On January 10, 2018, Dr. Jim Olds’ term as Assistant Director for Biological Sciences came to an end. Since taking up the post in September 2014, Dr. Olds has led BIO through many big changes, including the conception of the Rules of Life Big Idea and implementation of a no-deadline submission mechanism for receiving and reviewing proposals. All of us at BIO would like to thank Dr. Olds for his excellent leadership over the past three and a half years, and wish him the best as he returns to George Mason University.
Dr. Joanne Tornow, Head of the Office of Information and Resource Management (OIRM) and former BIO Acting Deputy Assistant Director, will be taking up the mantle as Acting Assistant Director for BIO while the search for Dr. Olds’ successor is underway. Stay tuned to learn more about Dr. Tornow and the exciting things she has planned for the directorate in the coming months!
“Karma” means a lot of things to a lot of different people. For Rob Martienssen, a pioneer in epigenetics and professor at Cold Spring Harbor Laboratory, it refers to a specific transposon – a DNA sequence that can change its position within a genome – that can mean the difference between a plentiful crop and ten years of wasted labor.
Some of the biggest names in plant science have guided Martienssen throughout his career, from his Cambridge University doctoral mentor David Baulcombe – who, with Andrew Hamilton, discovered small interfering RNA – to his postdoctoral mentors, William Taylor and Michael Freeling, at the University of California, Berkeley. As a junior faculty member at Cold Spring Harbor Laboratory, Martienssen even had the chance to work with Barbara McClintock, whose discovery of mobile genetic elements won her the Nobel Prize in 1983.
Today, Martienssen, who has received several NSF awards for his work, is building on that legacy as a professor at Cold Spring Harbor and Howard Hughes Medical Institute. Martienssen recently discussed his lab’s research on epigenomic modification of Karma transposons in the African oil palm in a BIO distinguished lecture titled, “Germline reprogramming and epigenetic inheritance: How to avoid BadKarma.” Afterward, he spoke to us how epigenetics shapes the world around us and just what “bad Karma” means to a plant scientist.
OAD: What is “epigenetics”? How is it different from the genetics we learn about in high school biology?
A: The concept of epigenetics actually has a really long history. Throughout most of the Middle Ages there was this controversy about developmental biology: you could either imagine a germ cell as being very naïve and having to be programmed to make the next generation, or in those days, there was also this idea that maybe there was a homunculus in the sperm that was fully formed and simply had to grow into a baby. Aristotle was very much in the former camp and William Harvey used the term “epigenesis” as a way to talk about this programming that happened to very naïve germ cells to allow them to become a new body – and of course, that’s how we think about development now.
Then in the 1940s, Conrad Waddington wrote a famous article and subsequently a book on something he called “epigenetic landscapes.” He went a bit further with this idea, saying that there was this underlying genetic program, but that depending how it was interpreted in every cell, you would get different fates for those cells. So, this was the idea that you don’t access all the information in the genome in every single cell, you only access some of it – and that was determined by epigenetics. He was using the term because it was sort of superimposed on genetics – it was “above” genetics.
OAD: Did he have a concept of how we interpret epigenetics today?
A: He’s often regarded as the father of epigenetics – he really did have a good idea of what was going on. He had done experiments in Drosophila where he’d selected different wing shapes over multiple generations and was able to select new forms without making mutations – or without making mutations that he could readily identify as a geneticist. So, he really did get it, and was the first person to propose this sort of transgenerational inheritance being based on genes.
At the same time, Barbara McClintock and Alexander Brink were maize geneticists working in the 1940s and 50s, and they actually came up with real examples of traits controlled by genes affecting plant color – like the color of kernels on a corn cob – that were under epigenetic control. They could go in one direction or another from one generation to the next, and Barbara was convinced that all of this was controlled by her “controlling elements” – transposable elements. So those were really the first definitive examples of “transgenerational” epigenetics.
OAD: So, epigenetics led to changes in these traits – wing shape and corn kernel color – without any mutations in the genes that encode them. And even though the change wasn’t genetic, it was able to be shared from one generation to the next. Do we know how this happens?
A: With the discovery of DNA as the genetic material and the composition of chromosomes over the next several decades, mechanisms that might explain this started to come forward and that’s how we really think about epigenetics today. These mechanisms are ways of modifying the chromosomes without changing the DNA sequence. Primary among these – at least in plants and mammals – is DNA methylation, which is very widespread. You can methylate and demethylate DNA chemically using enzymes in the cell, and you can also just replicate DNA without methylation and that will remove methylation passively.
