Koch Lab NSF CAREER Award Intro--Single-Molecule Analysis of Yeast Chromatin Remodeling

Any day now I should be hearing the results of my NSF CAREER award application. I've talked about this in one of my earlier blogs, where I pointed out that there is very little chance the grant will get funded--this is due to overall odds and the fact that it's my first submission. The latter point reduces the odds in two ways. First, I've been told by numerous sources that there is a bias (whether intended or not) towards 3rd-submission proposals (by rule, the final submission). The other reason it being my first submission reduces my chances is likely by far the most strong -- I have a lot to learn from the feedback I will receive! My resubmission in July 2009 will be much stronger due to this critical feedback as well as the very cool preliminary data my students have been acquiring (and which I hope to start telling you about in a couple weeks).

(As an aside, I feel compelled to insert this note: If you're my NSF program manager and you happen to have the time to to read this random blog, and you are in the middle of dialing my number to tell me that my grant was funded, and are now having second thoughts after having read that paragraph above, PLEASE KEEP DIALING!)

Aside from the fact that I lack some talents helpful for grant writing--and therefore find it painful--I did enjoy aspects of the NSF CAREER award writing. This is because the award is, by design, tailored towards research university professors and has required components on research, education, broader impacts, etc. This made me think deeply about my whole career (research, teaching, service, family) and even now when I go back and read my proposal (6 months later), I am excited about the integrated career plan. One particularly satisfying aspect was that I was able to include (admittedly vague) plans for open science in a very natural way and aligned with the mission of NSF.

So, I am really looking forward to the feedback about this proposal, and I think it will be the most helpful feedback I will have received so far. Up to this point, I have received some helpful critical feedback from the DoD Breast Cancer Research Program (BCRP) Idea Award (although that backfired on me...subject of another post), some internal awards, and that's about it. Many of the other programs--private foundations--provide little or no feedback (usually none) as a matter of policy, which makes the rejection somewhat less rewarding (ha ha). I am still considering the idea of posting my whole proposal (perhaps on Scribd per Cameron Neylon and Jean-Claude Bradley's suggestions). Until I figure that out, I figured I'd post the first page of my proposal, which gives an overview of my career plan 6 months ago. Please give me any negative or positive feedback you have!

CAREER: Single-Molecule Analysis of S. Cerevisiae Chromatin Remodeling

Career Mission

The long-term mission of our laboratory is to enable important discoveries in molecular cell biology by innovating new biophysical methods and culturing interdisciplinary research and education partnerships. The specific research goals of this 5-year proposal are to develop new methods for single-molecule analysis of DNA and chromatin extracted from living yeast cells, and thus open a new research area that combines the powers of single-molecule and genetic approaches. Our long-term mission is also supported by our specific educational and broader impacts goals in this proposal, which will multiply the impact of our research goals. These include participation in Open Science, integration of research and university education, and community and local school outreach. Together, these research and education goals in this proposal will establish a successful career path for this PI as leader of an exciting biophysics research laboratory collaborating with leading chromatin and transcription biologists, successful university educator, and recruiter of underrepresented minorities to research careers.

Research Overview

DNA in eukaryotic cells exists as chromatin, which is repeating units of DNA wrapped around histone proteins. These DNA-histone units are called nucleosomes, and play a fundamental role in both positive and negative regulation of proteins that require access to the DNA code. Cells have a variety of enzymes that can modify the structure of the chromatin by moving, removing, or adding histones, or by modifying specific amino acid residues on the histones. This chromatin remodeling affects the ability of other proteins to access the DNA and has a profound impact on critical processes such as DNA repair and gene transcription by RNA polymerase. Understanding of these dynamic processes is currently hampered by the inability to characterize with high spatial and temporal resolution the changes to chromatin inside living cells. Therefore, we are developing biophysical tools with single-molecule sensitivity to address this need. One of the main goals we are pursuing is to develop a single-molecule method (see Fig. 1) for mapping proteins on chromatin that will far surpass the capabilities of the currently most powerful technique—chromatin Immunoprecipitation (ChIP). We are also pursuing other goals for analysis of genomic DNA and chromatin with optical and magnetic tweezers and nanostructured devices. The unifying themes of our research goals are single-molecule analysis and chromatin biology, and we are seeking to build a career foundation in a new arena of single-molecule biophysics applied to in vivo systems.