Category Archives: Molecular Genetics

Scientists at theHudsonAlpha Institute for Biotechnologyhave pinpointed epigenetic differences in the way lupus affects black women compared to other lupus patients, revealing important mechanics of the puzzling disease. Epidemiologists have identified that lupus impacts black women with greater frequency and severity than other populations. Scientists inDevin Absher's Labat HudsonAlpha published findings in August showing that increased risk and harm to lupus patients can be linked to epigenetic differences--essentially, the degree to which certain genes are functioning.

The finding, published inArthritis & Rheumatology, helps create a more complete understanding of an often misunderstood disease, revealing some of the mechanisms that contribute to it. It also reveals a gap in genetic research, highlighting the lack of information scientists have regarding racial differences on the genetic level.

Devastating Disease

Lupus is an autoimmune disorder, meaning that the immune system attacks healthy cells in the body. It causes symptoms that are often difficult to quantify, including fatigue and extreme joint pain.

Lupus is one of the most historically chronicled diseases, having first been documented by Socrates in 400 BC. The disease gets its name from a common rash that forms on the face which is said to resemble the markings of wolves, hence the latin name "lupus" meaning wolf.

There are more than 200,000 cases of lupus in the US every year, yet there is no universally accepted cause or cure. The disease is chronic, meaning it can last for years or even an entire lifetime.

Megan Breitbach, PhD, is the lead author on the paper. She notes, "The diagnostic process can also prove long and tedious, because the symptoms come and go and often can only be observed through patient description."

"On average," she adds, "it takes six years to diagnose someone with lupus."

While treatment can help manage lupus, the condition cannot be cured. Instead, patients and their physicians try to address symptoms and take the edge off flare-ups.

Molecular Differences

While the disease on the whole remains a mystery, scientists hope to find some answers in the ways that the condition affects different populations. In the United States, lupus has a much higher prevalence in non-white populations. In fact, lupus is the 5th leading cause of death for black women ages 15-24.

Ancestry can dramatically impact disease genetics, so understanding why the disease affects populations differently could go a long way toward telling us what genetic factors play a part in developing the condition.

In the case of lupus, the body's immune B cells function distinctive epigenetic signatures of the disease are found in B cells, which are part of the immune system. The analysis performed by the Absher Lab revealed lupus-specific differences in methylation throughout B cell development between black and white women.

Methylation changes can alter the degree to which a stretch of DNA functions without changing the genetic code itself. This research shows the most significant changes in methylation occur around genes related to Interferons, which are proteins that regulate immune response.

These differences in B cell development could help explain the more severe symptoms and earlier age of onset for lupus in black women.

"What we found," explains Devin Absher, PhD, "was that there are a number of methylation changes we can link to lupus. When you isolate them, you see that the changes are far greater in black women. The population differences could be key to a more complete understanding of the disease on the whole."

Gaps in Understanding

The genetic gap between these two groups of patients with lupus illustrates a broader gap in knowledge. One key limitation of genetics stems from a lack of diverse data, which hurts all populations.

Disease genetics frequently relies on genome-wide association studies (GWAS) to link genes with various health conditions. However the most recent aggregations of GWAS show nearly 88% of participants come from European ancestry. These eurocentric results can make it harder to identify genetic components of diseases that disproportionately affect underrepresented populations.

A lack of diversity in genetic research slows progress across the board. The unique genetic factories of all kinds of ancestry can help us better understand the human genome and even find potential ways to share the benefits of natural resistance. For example, Americans of African descent were found to have mutations on their PCSK9 genes which led to lower levels of cholesterol in their bloodstream. With that information, researchers developed PCSK9 inhibitors to lower cholesterol and heart disease risk across ancestries.

This lupus research from the Devin Absher Lab further illustrates the importance of understanding racial diversity when examining genetic components for diseases.

Absher is involved in a number of efforts to drive greater diversity in genetic research, including the Alabama Genomic Health Initiative, which aims to bring the value of genetic sequencing to diverse populations across the state.

The Way Forward

This lupus research helps open the door for future exploration of methylation around Interferon sites as it relates to the disease. However, the finding is only possible because of an active consideration of the value of diversity in genetic research. HudsonAlpha remains dedicated to bringing the value of genomics to all, as a diverse approach to research opens doors that would otherwise remain closed.

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Lupus Study Illustrates the Importance of Diversity in Genetic Research - Nature World News

PARSIPPANY, NJ, Oct. 29, 2019 (GLOBE NEWSWIRE) -- Interpace (IDXG) announced today that it will be presenting new data on the performance of its molecular thyroid products at the upcoming 89th Annual Meeting of the American Thyroid Association (ATA), being held October 30th to November 3rd, 2019 in Chicago, IL. The ATA meeting is one of the largest gatherings of endocrinologists, ENTs, surgeons and other providers who focus on the diagnosis and treatment of thyroid cancer.

Interpace will be presenting three separate posters focused on the performance of the companys molecular tests for indeterminate thyroid nodules, ThyGeNEXT and ThyraMIR, and are titled:

Together these posters underline the clinical utility of ThyGeNEXT and ThyraMIR in assessing the risk of thyroid nodules with indeterminate cytology results progressing to cancer. They also highlight progress made by the Company to provide quality diagnostic information for the detection of aggressive forms of thyroid cancer.

Jack Stover, CEO of Interpace, stated, We are pleased that our data has been accepted for presentation in this prestigious forum and look forward to sharing our work with such an established group of attendees. Mr. Stover continued, The acceptance of our data supports our belief that our molecular products continue to add value to physicians and patients at risk of thyroid cancer.

About Thyroid Nodules, ThyGeNEXT and ThyraMIR Testing

According to the American Thyroid Association, approximately 20% of the 525,000 thyroid fine needle aspirations (FNAs) performed on an annual basis in the U.S. are indeterminate for malignancy based on standard cytological evaluation, and thus are candidates for ThyGeNEXT and ThyraMIR.

ThyGeNEXT and ThyraMIR reflex testing yields high predictive value in determining the presence and absence of cancer in thyroid nodules. The combination of both tests can improve risk stratification and surgical decision-making when standard cytopathology does not provide a clear diagnosis.