This turned out to be one of the major mechanisms of epigenetic inheritance, but it wasn’t the only one. Chromosomes are not only composed of DNA but also histones, which are the proteins that DNA is wrapped around – you can think of it like a spool of string or wool – and those histones can also be chemically modified in a reversible way. Those modifications are just as important as the ones on DNA, but they have to be associated with specific genes, and so how these modifications only end up on specific genes has been a major part of research in the last few decades.
OAD: What are the prevailing theories for how that happens – how does the cell know where to put those modifications?
One of the things I was involved in about 15 years ago was the realization that some of that instruction about where these modifications were made – both DNA methylation and histone modifications – was through RNA, and in particular small RNA, which David Baulcombe discovered in plants. It’s not the only way – there are lots of DNA-binding proteins that also instruct the cell where to make these epigenetic modifications – but RNA turns out to be very important. More and more we believe that in plants and in some animals like C. elegans, this RNA can actually pass from generation to generation, and could actually have this transgenerational epigenetic effect.
OAD: Much of your work focuses on the African oil palm. Why that plant specifically? What are the “real world” ramifications of the questions you study?
A: The African oil palm is propagated by cloning, and this was done starting in the 1970s. There are some very good reasons for that – it allows you to clone elite germplasm [living seeds or tissues kept as genetic resources for breeding plants or animals] without having to breed it any further, because the clones are all supposedly the same and they’re all going to have the same elite properties. But it turns out that epigenetics raises its ugly head, and in fact these clones are not identical. The reason they’re not is because of transposons that lose DNA methylation in the cloning process – and we’re trying to understand why that happens. When they lose methylation in the cloning process, the next generation has really nasty phenotypes that are really important economically – they develop abnormal flowers and dry, shriveled fruit that yield much less oil.
The reason the oil palm is so important from this point of view is that it only grows in very sensitive parts of the world where it competes with rainforest, and if you transplant an oil plant from the nursery into the plantation, you have to do that before it fruits. It isn’t until 10 years later that you realize there’s a problem – that it has fruit that won’t yield any oil because of this epigenetic change – and you’re sort of stuck, so the temptation is to burn down a bit more of the rainforest and plant a bunch more. Now for big palm oil companies, they can afford to not do that, but for a small holder, it’s a different matter altogether. This is a major problem in Malaysia and Indonesia, and so I’ve been very fortunate to work with the Malaysian government, with the MPOB – the Malaysian Palm Oil Board – and some biotech companies in the U.S. – and I should say in full disclosure that I’m a founder of one – for the last ten years to figure out what was going on.
OAD: What does “bad Karma” mean in this context?
A: We discovered that there was indeed a single transposon that’s responsible for this phenotype. It’s in a gene that is very well known in other plants – and I should say if we hadn’t had all of that basic research in Arabidopsis [a flowering plant used as a model organism in plant biology], we would have no idea what this gene actually does. We were able to develop a very simple test that can predict the phenotype of palm trees that are cloned. The test is based on a transposon called “Karma”, so we call it “good karma” when it’s methylated and you have normal fruit, and “bad Karma” when it’s unmethylated and you have this horrible phenotype. It’s a nice story that goes from really basic principles in epigenetics in model systems to a real-world consequence.
OAD: You work in a field that has – like many others – evolved rapidly over the course of your career, due in no small part to significant technological advances over the last few decades. What is it like to work in your field now versus when you were a graduate student at Cambridge?
A: I’m sure everyone has stories like this, but I got my Ph.D. based on about 1.5 kilobases of DNA sequence, and it’s just amazing when you think about it. The idea of doing a whole genome wasn’t really seriously discussed until the 1990s, and now an individual graduate student or postdoc can easily knock off a genome. It’s amazing. Having the genome sequencing projects¬ has really changed how we do epigenetics and that’s been very exciting. We used to have to grind up a whole plant to get enough DNA to do anything, and now you can literally look at a single pollen grain and really get a good idea of what the epigenetic and genetic makeup of that pollen grain is.
But at the same time, it’s interesting that the same questions are still there and despite all of this fabulous technology, we don’t have a unified concept of what epigenetics really means. And I think that’s very exciting – that’s why we do it.
In 2016, NSF Director France Córdova unveiled ten “Big Ideas” to shape NSF’s priorities for investment at the frontiers of science and engineering, and drive American science into the future. One in particular – “Understanding the Rules of Life” – has reshaped how we at the BIO Directorate think about scientific inquiry in the biological sciences. The Rules of Life Big Idea seeks discoveries that will allow us to accurately predict change and outcomes in biological systems, and to develop infrastructure and innovative tools to help us ask more complex questions than ever before.
