will select the antibodies that can kill the virus in human cells before testing them on mice and, eventually, patients. Experiments on mice could start within three to six months, Sidhu says.

In addition to creating antibodies tailored to the new virus from scratch, the researchers will also modify existing SARS-blocking antibodies so that they attack COVID-19 and provide an additional route to the development of a therapeutic.

Given the global spread of the virus, its possible that it will become endemic and circulate in the population like seasonal flu. And, like the flu, it could mutate into new strains that will evade acquired immunity and the vaccines that are being developed. By generating a panel of different antibodies, the researchers aim to stay one step ahead of the virus.

Our advances in antibody engineering technologiesand access to the complete genomes of the COVID-19 virus and its relatives provides us with an opportunity to create tailored therapeutic antibodies at a scale and speed that was not possible even a few years ago, says Sidhu.

Ultimately, we aim to optimize methods to the point where the evolution of new drugs will keep pace with the evolution of the virus itself, providing new and effective drugs in response to new outbreaks.

The rest is here:
Researchers at U of T developing antibodies to 'neutralize' novel coronavirus before it invades cells - News@UofT

Michelle Kuppersmith's doctor recommended a bone marrow biopsy after suspecting she had a rare blood disorder. Though the biopsy was done by an in-network provider at an in-network hospital, Kuppersmith learned she was on the hook for $2,400 for out-of-network genetic profiling. Shelby Knowles for KHN hide caption

Michelle Kuppersmith's doctor recommended a bone marrow biopsy after suspecting she had a rare blood disorder. Though the biopsy was done by an in-network provider at an in-network hospital, Kuppersmith learned she was on the hook for $2,400 for out-of-network genetic profiling.

Michelle Kuppersmith feels great, works full time and exercises three to four times a week. So she was surprised when a routine blood test found that her body was making too many platelets, which help control bleeding.

Kuppersmith's doctor suspected the 32-year-old Manhattanite had a rare blood disorder called essential thrombocythemia, which can lead to blood clots, strokes and, in rare cases, leukemia.

Her doctor suggested a bone marrow biopsy, in which a large needle is used to suck out a sample of the spongy tissue at the center of the patient's hip bone.

Doctors examine the bone marrow under a microscope and analyze the DNA. The procedure allows doctors to judge a patient's prognosis and select treatment, if needed. Kuppersmith had heard the procedure can be intensely painful, so she put it off for months.

The biopsy performed by a provider in her insurance network, at a hospital in her network lasted only a few minutes, and Kuppersmith received relatively good news.

While a genetic analysis of her bone marrow confirmed her doctor's suspicions, it showed that the only treatment she needs, for now, is a daily, low-dose aspirin. She will check in with her doctor every three to four months to make sure the disease isn't getting worse.

All in all, Kuppersmith felt relieved.

Then she got a notice saying her insurer refused to pay for the genetic analysis, leaving her responsible for a $2,400 payment.

The patient: New York resident Michelle Kuppersmith, 32, who is insured by Maryland-based CareFirst Blue Cross Blue Shield. She works as director of special projects at a Washington-based watchdog group. Because she was treated in New York, Empire Blue Cross Blue Shield which covers that region handled part of her claim.

Total amount owed: $2,400 for out-of-network genetic profiling

The providers: Kuppersmith had her bone marrow removed at the Mount Sinai Ruttenberg Treatment Center in New York City, which sent her biopsy sample to a California lab, Genoptix, for testing.

Medical services: Bone marrow biopsy and molecular profiling, which involves looking for genetic mutations

What gives: The field of molecular diagnostics, which includes a variety of gene-based testing, is undergoing explosive growth, said Gillian Hooker, president of the National Society of Genetic Counselors and vice president of clinical development for Concert Genetics, a health IT company in Nashville, Tennessee.

A report from Concert Genetics, a company that helps clients manage genetic testing, found there are more than 140,000 molecular diagnostic products on the market, with 10 to 15 added each day.

The field is growing so quickly that even doctors are struggling to develop a common vocabulary, Hooker said.

Kuppersmith underwent a type of testing known as molecular profiling, which looks for DNA biomarkers to predict whether patients will benefit from new, targeted therapies. These mutations aren't inherited; they develop over the course of a patient's life, Hooker said.

Medicare spending on molecular diagnostics more than doubled from 2016 to 2018, increasing from $493 million to $1.1 billion, according to Laboratory Economics, a lab industry newsletter.

Charges range from hundreds to thousands of dollars, depending on how many genes are involved and which billing codes insurers use, Hooker said.

Based on Medicare data, at least 1,500 independent labs perform molecular testing, along with more than 500 hospital-based labs, said Jondavid Klipp, the newsletter's publisher.

In a fast-evolving field with lots of money at stake, tests that a doctor or lab may regard as state-of-the-art an insurer might view as experimental.

Worse still, many of the commercial labs that perform the novel tests are out-of-network, as was Genoptix.

Stephanie Bywater, chief compliance officer at NeoGenomics Laboratories, which owns Genoptix, said that insurance policies governing approval have not kept up with the rapid pace of scientific advances. Kuppersmith's doctor ordered a test that has been available since 2014 and was updated in 2017, Bywater said.

Although experts agree that molecular diagnostics is an essential part of care for patients like Kuppersmith, doctors and insurance companies may not agree on which specific test is best, said Dr. Gwen Nichols, chief medical officer of the Leukemia & Lymphoma Society.

Tests "can be performed a number of different ways by a number of different laboratories who charge different amounts," Nichols said.

Insurance plans are much more likely to refuse to pay for molecular diagnostics than other lab tests. Laboratory Economics found Medicare contractors denied almost half of all molecular diagnostics claims over the past five years, compared with 5-10% of routine lab tests.

With so many insurance plans, so many new tests and so many new companies, it is difficult for a doctor to know which labs are in a patient's network and which specific tests are covered, Nichols said.

"Different providers have contracts with different diagnostic companies," which can affect a patient's out-of-pocket costs, Nichols said. "It is incredibly complex and really difficult to determine the best, least expensive path."

Kuppersmith said she has always been careful to check that her doctors accept her insurance. She made sure Mount Sinai was in her insurance network, too. But it never occurred to her that the biopsy would be sent to an outside lab or that it would undergo genetic analysis.

She added: "The looming threat of a $2,400 bill has caused me, in many ways, more anxiety than the illness ever has."

The resolution: Despite making dozens of phone calls, Kuppersmith got nothing but confusing and contradictory answers when she tried to sort out the unexpected charge.

An agent for her insurer told her that her doctor hadn't gotten preauthorization for the testing. But in an email to Kuppersmith, a Genoptix employee told her the insurance company had denied the claim because molecular profiling was viewed as experimental.

A spokesperson for New York-based Empire Blue Cross Blue Shield, which handled part of Kuppersmith's claim, said her health plan "covers medically necessary genetic testing."

New York, one of 28 states with laws against surprise billing, requires hospitals to inform patients in writing if their care may include out-of-network providers, said attorney Elisabeth Benjamin, vice president of health initiatives at the Community Service Society, which provides free help with insurance problems.

A spokesperson for Mount Sinai said the hospital complies with that law, noting that Kuppersmith was given such a document in 2018 nearly one year before her bone marrow biopsy and signed it.

Benjamin said that's not OK, explaining: "I think a one-year-old, vague form like the one she signed would not comply with the state law and certainly not the spirit of it."

Instead of sending Kuppersmith a bill, Genoptix offered to help her appeal the denied coverage to CareFirst. At first, Genoptix asked Kuppersmith to designate the company as her personal health care representative. She was uncomfortable signing over what sounded like sweeping legal rights to strangers. Instead, she wrote an email granting the company permission to negotiate on her behalf. It was sufficient.

A few days after being contacted by KHN, Kuppersmith's insurer said it would pay Genoptix at the in-network rate, covering $1,200 of the $2,400 charge. Genoptix said it has no plans to bill Kuppersmith for the other half of the charge.

The takeaway: Kuppersmith is relieved her insurer changed its mind about her bill. But, she said: "I'm a relatively young, savvy person with a college degree. There are a lot of people who don't have the time or wherewithal to do this kind of fighting."

Patients should ask their health care providers if any outside contractors will be involved in their care, including pathologists, anesthesiologists, clinical labs or radiologists, experts said. And check if those involved are in-network.

"Try your best to ask in advance," said Jack Hoadley, a research professor emeritus at Georgetown University. "Ask, 'Do I have a choice about where [a blood or tissue sample] is sent?'"

Ask, too, if the sample will undergo molecular diagnostics. Since the testing is still relatively new and expensive most insurers require patients to obtain "prior authorization," or special permission, said Dr. Debra Regier, a medical geneticist at Children's National Hospital in Washington and an associate with NORD, the National Organization of Rare Diseases. Getting this permission in advance can prevent many headaches.

Finally, be wary of signing blanket consent forms telling you that some components of your care may be out-of-network. Tell your provider that you want to be informed on a case-by-case basis when an out-of-network provider is involved and to consent to their participation.

Bill of the Month is a crowdsourced investigation by Kaiser Health News and NPR that dissects and explains medical bills. Do you have a perplexing medical bill you want to share with us? Tell us about it here.

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Bill Of The Month: Pricey Genetic Test For Essential Thrombocythemia : Shots - Health News - NPR

NEW YORK, March 31, 2020 /PRNewswire/ -- 2020 World Molecular Diagnostic Analyzer and Reagent Forecasts for 100 Tests: Americas, EMEA, APAC--A 68-Country Analysis--Infectious and Genetic Diseases, Cancer, Forensic and Paternity Testing

Read the full report: https://www.reportlinker.com/p05876987/?utm_source=PRN

This new 68-country survey provides granular data and analysis not available from any other source. The report is designed to help current suppliers and potential market entrants identify and evaluate major business opportunities emerging in the molecular diagnostics market during the next five years.

Highlights

- Supplier sales and market shares in major countries

- Five-year test volume and sales forecasts

- Strategic profiles of market players and start-up firms developing innovative technologies and products

- Emerging technologies

- Review of molecular diagnostic analyzers

- Specific product and business opportunities for instrument and consumable suppliers

Rationale

The molecular diagnostics market is unquestionably the most rapidly growing segment of the in vitro diagnostics industry. The next five years will witness significant developments in reagent systems and automation, as well as introduction of a wide range of new products that will require innovative marketing approaches. The rate of market penetration into routine clinical laboratories, however, will depend on the introduction of cost-effective and automated systems with amplification methods.

In order to successfully capitalize on the opportunities presented by the molecular diagnostics market, many companies are already exploiting new molecular technologies as corporate strategic assets, managed in support of business and marketing strategies. Integrating new technology planning with business and corporate strategies will be one of the most challenging tasks for diagnostic companies during the next five years.

Geographic Regions

Asia-Pacific, Europe, Latin America, Middle East, North America

Country Analyses

Argentina, Australia, Austria, Bahrain, Bangladesh, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, India, Indonesia, Iran, Iraq, Ireland, Israel, Italy, Japan, Jordan, Kuwait, Latvia, Lebanon, Lithuania, Malaysia, Malta, Mexico, Myanmar, Netherlands, New Zealand, Norway, Oman, Pakistan, Peru, Philippines, Poland, Portugal, Qatar, Romania, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, UK, United Arab Emirates, USA, Venezuela, Vietnam

Market Segmentation Analysis

- Sales and market shares of key suppliers of molecular diagnostic reagent kits and components in major markets.

Five-year test volume and sales forecasts for major applications, including:

- Infectious Diseases - Forensic Testing- Cancer - Paternity Testing/HLA Typing- Genetic Diseases - Others

- Five-year test volume and sales projections for over 30 NAT assays.