ThyGeNEXT utilizes state-of-the-art next-generation sequencing (NGS) to identify more than 100 genetic alterations associated with papillary and follicular thyroid carcinomas, the two most common forms of thyroid cancer, as well as Meduallary Thyroid Carcinoma. ThyraMIR is the first microRNA gene expression classifier. MicroRNAs are small, non-coding RNAs that bind to messenger RNA and regulate expression of genes involved in human cancers, including every subtype of thyroid cancer. ThyraMIR measures the expression of 10 microRNAs. Both ThyGeNEXT and ThyraMIR are covered by both Medicare and Commercial insurers, with more than 280 million patients covered.

About Interpace

Interpace is a leader in enabling personalized medicine, offering specialized services along the therapeutic value chain from early diagnosis and prognostic planning to targeted therapeutic applications.

Interpaces Diagnostic Business is a fully integrated commercial and bioinformatics business unit that provides clinically useful molecular diagnostic tests, bioinformatics and pathology services for evaluating risk of cancer by leveraging the latest technology in personalized medicine for improved patient diagnosis and management. Interpace has four commercialized molecular tests and one test in a clinical evaluation process (CEP): PancraGEN for the diagnosis and prognosis of pancreatic cancer from pancreatic cysts; ThyGeNEXT for the diagnosis of thyroid cancer from thyroid nodules utilizing a next generation sequencing assay; ThyraMIR for the diagnosis of thyroid cancer from thyroid nodules utilizing a proprietary gene expression assay; and RespriDX that differentiates lung cancer of primary vs. metastatic origin. In addition, BarreGEN for Barretts Esophagus, is currently in a clinical evaluation program whereby we gather information from physicians using BarreGEN to assist us in positioning the product for full launch, partnering and potentially supporting reimbursement with payers.

Interpaces Biopharma Business provides pharmacogenomics testing, genotyping, biorepository and other customized services to the pharmaceutical and biotech industries. The Biopharma Business also advances personalized medicine by partnering with pharmaceutical, academic, and technology leaders to effectively integrate pharmacogenomics into their drug development and clinical trial programs with the goals of delivering safer, more effective drugs to market more quickly, and improving patient care.

For more information, please visit Interpaces website at http://www.interpacediagnostics.com.

Forward-looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, relating to the Company's future financial and operating performance. The Company has attempted to identify forward looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "projects," "intends," "potential," "may," "could," "might," "will," "should," "approximately" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are based on current expectations, assumptions and uncertainties involving judgments about, among other things, future economic, competitive and market conditions and future business decisions, all of which are difficult or impossible to predict accurately and many of which are beyond the Company's control. These statements also involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from those expressed or implied by any forward-looking statement. Known and unknown risks, uncertainties and other factors include, but are not limited to the fact that there is no assurance the acquisition of the BioPharma business of Cancer Genetics, Inc. will be successfully integrated with the Company, or that the potential benefits of the acquisition, including future revenues, will be successfully realized. Additionally, all forward-looking statements are subject to the Risk Factors detailed from time to time in the Company's most recent Annual Report on Form 10-K, Current Reports on Form 8-K and Quarterly Reports on Form 10-Q. Because of these and other risks, uncertainties and assumptions, undue reliance should not be placed on these forward-looking statements. In addition, these statements speak only as of the date of this press release and, except as may be required by law, the Company undertakes no obligation to revise or update publicly any forward-looking statements for any reason.

CONTACTS:Investor Relations - Edison GroupJoseph Green(646) 653-7030jgreen@edisongroup.com

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Interpace to Present Data at the ATA Annual Meeting - GlobeNewswire

Video: New research links excess neural activity the flickering light seen in this image to reduced longevity. Credit: Yankner lab, Harvard Medical School.

The brains neural activity long implicated in disorders ranging from dementia to epilepsy also plays a role in how long we live.

The study, led by scientists in the Blavatnik Institute at Harvard Medical School and based on findings from human brains, mice, and worms, suggests that excessive activity in the brain is linked to shorter life spans, while suppressing overactivity can extend life.

Neural activity refers to the constant flicker of electrical currents and transmissions in the brain. Excessive activity, or excitation, could manifest in numerous ways, from a muscle twitch to a change in mood or thought, according to the researchers.

An intriguing aspect of our findings is that something as transient as the activity state of neural circuits could have such far-ranging consequences for physiology and life span, said study senior author Dr. Bruce Yankner, a professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging.

Neural excitation appears to act along a chain of molecular events famously known to influence longevity the insulin and insulin-like growth factor (IGF) signaling pathway, the researchers explain.

The key in this signaling cascade appears to be a protein called REST, previously shown by researchers in the Yankner Lab to protect aging brains from dementia and other stresses.

Study results could lead to the design of new therapies for conditions that involve neural overactivity, such as Alzheimers disease and bipolar disorder, the researchers said.

The findings also raise the possibility that certain medicines, such as drugs that target REST, or certain behaviors, such as meditation, could extend life span by modulating neural activity, they said.

Human variation in neural activity might have both genetic and environmental causes, which would open future avenues for therapeutic intervention, Yankner added.

The researchers began their investigation by analyzing gene expression patterns the extent to which various genes are turned on and off in donated brain tissue from hundreds of people who died at ages ranging from 60 to over 100.

The information was collected through three separate research studies of older adults. Those analyzed in the current study were cognitively intact, meaning they had no dementia, the researchers noted.

The researchers immediately noticed a striking difference between the older and younger study participants, Yankner said. The longest-lived people those over 85 had lower expression of genes related to neural excitation than those who died between the ages of 60 and 80.

Next came the question that all scientists confront: Correlation or causation? Was this disparity in neural excitation merely occurring alongside more important factors determining life span or were excitation levels directly affecting longevity? If so, how?

To answer these questions, the researchers conducted a barrage of experiments, including genetic, cell, and molecular biology tests in the model organism Caenorhabditis elegans, analyses of genetically altered mice, and additional brain tissue analyses of people who lived for more than a century.

These experiments revealed that altering neural excitation does indeed affect life span and illuminated what might be happening on a molecular level, the researchers said, noting all signs pointed to the protein REST.

REST, which is known to regulate genes, also suppresses neural excitation, the researchers found.

Blocking REST or its equivalent in the animals led to higher neural activity and earlier deaths, while boosting REST did the opposite.