NSF has now published a Dear Colleague Letter (“DCL”; NSF 18-031) catalyzed by this Big Idea, titled, “Rules of Life: Forecasting and Emergence in Living Systems.” This DCL solicits research proposals to develop a better understanding of complex interactions within biological systems, and identify causal, predictive relationships across scales, levels of organization and layers of complexity – so-called “rules” for how life functions.
This DCL describes an initial opportunity to identify areas where such rules may exist, to drive progress toward their discovery, and to focus efforts on using these rules for prediction and design of biological systems. Activities supported through this DCL include conferences, EArly-concept Grants for Exploratory Research (EAGERs) and Research Advanced by Interdisciplinary Science and Engineering (RAISE) grants to create opportunities for enabling predictive capability.
Every PI knows that disseminating data is an essential part of the scientific process. From publishing manuscripts to presenting at meetings, a project’s biggest impacts only come after it has been shared. Promoting new discoveries and cutting-edge research throughout the general public is equally as critical as dissemination within the scientific community – and that’s where we need your help.
The quickest way for NSF to receive notice of an upcoming publication is for PIs to let their Program Officer know directly when a manuscript has been accepted for publication. We are interested in hearing about all BIO-funded research so we can share it in the form of press releases, stories pitched to major media outlets, NSF Discoveries, videos, radio features and more.
Ideally, we want to learn about upcoming publications shortly after they have been accepted. This allows us to prepare press releases or pitch the story to media outlets early enough to release them as soon as your manuscript is published. When you learn of an accepted publication that you think NSF would want to publicize, please send your Program Officer the following information:
Publication date (or if publication date is unavailable, the acceptance date)
Though we will not be able to share all of the research that is sent to us, we appreciate your help in sharing your work with audiences that might not otherwise hear about the exciting discoveries NSF-funded researchers are making every day. Thank you!
The NSF’s Office of International Science and Engineering has released an updated solicitation for the International Research Experiences for Students (IRES) program. IRES focuses on active research participation by U.S. students in high quality international research, education and professional development experiences in NSF-funded research areas. The updated solicitation can be found on the NSF website.
The overarching, long-term goal of the IRES program is to enhance U.S. leadership in research and education, and to strengthen economic competitiveness through training the next generation of research leaders.
The solicitation has three tracks, two of which are new to the program.
Track I: IRES Sites projects engage a group of undergraduate and/or graduate students in active, high-quality collaborative research at an international site with mentorship from researchers at a host facility. IRES Sites must be organized around a coherent intellectual theme that may involve a single discipline or multiple disciplines funded by NSF.
Track II (New): Advanced Studies Institutes (ASI) are intensive short courses with related activities that engage advanced graduate students in active learning and research. ASIs typically range in length from ten to 21 days and must be held outside the United States. ASIs must have a compelling rationale for their international location and should involve U.S. and foreign researchers. ASIs enable students to develop skills and broaden professional networks, leveraging international participation and complementary resources.
Track III (New): New Concepts in International Graduate Experience projects propose, implement and evaluate creative ideas for catalyzing the development of globally engaged U.S. scientists and engineers at the graduate student level. Professional societies and organizations in the U.S. are invited to propose innovative large-scale programs to provide high-quality international research and professional development experiences for U.S. graduate students.
Invoking Bob Dylan lyrics seems like the best way to transmit the new view of BIO – it is time to awaken, the world is changing. I’ve been immersed in scientific research my entire life, upon taking on the mantel of researcher and educator, moving into academic leadership positions, and finally leading the Directorate for Biological Sciences. Through these experiences, I have witnessed a common thread; scientists want to address questions that are more and more complex. Those complex questions require collaboration and interdisciplinary research, and BIO must be in a position to respond to our communities’ demands.
BIO’s first response is to change how we do business. We are going to move to a no-deadline, full proposal submission mechanism for receiving and reviewing proposals submitted to most core programs in all four divisions in BIO, the Division of Environmental Biology (DEB), the Division of Integrative Organismal Systems (IOS), the Division of Molecular and Cellular Biosciences (MCB), and in the programs in the Research Resources Cluster of the Division of Biological Infrastructure (DBI). Our goal in taking this step is to create an environment where program officers can work collaboratively among the divisions in BIO – uninhibited by varying deadlines across BIO and overwhelming workloads. Our experience (and others’) suggests this change will alleviate the demands on institutions, reviewers, applicants, and NSF staff caused by steadily increasing numbers of proposals submitted to BIO.