- A comprehensive analysis of the sequencing market, by country and laboratory segment,including:

- Industrial - Academic- Government- Commercial

- Market segmentation analysis, including review of the market dynamics, trends, structure, size, growth and suppliers in major countries.

Product/Technology Review

- Comparison of leading molecular diagnosticanalyzers marketed by Abbott, Beckman Coulter, BD, Bio-Rad, Gen-Probe, Roche, Tecan and other suppliers.

- Extensive review of molecular diagnostic technologies, test formats, detection methodologies, trends in testing automation and over 30 target/signal amplification methods, including:

- PCR - bDNA - SDA - NASBA - TMA - SSSR, and others - LCR

- Universities and research centers developing new molecular diagnostictechnologies and products.

Competitive Assessments

- Extensive strategic assessments of major suppliers and emerging market entrants, including their sales, product portfolios, marketing tactics, collaborative arrangements and new technologies/products in RandD.

- Companies developing and marketing molecular diagnostics products, by test and application.

Opportunities and Strategic Recommendations

Story continues

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2020 World Molecular Diagnostic Analyzer and Reagent Forecasts for 100 Tests: Americas, EMEA, APAC--A 68-Country Analysis--Infectious and Genetic...

By mining a vast trove of genetic data,researchers at theUniversity of Virginia School of Medicineare enhancing doctors ability to treat cancer, predict patient outcomes and determine which treatments will work best for individual patients.

The researchers have identified inherited variations in our genes that affect how well a patient will do after diagnosis and during treatment. With that information in hand, doctors will be able to examine a patients genetic makeup to provide truly personalized medicine.

Oncologists can estimate how a patient will do based on the grade of the tumor, the stage, the age of the patient, the type of tumor, etc. We found [adding a single genetic predictor] can improve our predictive ability by 5% to 10%, said UVAs Anindya Dutta. Many of the cancers had multiple inherited genetic change that were predictive of outcome, so if we add those in, instead of a 10% increase we might get a 30% increase in our ability to predict accurately how patients will do with our current therapy. Thats amazing.

Dutta, the chair of UVAs Department of Biochemistry and Molecular Genetics, believes reviewing the inherited genetic makeup of a patient can provide similar benefits for predicting outcome and choosing therapy for many, many other conditions, from diabetes to cardiac problems. As such, the approach represents a major step forward in doctors efforts to tailor treatments specifically to the individuals needs and genetic makeup.

The research offers answers to questions that have long perplexed doctors.Every clinician has this experience: Two patients come in with exactly the same cancersame grade, same stage, received the same treatment. One of them does very well, and the other one doesnt, Dutta said.The assumption has always been that there is something about the two that we didnt understand, like maybe there are some tumor-specific mutations that one patient had but the other did not. But it occurred to us that with all this genomic data, there is another hypothesis that we could test.

Instead of a 10% increase we might get a 30% increase in our ability to predict accurately how patients will do with our current therapy. Thats amazing.

- Anindya Dutta

To determine if genetic differences in the patients could be the answer, Dutta and his colleagues did a deep dive into the Cancer Genome Atlas, an enormous repository of genetic information assembled by the National Institutes of Healths National Cancer Institute. The researchers sought to correlate inherited genetic variations with patient outcomes.

This incredibly smart M.D.-Ph.D. student in the lab, Mr.Ajay Chatrath,decided that this was a perfect time to explore this, Dutta recalled. With the help of cloud computing services at UVA, we managed to download all this genomic sequencing data and identify what are known as germline variants not just tumor-specific mutations, but the mutations that were inherited from the parents and are present in all cells of the patient.

The researchers started small, but soon realized how quickly the work could be done and how big the benefits could be. Once we realized this was a very easy thing to do, we went on to do all 33 cancers and all 10,000 patients, and that took another six months, Dutta said. All of this came together beautifully. It was very exciting that every single member in the lab contributed to the analysis.

Dutta is eager to share his findings in hopes of finding collaborators and inspiring researchers and private industry to begin mining the data for other conditions. This is very low-hanging fruit, he said. Germline variants predicting outcome can be applicable to all types of diseases and not just cancer, and [they can predict] responsiveness to all types of therapy, and thats why Im particularly excited.

The researchers have published their findings in the scientific journal Genome Medicine. The studys authors were Chatrath, Roza Przanowska, Shashi Kiran, Zhangli Su, Shekhar Saha, Briana Wilson, Takaaki Tsunematsu,Ji-Hye Ahn, Kyung Yong Lee, Teressa Paulsen, Ewelina Sobierajska, Manjari Kiran, Xiwei Tang, Tianxi Li, Pankaj Kumar, Aakrosh Ratan and Dutta.

The research was supported by the National Institutes of Health, grants R01 CA166054, R01 1094 CA60499, T32 GM007267, AHA 18PRE33990261; and a Cancer 1095 Genomics Cloud Collaborative Support grant. The Seven Bridges Cancer 1096 Genomics Cloud has been funded by the National Cancer Institute, National Institutes of Health.

To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog.

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UVA Finds Way to Improve Cancer Outcomes by Examining Patients' Genes - University of Virginia

Michelle Kuppersmith, 32, feels great, works full time and exercises three to four times a week. So she was surprised when a routine blood test found that her body was making too many platelets, which help control bleeding. Kuppersmiths doctor suspected she had a rare blood disorder called essential thrombocythemia, which can lead to blood clots, strokes and, in rare cases, leukemia.

[khnslabs slabs="813866"]

Her doctor suggested a bone marrow biopsy, in which a large needle is used to suck out a sample of the spongy tissue at the center of the patients hip bone. Doctors examine the bone marrow under a microscope and analyze the DNA. The procedure allows doctors to judge a patients prognosis and select treatment, if needed. Kuppersmith had heard the procedure can be intensely painful, so she put it off for months.

The biopsy performed by a provider in her insurance network, at a hospital in her network lasted only a few minutes, and Kuppersmith received relatively good news. While a genetic analysis of her bone marrow confirmed her doctors suspicions, it showed that the only treatment she needs, for now, is a daily, low-dose aspirin. She will check in with her doctor every three to four months to make sure the disease isnt getting worse.

All in all, Kuppersmith felt relieved.

Then she got a notice saying her insurer refused to pay for the genetic analysis, leaving her responsible for a $2,400 payment.

The Patient: New York resident Michelle Kuppersmith, 32, who is insured by Maryland-based CareFirst Blue Cross Blue Shield. She works as director of special projects at a Washington-based, nonpartisan watchdog group. Because she was treated in New York, Empire Blue Cross Blue Shield which covers that region handled part of her claim.

Total Amount Owed: $2,400 for out-of-network genetic profiling

[khnslabs slabs="790331" view="inline" /]

The Providers: Kuppersmith had her bone marrow removed at the Mount Sinai Ruttenberg Treatment Center in New York City, which sent her biopsy sample to a California lab, Genoptix, for testing.

Medical Services: Bone marrow biopsy and molecular profiling, which involves looking for genetic mutations

What Gives: The field of molecular diagnostics, which includes a variety of gene-based testing, is undergoing explosive growth, said Gillian Hooker, president of the National Society of Genetic Counselors and vice president of clinical development for Concert Genetics, a health IT company in Nashville, Tennessee.

A Concert Genetics report found there are more than 140,000 molecular diagnostic products on the market, with 10 to 15 added each day.

The field is growing so quickly that even doctors are struggling to develop a common vocabulary, Hooker said.

Kuppersmith underwent a type of testing known as molecular profiling, which looks for DNA biomarkers to predict whether patients will benefit from new, targeted therapies. These mutations arent inherited; they develop over the course of a patients life, Hooker said.

[documentcloud url="http://www.documentcloud.org/documents/6815388-BOTM-March2020.html" responsive=true]

Medicare spending on molecular diagnostics more than doubled from 2016 to 2018, increasing from $493 million to $1.1 billion, according to Laboratory Economics, a lab industry newsletter.

Charges range from hundreds to thousands of dollars, depending on how many genes are involved and which billing codes laboratories use, Hooker said.

Based on Medicare data, at least 1,500 independent labs perform molecular testing, along with more than 500 hospital-based labs, said Jondavid Klipp, the newsletters publisher.

In a fast-evolving field with lots of money at stake, tests that a doctor or lab may regard as state-of-the-art an insurer might view as experimental.

Worse still, many of the commercial labs that perform the novel tests are out-of-network, as was Genoptix.

After lining up an in-network provider at an in-network hospital, Kuppersmith pushed back when she got a $2,400 charge for an out-of-network lab. She appealed and won but says, There are a lot of people who dont have the time or wherewithal to do this kind of fighting.

Stephanie Bywater, chief compliance officer at NeoGenomics Laboratories, which owns Genoptix, said that insurance policies governing approval have not kept up with the rapid pace of scientific advances. Kuppersmiths doctor ordered a test that has been available since 2014 and was updated in 2017, Bywater said.

Although experts agree that molecular diagnostics is an essential part of care for patients like Kuppersmith, doctors and insurance companies may not agree on which specific test is best, said Dr. Gwen Nichols, chief medical officer of the Leukemia & Lymphoma Society.

Tests can be performed a number of different ways by a number of different laboratories who charge different amounts, Nichols said.

Insurance plans are much more likely to refuse to pay for molecular diagnostics than other lab tests. Laboratory Economics found Medicare contractors denied almost half of all molecular diagnostics claims over the past five years, compared with 5-10% of routine lab tests.

With so many insurance plans, so many new tests and so many new companies, it is difficult for a doctor to know which labs are in a patients network and which specific tests are covered, Nichols said.

Different providers have contracts with different diagnostic companies, which can affect a patients out-of-pocket costs, Nichols said. It is incredibly complex and really difficult to determine the best, least expensive path.

Kuppersmith said she has always been careful to check that her doctors accept her insurance. She made sure Mount Sinai was in her insurance network, too. But it never occurred to her that the biopsy would be sent to an outside lab or that it would undergo genetic analysis.

She added: The looming threat of a $2,400 bill has caused me, in many ways, more anxiety than the illness ever has.

Kuppersmiths doctor recommended a bone marrow biopsy after suspecting she had a rare blood disorder. Though the biopsy was done by an in-network provider at an in-network hospital, Kuppersmith learned she was on the hook for $2,400 for out-of-network genetic profiling.

The Resolution: Despite making dozens of phone calls, Kuppersmith got nothing but confusing and contradictory answers when she tried to sort out the unexpected charge.

An agent for her insurer told her that her doctor hadnt gotten preauthorization for the testing. But in an email to Kuppersmith, a Genoptix employee told her the insurance company had denied the claim because molecular profiling was viewed as experimental.

[khnslabs slabs="822742"]

A spokesperson for New York-based Empire Blue Cross Blue Shield, which handled part of Kuppersmiths claim, said her health plan covers medically necessary genetic testing.

New York, one of 28 states with laws against surprise billing, requires hospitals to inform patients in writing if their care may include out-of-network providers, said attorney Elisabeth Benjamin, vice president of health initiatives at the Community Service Society, which provides free help with insurance problems.

A spokesperson for Mount Sinai said the hospital complies with that law, noting that Kuppersmith was given such a document in 2018 nearly one year before her bone marrow biopsy and signed it.

Benjamin said thats not OK, explaining: I think a one-year-old, vague form like the one she signed would not comply with the state law and certainly not the spirit of it.

Instead of sending Kuppersmith a bill, Genoptix offered to help her appeal the denied coverage to CareFirst. At first, Genoptix asked Kuppersmith to designate the company as her personal health care representative. She was uncomfortable signing over what sounded like sweeping legal rights to strangers. Instead, she wrote an email granting the company permission to negotiate on her behalf. It was sufficient.