The researchers also discovered that people who lived to 100 and beyond had significantly more REST in the nuclei of their brain cells than people who died in their 70s or 80s.

It was extremely exciting to see how all these different lines of evidence converged, said study co-author Dr. Monica Colaicovo, a professor of genetics at Harvard Medical School, whose lab collaborated on the C. elegans work.

The researchers found that from worms to mammals, REST suppresses the expression of genes that are centrally involved in neural excitation, such as ion channels, neurotransmitter receptors, and structural components of synapses.

Lower excitation activates a family of proteins known as forkhead transcription factors. These proteins have been shown to mediate a longevity pathway via insulin/IGF signaling in many animals. Its the same pathway that scientists believe can be activated by caloric restriction, according to the researchers.

In addition to its emerging role in staving off neurodegeneration, discovery of RESTs role in longevity provides additional motivation to develop drugs that target the protein, the researchers said.

Although it will take time and many tests to determine whether such treatments reduce neural excitation, promote healthy aging, or extend life span, the concept has captivated some researchers.

The possibility that being able to activate REST would reduce excitatory neural activity and slow aging in humans is extremely exciting, said Colaicovo.

The study was published in Nature.

Source: Harvard Medical School

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Excessive Brain Activity Linked to Shorter Life Span - PsychCentral.com

WALTHAM, Mass., Oct. 15, 2019 /PRNewswire/ -- Skyhawk Therapeutics, Inc. ("Skyhawk"), a drug discovery and development company focused on revolutionizing disease treatment with small molecules that modify RNA expression, today announced the appointment of four additional internationally recognized experts in RNA biology and disease to its Scientific Advisory Board.

"I am thrilled that we have assembled such a stellar group of RNA biology and human disease experts for Skyhawk's Scientific Advisory Board," said Prof. Tyler Jacks, Director of MIT's Koch Institute for Integrative Cancer Research and Chair of Skyhawk's SAB. "We look forward to having their combined knowledge and wisdom help guide Skyhawk's research and development efforts, to progress even more rapidly towards groundbreaking new approaches and therapies for patients with a variety of difficult-to-treat diseases."

Prof. Ben Blencowe is an internationally recognizedRNA biologist who has made pioneering contributions to the understanding of the molecular mechanisms controlling alternative splicing and their roles in evolution, development and disease. He holds the Banbury Chair of Medical Research and is Professor in the Donnelly Centre at the University of Toronto; he also serves as Director of the Donnelly Sequencing Centre. Prof. Blencowe has received numerous awards and honors for his research excellence and was recently elected Fellow of the Royal Society (UK).

Dr. Ben Ebert is the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, and Chair of Medical Oncology at the Dana-Farber Cancer Institute. His research focuses on the genetics, biology, and therapy of myeloid malignancies. His work has led to the characterization of clonal hematopoiesis as a pre-malignant state for hematologic malignancies, and elucidation of the mechanism of action of lenalidomide and related molecules that induce degradation of specific proteins. Dr. Ebert has served as president of the American Society for Clinical Investigation and is an elected member of the National Academy of Medicine and the Association of American Physicians.

Prof. Jeannie T. Lee is Professor of Genetics and Pathology at Harvard Medical School, the Blavatnik Institute, and the Massachusetts General Hospital. She specializes in the study of epigenetic regulation by long noncoding RNAs and uses X-chromosome inactivation as a model system. Prof. Lee also translates basic knowledge to find treatments for genetic disorders and co-founded two publicly traded companies Translate Bio and Fulcrum Therapeutics. She is a Member of the National Academy of Sciences, a 2018 Harrington Rare Disease Scholar, the 2016 recipient of the Lurie Prize, a 2016 recipient of the Centennial Award from the Genetics Society of America, the 2010 awardee of the Molecular Biology Prize from the National Academy of Sciences, and a Fellow of the American Association for the Advancement of Science.

Prof. Maurice Swanson is an expert on the regulation of RNA alternative processing during mammalian development and how this regulation is disrupted in neurological and neuromuscular diseases, including some types of muscular dystrophy and amyotrophic lateral sclerosis (ALS). Prof. Swanson is a Professor in the Department of Molecular Genetics and Microbiology at the University of Florida College of Medicine and Associate Director of the Center for NeuroGenetics. His lab focuses on the functions of repetitive DNA elements, particularly microsatellites or short tandem repeats (STRs), in RNA-mediated disorders. An important objective of these studies is to enhance tissue regeneration following treatment modalities designed to block the toxicity of STR.

These four new members join Skyhawk's existing Scientific Advisory Board members & advisors including:

About Skyhawk TherapeuticsSkyhawk Therapeutics is committed to discovering, developing and commercializing therapies that use its novel SkySTAR (Skyhawk Small molecule Therapeutics for Alternative splicing of RNA) platform to build small molecule drugs that bring breakthrough treatments to patients.

For more information visit: http://www.skyhawktx.com, https://twitter.com/Skyhawk_Tx, https://www.linkedin.com/company/skyhawk-therapeutics/

SKYHAWK MEDIA CONTACT:Anne Deconinckanne@skyhawktx.com

SOURCE Skyhawk Therapeutics

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World Renowned Experts Appointed to Skyhawk Therapeutics Scientific Advisory Board - PRNewswire

UNITED STATES

[This is an article from The Chronicle of Higher Education, Americas leading higher education publication. It is presented here under an agreement with University World News.]

I actually wasnt surprised, said Margee Louisias, an associate physician at Brigham and Womens Hospital who wants to study ways to reduce asthma in minority children.

Thats exactly what Ive seen in this early stage of my career, said Utibe Essien, an assistant professor at the University of Pittsburghs School of Medicine, who studies racial disparities in who gets the latest treatments for heart disease.

The NIH analysis also revealed a concerning double bind. Not only are health-disparity projects underfunded, but black applicants for the grant type the agency studied, called R01 grants, are disproportionately likely to propose those types of studies.

Meanwhile, white applicants are more likely to propose studying topics having to do with cells, molecules and genetics that are among the NIHs most funded.

In short: black academics, already under-represented in science, are less likely to land grants that are critical to advancing their careers, in part because they tend to want to study interventions that could improve the health of poor Americans of colour.

Getting the message

Early-career scientists said theyre getting the message from mentors, reviewers and their own observations that they might have a harder time getting funding in general for the research topics theyre passionate about.