We also hope, and preliminary evidence suggests this is the case, that eliminating deadlines increases the quality of proposals. Under a “no-deadline” review system, a proposal can be submitted on any day, at any time. Investigators are free to submit a proposal when it is as well-developed and competitive as possible, and when it is convenient for them. Submitting proposals at any time allows investigators to have more time to prepare proposals, build collaborations, think more creatively without the pressure of a deadline, and it supports better career-life balance for our investigators. All of these benefits improve the science because they contribute to the best final product for submission.
More information on this change can be found in the DCL, associated FAQs, and upcoming webinars and outreach events. Each Division (DEB, IOS, DBI, and MCB ) has produced a blog about this change, addressed specifically to their communities; I encourage you to check these out. Program officers are standing by for questions about the transition to this change, and I encourage you to call your program officers with specific questions. Additionally, if you have comments or questions about the change to no-deadlines, I would like to hear about them, so please direct them to BIOnodeadline@nsf.gov.
This week, NSF-funded research was on display on Capitol Hill for “The Arc of Science: Research to Results” event. Scientists whose work provides insights, products, or services to American citizens, businesses, and government interacted with congresspeople, congressional staffers, and representatives from various sectors of the economy, including health care, education, and industry. Guests enjoyed hands-on demonstrations of technologies directly stemming from NSF-funded research.
Attendees learned about BIO-funded research at the exhibit, “QSTORM: Achieving Pinpoint Surveillance Capacity Inside Living Cells.” The Principal Investigator, Dr. Jessica Winter (Ohio State University) and colleagues from the Museum of Science Boston showed how NSF is supporting teams of scientists and engineers to come together to tackle one of the last frontiers of microscopy – obtaining detailed images of the inner workings of living cells. The researchers explained to attendees how new breakthroughs in nanotechnology, chemical engineering, optics, and computer programming are allowing them to address this challenge.
Visitors to the exhibit had the opportunity to “turn on” a real set of amazingly bright and colorful quantum dots–the researchers use these to illuminate the tiniest features inside cells. Then, using a styrofoam and slinky model, the team demonstrated how they “turn off” a quantum dot using a gold nanoparticle tethered by a strand of DNA. Attendees learned how STORM super-resolution microscopy can reconstruct detailed images from overlays of pinpoint dots of light.
The QSTORM project, originally funded in 2010, has since received a second grant from NSF to work on implementing new imaging techniques made possible by the original science and to help establish partnerships which otherwise may not have come to be. Dr. Winter is working with the Museum of Science Boston to develop several hands-on demonstrations to explain the science of quantum dots to a broader audience.
The Arc of Science event was coordinated by the National Science Foundation and the Coalition for National Science Funding. Invited speakers included NSF Director Dr. France A. Córdova, Congressman Lamar Smith (R-TX), Congresswoman Eddie Bernice Johnson (D-TX), and Senator Gary Peters (D-MI).
To see additional highlights from the event, look for Tweets from @NSF with the hashtag #ArcOfScience.
The National Science Foundation has made some changes to the guidance documents for proposal and award policies and procedures. Instead of the current two-guide structure of a Grant Proposal Guide (GPG) and an Award and Administration Guide (AAG), there will be one guide—the Proposal and Award Policies and Procedures Guide (PAPPG; NSF 17-1)—comprising two parts:
Part I: Proposal Preparation and Submission Guidelines
Part II: Award, Administration and Monitoring of Grants and Cooperative Agreements
For proposals submitted or due, or awards made, on or after January 30, 2017, the guidelines in PAPPG 17-1 apply.
In the future you will not see references to the GPG in NSF documents and on NSF web pages (the NSF will be updating existing references to the GPG on all web pages over time).
The NSF has also issued a revised version of the Grants.gov Application Guide (.pdf download). It has been updated to align with changes in the new PAPPG (NSF 17-1).
If you have any questions or concerns about the PAPPG (NSF 17-1), FAQs, or the Grants.gov Application Guide, you can contact the NSF Policy Office at policy[at]nsf.gov. For technical questions related to Grants.gov, please email support[at]grants.gov.
~Happy New Year! The Directorate for Biological Sciences looks forward to supporting exciting new discoveries and outstanding continuing basic science research in 2017.~
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On November 8, 2016, the NSF’s Assistant Director for Biological Sciences, Dr. Jim Olds, presented to the National Science Board an overview of the BIO Directorate’s research and infrastructure investments. This is a brief summary of his major talking points.