A few days after being contacted by KHN, Kuppersmiths insurer said it would pay Genoptix at the in-network rate, covering $1,200 of the $2,400 charge. Genoptix said it has no plans to bill Kuppersmith for the other half of the charge.

The Takeaway: Kuppersmith is relieved her insurer changed its mind about her bill. But, she said: Im a relatively young, savvy person with a college degree. There are a lot of people who dont have the time or wherewithal to do this kind of fighting.

[khnslabs slabs="975218"]

Patients should ask their health care providers if any outside contractors will be involved in their care, including pathologists, anesthesiologists, clinical labs or radiologists, experts said. And check if those involved are in-network.

Try your best to ask in advance, said Jack Hoadley, a research professor emeritus at Georgetown University. Ask, Do I have a choice about where [a blood or tissue sample] is sent?

Ask, too, if the sample will undergo molecular diagnostics. Since the testing is still relatively new and expensive most insurers require patients to obtain prior authorization, or special permission, said Dr. Debra Regier, a medical geneticist at Childrens National Hospital in Washington and an associate with NORD, the National Organization of Rare Diseases. Getting this permission in advance can prevent many headaches.

Finally, be wary of signing blanket consent forms telling you that some components of your care may be out-of-network. Tell your provider that you want to be informed on a case-by-case basis when an out-of-network provider is involved and to consent to their participation.

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Her Genetic Test Revealed A Microscopic Problem And A Jumbo Price Tag - Bryan-College Station Eagle

English naturalist Charles Robert Darwins seminal book On the Origin of Species by Means of Natural Selection went to press in 1859. That was 40 years before the concept of viruses was introduced to the world of science by Russian botanist Dmitri Ivanovsk. It took another century for viral researchers to decipher the genetic make-up of these infectious agents, to find out how they replicate and spread disease.

Darwin shunned and ridiculed after the publication of his book would probably be amazed to know that viruses such as the Covid-19 are considered living evidence of his theory of evolution.

If Charles Darwin reappeared today, he might be surprised to learn that humans are descended from viruses as well as from apes, British microbiologist Robin Weiss wrote in the journal Retrovirology. He was referring to fragments of retroviruses close cousins of the coronavirus found in the human genome.

These fragments are the fossils of a number of killer viruses, including several novel reassortments of influenza or coronaviruses that ravaged humans on a large scale in the past. These so-called endogeneous retroviruses (ERVs) are actually trophies of ancient molecular battles between viruses and their human hosts one which the humans eventually won. Some 8 per cent of human DNA represents fossil retroviral genomes, pointed out Weiss in his seminal research paper in 2010.

When competing groups of scientists in different parts of the world fully mapped the human genome in 2003, they found something they had never anticipated: bits that have no known function. Many scientists termed these seemingly inert shards junk DNA that littered our bodies. In the following decade, however, geneticists realised that some of those bits were actually endogenous retroviruses, fossils of defeated viruses that managed to invade our bodies but were disabled by our immune system. In Darwinian terms, in the struggle for existence our immune system got better of them and there was survival of the fittest through natural selection. Instead of getting buried as mineralised relics, these viruses reside within our DNA as bits of genetic code carrying records of millions of years but forever disabled, with no power to make us sick.

The discovery of the human genome as a living document of ancient and now extinct viruses prompted the emergence of a new field called palaeovirology. Two of its proponents, Michael Emerman and Harmit S. Malik, at the Fred Hutchinson Cancer Research Center in Seattle, US, define palaeovirology as the study of extinct viruses (called palaeoviruses) and the effects these agents have had on the evolution of their hosts. In other words, indirect evidence of these viral fossils can help reconstruct the past and offer clues on how to fight emerging viral epidemics or pandemics.

Malik grew up in Bombay and studied chemical engineering at the Indian Institute of Technology there. He studies evolving proteins and the genetics of evolutionary conflict embedded in the molecules, which has helped him uncover previously unrecognised sources of conflict.

As a pioneer palaeovirologist, Malik is fascinated by the constant battle being waged between humans and viruses for hundreds of thousands of years. In the course of his study, he found telltale imprints in our genome that narrate the story of how viruses infected our cells, how sometimes we have fought back by changing our protein and how sometimes viruses evaded them to get an upper hand. This evolutionary cat-and-mouse game has shaped our defence against viruses.

Palaeovirologists have also studied how similar viruses have attacked our close relatives, the primates chimpanzees and gorillas and compared how we have fared in these battles. For instance, the virus that leads to to the killer disease Aids in humans does not have much of an effect on chimps. What makes chimps relatively immune to this scary virus? Malik and Emerman found the clue to this mystery in an endogenous retrovirus called Pterv found in chimps (and other apes) but not in humans. They surmised that the retrovirus may have infected both humans and chimps about 4 million years ago. We learnt to stave off the virus while the chimps were hit by an epidemic. A gene called Trim 5 alpha is believed to have helped humans make a protein to purge the virus.

Malik and his colleagues reconstructed a part of the Pterv through computer modelling and found that while Trim 5 alpha helped us prevent the entry of the virus, it made us vulnerable to the HIV virus that causes Aids. However, the monkey version of the gene helps protect the apes from HIV and Aids. They concluded that if we can develop a therapy based on the Trim 5 alpha protein, it could defeat HIV. Research on drugs based on such evolutionary principles, however, is few and far between

Scientists have been studying several resurrected palaeoviruses like Pterv through evolution-guided reconstruction procedures. In 2005, researchers at the US Centers for Disease Control and Prevention (CDC), reconstructed the influenza virus that caused the 1918-19 flu pandemic, which killed as many as 50 million people worldwide. According to CDC, the research provides new information about the properties that contributed to its exceptional virulence. The natural emergence of another pandemic virus is considered highly likely by many experts, and therefore insights into pathogenic mechanisms can and are contributing to the development of prophylactic and therapeutic interventions needed to prepare for future pandemic viruses, says a CDC release.

The rapid evolution of viruses and emergence of the new coronavirus Covid-19 has once again shown that viruses evolve by the same means as humans. Many of these viruses hop from animals to humans and evolve, swapping genetic material in and out of respective genomes. Thats why we can have immunity to a virus weve had in the past, but get seriously affected by one our body has never seen before.

Somewhere, Darwin must be feeling vindicated that his theory is so starkly exposed in a viral machinery.

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The human DNA is littered with fossils of viruses past that attacked us. And lost - Telegraph India

There is always a well-known solution to every human problem neat, plausible, and wrong.From Prejudices (1920) by H L Mencken

There has never been a problem facing mankind more complex than understanding our own human nature. And no shortage of neat, plausible, and wrong answers purporting to plumb its depths.

Having treated many thousands of psychiatric patients in my career, and having worked on the American Psychiatric Associations efforts to classify psychiatric symptoms (published as the Diagnostic and Statistical Manual of Mental Disorders, or DSM-IV and DSM-5), I can affirm confidently that there are no neat answers in psychiatry. The best we can do is embrace an ecumenical four-dimensional model that includes all possible contributors to human functioning: the biological, the psychological, the social, and the spiritual. Reducing people to just one element their brain functioning, or their psychological tendencies, or their social context, or their struggle for meaning results in a flat, distorted image that leaves out more than it can capture.

The National Institute of Mental Health (NIMH) was established in 1949 by the federal government in the United States with the practical goal of providing an objective, thorough, nationwide analysis and reevaluation of the human and economic problems of mental health. Until 30 years ago, the NIMH appreciated the need for this well-rounded approach and maintained a balanced research budget that covered an extraordinarily wide range of topics and techniques.

But in 1990, the NIMH suddenly and radically switched course, embarking on what it tellingly named the Decade of the Brain. Ever since, the NIMH has increasingly narrowed its focus almost exclusively to brain biology leaving out everything else that makes us human, both in sickness and in health. Having largely lost interest in the plight of real people, the NIMH could now more accurately be renamed the National Institute of Brain Research.

Read: [How tech is helping brain-injured patients with decision-making]

This misplaced reductionism arose from the availability of spectacular research tools (eg, the Human Genome Project, functional magnetic resonance imaging, molecular biology, and machine learning) combined with the naive belief that brain biology could eventually explain all aspects of mental functioning. The results have been a grand intellectual adventure, but a colossal clinical flop. We have acquired a fantastic window into gene and brain functioning, but little to help clinical practice.

The more we learn about genetics and the brain, the more impossibly complicated both reveal themselves to be. We have picked no low-hanging fruit after three decades and $50 billion because there simply is no low-hanging fruit to pick. The human brain has around 86 billion neurons, each communicating with thousands of others via hundreds of chemical modulators, leading to trillions of potential connections. No wonder it reveals its secrets only very gradually and in a piecemeal fashion.

Genetics offers the same baffling complexity. For instance, variation in more than 100 genes contributes to vulnerability to schizophrenia, with each gene contributing just the tiniest bit, and interacting in the most impossibly complicated ways with other genes, and also with the physical and social environment. Even more discouraging, the same genes are often implicated in vulnerability to multiple mental disorders defeating any effort to establish specificity. The almost endless permutations will defeat any easy genetic answers, no matter how many decades and billions we invest.

The NIMH has boxed itself into a badly unbalanced research portfolio. Playing with cool brain and gene research toys trumps the much harder and less intellectually rewarding task of helping real people.

Contrast this current NIMH failure with a great success story from NIMHs distant past. One of the high points of my career was sitting on the NIMH granting committee that funded psychotherapy studies in the 1980s. We helped to support the US psychologist Marsha Linehans research that led her to develop dialectical behavior therapy; the US psychiatrist Aaron T Becks development of cognitive therapy; along with numerous other investigators and themes. Subsequent studies have established that psychotherapy is as effective as medications for mild-to-moderate depression, anxiety, and other psychiatric problems, and avoids the burden of medication side-effects and complications. Many millions of people around the world have already been helped by NIMH psychotherapy research.

In a rational world, the NIMH would continue to fund a robust psychotherapy research budget and promote its use as a public-health initiative to reduce the current massive overprescription of psychiatric medication in the US. Brief psychotherapy would be the first-line treatment of most psychiatric problems that require intervention. Drug treatments would be reserved for severe psychiatric problems and for those people who havent responded sufficiently to watchful waiting or psychotherapy.

Unfortunately, we dont live in a rational world. Drug companies spend hundreds of millions of dollars every year influencing politicians, marketing misleadingly to doctors, and pushing pharmaceutical treatments on the public. They successfully sold the fake marketing jingle that all emotional symptoms are due to a chemical imbalance in the brain and therefore all require a pill solution. The result: 20% of US citizens use psychotropic drugs, most of which are no more than expensive placebos, all of which can produce harmful side-effects.

Drug companies are commercial Goliath with enormous political and economic power. Psychotherapy is a tiny David with no marketing budget; no salespeople mobbing doctors offices; no TV ads; no internet pop-ups; no influence with politicians or insurance companies. No surprise then that the NIMHs neglect of psychotherapy research has been accompanied by its neglect in clinical practice. And the NIMHs embrace of biological reductionism provides an unintended and unwarranted legitimization of the drug-company promotion that there is a pill for every problem.

A balanced NIMH budget would go a long way toward correcting the two biggest mental-health catastrophes of today. Studies comparing psychotherapy versus medication for a wide variety of mild to moderate mental disorders would help to level the playing field for the two, and eventually reduce our massive overdependence on drug treatments for nonexistent chemical imbalances. Health service research is desperately needed to determine best practices to help people with severe mental illness avoid incarceration and homelessness, and also escape from them.