Mya Roberson, a doctoral student in epidemiology at the University of North Carolina at Chapel Hill, is rewriting a grant application thats been rejected by the Agency for Healthcare Research and Quality, which, like the NIH, is an agency under the Department of Health and Human Services.

Roberson proposed studying black women with breast cancer. In the feedback she received with her rejection, she said: What had been said, nearly verbatim, is that the major limitation of my study was that it was an all-black study. Without including white women, I would be limited in the interventions I could suggest.

She declined to share the rejection letter, citing rules about not sharing grant applications that are being resubmitted.

Roberson was frustrated; her sister and aunt are cancer survivors. Black women are about 20% more likely to die of breast cancer than white women are, according to the American Cancer Society, though that gap has narrowed recently. Roberson remains unsure of whether to hold her ground or change her study for the chance to get funding.

Louisias, the physician who wants to study asthma disparities, recalled her mentors telling her that she should apply for funding from private foundations and federal agencies beyond the NIH because the people in the room may be basic scientists and translational researchers, and they may not get it.

Wanda Phipatanakul, a professor at Harvard Medical School, is one of those mentors. She told The Chronicle that reviewers who focus on basic science think experiments on cells and lab animals, not people may not know whats feasible in population studies and have biases against them. But she added that it is possible to be funded through the NIH; it just might take a few tries, as it did for her before she built a reputation for her work.

I started from the ground up, she said. I took three times to get my first R01. Its an uphill battle for everybody.

Despite the greater success they might have with other funding sources, aspiring population-health scientists said they want NIH grants, which are seen as more prestigious. Depending on the institution where they work, landing one or more R01s may even be a requirement for promotion.

The NIH, getting a grant from there is seen to be a metric of, Youve really reached that level of success, Louisias said.

The NIH analysis found black applicants face barriers beyond the choice of research topic. For example, while all proposals to study areas such as socio-economic class and health were less likely than average to be funded, black applicants nevertheless had an even harder time getting the green light than whites did. The NIH is studying what role implicit bias plays in its process for peer-reviewing grant applications.

Its all made early-career scientists feel they need to take extraordinary measures to ensure they can stay in their field. I have to think so far ahead, Roberson said. This study makes me feel like I have to really be on top of it.

Officials at the NIH said they care about population-health research and diversity among scientists.

Those topics are clearly extremely important, are in our mission, and are being funded. We would like to see more equivalent rates of funding, said Hannah Valantine, the NIHs chief officer for scientific work-force diversity, who worked on the recent NIH study.

In the past few years, efforts by the NIH to link under-represented minority scientists with mentors have helped reduce the black-white funding gap in R01 grants and eliminated it among K grants, which are for scientists with less experience, according to agency numbers.

Scientists, on the other hand, said theyre getting mixed messages. They knew of and appreciated the NIHs projects aimed at improving diversity among scientists. Yet they chafed at the fact that the NIHs one institute focused on Americans who systematically suffer from worse health, the National Institute on Minority Health and Health Disparities, is one of the poorest funded by Congress. Of the NIHs 27 institutes and centres, its budget was ranked 23rd in 2019.

Theres little research on why American scientists might undervalue population-health research, compared with molecular biology, but scholars have theories.

Aimee Medeiros, a historian at the University of California at San Francisco, pointed to the Scientific Revolution as the beginning of the scientific communitys privileging of lab science over real-world observations.

Roberson and Louisias thought lab experiments might seem sexier because thats the kind of science that leads to new drugs treatments that might seem like easier solutions than untangling the effects of discrimination and environmental exposures that lead to health disparities.

Nevertheless, the scientists interviewed said they were inspired to study population health, rather than bench science, because they thought it could help make an immediate difference.

Essien, who is a doctor as well as a researcher, said: I felt like being a physician was much more than the biology and the science of disease, but really what our patients lived experiences are, before they even get to us in the clinic.

Francie Diep is a staff reporter covering money in higher education. Follow her on Twitter @franciediep, or email her at francie.diep@chronicle.com.

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The double bind faced by black research applicants - University World News

Rechavi says that exactly how the changes in the neurons are communicated to the germline and how thataffects the nervous system of the next generation are still open questions. He hypothesizes that the process involves one or more molecules released by the nervous system perhaps small RNAs, perhaps something secreted like a hormone. But somehow those germ cells then influence the behavior of the next generation and seem to circumvent the normal need for rde-4 in the production of the small RNAs for chemotaxis in the progeny.

In another paper on epigenetic behavior that appeared in the same June issue of Cell, Rebecca Moore, Rachel Kaletsky and Coleen Murphy, the molecular biologist who leads their laboratory at Princeton University, reported that C. elegans worms exposed to the pathogenic bacterium Pseudomonas aeruginosa learn to avoid it, and they transmit this learned avoidance for approximately four generations. Normally, the worms seem to prefer Pseudomonas to the bacteria on which they routinely feed.

The researchers sought to understand how this behavior is controlled at a molecular level. They discovered that double-stranded RNA from the pathogen triggered the worms response, a finding that they further investigated with Lance Parsons of Princeton University and described in a biorxiv preprint posted on July 11.

In the worms exposed to the pathogen, they detected changes in the expression of a gene, daf-7, in a specific neuron called ASI that is required for the avoidance behavior. They also found a huge number of changes in the small RNAs in the germline, Murphy said, including the ones called Piwi-interacting RNA (piRNA). As the name suggests, piRNAs interact with piwi genes, which help to regulate stem cell differentiation.

Moore, Kaletsky and Murphy found that animals without the piRNA pathway can learn to avoid Pseudomonas but do not pass on this avoidance behavior to their progeny. Thus, the piRNA pathway is critical for inheritance of the behavior. Thats why were excited about the piRNA pathway, Murphy said.

Sarkies thinks these findings may help to explain the curious ability of C. elegans to take up double-stranded RNA from the environment and use it to silence endogenous genes. For years, geneticists have exploited this property of worms: By synthesizing double RNAs that match any gene, researchers can silence it and study what it does.

