Q&A: Talking epigenetics with Rob Martienssen

Robert Martienssen, a plant geneticist studying epigenetic modification at Cold Spring Harbor Laboratory (Image: Kathy Kmonicek)

“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.

For the Times They are A-changin’ – Going to no-deadlines in BIO

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.


Basic Research Goes to Washington

February 15, 2017

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.

Dr. Olds peers into a small box sitting on a table by lifting up a small flap on the box. Researchers look on.
NSF Assistant Director for Biological Sciences, Dr. Jim Olds, used models of QSTORM quantum dots to discover how they enable scientists to look inside living cells. (Photo credit: NSF)

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.

#PollinatorWeek has US Buzzing

June 22, 2016

This afternoon the White House Office of Science and Technology Policy (OSTP) released the Pollinator Partnership Action Plan (PPAP). The PPAP accompanies the National Strategy to Promote Pollinator Health, released by OSTP in 2015 along with the science-based Pollinator Research Action Plan.

The National Strategy to Promote Pollinator Health has three goals:

  1. Reduce honey bee colony losses to economically sustainable levels;
  2. Increase monarch butterfly numbers to protect the annual migration; and
  3. Restore or enhance millions of acres of land for pollinators through combined public and private action.

To compliment today’s PPAP release, the National Science Foundation (NSF) summarized the agency’s pollinator portfolio (i.e., what the NSF funds in this area). The NSF supports many basic research and education programs and projects relevant to the National Strategy to Promote Pollinator Health. The majority of awards related to pollinators are made through the Directorate for Biological Sciences, but pollinator research is supported throughout the NSF. The NSF Pollinator Portfolio summary can be found here: http://go.usa.gov/xq5QB.

A bumblebee foraging on the petals of a larkspur flower.
A larkspur flower with a guest—a bumblebee foraging on its petals. (Credit: Karen Levy, Emory University)

To celebrate #PollinatorWeek, the NSF has also published an article on Medium highlighting NSF-funded research news and discoveries related to pollinator health.

Learn more about the National Strategy to Promote Pollinator Health, the PPAP, and how you can nurture and celebrate pollinators on the OSTP blog.

BIO’s FY 2017 Budget Request

On February 9, 2016, the National Science Foundation rolled-out its FY 2017 budget request to Congress.

Information about the NSF’s budget request can be found on nsf.gov, including a summary brochure, a press release, fact sheets, the Director’s presentation slides, and more.

Dr. Jim Olds, NSF Assistant Director for Biological Sciences, rolled-out the budget request for the Directorate for Biological Sciences (BIO). BIO currently supports 68% of academic basic research in non-medical biology.


The total FY 2017 request for BIO is $790.52 million, a 6.2% increase over the FY 2016 estimate. Of the $790.52 million, $745.73 million is discretionary funding and $44.79 million is new mandatory funding*.

The table below identifies how BIO’s request is distributed across its Divisions.

FY 2017 Request (millions)
Molecular and Cellular Biosciences $136.77
Integrative Organismal Systems $215.40
Environmental Biology $145.17
Biological Infrastructure $135.74
Emerging Frontiers $157.44 (includes mandatory funding)

BIO’s top priority is core research across biology. Broad support for academic basic research in biology is necessary to produce the knowledge that will address national needs in agriculture, health, the environment, and continuing innovation for the bioeconomy, which has already shown progress in areas such as biofuels, biorenewable chemicals, and nanotechnology.

BIO funding priorities for FY 2017 include the following:


BIO support for clean energy technology would provide funds for research in areas such as: systems and synthetic biology to streamline and scale the metabolic and energetic potential of living organisms, to produce non-petroleum based sources of important chemicals, materials, feed stocks, and fuels; bioinspired design of new proteins and other complex biomaterials that can transform light into energy; and investigations to assess the impact of fuel and/or bio-renewable chemical production to assess the potential environmental impacts of these technologies.

Understanding the Brain combines support for activities relevant to the the White House’s BRAIN Initiative and continuing NSF support for activities in the areas of cognitive and neuroscience.

Innovations at the Nexus of Food, Energy, and Water Systems (INFEWS) will be stressed in NSF-wide and BIO specific programs, such as Dynamics of Coupled Natural and Human Systems (CNH) and Macrosystems Biology (MSB). Also, a joint solicitation between BIO’s Division of Integrative Organismal Systems and USDA NIFA, called Plant Biotic Interactions (PBI), will be issued in FY 2016, with initial awards funded in FY 2017.

BIO’s budget request includes increased support for microbiome research. Microbiome investments support research on the role of microbes in plant and animal function, productivity, health, and resilience to environmental change, as well as microbes’ role in soil and marine ecosystems. Studies of microbiomes occur on a broad range of scales from metagenomics, which looks at the entirety of collective genomes in microbial communities, to individual community composition and collective metabolic activity. The joint IOS/NIFA solicitation mentioned above will include support for microbiome research.

major investments

In FY 2017, as NEON nears completion, BIO will assume full responsibility for NEON operations and oversight. With the need for increased oversight, BIO will transfer program management for NEON operations from Emerging Frontiers (EF) into the Division of Biological Infrastructure (DBI),   which   has   long-standing   experience   managing   cooperative   agreements and infrastructure, such as Science and Technology Centers (STCs), iPlant (now CyVerse), and other BIO Centers for Analysis and Synthesis. Funding for early NEON science, including continuing support for the MacroSystems Biology (MSB) program, remains a priority.   NSF is in the process of evaluating new managing organizations for NEON operations and maintenance.