The NIMH is entitled to keep an eye on the future, but not at the expense of the desperate needs of the present. Brain research should remain an important part of a balanced NIMH agenda, not its sole preoccupation. After 30 years of running down a bio-reductionistic blind alley, it is long past time for the NIMH to consider a biopsychosocial reset, and to rebalance its badly uneven research portfolio.

This article was originally published at Aeonby Allen Frances and has been republished under Creative Commons.

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The distorted idea of 'cool' brain research is stifling psychotherapy - The Next Web

March 27, 2020

Dear President Trump, Vice President Pence, and Ambassador Birx:

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Thank you for actively engaging the health care communityparticularly the nations physicians and the organizations that represent themin addressing the COVID-19 pandemic in the United States.

As more than 800,000 physicians across more than 40 specialties in medicine, we continue to support travel and gathering restrictions to slow the transmission of coronavirus disease 2019 (COVID-19). Physicians, other health professionals, and staff are putting themselves in harms way without adequate personal protective equipment or necessary tools (such as ventilators) as well as with no proven treatment or vaccine for the virus.

Significant COVID-19 transmission continues across the United States, and we need your leadership in supporting science-based recommendations on social distancing that can slow the virus. Our societies have closely adhered to these measures by moving our staff to fulltime telework and canceling in-person meetings (including annual meetings). These actions have helped to keep physicians and other health professionals in health care facilities, including hospitals, and reduce the risk of spreading COVID-19.

Statewide efforts alone will not sufficiently control this public health crisis. A strong nationwide plan that supports and enforces social distancingand recognizes that our health and our economy are inextricably linkedshould remain in place until public health and medical experts indicate it can be lifted.

Federal, state, and local governments should only set a date for lifting nationwide social distancing restrictions consistent with assessments by public health and medical experts. Lifting restrictions sooner will gravely jeopardize the health of all Americans and extend the devastation of the COVID-19 pandemic.

Again, thank you for actively engaging the nations physicians and the organizations that represent them. We appreciate your considering these comments and welcome an opportunity for further dialogue.

Sincerely,

Council of Medical Specialty Societies

American Academy of Allergy, Asthma & ImmunologyAmerican Academy of DermatologyAmerican Academy of Family PhysiciansAmerican Academy of Hospice and Palliative MedicineAmerican Academy of NeurologyAmerican Academy of OphthalmologyAmerican Academy of Orthopaedic SurgeonsAmerican Academy of PediatricsAmerican Academy of Physical Medicine and RehabilitationAmerican Association of Clinical EndocrinologistsAmerican College of CardiologyAmerican College of Emergency PhysiciansAmerican College of Medical Genetics and GenomicsAmerican College of Obstetricians and GynecologistsAmerican College of Occupational and Environmental MedicineAmerican College of PhysiciansAmerican College of Preventive MedicineAmerican College of RadiologyAmerican College of RheumatologyAmerican College of SurgeonsAmerican Epilepsy SocietyAmerican Gastroenterological AssociationAmerican Geriatrics SocietyAmerican Medical Informatics AssociationAmerican Psychiatric AssociationAmerican Society of AnesthesiologistsAmerican Society for Clinical PathologyAmerican Society of Colon and Rectal SurgeonsAmerican Society of HematologyAmerican Society of NephrologyAmerican Society for Radiation OncologyAmerican Society for Reproductive MedicineAmerican Thoracic SocietyAmerican Urological AssociationAssociation for Clinical OncologyInfectious Diseases Society of AmericaNorth American Spine SocietySociety of Critical Care MedicineSociety of Gynecologic OncologySociety of Hospital MedicineSociety of Interventional RadiologySociety of Nuclear Medicine and Molecular ImagingSociety of Thoracic SurgeonsSociety for Vascular Surgery

Founded in 1965 as the Tri-College Council, CMSS was created to provide an independent forum for the discussion by medical specialists of issues of national interest and mutual concern.Founding members were the American College of Obstetricians and Gynecologists, the American College of Physicians, and the American College of Surgeons.In 1967, as other specialty societies joined, CMSS adopted its current name.Today,43 societies with more than 790,000 U.S. physician membersare members of CMSS. CMSS is a 501(c)(3) not-for-profit association incorporated in the state of Illinois. http://www.cmss.org

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CMSS: 800000 physicians across 40 specialties continue to support travel and gathering restrictions - YubaNet

A virus is a microscopic package of genetic material surrounded by a molecular envelope. The genetic material can be either DNA or RNA.

DNA is a two-strand molecule that is found in all organisms, such as animals, plants, and viruses, and it holds the genetic code, or blueprint, for how these organisms are made and develop.

RNA is generally a one-strand molecule that copies, transcribes and transmits parts of the genetic code to proteins so they can synthetize and carry out functions that keep organisms alive and developing. There are different variations of RNA that do the copying, transcribing and transmitting.

Some viruses such as the coronavirus (SARS-Cov2) only contain RNA, which means they rely on infiltrating healthy cells to multiply and survive. Once inside the cell, the virus uses its own genetic code RNA in the case of the coronavirus to take control of and reprogramme the cells so that they become virus-making factories.

In order for a virus like the coronavirus to be detected early in the body using real time RT-PCR, scientists need to convert the RNA to DNA. This is a process called reverse transcription. They do this because only DNA can be copied or amplified which is a key part of the real time RT-PCR process for detecting viruses.

Scientists amplify a specific part of the transcribed viral DNA hundreds of thousands of times. Amplification is important so that instead of trying to spot a minuscule amount of the virus among millions of strands of genetic information, scientists have a large enough quantity of the target sections of viral DNA to accurately confirm that the virus is present.

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How is the COVID-19 Virus Detected using Real Time RT-PCR? - International Atomic Energy Agency

A patient in Italy receives intensive care for COVID-19. Human geneticists are coming together to look for genes that make some people more vulnerable to the disease.

By Jocelyn KaiserMar. 27, 2020 , 3:25 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center.

COVID-19, caused by the new pandemic coronavirus, is strangelyand tragicallyselective. Only some infected people get sick, and although most of the critically ill are elderly or have complicating problems such as heart disease, some killed by the disease are previously healthy and even relatively young. Researchers are now gearing up to scour the patients genomes for DNA variations that explain this mystery. The findings could be used to identify those most at risk of serious illness and those who might be protected, and they might also guide the search for new treatments.

The projects range from ongoing studies with DNA for many thousands of participants, some now getting infected with the coronavirus, to new efforts that are collecting DNA from COVID-19 patients in hard-hit places such as Italy. The goal is to compare the DNA of people who have serious cases of COVID-19 (which stands for coronavirus disease 2019)but no underlying disease like diabetes, heart or lung diseasewith those with mild or no disease. We see huge differences in clinical outcomes and across countries. How much of that is explained by genetic susceptibility is a very open question, says geneticist Andrea Ganna of the University of Helsinkis Institute for Molecular Medicine Finland (FIMM).

Its hard to predict what will pop out from these gene hunts, some researchers say. But there are obvious suspects, such as the gene coding for the cell surface protein angiotensin-converting enzyme 2 (ACE2), which the coronavirus uses to enter airway cells. Variations in the ACE2 gene that alter the receptor could make it easier or harder for the virus to get into cells, says immunologist Philip Murphy of the National Institute of Allergy and Infectious Diseases, whose lab identified a relatively common mutation in another human cell surface protein, CCR5, that makes some people highly resistant to HIV.

Ganna heads up a major effort to pool COVID-19 patients genetic data from around the world. The idea came quite spontaneously about 2 weeks ago when everyone was sitting at their computers watching this crisis, says Ganna, who is also affiliated with the Broad Institute, a U.S. genomic powerhouse.

He and FIMM Director Mark Daly quickly created a website for their project, the COVID-19 Host Genetics Initiative, and reached out to colleagues who run large biobank studies that follow thousands of volunteers for years to look for links between their DNA and health. At least a dozen biobanks, mostly in Europe and the United States, have expressed interest in contributing COVID-19 data from participants who agreed to this. Among them are FinnGen, which has DNA samples and health data for 5% of the 5 millionperson Finnish population, and the 50,000-participant biobank at the Icahn School of Medicine at Mount Sinai.

The UK Biobank, one of worlds largest with DNA data for 500,000 participants, also plans to add COVID-19 health data from participants to its data set, the project tweeted this month. And the Icelandic company deCODE Genetics, which is helping test much of the nations population to see who is infected with the new coronavirus, has received government permission to add these data and any subsequent COVID-19 symptoms to its database, which contains genome and health data on half of Icelands 364,000 inhabitants, says its CEO Kri Stefnsson. We will do our best to contribute to figuring this out, Stefnsson says.

Another effort to identify protective or susceptibility DNA variants is the Personal Genome Project led by Harvard Universitys George Church, which recruits people willing to share their full genome, tissue samples, and health data for research. Earlier this month, it sent questionnaires to its thousands of participants, asking about their COVID-19 status. More than 600 in the United States responded within 48 hours. It seems that most people want to do their part, says Church, whose group isnt yet part of Gannas collaboration.

Other researchers working with Gannas initiative are recruiting COVID-19 patients directly within hospitals for such genomics studies. Italian geneticist Alessandra Renieri of the University of Siena expects at least 11 hospitals in the nation to give ethics approval for her team to collect DNA samples from willing patients. It is my opinion that [host] genetic differences are a key factor for susceptibility to severe acute pneumonia, Renieri says.

Pediatrics researcher Jean-Laurent Casanova at the Rockefeller University, who specializes in identifying rare genes that can make healthy young people susceptible to certain serious diseases, is drawing on a network of pediatricians around the world to look for the relatively few young people who develop COVID-19 serious enough to get admitted to intensive care. We study exclusively patients who were previously healthy and under 50, as their serious COVID-19 illness is more likely to have a genetic basis, he explains.

In addition to genetic variants of the ACE2 receptor, scientists want to see whether differences in the human leukocyte antigen genes, which influence the immune systems response to viruses and bacteria, affect disease severity. And some investigators want to follow up a finding, which a Chinese team reported in a preprint: that people with type O blood may be protected from the virus. Were trying to figure out if those findings are robust, says Stanford University human geneticist Manuel Rivas, who is contributing to Gannas initiative.

The catastrophic spread of the coronavirus should soon increase the number of COVID-19 patients available to these gene hunts. And that could speed findings. Ganna expects the first susceptibility genes could be identified within a couple of months.

With reporting by Elizabeth Pennisi.

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How sick will the coronavirus make you? The answer may be in your genes - Science Magazine

Heather Ray, a developmental biology postdoc at the University of Alabama at Birmingham who studies the genetics of birth defects, received an email on March 24 from the search committee for a faculty job to which she had applied. Due to the COVID-19 pandemic and a resulting hiring freeze at the university, Ray says the email read, the search and position had been canceled.

I hadnt even thought that this might happen, she says.

A few minutes later, Ray received an email from a search committee in her own department that had been interviewing applicants for two open positions. Three candidates had completed in-person interviews for those positions, and all three had been invited back to campus for a second round of interviews. The University of Alabama at Birmingham had recently announced that it too was suspending hiring for individuals who did not have a documented offer, which meant that the search in Rays department was also called off.

All of the work that they did, thats just gone away, she says, because when the job is posted again in the fall, or the following year, the search committee will have to start all over.

A day earlier, on March 23, Brown University announced the suspension of all new hiring for the current year and for the fiscal year starting on July 1. At the same time that supporting our communitys health and safety remain a top priority, reads the universitys press release, the financial consequences resulting from the increased expenditures and the dramatic reductions in revenue provoked by the current pandemic demand prompt attention.

