Nobel Prize Brings More Attention to DNA Repair Research

We’re pleased that two long-time NIGMS grantees have been recognized with the 2015 Nobel Prize in chemistry for their studies of the repair processes that correct damage affecting base pairing or causing a distortion in the helical structure of DNA. This comes on the heels of the 2015 Albert Lasker Basic Medical Research Award, which was also given for discoveries concerning the DNA-damage response.

Paul Modrich and Aziz Sancar, who will share the Nobel Prize with Tomas Lindahl, have received continuous support from us since 1975 and 1982, respectively. By asking questions about basic cellular processes, these scientists have provided a detailed understanding of some of the molecular repair mechanisms involved in health and disease.

Like any groundbreaking research, their studies have raised numerous other important questions. Some of these include: How do cells sense damaged DNA? How are the proteins that repair damaged regions cleared from the DNA after repairs are complete? How can we specifically undermine the DNA repair systems in cancerous cells so that those cells die?

For more details about the Nobel Prize-winning work, see our statement and links to additional material.

Support of Structural Biology and PSI Resources

The 15-year Protein Structure Initiative (PSI) ended on June 30, 2015. In preparation for the termination of the program, an external committee of structural biologists and biomedical researchers identified high-priority areas for NIGMS’ future support of structural biology and the preservation of certain PSI resources. Here are some of their key recommendations and what we’re planning to do in response.

Continue to support synchrotron beamlines for macromolecular crystallography.

Recognizing the importance of synchrotron beamlines in modern structural biology, we intend to continue to support these community resources. Part of this effort includes using a new funding approach to ensure that NIH-supported investigators have reliable access to mature synchrotron-based resources.

Maintain the technologies that make structural investigations possible at the most advanced level; meet the need for modern cryo-electron microscopy resources.

We’ll continue to use existing grant mechanisms to support structural biology research, including
X-ray crystallography, NMR, cryo-EM and integrative or hybrid methods. To facilitate the use of
cryo-EM for structure determination we have started a program to provide support for consortia of
cryo-EM labs to upgrade their facilities
. NIGMS is also developing plans for establishing regional
cryo-EM centers that could provide access to state-of-the-art cryo-EM resources for the broader structural biology community.

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Help Spread the Word About Cell Day

Cell Day 2015On November 5, we’ll host my favorite NIGMS science education event: Cell Day! As in previous years, we hope this free, interactive Web chat geared for middle and high school students will spark interest in cell biology, biochemistry and research careers. Please help us spread the word by letting people in your local schools and communities know about this special event and encouraging them to register. It runs from 10 a.m. to 3 p.m. EST and is open to all.

As the moderator of these Cell Day chats, I’ve fielded a lot of great questions, including “Why are centrioles not found in plant cells?” and “If you cut a cell in half and then turn it upside down will the nucleus, ribosomes, and other parts of the cell fall out?” It’s always amazing to hear what science students are thinking or wondering about. I’m looking forward to seeing what fantastic questions we’ll get this year!

Early Notice: Mature Synchrotron-Based Resources Funding Opportunity Plan

At its September 2015 meeting, our Advisory Council endorsed a concept for funding existing NIGMS-supported synchrotron resources in which the technologies have become mature. This plan will align the funding mechanism used to support the beamlines with the goal of ensuring reliable access to these essential resources for structural biology.

In place of the variety of mechanisms we currently use, we intend to issue a funding opportunity announcement (FOA) called Mature Synchrotron Resources (P30) for 5-year, renewable grants in the range of $1-3 million per year in direct costs. The Institute intends to maintain overall support for mature beamline facilities at the same level it has in the past, but to replace the previous constellation of funding mechanisms with a single, more coherent one.

The focus of the FOA will be on user access, training and support in data collection, processing and analysis. Peer review will assess the resources primarily on their ability to meet the research needs of the user community and on the impact the resources have on their users’ scientific productivity. To ensure that the beamlines maintain their state-of-the-art operations, the FOA will also include support for a limited amount of technology development and implementation.

Since the goal of the effort is to improve the stability of current NIGMS-supported synchrotron structural biology resources for community use, the initial funding opportunity will be open only to synchrotron-based resources already supported by NIGMS.

We welcome your input and feedback on these plans. You can email your comments to me or post them here.

Charles Edmonds, Susan Gregurick, Ward Smith and Mary Ann Wu contributed to this blog post.

Request for Input on the Science Drivers Requiring Capable Exascale High-Performance Computing

UPDATE: The response deadline has been extended to November 13.

On July 29, 2015, the White House issued an Executive Order establishing the National Strategic Computing Initiative as a government-wide effort to create a coordinated, cohesive, multi-agency strategy to maximize the benefits of High Performance Computing (HPC) for the United States. In support of this initiative, the Department of Energy, National Science Foundation and National Institutes of Health are seeking your input to identify scientific research that would benefit from a greatly enhanced new generation of HPC computing technologies and architectures. The request for information (RFI) asks for responses in scientific domains including the biomedical and physical sciences, mathematics, geosciences, energy sciences and engineering research.

We hope to hear from our research communities on topics that include:

    • Research challenges that would need the projected 100-fold increase in application performance.
    • Specific barriers in current HPC systems that limit scientific research.
    • Capabilities needed for the data-intensive sciences.
    • Additional barriers in such areas as training, workforce development or collaborative environments.