But why the worm has this ability was mysterious. It obviously didnt evolve it in order to make life easy for scientists, and we dont really understand what ecological role it might have, Sarkies said. Whats quite exciting in principle about the studies from the Murphy lab is that they suggest that this might be a way in which C. elegans is able to adapt to pathogenic bacteria. Hypothetically, when the worm takes up double-stranded RNA from bacteria in its environment, the molecules could silence some of the worms genes and induce adaptive responses. Those adaptations could then be passed to the next generation.

Most in the field still approach such conjectures with skepticism. I believe that today, there is not a single solid paper showing that only small RNAs are involved in epigenetic inheritance, said Isabelle Mansuy, a neuroepigenetics researcher at the Swiss Federal Institute of Technology Zurich and the University of Zurich who studies the inheritance of trauma in humans and mice. In the mouse model she works with, she knows that small RNAs are not sufficient because if she injects small RNAs alone into fertilized mouse eggs, the resulting animals do not show the RNA-associated trait.

Mansuy believes that a multitude of factors may contribute in different ways to epigenetic inheritance, and their importance may vary with the trait or behavior. Very often people like to simplify the matter and think either its DNA methylation or its microRNA. I think its totally misleading to think that way, she said. People should not dismiss one or the other but just think about all these factors together.

She added that errors have crept into the literature on epigenetic inheritance, making some findings seem more definitive than they are. For example, some review articles claim that Mansuy demonstrated that injecting microRNAs into fertilized eggs is sufficient to cause the inheritance of behavioral symptoms in mice. We never showed this, she emphasized. Authors of review articles often dont go back to check the original findings, so when the review is cited subsequently, it creates an auto-feeding system that perpetuates errors. Its polluting the field, she said. Now many people work only on RNA epigenetic inheritance because they think it is well established, she added.

Unreliable findings have also sometimes appeared in high-profile journals. As a result, she argues, the field as a whole may be on thinner ice than it seems. The lack of rigor can lead to a misleading thought and perception, she warned.

Validation of Mansuys skepticism can be found in a recent study in eLife on epigenetic inheritance in fruit flies. Giovanni Bosco and his colleagues at Dartmouth College demonstrated that learned adaptive behaviors in fruit flies can be epigenetically inherited but that small RNAs are not sufficient to transmit this behavior.

In Drosophila, adult females raised with parasitic wasps learn to lay their eggs on food that contains ethanol, which protects the eggs and larvae from being parasitized by the wasps. This egg-laying preference occurs even when the mother herself was never exposed to ethanol, Bosco emphasized. Exposure to the wasp was in and of itself sufficient for the females to somehow epigenetically reprogram their eggs so that their daughters would be predisposed to have this behavior, he said.

The preference for egg laying on ethanol persists for five generations. Bosco, his graduate student Julianna Bozler, and Balint Kacsoh (now a postdoc at the University of Pennsylvania) hypothesized that small RNAs were involved in the inheritance of this behavior. To test this idea, they used a quirk of fly genetics to create flies with a pair of chromosomes that both came from the same parent (normally, both parents contribute to each pair). Boscos team reasoned that if small RNAs in the cytoplasm of the mothers egg were sufficient for inheritance of the learned behavior, then the offspring should exhibit the inherited behavior even if it received both pairs of chromosomes from the father.

In a series of experiments, Bozler, Kacsoh and Bosco demonstrated that small noncoding RNAs from the mother were not sufficient for transmitting the behavior between generations; an as yet unidentified epigenetic modification on chromosome 3 was also essential. They are currently investigating the nature of this epigenetic change.

To Bosco, the big question is: How does the signal from the brain reach an egg and change the information thats in the egg? Figuring this out would open the floodgates to ask: What else is the brain doing to the germline? What else are our cognitive experiences and environmental exposures impinging on the epigenome of the egg or sperm?

Most people, Bosco continued, would have no trouble accepting that exposure to a toxic chemical in our water or food could interact with the germline and change the epigenetic state of germ cells.

What I would suggest is that our brains are our pharmacies, Bosco said. Our brains are making chemicals all the time, such as neuropeptides and other neuromodulatory molecules with diverse functions. Some of those functions impinge directly on processes in other organs, including the reproductive system. If we can ingest a chemical from our environment that changes the epigenomes of the egg or sperm, why couldnt our brain make a similar molecule that does the same thing? he said.

At Cambridge, Burton has identified at least one of the ways in which information from the nervous system can be transmitted to the germline. In a 2017 Nature Cell Biology paper, he and his colleagues exposed C. elegans to high levels of salt to induce a state called osmotic stress. They discovered that the worms brain responded by secreting insulin-like peptides that change the egg-making cells (oocytes) in ways that induce an epigenetic change. The resulting alterations in gene expression in the oocytes lead the offspring to produce more glycerol, which protects them against osmotic stress.

You have a neuronal signal affecting the germ cells that looks to be adaptive, Burton said.

Mansuy has found that early-life trauma in mice leads to the release of stress hormones that affect the animal throughout its life span, producing depressed or risk-taking behaviors, metabolic dysregulation, and other health problems. They also affect the developing germ cells, causing the same behaviors and metabolic alterations to be inherited in the offspring for up to five generations. Previously, Mansuy had found that small RNAs were not sufficient to transmit these phenotypes in mice, just as they were not sufficient in the fruit flies. Something else was going on.

In a preprint recently posted on biorxiv.org, she and her colleagues report that by injecting the blood of traumatized mice into control mice, they could induce similar metabolic symptoms. The injected blood also appeared to affect the mices germ cells because their offspring inherited the metabolic abnormalities too.

The researchers identified some of the signaling molecules that transmitted the metabolic effects as fatty acids that can bind to receptor molecules, move into the nucleus and help activate the transcription of certain targeted genes. The receptors exist in germ cells, too, so they could be one of the ways in which information moves between blood and germ cells, Mansuy suggests.

One of the outstanding questions in the field is why epigenetic inheritance only lasts for a handful of generations and then stops, said Eric Greer, an epigeneticist at Harvard Medical School and Boston Childrens Hospital who studies the epigenetic inheritance of longevity and fertility in C. elegans. It appears to be a regulated process, in part because the effect persists at the same magnitude from one generation to the next, and then abruptly disappears. Moreover, in a paper published in Cell in 2016, Rechavi and colleagues described dedicated cell machinery and specific genes that control the duration of the epigenetically inherited response. So its an evolved mechanism that likely serves many important functions, Rechavi said.