Numerous other universities have made similar announcements about the suspension of hiring, including Miami University of Ohio, Wright State University, Villanova University, the University of Nevada, Reno, Indiana University, and the University of Auckland in New Zealand, which cites the travel ban affecting Chinese students as one of the main causes of its freeze. The Professor Is In, a website and consulting service for applicants on the academic job market, posted yesterday an unofficial list of 58 universities that had issued some form of a hiring freeze. Comments in response to that post point to additional universities that have also scaled back hiring to various degrees.

James McGrath, a postdoc in digital public humanities at Brown University, tweeted about Browns announcement on Tuesday, eliciting responses from students and academics in various disciplines.

The worry is with an institution like Brown that has the endowment that it has and the resources that it has, McGrath tells The Scientist. If theyre making this decision, you can only wonder . . . what kinds of decisions [institutions with fewer resources] are going to be making. He says the hiring freezes in response to the coronavirus pandemic are a sign that the whole higher ed job market, which is already in bad shape, is heading for darker times.

A summary from the Senate Appropriations Committee released yesterday specified that the $2 trillion stimulus package passed by the Senate Wednesday (March 25) and currently being considered by the House would include at least $1.25 billion for federal research agencies working on the coronavirus, as well as $14.25 billion for universities that have been forced to shut down during the pandemic, which may funnel aid to labs whose work has been disrupted, Science reports.

But how that stimulus package may affect those currently searching for academic positions remains unclear.

Its definitely scary as someone who is looking for another postdoc or potentially applying to faculty jobs to have this looming situation, says Kishana Taylor, a postdoc in microbiology and molecular genetics at the University of California, Davis. If universities are going along the same lines as Brown, Taylor says, essentially, there wont be any applications to put in in the fall. She notes that the job market is always competitive, especially in the biomedical sciences, and that the hiring freezes will only increase that competition.

Ray agrees, adding that if the current situation persists, universities may experience a bottleneck where two or three years worth of applicants [are] all trying for the same number of positions at one time.

Julie Craft Van De Weghe, a cellular biology postdoc at the University of Washington whose research focuses on primary cilia and Joubert syndrome, says she wonders whether the terms of her K99 Pathway to Independence Award from the National Institutes of Health will be adjusted if the current lack of hiring in academia persists. The grant is supposed to cover two years of a postdoc and the first three years of a faculty position, according to Craft Van De Weghe, but she is unsure what would happen if shes unable to secure an academic job in the coming year. I will be reevaluating my contingency plans, she says.

The hiring freezes and their effects on the larger scientific community also concern Craft Van De Weghe. Although universities are producing researchers well-trained to contribute to humanitys knowledge of how science works, she says, well lose a ton of good people who could have made substantial contributions.

Roughly two weeks ago, Ray signed an offer letter from a university, completing her extended search for a faculty position that began in June of last year, and had pulled her application from the university that later notified her of its hiring freeze. The timing had been perfect, she says, because she was able to travel for an in-person interview and negotiate her contract before universities starting closing their campuses. But on the morning of March 25, a day after she had received the emails about hiring freezes and canceled searches, Ray learned that the university where she had accepted an offer had issued its own hiring freeze. She immediately emailed the committee chair asking whether her position was under threat.

I wasnt left waiting too long, Ray says, but it was a brief moment of almost panic. Her new job, she reports, is secure.

Amy Schleunes is an intern atThe Scientist. Email her ataschleunes@the-scientist.com.

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Universities Issue Hiring Freezes in Response to COVID-19 - The Scientist

When I first arrived at the Weizmann Institute of Science (WIS), Tel Aviv, in May 2013 as a summer trainee, little did I know that I will be spending a good part of my life in Israel. There is some inexplicable aura of scientific aptitude in the beautiful campus nestled just outside the bustling city of Tel Aviv. It was rather an easy decision to return for a Ph.D. in Molecular Genetics at the institute after graduating with an Integrated BS-MS in Biology from the Indian Institute of Science Education and Research (IISER), Kolkata.

Unparalleled quality

WIS is a rather unusual destination for graduate school, as compared to other major schools in the U.S. and Europe as it offers only MSc and Ph.D. programmes in natural sciences (Physics, Chemistry, Mathematics/CS, Biology). Quite naturally, the student/post-doc body is compact leading to thought-provoking scientific conversations, often leading to interesting scientific collaborations. In addition to roughly 250 professors across 18 departments, there are numerous staff scientists, many of whom serve as an immediate source of guidance and mentorship.

Weizmann supports services for almost all major advanced scientific tools and techniques. This enables the students and other researchers to answer tough questions. For instance, discoveries at the institute have enabled the treatment of diseases such as multiple sclerosis, lung cancer, prostate cancer, and lymphoma. Not only is the quality of science unparalleled, but also, Weizmann Institute is a great place to work. The continual support of the mostly English-speaking administrative staff makes it probably the best place to be for an international student in Israel.

Co-curricular activities

Outside the lab, the institute provides ample opportunities for personal and professional growth. There are multiple student clubs such as Entrepreneurship, Debate and LGBTQ clubs that train students with various hard and soft skills such as innovation, management and persuasive speaking. In fact, I have been involved in establishing the Weizmann Biotech Club, which is a forum for Ph.D. students and post-docs to interact with life-science industry leaders, learn about the industry trends and provide career development support.

Finally, Israel is a great place to begin ones professional career. It is known to be the start up nation and provides a plethora of opportunities to engage with the booming innovation ecosystem of the country for aspiring technology entrepreneurs.

Israel is opening its doors to foreign entrepreneurs with the recent launch of an innovation visa, that comes with generous support from the Israel Innovation Authority.

The writer is a Ph.D. student at the Dept. of Molecular Genetics, Weizmann Institute of Science, Israel

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In the start-up nation - The Hindu

The cerebral cortex is the relatively thin, folded, outer gray matter layer of the brain crucial for thinking, information processing, memory, and attention. Not much has been revealed about the genetic underpinnings that influence the size of the cortexs surface area and its thickness, both of which have previously been linked to various psychiatric traits, including schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder (ADHD), and autism.Now, for the first time, more 360 scientists from 184 different institutions including UNC-Chapel Hill have contributed to a global effort to find more than 200 regions of the genome and more than 300 specific genetic variations that affect the structure of the cerebral cortex and likely play important roles in psychiatric and neurological conditions.

The study was led by co-senior authors Jason Stein, PhD, assistant professor in the Department of Genetics at the UNC School of Medicine; Sarah Medland, PhD, senior research fellow at the QIMR Berghofer Medical Research Institute in Australia; and Paul Thompson, PhD, associate director of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the University of Southern California. Ten years ago, these scientists cofounded the ENIGMA Consortium, an international research network that has brought together hundreds of imaging genomics researchers to understand brain structure, function, and disease based on brain imaging and genetic data.

This study was only possible due to a huge scientific collaboration of more than 60 sites involved in MRI scanning and genotyping participants, Stein said. This study is the crown jewel of the ENIGMA Consortium, so far.

The researchers studied MRI scans and DNA from more than 50,000 people to identify 306 genetic variants that influence brain structure in order to shed light on how genetics contribute to differences in the cerebral cortex of individuals. Genetic variants or variations are simply the slight genetic differences that make us unique. Generally speaking, some variants contribute to differences such as hair color or blood type. Some are involved in diseases. Most of the millions of genetic variants, though, have no known significance. This is why pinpointing genetic variants associated with cortex size and structure is a big deal. Stein and colleagues consider their new genetic roadmap of the brain a sort of Rosetta stone that will help translate how some genes impact physical brain structure and neurological consequences for individuals.

Among the findings of the research:

Most of our previous understanding of genes affecting the brain are from model systems, like mice, Stein said. With mice, we can find genes, knock out genes, or over express genes to see how they influence the structure or function of the brain. But there are a couple of problems with this.One problem is, quite simply, a mouse is not a human. There are many human-specific features that scientists can only study in the human brain.

The genetic basis for a mouse is very different than the genetic basis for humans, Stein said, especially in in the noncoding regions of the genome.

Genes contain DNA, the basic human code that, when translated into action, creates proteins that do things, such as help your finger muscles type or your heart beat or your liver process toxins. But only about 3 percent of the human genome codes for proteins. The vast majority of the human genome is called the noncoding genome. Much of this region is not shared between mice and humans. This noncoding genome consists of tiny molecular switches that can modulate the expression of other genes. These switches dont directly alter the function of a protein, but they can affect the amounts of a protein that is expressed. Turns out, most genetic variants associated with psychiatric disorders are found in the noncoding region of the genome.

These findings can now be a resource for scientists to help answer important questions about the genetic influences on the brain and how they relate to numerous conditions.ReferenceGrasby et al. (2020) The genetic architecture of the human cerebral cortex. Science. DOI: https://doi.org/10.1126/science.aay6690

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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The First Genetic Map of the Cerebral Cortex - Technology Networks

Scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) and Fox Chase Cancer Center show that EGR4, known mainly for its role in male fertility, serves as a critical brake on immune activation. The new study Suppression of Ca2+signals by EGR4 controls Th1 differentiation and anticancer immunityin vivo,published online inEMBO Reports, demonstrates that taking EGR4 away, thus effectively releasing the brake, promotes the activation of killer T cells, which infiltrate and attack tumors and thereby boost anticancer immunity.

While the zinc finger transcription factors EGR1, EGR2, and EGR3 are recognized as critical for Tcell function, the role of EGR4 remains unstudied. Here, we show that EGR4 is rapidly upregulated upon TCR engagement, serving as a critical brake on Tcell activation. Hence, TCR engagement of EGR4/T cells leads to enhanced Ca2+responses, driving sustained NFAT activation and hyperproliferation. This causes profound increases in IFN production under resting and diverse polarizing conditions that could be reversed by pharmacological attenuation of Ca2+ entry, wrote the investigators.

Finally, aninvivomelanoma lung colonization assay reveals enhanced antitumor immunity in EGR4/mice, attributable to Th1 bias, Treg loss, and increased CTL generation in the tumor microenvironment. Overall, these observations reveal for the first time that EGR4 is a key regulator of Tcell differentiation and function.

Other early growth response proteins, or EGRs, are important to T cell activity, but whether EGR4 also has a role in immunity has been largely overlooked, explained Jonathan Soboloff, Ph.D., professor of Medical Genetics and Molecular Biochemistry at the Fels Institute for Cancer Research and Molecular Biology at LKSOM. Our study reveals a new side to the importance of EGR4.

Soboloffs team examined the influence of EGR4 expression in immune cells in collaboration with Dietmar J. Kappes, Ph.D., professor of Blood Cell Development and Cancer at Fox Chase Cancer Center. In initial experiments, the researchers found that T cell activation is associated with EGR4 upregulation. They then showed that knocking-out, or eliminating, EGR4 from immune cells results in a dramatic increase in calcium signaling and expansion of T helper type 1 (Th1) cell populations. Th1 cells, in response to the presence of foreign entities, including tumor cells, activate cytotoxic, or killer, T cells, which then wipe out the invader.

We know from our previous work that T cells control calcium signaling and that when intracellular calcium levels are elevated, calcium signaling can drive T cell activation, Soboloff said.

The Soboloff and Kappes labs next studied the functional importance of EGR4 in cancer immunity by utilizing an adoptive mouse model of melanoma in which some host animals lacked EGR4 expression. Compared to mice with typical EGR4 levels, EGR4 knockout animals showed evidence of expanded populations of Th1 cells and enhanced anticancer immunity. In particular, EGR4 knockout mice had reduced lung tumor burden and fewer metastases than mice with normal EGR4 expression.

