NSF GRFP annual report

That time of year again, listing progress.  Never get any feedback on these so I’m getting hasty in my presentation.

Achievements listed this year:

NSF Activities Report 2010-2011

I have been engaged in mathematical modeling of transcriptional regulation through release of a promoter-proximal paused polymerase.  The experimental observations I published in 2009 showed that genes regulated under this scheme activated substantially faster and more synchronously than similar initiation regulated genes (Boettiger and Levine, Science 2009), and I wanted to understand this difference from a mechanistic perspective.   Working with Dr. Peter Ralph (UC Davis, Dept Ecology) and Dr. Steve Evans (UC Berkeley, Dept. Statistics), I have developed a general explanation for this trend.  If the paused state is sufficiently stable, regulation of expression downstream of this checkpoint will provide faster and more synchronous activation than regulation upstream.  In addition, the cell-cell variation in total mRNA will be less.  This work has recently been accepted for publication in PLoS Computational Biology.  I also had the opportunity to present this work in a poster at the 2010 Q-Bio Conference in Santa Fe, NM.

My other primary focus has been on understanding the molecular consequences of gene regulation through multiple, simultaneously active and seemingly redundant genetic control sequences (called enhancers).  I continued research on the apparently redundant enhancers, which drive expression of the gene snail in the presumptive muscle tissue of the early Drosophila (fruit fly) embryo.  Working with my colleague Mike Perry who made the transgenic flies, we were able to show that either enhancer is sufficient for normal gene expression and gastrulation in unstressed conditions, but that under thermal stress some embryos experience erratic patterns of expression and deficiencies in gastrulation, work we published in Current Biology in the summer.  We have been extending our analysis to the gap-gene patterning network, which make similar use of such apparent redundancies to ensure correct expression patterns at the appropriate level in a greater fraction of embryos.  This work is currently in review in Developmental Cell.  I have had the opportunity to present these findings at ASBMB meeting in Tahoe, CA, in December, the Advanced Imaging Workshop in Berkeley (where it received a poster prize), and the Gordon Conference on Stochastic Physics in Biology in January in Ventura, CA.

To follow up these investigations in greater detail, I have recently developed single molecule imaging techniques which can applied to whole-mount Drosophila embryos.  With this technique I am working to distinguish more detailed mechanisms of regulation in the early gene expression of the embryo.  I had the opportunity to give oral presentations on this work at the Annual Drosophila Conference in San Diego this year, and to departmental research seminars at Princeton University and the Memorial Sloan-Kettering Cancer Center in NY, where I was interviewing for post-doctoral positions.

To improve communication of my research I have a new website to communicate my research interests and findings enabled by the GRFP and a mostly open online lab notebook where I communicate my daily research activities.  This enables an easy look into ‘a day of the life of a graduate student’ in my position, as well as promoting the spirit of more completely open, transparent, and publically documented research.


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