But what exactly is adaptive about it? If the response is adaptive, why not hardwire it into the genome, where it could be permanently and reliably inherited?

In Murphys C. elegans model, because the learned avoidance behavior is transient (even if it is transgenerational), it allows animals to go back to eating bacteria that are nutritious but smell a lot like those pathogens, she explained. Sniffing out the difference between food and foes can be difficult, so worms that permanently avoid pathogens will miss out on nutritious food sources.

Greer concurs that there could generally be a cost to deploying an adaptive response permanently. For example, deploying antiviral defenses when pathogens arent around is a waste of resources that could be used instead for growth and reproduction.

Trade-offs could also constrain other adaptations. In Burtons 2017 study, worms exposed to P. aeruginosa produced offspring resistant to the pathogen, but that adaptation was deleterious to the offsprings ability to respond to other challenges, like osmotic stress. Unavoidable trade-offs between adaptations to different stresses make it impossible for the worms to be optimally adapted across the board.

In that scenario, you wouldnt want it hardwired into your genetics. Youd want this plasticity where you could program the adaptation, but also get rid of it, Burton explained. That may explain why stress appears to reset transgenerational small-RNA inheritance, as reported by Rechavi and his colleagues in a new preprint on biorxiv.org.

Very little work has been done to investigate mismatched stresses between parents and offspring, but a lot of literature suggests that these mismatched stresses might play a role in human diseases, Burton said. I think mechanistically looking at that is going to be really interesting, going forward.

Correction added on Oct. 16, 2019: The beginning of one sentence was rephrased to clarify that the described work in Murphys lab was not related to Rechavis experiments.

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Inherited Learning? It Happens, but How Is Uncertain - Quanta Magazine

TROY LAWRENCE/THE VARSITY

The hubbub of election season sees parties and candidates promoting and revamping policies and agendas, but theres one policy discussion that has yet to materialize government funding for fundamental science research.

The platforms of the Conservative Party, Liberal Party, and New Democratic Party (NDP) all have sparse information on science research, though the Green Party has provided a detailed strategy on funding.

Science research funding is lower than it was 10 years ago. The three main agencies that finance most of Canadas federal research the National Sciences and Engineering Research Council of Canada; the Canadian Institutes of Health Research (CIHR); and the Social Sciences and Humanities Research Council (SSHRC) have substantially decreased the amount of funding theyre willing to give, with the approval rate of grant applications by these agencies dropping to as low as 13 per cent.

Since winning the last federal election in 2015, Liberal leader Justin Trudeau appointed Dr. Kirsty Duncan as the chief scientific officer. Duncan commissioned an expert panel to carry out the fundamental science review, surveying the current landscape of science research in Canada.

In a 2015 mandate letter to the minister of science, Trudeau committed to the creation of more opportunities for students in STEM and business programs, enhanced research funding across the board, and strengthened recognition of the importance of fundamental research in discovery. According to the federal government, these mandates have been fulfilled.

However, the Canadian Association of University Teachers has contended that federal research funding has not been optimally allocated. The Liberals allotted $900 million to science research from the Canada First Research Excellence Fund, but the association maintains that it did not make a substantial impact on the larger science community. It wrote that the amount was only shared between 13 postsecondary institutes and their researchers.

Voters might expect a more coherent plan for research funding developed by each of the main parties. In the absence of a clear commitment to science research funding from the Liberals, the NDP, and the Conservatives, The Varsity reached out to party representatives.

Different parties pledges to research funding

According to a spokesperson from the Liberal Party, the party plans on providing$354.7millionoverfiveyears, and$90.1millionperyearongoing,tothe CIHR. It also plans to invest $265 million in the SSHRC.

A spokesperson for the NDP wrote that they will work with universities and health professionals to make sure that public research on critical health issues continues to flourish, and will invest in public agriculture research.

A representative from the Green Party referred to its in-depth funding strategy, which mentions that it plans on incorporating conclusions of the Fundamental Science Review and increasing funding to postsecondary institutions and universities for science research.

The Conservatives did not respond to The Varsitys request for comment.

U of T professor highlights reticence on science funding

A major issue for voters is that none of the parties seem to want to talk about science research funding in-depth, according to an op-ed to the Toronto Star written by Dr. David Naylor, a former U of T President, and Dr. Mark Lautens, a professor at U of Ts Department of Chemistry.

Lautens underscored the importance of federal research investment in an interview with The Varsity. He noted that it enables scientists to improve the publics quality of life by developing disease therapies, finding solutions to environmental issues, and bettering waste reduction. He noted that funding also provides research opportunities to better train the countrys future researchers.

Lautens has supported the rebound of federal funding since cuts in the mid-2000s, but he still believes that a lot more needs to be done. He highlighted the low rates of CIHR grant approval for medical research funding as a critical area of improvement.

Whats at stake for students?

Farah Qaiser, a Masters student in molecular genetics at U of T and a head spokesperson for #VoteScience, a national nonpartisan effort to advocate for science in the upcoming election, explained how voters can learn more about the parties positions on supporting research.

In an email to The Varsity, Qaiser advocated for voters to reach out to their candidates as soon as possible to ask where they stand on science issues that matter to their electorate such as funding research or better supporting the next generation of scientists.

She recommended voters to do so by reaching out to candidates in-person, calling, emailing, or using the #VoteScience campaigns email form.

To learn more, Qaiser further recommended students check CBCs non-partisan science and environmental policy debate between federal candidates, as well as the conclusions of a survey sent to the federal parties to determine their environmental policies.

The Evidence for Democracy advocacy group, along with members of the #VoteScience campaign, have also published results of a questionnaire sent to the federal parties about their positions on science policy.

The Liberals, NDP, and Greens submitted responses to the survey. According to Evidence for Democracy, the Conservatives declined to participate due to time constraints.

Tags: federal election, money, politics, Science

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Where do Canada's federal parties stand on research funding? - Varsity

An Ottawa astrophotographer who has been fascinated with space for years has earned recognition from NASA scientists for a dramatic image of the aftermath of two galaxies colliding.

In the photo, what looks like a pale but fiery strip of orange curls around a blue and purple swirl of stars. The two forms meet in a bright flare in the middle, creating the impression, as NASAs Astronomy Picture of the Day description puts it, that this galaxy is jumping through a giant ring of stars.