In future work, the Soboloff and Kappes groups plan to further explore strategies for EGR4 targeting. The development of an agent to target EGR4 specifically may be difficult, due to the diverse actions of EGR pathways. But eliminating EGR4 specifically from a patients T cells, and then putting those cells back into the patient, may be a viable immunotherapeutic approach, Kappes said.

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Removing EGR4 "Brake" on Immune Activation May Be Viable I/O Therapeutic Approach - Clinical OMICs News

Genomics has come a long way since the central dogma (the notion that DNA is the master controller that calls all the shots) and junk DNA (the expectation that much of the genome is non-functional). If scientists ditch those old dogmas and approach the genome expecting to find reasons for things, they often do.

To-may-to or to-mah-to? The British write flavour; the Americans write flavor, but generally each understands the other without too much difficulty. Genomes, too, have alternate ways of spelling things: GGU and GGC in messenger RNA both spell glycine. No big deal, thought geneticists; these silent mutations cause no change in the resulting protein. At the University of Notre Dame, however, biochemists are finding that the differences in spelling are not just background noise; they alter the proteins folding. Is that good or bad?

Synonymous mutations were long considered to be genomic background noise, but we found they do indeed lead to altered protein folding, and in turn impair cell function, said Patricia Clark, the Rev. John Cardinal OHara professor of biochemistry at the University of Notre Dame, and lead author of the study. Our results show that synonymous variations in our DNA sequences which account for most of our genetic variation can have a significant impact on shaping the fitness level of cellular proteins.

Surely many of these mutations are harmful, as are random mutations in humans that cause genetic disease. But E. coli has been around for a long time. Wouldnt the species have gone extinct by now with the accumulation of defective spellings if they are always deleterious? Other work has suggested a secret code in synonymous variations that fine-tunes expression rates or regulates the supply of a given protein based on environmental conditions. The news release only mentions impairments caused by synonymous variations, but Notre Dame teams paper in PNAS suggests some possible advantages:

Synonymous codon substitutions alter the mRNA coding sequence but preserve the encoded amino acid sequence. For this reason, these substitutions were historically considered to be phenotypically silent and often disregarded in studies of human genetic variation. In recent years, however, it has become clear that synonymous substitutions can significantly alter protein function in vivo through a wide variety of mechanisms that can change protein level, translational accuracy, secretion efficiency, the final folded structure and posttranslational modifications. The full range of synonymous codon effects on protein production is, however, still emerging, and much remains to be learned regarding the precise mechanisms that regulate these effects. [Emphasis added.]

A design perspective would consider every possible function before rendering a judgment that all synonymous variations reduce fitness.

Keeping the genome accurate to a high degree preserves it from collapsing due to error catastrophe. At the time of cell division, proofreading enzymes (what a concept!) perform this vital function. Chelsea R. Bulock et al., writing in PNAS, have found one duplication enzyme that proofreads itself while proofreading its partner! DNA polymerase proofreads errors made by DNA polymerase , the paper is titled.

Pol and Pol are the two major replicative polymerases in eukaryotes, but their precise roles at the replication fork remain a subject of debate. A bulk of data supports a model where Pol and Pol synthesize leading and lagging DNA strands, respectively. However, this model has been difficult to reconcile with the fact that mutations in Pol have much stronger consequences for genome stability than equivalent mutations in Pol. We provide direct evidence for a long-entertained idea that Pol can proofread errors made by Pol in addition to its own errors, thus, making a more prominent contribution to mutation avoidance. This paper provides an essential advance in the understanding of the mechanism of eukaryotic DNA replication.

In other words, Pol is a proofreader of a proofreader. The paper says that Pol is a versatile extrinsic proofreading enzyme. One could think of it as a supervisor checking the work of a subordinate, or better yet, as an auditor or inspector able to fix errors before they cause harm to the product. Why would this be necessary during replication? The authors see a seniority system:

Thus, the high efficiency of Pol at correcting errors made by Pol may result from a combination of two factors: the high proclivity of Pol to yield to another polymerase and the greater flexibility and robustness of Pol when associating with new primer termini.

One proofreader is amazing to consider evolving by a Darwinian mechanism. A proofreader of a proofreader is astonishing. Consider, too, that this proofreading operation occurs in the dark by feel, automatically, without eyes to see.

Now that genetics is long past the heady days of finding that DNA forms a code that is translated, additional discoveries continue to show additional codes and factors that contribute to genomic function. One factor is the high-order structure of DNA. Researchers at South Koreas UNIST center have explored further into the formation of this structure, which involves chromatin wrapping around histone proteins so that long strands of DNA can fit within the compact space of the cell nucleus. As with everything else in genomics, the structure doesnt just happen. It requires a lot of help.

Regulation of histone proteins allows the DNA strands become more tightly or loosely coiled during the processes of DNA replication and gene expression. However, problems may arise when histones clump together or when DNA strands intertwine. Indeed, the misregulation of chromatin structures could result in aberrant gene expression and can ultimately lead to developmental disorders or cancers.

Histone chaperones are those proteins, responsible for adding and removing specific histones [found] at the wrong time and place during the DNA packaging process. Thus, they also play a key role in the assembly and disassembly of chromatin.

Cryo-EM imaging allowed the team to envision the molecular structure of some of these chaperone proteins. Their paper in Nature Communications begins, The fundamental unit of chromatin, the nucleosome, is an intricate structure that requires histone chaperones for assembly. Their cryo-EM images of one particular chaperone named Abo1 reveals a six-fold symmetry with precise locations for docking to histones, its hexameric ring thus creating a unique pocket where histones could bind with energy from ATP. Not only is Abo1 distinct as a histone chaperone, they write, but Abo1 is also unique compared to other canonical AAA+protein structures. Like Lego blocks, Abo1 features tight knob-and-hole packing of individual subunits plus linkers and other binding sites, such as for ATP. And unlike static blocks, these blocks undergo conformational changes as they work.

Such sophistication is far beyond the old picture of DNA as a master molecule directing all the work. It couldnt work without the help of many precision machines like this.

These stories are mere samples from a vast and growing literature indicating higher order in the genome than expected. Here are some more samples readers may wish to investigate:

Researchers at the University of Seville found additional factors involved in the repair of DNA strand breaks. These repairs are essential for the maintenance of genome integrity. The factors they discovered help maintain the right tension in cohesin molecules that hold the chromosomes together until the right time to separate. The news was relayed by EurekAlert!and published in Nature Communications.

Remember Paleys Watch? Researchers at the University of Basel discovered that Inner clockwork sets the time for cell division in bacteria. In PNAS and in Nature Communications, the Basel team elucidates the structure and function of a small signaling molecule that starts the clock, which then informs the cell about the right time to reproduce. They report in the news release:

A team at the Biozentrum of the University of Basel, led by Prof. Urs Jenal has now identified a central switch for reproduction in the model bacteriumCaulobacter crescentus: the signaling molecule c-di-GMP. In their current study,published in the journalNature Communications,they report that this molecule initiates a clock-like mechanism, which determines whether individual bacteria reproduce.

Proteins must fold properly to perform their functions. Small proteins usually fold successfully on their own, but large ones can fall into several misfolding traps that are equally likely as the canonical fold. It appears that the sequence of the sequence in a gene has something to do with this. Interestingly, many of these proteins sequences contain conserved rare codons that may slow down synthesis at this optimal window, explain Amir Bitran et al. in a January 21 paper in PNAS, discovering that Cotranslational folding (i.e., folding that begins as the polypeptide exits the ribosome) allows misfolding-prone proteins to circumvent deep kinetic traps.

Design advocates and evolutionists need to fathom what they are dealing with when discussing origins. Theres nothing like some low-level detail to put the challenge in perspective.

Image credit: Caulobacter crescentus, by University of Basel, Swiss Nanoscience Institute/Biozentrum, via EurekAlert!

Continued here:
More Hints of Order in the Genome - Discovery Institute

BOSTON, March 25, 2020 /PRNewswire/ -- The burgeoning coronavirus (COVID-19) global pandemic has already killed thousands of people worldwide and is threatening the lives of many more. In an effort to limit the virus from spreading, Harvard University was among the first organizations to promote social distancing by requiring all but the most essential personnel to work remotely. However, labs that perform vital COVID-19-related research are permitted to continue their potentially life-saving work and many of these activities are currently ongoing at the Wyss Institute for Biologically Inspired Engineering.

Essentially all medical treatment centers impacted by SARS-CoV2 (CoV2), the SARS-family virus that causes COVID-19, are overstrained or unable to confront the virus, starting from their ability to diagnose the virus' presence in the human body, treat all infected individuals, or prevent its spread among those that have not been infected yet. Therefore, finding better solutions to diagnose, treat, and prevent the disease, is key to combating this menace and bringing this pandemic under control. Equally concerning, there are worldwide shortages on the front lines in hospitals in our region and around the world, including rapidly depleting supplies of personal protective equipment, such as N95 face masks, and nasopharyngeal swabs needed for COVID-19 diagnostic testing. Solving these challenges requires rapid responses and creative solutions.

"With our highly multi-disciplinary and translation-focused organization, we [the Wyss Institute] were able to quickly pivot, and refocus our unique engineering capabilities on much needed diagnostic, therapeutic, and vaccine solutions, and we hope to be part of the solution for many of the innumerable problems the present pandemic poses," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who also is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "We strive to make a major contribution to bringing this crisis under control, and are confident that what we accomplish under duress now will help prevent future epidemics."

Meeting challenges on the front lines of patient care

Many of the Institute's hospital partner institutions and government agencies have reached out to Institute leadership to assist in this rapidly escalating battle against COVID-19. Ingber's team is working closely with collaborators at Beth Israel Deaconess Medical Center (BIDMC), other Harvard-affiliated hospitals, and generous corporate partners to develop potential solutions to the increasing shortage of nasopharyngeal swabs and N95 face masks. Senior Staff Engineers Richard Novak, Ph.D., and Adama Sesay, Ph.D., and Senior Research Scientist Pawan Jolly, Ph.D., are working diligently with our clinical partners to help devise a solution as quickly as possible.

Diagnosing COVID-19 more quickly, easily, and broadly

With COVID-19 rapidly spreading around the planet, the efficient detection of the CoV2 virus is pivotal to isolate infected individuals as early as possible, support them in whatever way possible, and thus prevent the further uncontrolled spread of the disease. Currently, the most-performed tests are detecting snippets of the virus' genetic material, its RNA, by amplifying them with a technique known as "polymerase chain reaction" (PCR) from nasopharyngeal swabs taken from individuals' noses and throats.