While this RFI invites comments on several specific topics, we would also welcome any comments that you feel are relevant to this initiative.

To respond to this RFI, send an email to NIGMS_exascale@nigms.nih.gov by October 16.

If you have any specific questions about the RFI, please let me know.

NIH Workshop on Reproducibility in Cell Culture Studies

NIGMS is actively involved in NIH-wide efforts to enhance rigor and reproducibility in research. As part of our work on this issue, we will co-host a trans-NIH workshop on September 28-29, 2015, to examine current quality-control challenges in cell culture research and identify opportunities for expanding its capabilities and applications. The meeting will be videocast and archived on the NIH Videocasting site.

The workshop agenda includes panel discussions led by researchers from academia and industry on cell line identification, genetic and phenotypic characterization of cells, heterogeneity in populations of cells, reagents, and research and reporting standards. The meeting will also cover new approaches to understanding the characteristics and behaviors of cultured cells and technologies for enhancing their usefulness in research.

Comment on Proposed Rules for Protection of Human Subjects

UPDATE: The proposed rulemaking comment period has been extended to January 6, 2016.

I would like to draw your attention to proposed revisions to the federal policy for the protection of human subjects exit icon, often referred to as the Common Rule. Even if you’re not currently involved in human subjects research activities, your research might be affected by the proposed changes.

The modifications are intended to enhance the ability of individuals to make informed decisions about participating in clinical research and also to modernize and streamline the regulatory approval process. One of the major reforms would expand the definition of human subjects research to include the secondary use of human biospecimens, regardless of identifiability. Some of the other proposed changes would affect the processes for obtaining informed consent and for determining the exemption status of human subjects research activities.

I encourage you to review the notice of proposed rulemaking and submit comments by the December 7, 2015, deadline. Please note that each proposed change described in the document includes specific questions for public comment.

Wanted: Pharmacology, Physiology, and Biological Chemistry Division Director

Search Committee Members:

Helen Sunshine, National Institute of General Medical Sciences, Chair

René Etcheberrigaray, Center for Scientific Review

Irene Glowinski, National Institute of Allergy and Infectious Diseases

Sherry Mills, Office of Extramural Research, NIH

Philip Cole, Johns Hopkins University School of Medicine

Judith James, University of Oklahoma Health Sciences Center

Scott Miller, Yale University

With the recent retirement of Dr. Michael Rogers, the search is now open for an outstanding individual to serve as director of our Division of Pharmacology, Physiology, and Biological Chemistry (PPBC).

This position offers significant opportunities to set scientific priorities, lead change and improve the biomedical research enterprise.

PPBC has a very broad scope, ranging from basic science to clinical areas. It supports research in fields including chemistry, biochemistry, chemical biology, enzymology, glycoscience, biotechnology, pharmacology, pharmacogenomics, anesthesiology, sepsis, trauma, burn injury and wound healing.There are tremendous opportunities to build bridges among these scientific disciplines, such as employing chemical methods to build tools for the life sciences and medicine, understanding fundamental biochemistry in its in vivo context and using systems approaches to solve physiological and pharmacological problems.

The division is organized into two branches, one focused on biochemistry and biorelated chemistry and the other on the pharmacological and physiological sciences. PPBC has 11 scientific staff members who serve as program officers.

The PPBC division director reports to the NIGMS director and is a member of our senior leadership team, which helps set policies and priorities for the Institute. There are also opportunities to participate in and advise on NIH-wide activities and collaborations with other federal agencies and scientific organizations.

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Lasker Award Recognizes Sustained Effort to Understand DNA-Damage Response

We congratulate our long-time grantee Steve Elledge of Brigham and Women’s Hospital on being recognized with the 2015 Albert Lasker Basic Medical Research Award exit icon for “discoveries concerning the DNA-damage response—a fundamental mechanism that protects the genomes of all living organisms.” He shares the honor with Evelyn M. Witkin of Rutgers University.

For a quarter century, we’ve funded Elledge’s investigations of the molecular underpinnings of this fundamental biological process. While working with the yeast model system in the 1990s, his group showed that the Rad53 kinase plays an important role in coordinating DNA repair with progression through the cell cycle.

More recently, Elledge and his team have identified over 1,000 candidate proteins that may participate in the mammalian DNA-damage response. They are now seeking to uncover the precise functions of these proteins.

The Lasker Award is a fitting occasion to reflect on how far we’ve come in this field and the exciting opportunities that lie ahead.

Early Career Investigators to Join Advisory Council Deliberations

Beginning at this month’s meeting of the National Advisory General Medical Sciences Council, some of the ad hoc Council members will be early career investigators. We expect to benefit from their ideas and insights, and we also hope that they will get a better understanding of the workings of Council and share what they learn with peers.

As most of you know, the Advisory Council provides the second level of review required before any grant can be funded. The Council also advises the Institute on policy and scientific matters. Regular Council members are appointed by the HHS Secretary, but for most meetings, we invite ad hoc consultants to expand the Council’s breadth of expertise. Both regular and ad hoc members are typically at fairly senior career levels—often full professors or deans. We think there is value in inviting one or two early career investigators to each Council meeting as ad hocs to provide a greater diversity of views.

We’ve identified a perfect pool to draw from: the Early Career Reviewers who have participated in a study section for NIH’s Center for Scientific Review. If you are interested in applying to this CSR program, see How to Apply.