Rudy Pohl, the Ottawa man behind the processing of the image, said that theres a gravitational force that has been set up between them, sort of pulling it apart, though he was quick to add that he was not an astronomer himself.

In a phone interview with CTVNews.ca, Pohl said he was thrilled to have his photo chosen by NASAs Astronomy Picture of the Day -- his second image since he started submitting to NASA.

It's really extraordinary to get one of those, he said. Hundreds of images get submitted every day to NASA for this.

Astronomy Picture of the Day has been running since 1995, and each photo comes with an explanation of the image, provided by a professional astronomer.

Although it appears as though two galaxies are wrestling in front of our eyes, both the blue and orange arms in the picture are all part of the same galaxy: NGC 7714.

According to the description, the image shows how NGC 7714 has been stretched and distorted by a recent collision, with NGC 7715, a smaller, neighboring galaxy, that is off to the left out of the frame of the image.

Scientists believe that NGC 7715 charged right through NGC 7714.

The ring of golden light in the image is made up of millions of older stars thought to be similar to our sun, the description says, while the bright centre of NGC 7714 is the nexus of a new star formation for the galaxy.

Youd never guess it, looking at the vibrant colours in the picture, but this image started out life as a series of black and white photos taken by NASAs Hubble telescope.

It took hours of work to process the image, but it was work that Pohl, 69, was happy to do.

Pohl is part of an online community of astrophotographers who create stunning colour photographs of space. Although some have their own telescopes and equipment to take photos of the sky themselves, others rely on free archives, such as the Hubble Legacy Archive, to find the source images to create their masterpieces.

If the source images are black and white, does that mean those who process the images are choosing colours at random?

Not according to Pohl. The colour clues are in the filters used by Hubble, he said.

What they do is they put a colored filter in front of that black and white camera. In this case there are three colors, red, green, and blue. It's called RGB imaging. It's the same imaging as in our computer monitors and in our televisions, he explained.

Every single pixel is made up of a percentage of red, percentage of green and percentage of blue.

So the Hubble camera first puts a red filter in front of it, which means it blocks out everything but the red, and so the red wavelength hits the camera and you get an image.

Although the image still comes out looking black and white, it is effectively a picture of what the galaxy would look like if it was composed of only red light.

The process is repeated with blue filters and green filters, Pohl said, producing numerous images that -- while technically greyscale images -- contain a massive amount of information regarding where different wavelengths of light, and thus different colours, are concentrated in the image.

Astrophotographers take these different greyscale images and fill them with colour corresponding to the filter they were taken with, so they end up with numerous red, blue, and green layers of the same deep space object. When they line the different images up on top of each other, thats when the real picture of a galaxy, star or nebula starts to form.

It takes a lot of processing and refining of the different layers to filter out the noise in the images and produce a final photo that looks as crystal clear as Pohls picture of NGC 7714. Pohl said it can take anywhere from 12 to 16 hours to finish an image.

He used to have his own telescopes and equipment to image the heavens with, but when chronic illness advanced on him, he said he had to sell his gear.

Broke my heart to do it, he said.

Working with public archives of space images allowed him to hold onto his passion.

A love of science is something that has informed almost his entire life. Pohl got his undergraduate degree in molecular genetics at Carleton University, and met his wife while he was at it, who was also studying science. He only started posting astrophotography pictures within the last few years, but he's not slowing down now.

I'm going to be doing it for the rest of my life now, he said. I am so blown away, like when I think of the vastness of space.

NGC 7714 is around 100 million light years away from Earth, which makes it a relatively close cosmic neighbor.

According to APOD, NGC 7714 and NGC 7715 first started interacting around 150 million years ago, and are expected to continue for several hundred million years more, possibly resulting in the two combining into a single galaxy.

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This image shows the aftermath of two galaxies colliding - CTV News

Why anyone feels the need to keep remaking shows again and again is hard to imagine, but apparently enough people are willing to sit through another version of a show that they might have watched when it first aired simply because theres a new cast and, as a lot of people are praising, its more diverse now. Neetha K of Meaww still isnt convinced and I cant blame her. Im still trying to figure out how thats going to immediately make the show better but its definitely appeasing the people who have presented the loudest and most insistent voices throughout the years but havent seemed to realize that if actors are going to be selected they have to actually know how to act and not get their parts based on their race, gender, or any other factor apart from their talent. As if this wasnt enough, the middle sister is a lesbian and they all play Latina sisters despite the fact that one of them is Afro-Caribbean, one is Puerto Rican, and the other is a mix of African American, English, and Indigenous Canadian. At this point just using names must be too difficult since so many people have to display their pedigree so that others know how to address and think about them. At any rate, here are the cast members that are currently rounding out the second season of Charmed.

The middle sister of the bunch is portrayed as a very strong-willed feminist and is also an activist. Shes a graduate student and as mentioned is an open lesbian that had to wipe the memory of herself from her lovers mind. The power shes been given is to freeze time, which seems like a rather dangerous power when one really stops to think about it since the implications for such a thing are kind of dire. Eventually though it was revealed that Mel is the half-sister and not Macy.

Macy is a lot more practical than her sisters and is even labeled as a science nerd in a way. She has her PhD in molecular genetics and eventually moves to Hilltowne to work in the university. The revelation that she has two half-sisters in town is something of a shock but is necessary since the story kind of hinges on the trio getting together and discovering their powers so that they can act as the saviors of the town. The power she wields is telekinesis, being able to move objects with her mind, and once again its kind of a dangerous power to have but one that seems a lot more common in supernatural tales.

Maggie is the youngest and most upbeat of the sisters and shes the only one of them that seems to want to hide what she is and not really embrace it as shes trying to pledge a sorority and being a witch could ruin everything. Instead of having the power of premonition however as was seen in the original show Maggie has the power of empathy, meaning that she can read the emotions of other people and understand what theyre feeling and their emotional state at that moment. This is perhaps the most passive of the powers that the witches possess and seems as though it might be kind of useless, but it has shown to be an asset in past movies and shows that have utilized it.

Harry is the guy thats known as a Whitelighter, a guardian angel that protects and guides the witches when hes needed. Its kind of amusing in such a woke show that theres still a white male that is being used as a guide and a mentor for three diverse young women that are bound to become stronger when they unite, but it does seem to be introduced as a positive idea since hes more hands off and allows them to simply learn the ropes on their own while sticking around to see how things go.