The tests, however, have severe limitations that stand in the way of effectively deciding whether people in the wider communities are infected or not. Although PCR-based tests can detect the virus's RNA early on in the disease, test kits are only available for a fraction of people that need to be tested, and they require trained health care workers, specialized laboratory equipment, and significant time to be performed. In addition, health care workers that are carrying out testing are especially prone to being infected by CoV2. To shorten patient-specific and community-wide response times, Wyss Institute researchers are taking different parallel approaches:

Via one route, a team led by Wyss Core Faculty member

, Ph.D., and Senior Staff Scientist

, M.D., Ph.D., in the Institute's Molecular Robotics Initiative are developing a disposable test that makes use of a "lateral flow device" (LFD) much like a home pregnancy test easy to manufacture at a large scale, and able to be handled without special equipment or expertise. The team is adapting a suite of bioinspired DNA nanotechnology techniques that Yin's lab has previously developed to enable the detection of virus RNA or protein from simple nasopharyngeal swabs with high sensitivity and accuracy. In the handheld LFD device, these tools would enable users to transform the presence of viral RNA or protein in a sample into the formation of a colored line on a simple strip of nitrocellulose paper. Yin is one of the leaders of the Wyss Institute's Molecular Robotics Initiative and also Professor of Systems Biology at Harvard Medical School (HMS).Better viral RNA detection methods are also being pursued by

, a molecular diagnostics startup spun out of the Wyss Institute and Broad Institute in 2019. The company licensed the

developed by Wyss Core Faculty member

, Ph.D., and his group, including former Wyss Business Development Lead William Blake, Ph.D., who joined Sherlock Biosciences from the Wyss Institute as the company's CTO. Collins is a co-founder of Sherlock Biosciences, and also the Termeer Professor of Medical Engineering & Sciences at the Massachusetts Institute of Technology (MIT). According to Rahul Dhanda, M.B.A., the CEO and a co-founder of Sherlock Biosciences, the company is currently working on different solutions for diagnosing COVID-19, one of which deploys the INSPECTRTM technology. INSPECTRTM consists of DNA-based sensors, which can be programmed to detect CoV2 RNA with specificity down to a single one of its nucleotide building blocks; the sensors are coupled with paper-based synthetic gene networks that produce a bioluminescent signal. The signals can be generated at room temperature, captured on instant film and read from a simple device without sophisticated equipment, and the test is currently designed to perform similarly to an off-the-shelf pregnancy test. Like the LFD approach developed in Yin's group, INSPECTRTM technology can be readily adjusted to allow specific detection of the different continuously arising CoV2 variants, and to follow their spread through the population.In a different project led by Collins and spearheaded by Research Scientists

, Ph.D., and

, and former graduate student

at the Wyss Institute, the team is developing a rapid self-activating COVID-19 diagnostic face mask as a wearable diagnostic. Worn by patients or individuals at home with symptoms of the disease, the face mask could rapidly signal the presence of the virus without any need for hands-on manipulation so that patients can be quickly triaged for proper medical care, while healthcare workers and patients that are nearby are protected. Emerging from Collins' team's

created in the Wyss Institute's Living Cellular Devices Initiative, the approach will use highly sensitive molecular sensors that, coupled to synthetic biology networks, could enable the production of an immediately visible or fluorescent color signal in the event that CoV2 is encountered. The entire cell-free molecular machinery can be freeze-dried and integrated with the synthetic material on the interior side of face masks. Exposed to small droplets that are expelled by wearers during normal breathing, sneezing, and coughing, and the humidity of exhaled air, the reactions are re-hydrated and thus activated to produce a positive or negative signal within 1 to 3 hours.A method to capture CoV2 virus particles from human samples in a single step and identify them within 1 hour is being explored by Senior Staff Scientist,

, Ph.D., working on Don Ingber's Bioinspired Therapeutics & Diagnostics platform. The researchers are leveraging the Wyss Institute's

to bind CoV2 virus particles, which they hope to rapidly identify using mass spectrometry. FcMBL is a genetically engineered variant of the "Mannose Binding Lectin" (MBL) immune protein that binds to molecules on the surface of over 100 different pathogens, including certain viruses. Ingber's team has confirmed that FcMBL binds to a non-infectious pseudotyped CoV2 virus that displays the CoV2 Spike protein on its surface.Ultrasensitive assays to detect the levels of cytokines molecules that are secreted by certain immune cells to affect other cells are being developed by

, Ph.D., leader of the Wyss Diagnostics Accelerator, to help identify effective therapeutic interventions that can prevent the deadly cytokine storm that can be triggered by overproduction of immune cells. The lab is also developing a serological test to ascertain individuals who are not showing any symptoms yet, but have been exposed to virus and have mounted an immune response. Walt is also the Hansjrg Wyss Professor of Biologically Inspired Engineering at HMS, Professor of Pathology at Boston's Brigham and Women's Hospital, and Institute Professor of the Howard Hughes Medical Institute.

Advancing antiviral therapeutics on the fast track

To date there is no antiviral drug that has been proven to reduce the intensity and duration of the infection in more seriously affected patients, or protect vulnerable patients from CoV2 infection. Doctors can merely provide supportive care to their COVID-19 patients by making sure they receive enough oxygen, managing their fever, and generally supporting their immune systems to buy them time to fight the infection themselves. Research groups in academia and industry working at breakneck pace by now have compiled a list of candidate therapeutics and vaccines to could offer some help. However, given the high failure rates of candidate drugs in clinical trials, more efforts are needed to develop effective medicines for a world population that likely will vary with regards to their susceptibility and access to new therapeutic technologies.

The ongoing COVID-19 pandemic requires rapid action, and the fastest way to combat this challenge is by repurposing existing drugs that are already FDA approved for other medical applications as COVID-19 therapeutics. While clinicians around the world are attempting to do this, the approaches have been haphazard, and there is a great need to attack this problem in a systematic way.

Ingber's team, co-led by Senior Staff Scientist

, Ph.D. and Senior Research Scientist

, Ph.D., has developed a preclinical CoV2 infection model that leverages the Wyss Institute's human

(Organ Chip) in vitro human emulation technology. The team engineered a CoV2 pseudovirus that is safe to use in the laboratory and expresses the key surface Spike protein, which mediates its entry into cells. They also demonstrated that it successfully infects human Lung Chips lined by highly differentiated human lung airway epithelial cells, which the team previously has shown to recapitulate human lung pathophysiology, including responses to Influenza virus infection, with high fidelity. Other members of the team, including Senior Staff Engineer Richard Novak and Senior Staff Scientist

, Ph.D. are respectively using network analysis algorithms and molecular dynamic simulation-enabled rational drug design approaches to identify existing FDA approved drugs and novel compounds that can be tested in the Organ Chip-based COVID-19 therapeutic repurposing pipeline. Senior Staff Scientist

, Ph.D., working in the Wyss Institute's Predictive Biodiscovery Initiative led by Jim Collins is also applying new machine learning-enabled computational tools to confront this repurposing challenge. The team is now in active collaborations with researchers who can study the native infectious CoV2 virus in approved BSL3 biosafety laboratories, and they are working hard to rapidly identify existing FDA approved drugs and drug combinations that may be used as COVID-19 therapeutics, or as prophylactic therapies for healthcare workers or patients who are particularly vulnerable to this disease. Reilly, working with Senior Staff Scientist Ken Carlson, Ph.D., is also using his molecular dynamics simulation approach to develop new broad spectrum Coronavirus therapeutics targeted against a conserved region of its surface Spike protein that would both help infected patients survive the current COVID-19 pandemic, and allow us to be prepared to prevent infections by related Corona viruses that might emerge in the future.Collins' team is also deploying computational algorithms to predict chemical structures that could inhibit different aspects of virus biology or disease pathology and be developed into therapeutics. In a collaboration with

, Ph.D., a Professor at MIT's Department of Electrical Engineering and Computer Science, his team is leveraging deep neural networks to develop therapeutic strategies that could help treat bacterial pneumonia, which can overlay pneumonia caused by the CoV2 virus and further endanger patients' lives. In a recent study, motivated by the present dearth of antibiotics, Collins' group successfully pioneered a deep learning approach to

that led the researchers to discover new molecules with antibacterial effects towards different pathogenic strains.Wyss Core Faculty member

, Ph.D., and his graduate student Kettner Griswold are taking yet another route. One way the CoV2 virus could be fought is to harness the power of the immune system. Church and Griswold are engineering antibodies that specifically bind to the virus and could enable a potent immune attack on it. Starting from an already existing "neutralizing antibody" that binds the Spike protein of the virus responsible for the 2003 SARS epidemic, they hope to make the antibody fit the closely related CoV2 virus. Such a neutralizing agent would be akin to treatments in which patients with infectious diseases receive "blood plasma" (the liquid part of blood that holds the blood cells) from individuals that have recovered from the infection, which contains neutralizing antibodies against the pathogen. However, an engineered antibody could be manufactured in large quantities and supplied to COVID-19 patients much more quickly and easily than blood plasma. Church is also Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard and MIT.

In search of ultimate protection a vaccine

With no vaccine currently available, but several vaccine candidates being explored around the world, Wyss Institute researchers led by Wyss Core Faculty member David Mooney, Ph.D., are developing a material that could make vaccinations more effective. Previously, Mooney's team has developed implantable and injectable cancer vaccines that can induce the immune system to attack and destroy cancer cells.

A key ingredient in vaccines is a fragment of the infectious agent, called an antigen, but the immune response to many antigens is weak. The bioactive materials of the Wyss's vaccine are programmed with molecules that orchestrate the recruitment and stimulation of immune cells with presentation of the antigen. This results in robust responses that in relation to COVID-19, in theory, may enable the immune system to both kill the virus immediately in infected individuals, as well as create a memory in infected and uninfected individuals without the need of additional boosts. Given the material's highly modular structure, one can easily plug-and-play various antigens that are being identified by researchers across the world, optimizing the response to each. This approach may yield a highly versatile platform in the fight against future epidemics and many infectious diseases. Mooney leads the Wyss Institute's Immuno-Materials Focus Area and also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

Understanding how COVID-19 develops and how to control it

COVID-19 does not strike equally strong in every individual that it infects. Independent of age, some are prone to become seriously ill, while others show an astonishing level of resilience against the disease. Figuring out the biological basis for these differences could lead to new protective strategies.

Church and Wyss Associate Faculty member

, Ph.D., are working with "

" (PGP), an international initiative that creates public genome, health, and genetic trait data to be mined by the biomedical research community for driving scientific progress in many areas. Wu is also Professor of Genetics at HMS. Church was instrumental in founding the initiative in 2005, and has been advancing its reach with key technological advances and his emphatic stewardship. The two Wyss researchers and their teams led by Sarah Wait Zaranek, Ph.D., Curie President and PGP informatics co-Director, are now launching a project to harness the PGP platform by comparing the genomes, microbiomes, viromes, and immune systems of consenting individuals with extreme COVID-19 susceptibility and individuals that exhibit resistance. Their far-flung systems biology approach could lead to unexpected insights about the disease, and reveal key levers that could be adjusted with existing drugs to control the infection, help prioritize individuals for urgent care, as well as provide guidance as to which healthcare workers would do better on the front-lines of care.Besides pursuing various COVID-19-focused activities in its laboratories, the Wyss Institute is working with the broader research, hospital, and public health communities to integrate its efforts nationally. For example, Church is fastening ties with his former Postdoctoral Fellow

, Ph.D., Professor of Genome Sciences at the University of Washington, Seattle, who leads the "

," which pivoted to COVID-19, as well as

, Ph.D., Director of the

in Seattle, and

, Ph.D., founder of life science company 4Bionics, among other companies, to develop a simple, yet different home test kit. On the national level, Walt is a member of a

started at the National Academies' newly formed "Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats." The committee is strongly focusing now on the present coronavirus pandemic to find ways to help the federal government consolidate and streamline efforts across the nation but will also work long-term to develop strategies and make recommendations for future health threats.

At the international level, the Wyss Institute functions as a Center of Excellence of the Global Virus Network (GVN), with Ingber as leader and the other Wyss Faculty as key participating members. The GVN is designed to integrate surveillance and response efforts for biothreats, epidemics, and pandemics by integrating efforts of top virus research institutions from around the world. Ingber is also currently working closely with the Defense Advanced Research Projects Agency (DARPA) and Bill & Melinda Gates Foundation, as well as in active discussions with the NIH's National Institute of Allergy and Infectious Diseases (NIAID), Biomedical Advanced Research and Development Authority (BARDA), and Public Health England, as they all try to align and coordinate efforts to meet this monumental health challenge.

"The Wyss Institute and its collaborators are taking exactly the type of comprehensive, integrated approach to addressing this pandemic that is required at local, national, and international levels," said Walt.

