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

http://www.skyhawktx.com

See the rest here:
World Renowned Experts Appointed to Skyhawk Therapeutics Scientific Advisory Board - PRNewswire

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

Related Articles

Originally posted here:
Excessive Brain Activity Linked to Shorter Life Span - PsychCentral.com

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.

Receive UWN's free weekly e-newsletters

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

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

Go here to read the rest:
Where do Canada's federal parties stand on research funding? - Varsity

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.

Read the rest here:
Inherited Learning? It Happens, but How Is Uncertain - Quanta Magazine