You had to know that there would be a demon presence in this show and that eventually it would end up coming down to being one of the love interests of one of the witches. Maggie and Nick obviously cant stay together since he has to deal with the demon side of his being, but it feels safe to say that hell be back at some point since the two of them share something thats not bound to be thrown away.

It would seem that as different as the show is striving to be that there are still a lot of similarities that are being kept for good or ill, and at this moment its hard to say whether or not its bound to continue for more than a couple of seasons. As of now season 2 has been approved as per Abby Robinson of DigitalSpy, but its going to have step things up if it wants to improve.

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Meet The Cast of Charmed Season 2 - TVOvermind

A recent study looked at funding rates for R01 grant applications, which are designed to support "health-related research and development based on the mission of the NIH." In general, population-based projects were less likely to be funded than explorations of cellular mechanisms, the study found. Will & Deni McIntyre/Science Source hide caption

A recent study looked at funding rates for R01 grant applications, which are designed to support "health-related research and development based on the mission of the NIH." In general, population-based projects were less likely to be funded than explorations of cellular mechanisms, the study found.

Black applicants to a prestigious research grant program at the National Institutes of Health are awarded funding at a significantly lower rate than their white peers. The NIH has been intensively investigating this funding gap since a 2011 report revealed the extent of the problem, looking for underlying mechanisms to use as opportunities for corrective intervention.

NIH's latest finding, described in a study released this month in the open-access journal Science Advances, reveals that part of the gap can be attributed to differences in the types of topics scientists propose studying and how those topics are valued by grant reviewers.

The study of grant applications submitted between 2011 and 2015 suggests African American scientists may be more likely to pursue research in topic areas such as community-oriented research on disease prevention, for example, versus more microscopic-level research on cellular mechanisms or the basics of genetics. Those population-based topics aren't being funded as readily.

And that's a problem with the system, some outside researchers point out not with the choice of research topic.

"I do think that the areas of research that apparently are being funded at a lower rate are important," says David Asai, senior director for science education at Howard Hughes Medical Institute and an advocate for diversity in STEM, who was not involved in the NIH analysis. "This study might prompt the community to think about the underlying biases we might have in deciding what sorts of research deserve greater attention."

The NIH study looked at funding rates in the form of successful applications for R01 grants, which are designed to support "health-related research and development based on the mission of the NIH."

Despite NIH efforts to diversify the pool of scholars doing medical research, white applicants for these grants continue to receive funding at nearly twice the rate of black applicants 17.7% of white applicants were approved in fiscal years 2011-2015 compared with 10.7% of black applicants.

The researchers analyzed keywords in the topics of 157,549 grant applications and found that some topics were close to four times more likely to gain funding support.

"Among the less favored [topics] are areas that include study of groups of people," says Dr. James Anderson, deputy director for program coordination, planning and strategic initiatives at the NIH and one of the authors of the paper.

"These topics are are described by words like socioeconomic status, physical activity, pregnancy," Anderson says. "The ones that did best were really about molecular mechanisms cells, or parts of cells. Words like cilium, DNA polymerase, chimeral chemistry, ribosome. It's not absolute, but it's really quite a striking distinction." The success rates by topic ranged from about 29% to 7.5%.

The researchers used self-reported demographic data in an optional portion of the application one that was not visible to the grant reviewers to identify each applicant's race. They found that over a third of the applications from black scientists were tied to just eight of the 150 topic clusters.

Six of those eight topics involved "communities, or health disparities, and so on," says Anderson, "and those were in the topics that didn't do quite as well" in the funding process.

This difference in topic preference can account for 20% of the overall funding gap for black applicants, the study found, after controlling for other variables such as the applicant's prior academic and professional experience and accomplishments.

Dr. Hannah Valantine, director of the Office of Scientific Workforce Diversity at the NIH and another author on the paper, says black scientists might be more drawn to certain topic areas at the population level because "connection to one's community, and seeing the disparities, drives people to go into science to create a better environment for their community."

"It's critically important that African American scientists are able to advance their career and stay in academia, not only for their own success, but for enhancing the diversity of the biomedical workforce," Valantine says. "Because we know already that when we have a diverse scientific enterprise, we come up with more creative solutions to the problems that we seek to solve."

That concern resonates with Stephani Page, a postdoctoral fellow in biophysics at Duke University Molecular Physiology Institute and initiator of the Twitter hashtag #BLACKandSTEM, even though her field of study lies on the more statistically successful end of the grant-getting spectrum.

"For me, personally," Page says, "the science that gets me really excited, and I get tingles about, tends to be more quantitative, mechanistic science. But I also have the experience of coming up growing up and being a mom as a black woman in this skin. So when I think about what I want my career to be, it's difficult for me to detach from my career meaning something to my community more broadly."

Page says she is losing hope that she can have the community impact she wants helping black scientists feel affirmed while working in her current field. "I don't want to be a scientist who can't be committed and devoted to changing the system," she says.

One underlying cause of the disparity this study documented, Page says, might be that many of the NIH reviewers who evaluate grant proposals only 2.4% of whom were black in this study lack a certain lens when evaluating what research topics deserve priority.

"If you haven't grown up with inequity as deeply ingrained in your lived experience, it's not going to be as important a lens in your life decisions," she says. "The fact that there's data behind it now gives us a space to talk about it differently. Now we can begin to say that the lens makes a difference."

Valantine says the NIH is also actively evaluating whether the disparity is partly due to racial bias by reviewers. A study to be published early next year, she says, "will tell us whether, if we anonymize an application, we can close this gap."

Whatever the causes of the diversity gap, she says, the NIH is committed to closing it, and the study's results suggest several areas of intervention that could help. For one, the NIH has already begun mentoring programs aimed at increasing the diversity of the grant applicant pool.

"Black applicants submitted only 1.5% of the total applications for these R01s," Valantine says, adding that "we must do all we can" to increase that percentage.

In the meantime, the underfunded topics that the study identified are " 'mission critical' areas of NIH," Valantine says. "The solution is figuring out, within NIH, how we can make sure that those areas are funded."

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Racial Disparities In NIH R01 Funding May Be Partly Caused By Topic Choice : Shots - Health News - NPR