PRESS CONTACTS

Wyss Institute for Biologically Inspired Engineering at Harvard University Benjamin Boettner, benjamin.boettner@wyss.harvard.edu, +1 917-913-8051

The Wyss Institute for Biologically Inspired Engineering at Harvard University ( http://wyss.harvard.edu ) uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new startups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, DanaFarber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, Charit Universittsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology.

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The Harvard Wyss Institute's response to COVID-19: beating back the coronavirus - Champaign/Urbana News-Gazette

Sean Diehl likens the development of a new vaccine to the construction of a house. Before workers can turn a shovelful of dirt or hammer a nail, an architect must create a blueprint that shows how the building's thousands of components fit together and in what order.

Similarly, vaccine researchers trying to stop the spread of a deadly virus must start by mapping its messenger RNA. Decoding that genetic blueprint allows them to construct a safe and reliable vaccine that, they hope, will provide immunity for decades.

This time, researchers are racing to devise a vaccine that will stop a pandemic that's already upon us, using a never-before-tried method. It's akin to erecting a storm shelter using a new construction technique just as a Category 5 hurricane makes landfall.

Diehl is an assistant professor in the Department of Microbiology and Molecular Genetics at the University of Vermont's Larner College of Medicine. Since 2008, he's collaborated with the college's Vaccine Testing Center on projects involving infectious diseases, autoimmune disorders and vaccine development. In the past few years, Diehl's laboratory has focused on developing new protections against rotavirus, which is one of the most common and deadly causes of childhood diarrhea, and two mosquito-borne viruses dengue and Zika which infect tens of millions of people worldwide each year.

The 44-year-old Shelburne resident agreed to an interview with Seven Days months before the novel coronavirus made headlines. Since then, Diehl has joined the global effort to develop a vaccine against COVID-19.

On that front, researchers are already working at breakneck speed. They began in late December, when health authorities in Wuhan, China, first reported the outbreak of a viral pneumonia of unknown origin. On January 12, Chinese health authorities and the World Health Organization announced that they had mapped the entire sequence of the new coronavirus genome and shared it with researchers around the world.

On March 16, the National Institutes of Health announced the launch of a Phase 1 clinical trial to evaluate an experimental COVID-19 vaccine. In that study, being conducted at the Kaiser Permanente Washington Health Research Institute in Seattle, 45 healthy volunteers, ages 18 to 55, were injected with different doses of an experimental vaccine to evaluate its safety and efficacy in inducing immune responses.

Diehl is not involved in the Washington study. But, using the expertise he gained from researching dengue and Zika vaccines, he explained how a COVID-19 vaccine will be developed, how long it could last and how we can create more effective versions in the future.

"This is a brand-new approach," he said of the experimental coronavirus shot. "There is no current vaccine that's ever been developed this way."

How long before the public can be immunized? That's difficult to say. Diehl wouldn't offer a prediction beyond saying that "there are some aggressive timelines being talked about."

Ordinarily, vaccines involve years of research before human trials begin. But advanced genetic technologies and reductions in bureaucratic red tape could significantly shorten that timeline for COVID-19, with some estimates saying a vaccine could be available as early as this fall.

Several methods are used to create a vaccine, Diehl said. Under normal circumstances, the most common is to start with an attenuated, or weakened, version of a virus. Scientists inject this weaker version into laboratory animals, typically mice and nonhuman primates, hoping to trigger an immune response that doesn't make the animal sick. Only after long and rigorous study do vaccine developers request approval from the U.S. Food & Drug Administration to move on to human trials.

Consider the lengthy path that brought researchers to a vaccine for just one of four serotypes, or strains, of dengue (known as "Dengue 1, 2," etc.). Versions of the deadly virus are found in more than 100 countries around the world, posing a risk to about 40 percent of the world's population, or 3 billion people. According to the U.S. Centers for Disease Control and Prevention, as many as 400 million people are infected with dengue each year, of whom 100 million get sick and 22,000 die.

Though dengue's mortality rate is about 0.1 percent, comparable to seasonal flu, Diehl pointed out that its symptoms are much worse. "Dengue" may derive from the Spanish word for fastidious or careful, which describes the gait of a patient suffering from the disease.

The disease causes a very high fever that progresses into terrible joint, muscle and bone aches hence its nickname, "breakbone fever." Patients feel that their eyes are about to pop out of their heads.

Dengue is a particularly complicated disease to combat because of its four serotypes; an immunity to one offers no protection against the other three. If a person contracts Dengue 1 in, say, the Dominican Republic, they may recover without even knowing they were infected. However, if that person later travels to Puerto Rico and contracts Dengue 2, they have a greater chance of getting sick from the second exposure.

"For dengue," Diehl said, "it's taken, so far, 20 years and several billion dollars to get to the point of [having] the one vaccine that's on the market right now, for a very limited use."

What does this mean to researchers racing for a coronavirus vaccine? Speaking in "really broad brushstrokes," Diehl said, the way genetic material is encoded in the coronavirus is "very similar" to the coding of dengue. Both viruses have one long, continuous string of nucleic acid, or mRNA, that is "read" as a series of letters representing its chemical components: adenine (A), guanine (G), cytosine (C) and thymine (T).

In the case of dengue, that string is 10,000 letters long. In COVID-19, Diehl said, it's 25,000.

Working with a much longer string of information naturally presents more challenges. But, Diehl said, COVID-19 researchers don't need a full understanding of how all 25,000 letters of the genome function. The novel approach they're using to develop a vaccine is focused on the 3,000 to 5,000 letters that they believe may induce an early protective immune response. If they can pinpoint those letters, they will, in effect, buy themselves more time.

By now, most people who are following news of the unfolding pandemic have seen images of the COVID-19 virus, which resembles a fuzzy tennis ball riddled with darts or crowns. Those darts, which are called spike proteins, enable the virus to attach itself to a target cell, pass along its genetic material and reproduce.

A vaccine is essentially useless, Diehl said, if it triggers an immune response "post-fusion," or after the virus binds to the cell. The aim of this experimental vaccine is to induce an immune response before fusion happens.

"If we can block that," he said, "the virus has nowhere to go, and it dies."

The good news: Vaccine developers now have machines that can rapidly synthesize and mass produce the crucial 3,000- to 5,000-letter sequences that can be used to induce a pre-fusion immune response.

The bad news: That immune response won't last for long, because the mRNA used to produce it is an unstable molecule that degrades quickly in the body. "A good vaccine will last decades. This is probably single years," Diehl said.

That may be enough, though. Here's where Diehl joins the global effort: He has submitted a protocol seeking permission to collect and study blood samples from patients who have recovered from COVID-19. Once researchers better understand how all 25,000 nucleotides work together, he said, they can move on to developing vaccine "versions 2.0, 3.0 and beyond" that will induce "immune memory."

It's no surprise that Diehl uses construction metaphors to describe the microscopic workings of cells and viruses; his father, who's now retired, worked for years in construction. To his mother, a nurse, Diehl attributes his desire to work in a public health field and help others.

A native of Rome, N.Y., Diehl earned a bachelor's degree in chemistry at the State University of New York Geneseo. There, he developed an interest in immunology, and a professor suggested he pursue a doctoral degree. The first member of his family to attend a four-year college, Diehl hadn't known until then that students could get funding to pursue graduate degrees.

Earning his PhD at UVM, Diehl met his now-wife, Sandra. When he completed the degree, they moved to the Netherlands, where Sandra was born and raised.

After spending 2003 to 2008 at the University of Amsterdam, Diehl returned to Vermont and joined the faculty at UVM, where he's been ever since. Sandra works as a pediatric nurse at the UVM Medical Center. The couple has two daughters, Jill, 11, and Vera, 9.

Diehl admitted that it's frustrating to see vaccines demonized by the public when he knows how much "blood, sweat and tears" go into making them. He sees them as a "miracle product" that saves lives. "And then some people just choose not to believe in them."

What keeps him interested in immunology?

"The fact that we'll never figure it all out," he said. Unlike the study of many processes in the human body, such as the cardiopulmonary system, immunology is constantly evolving and discovering new cell types. And those discoveries almost always have real-world health applications, whether it's combating an autoimmune disorder or working to end a global pandemic. Given its complexity, COVID-19 could keep researchers busy for years to come.

"At the root of it," Diehl said, "I always know that there's so much still to be learned."

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UVM Researcher Offers Insights on Vaccines and COVID-19 - Seven Days

Hurricanes, floods, drought and fire. Extreme weather events are becoming more frequent as the climate changes and can destroy entire landscapes both visible and invisible.

Like humans, microbes need disaster response strategies that facilitate the rescue and recovery of their ecologically crucial communities.

But what do microscopic rescue efforts look like, and can humans help?

In a new study, published in a special issue of Philosophical Transactions of the Royal Society B, researchers in the lab of Michigan State University microbial ecologist Ashley Shade put microbes under extreme heat to find out.

We know microbes provide crucial functions for maintaining the health of their ecosystems they cycle nutrients, carbon and have important feedback with climate change processes, said Shade, an assistant professor in MSU College of Natural Sciences Department of Microbiology and Molecular Genetics, whose research is supported by an National Science Foundation Early CAREER Award. We want to get a good handle on how their function might change by exploring how quickly microbes recover after the change takes place, and what we might we be able to do to manage them back to stability.

Between 20% and 80% of all microbes in the environment exist in a dormant state, like microbial sleeping beauties waiting for the right moment to wake up and function. In fact, dormancy is a widespread, bet-hedging strategy against famine and other suboptimal conditions that has evolved separately along every major branch of life. Some microbes can exist in this suspended, but viable, state for thousands of years.

We know that there are ways microbes recover after a disturbance by replenishing their populations through dispersal through air and water, Shade said. What is special about this study is that we looked at the contributions of dormant microbes as well.

Using sterilized canning jars filled with soil and their microbial communities, Shade and graduate student Jackson Sorensen designed three separate treatments.

The control received no treatment, but the second and third treatments were cooked to a sweltering 60 degrees Celsius the temperature of an underground coal fire in Centralia, Pennsylvania that Shade has been studying for six years. After cooling, the second treatment was given dispersed cells from the control jars to boost recovery.

We reproduced what would happen in the environment after a disturbance where dispersal is most likely from the next neighborhood over, Shade said. We used just a tiny bit of it, not comprising a substantial volume, and the microbes grew after the disturbance subsided, showing a little dispersal can go a long way.

The third treatment was denied outside assistance. Instead, Shade and her team watched the jars to see what role dormant microbes played in returning the microbial community to a healthy, stable state.

What we found was that both reactivation and dispersal contributed to how microbes respond to the extreme event, Shade said. This is an important finding because it suggests that it is not just outside cells rescuing the population but also dormant microbes in the disturbed environment that reactivate and support recovery.

The nearly yearlong experiment was not long enough to see the communities of microbes fully recover, even with the combined tools of dormant reactivation and outside dispersal. Still, Shade found value in what she describes as dormancy dynamics.

This experiment gives us another strategy to manage microbial communities, she said. Think about taking antibiotics for an ear infection that, as a side effect, kills beneficial microbes in the gut. Dispersal might be analogous to eating yogurt to recover those beneficial microbial functions, but another strategy could be to encourage the already existing, viable gut microbes to wake up and contribute to healthy functionality.

Rousing dormant microbes and understanding why they go into dormancy is an area of active research.

Controlling dispersal in the environment is hard, Shade said. Microbes can travel through water, the air, on insects and inside insect guts and by hitchhiking on other animals as well. But controlling when microbes wake up and go to sleep could be another interesting strategy for managing them to support a healthy environment as we face a changing climate. One day, we may be able to wake up local microbes to help environments recover even faster after extreme events.

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MSU scientists put the heat on microbes - MSUToday