The NSF provides approximately 68 percent of federal support for basic research in biological sciences (not including support from the National Institutes of Health).
NSF Support of Academic Basic Research in Selected Fields as a Percentage of Total Federal Support. “Biology” includes biological sciences and environmental biology; excludes NIH. Source: NSF/NCSES FY2014
One of the ways in which NSF ensures that basic biology achieves downstream impacts is through partnerships with other agencies, in the U.S. and internationally, and public-private partnerships; for example, with the USDA, NIH, BBSRC, Bill and Melinda Gates Foundation and others.
The research supported by BIO’s Divisions crosses scales of size, space, time, and complexity.
The total FY2017 budget request for BIO is $791 million, which is about 1/10th of the NSF’s total request.
Part of the FY2017 budget request includes funds to support research across the Directorate related to the “Rules of Life” framing device which includes, but is not limited to, research focused on: the relationship between genes, the environment, and phenotype; plant and microbial sciences (microbiomes); synthetic biology; the origins of life; as well as support for quantitative, interdisciplinary approaches and resources for training and early career science. Support for projects that involve sophisticated modeling and theory development are seen as opportunities for partnerships with other NSF Directorates.
BIO’s “Rules of Life” framing device contributed to the development of the Ten Big Ideas for Future NSF Investments, specifically the “Predicting Phenotype” research challenge. Among the biggest gaps in our biological knowledge is how to predict the phenotype of a cell or organism from what we know about the genome and environment. The traits of an organism are emergent properties of multiple types of information process across multiple scales. Unpacking phenotypic complexity will require convergence across biology, computer science, mathematics, the physical sciences, behavioral sciences, and engineering.
More than a dozen initiatives constitute the “Major Investments” of BIO’s FY2017 request. Among these are Understanding the Brain, Clean Energy Technology, Microbiome, and support for training and education.
Using amazing new technologies, evolutionary neuroscientist Dr. Melina Hale and her graduate students at the University of Chicago are discovering that the basic movements of one tiny fish can teach us big ideas about how the brain’s circuitry works. Source: “Mysteries of the Brain,” produced by NBC Learn in partnership with the NSF (Full video: https://youtu.be/BUzeEpcO238)
“I love watching these cells be active while the animal is behaving. It’s just remarkable to me that we can see the brain work and try to understand how it’s functioning.” – PI Melina Hale
A new BIO program, Next Generation Network for Neuroscience (NeuroNex), will fund research with the goals of: developing theoretical frameworks for understanding brain function across organizational levels, scales of analysis, and/or a wider range of species; and the development and dissemination of innovative research resources, instrumentation and neurotechnology. We anticipate this portfolio will be transformative, integrative, and synergistic.
Support for clean energy technology-related research will involve funding for enhancing photosynthesis, for systems and synthetic biology, for bioinspired-design of proteins, for exploring the metabolic and energetic potential of living organisms, and for modeling environmental impacts, as well as impacts on genome stability, fitness, and phenotype.
In BIO’s FY2017 budget request, approximately $43 million is designated for programs that will enhance training and education, provide support for early career researchers, and broaden participation. BIO will continue participation in NSF INCLUDES, ADVANCE, CAREER, and Improving Undergraduate STEM Education. In addition, BIO will provide new opportunities for research traineeships (details to come!). It is also important to think about how we track students who are supported by BIO funding along their career trajectory and this will be a topic of discussion throughout the Directorate in 2017.
The Biological Science Directorate also recognizes how critical research resources (infrastructure), centers, observatories, networks, and support for data science are to the success of basic scientific research. CyVerse (was iPlant) integrates many aspects of data science, including providing key infrastructure for data management and analysis. This resource democratizes access to high-throughput computing. Continued investment in cyberinfrastructure would be congruent with some of the Ten Big Ideas for Future NSF Investments and would provide an avenue for BIO to continue to engage with partners in other NSF Directorates. The NSF recently announced awards for four new Science and Technology Centers – the Center for Cellular Construction is BIO-managed and will allow for the development and use of tools for controlling cell trajectories across the phenotypic landscape, which is important for understanding, for example, how cells become malignant.
The big picture for the future of the Directorate for Biological Sciences is this — biology is the engine of innovation in the 21st century. As President Obama said in his weekly address of October 16, 2016, “Innovation is in our DNA.”
In this Science Spotlight from the Kavli Foundation, a group comprising scientists and funders, including the NSF’s Assistant Director for Biological Sciences, Dr. Jim Olds, reflects on what the BRAIN Initiative has already achieved and how it is evolving.