BIO will sustain support for new mid-scale projects to advance data, software, and collaborative infrastructure in support of several priority areas through the Advances in Biological Informatics (ABI) Program, BIO Synthesis Centers, as well as ongoing solicitations, e.g., Software Infrastructure for Sustained Innovation (SI2). In FY 2017, SI2 will begin to focus on software infrastructure for major projects and awards including STCs, iPlant (now CyVerse), and Major Research Facilities and Construction (MREFC) projects.

The NSF-wide BioMaPS investment seeks to discover fundamental new knowledge to enable innovation in national priorities such as clean energy, climate science, and advanced manufacturing. In FY 2017, BIO will sustain support for this activity. One area of emphasis will be synthetic biology, which is a convergent area at the intersection of biology, engineering, and physical sciences that informs our ability to design and build novel biological functions and systems using engineering principles.

Understanding the Rules of Life represents our shared vision for core research. Support for this new emphasis includes research areas such as the genotype to phenotype challenge, plant and microbial sciences, including the study of microbiomes, synthetic biology, origins of life, and developing biological theory as a framework for the rules of life. Quantitative approaches that integrate the mathematical and physical sciences, computer science, and engineering into advancing basic biological understanding underpinning the study of the rules of life will be encouraged.


BIO’s FY 2017 budget request also includes support for early career scientists through enhanced funding for PIs, new efforts to train graduate students, and targeted support for postdoctoral fellows. BIO will participate in the NSF Research Traineeship (NRT) program. And a BIO Research Training Grant (RTG) Program would provide $6.16 million to improve graduate education.

BIO will participate in the NSF initiative, Inclusion across the Nation of Communities of Learners that have been Underrepresented for Diversity in Engineering and Science (INCLUDES), an effort to increase the preparation, participation, advancement, and potential contributions of those who have been traditionally underserved and/or underrepresented in STEM fields. BIO will also continue participation in the NSF-wide program ADVANCE as part of its ongoing commitment to broaden participation to build strategies and models to increase the participation, retention, and advancement of women in all STEM academic careers.

Finally, in the area of innovation activities, the FY 2017 budget includes support for an Origin of Life Ideas Lab – a partnership between NSF BIO and NASA Astrobiology to stimulate creative thinking and new research on the earliest events leading to life on Earth. Projects resulting from the Ideas Lab would explore plausible pathways for the origin of life that would contribute directly to our understanding of the indispensable properties of life on Earth and inform our search for life on other worlds, and would contribute to a theoretical framework for the “metabolism first” and “RNA first” hypotheses for the origin of life.

*Mandatory funding, also known as “direct spending,” is a different category of Federal spending than NSF typically sees. It is most commonly associated with entitlement programs (Social Security, Medicare, etc.) and is not subject to discretionary caps. In FY 2017, the Administration is seeking legislation to provide mandatory funding for NSF and other R&D agencies on a one-time basis.



Draft of revisions to NSF-wide grant and proposal policies up for public comment


Each year or so, NSF releases an updated version of its agency-wide guidance for proposals and grants, called the Proposal and Award Policies and Procedures Guide (PAPPG). This big document consists of two parts: instructions for proposers (the GPG, or Grant Proposal Guide) and instructions for awardees (the AAG, or Award Administration Guide).

The PAPPG sets the ground-rules for NSF programs. Solicitations, like the DEB Core Programs solicitation, exist to enumerate specific variances from the basic rules, for example the format and contents of a preliminary proposal. Solicitations, however, also refer back to the PAPPG and follow the ground-rules for everything except those specific variances. A good example of this is that the requirements for proposal font size are detailed in the PAPPG and we have no reason to repeat or modify that in the DEB Core Programs solicitation but they apply to both preliminary and full proposals.

Changes to…

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A reminder to check your FastLane Profiles


For any demographic analysis or comparison, NSF is reliant on the self-reported characteristics of participants in all phases of proposals and awards. Completion of the profiles is voluntary but critical for linking demographic data to proposal, funding, and review patterns. And, importantly, your profile provides the contact information that we use to reach out to you. So if your email address and institutional information are not up to date you may miss out on funding opportunities or critical notifications that affect your eligibility for funding.

So, is your FastLane PI profile complete, up to date, and error-free?

What about your OTHER FastLane profile? When was the last time you completed your Reviewer information?

Yes, that’s right; if you’ve taken part in both sides of the NSF merit review process you have two[i] separate FastLane profiles: one as a PI and another as a reviewer (or panelist).

Across NSF, our…

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