gene logic

Gentle Reader, I presume thou wilt be very inquisitive to know what antic or personate actor this is, that so insolently intrudes upon this common theatre to the world’s view…

- Robert Burton

Welcome to Gene Logic. Your host is Michael A. White, PhD, a biochemist/systems biologist/geneticist/genomicist, currently working as a postdoctoral researcher in the Department of Genetics and the Center for Genome Sciences & Systems Biology at the Washington University School of Medicine in St. Louis.

I am interested in how the universe is seen by DNA. Imagine that you are a stretch of DNA, ensconced in the nucleus of the cell.  The entire external world, both inside of the cell and outside, is represented to you almost exclusively as quantities and activity states of nuclear proteins and regulatory RNA. From that information alone, you are able to read the state of the world and properly compute the correct transcriptional response.

Read about my research and publications below. My CV is here. Grab your favorite brew and join me for conversation at The Finch and Pea.  See what I’m reading over at the stack.  Follow my latest findings on science and whatever else. My tweets are @genologos. And see what we’re doing in the Cohen lab. Contact me via Gmail:  vheissu1974@gmail.com

The biophysical basis of gene logic and cis-regulation

A major function of the genome is to encode regulatory information, yet we do not understand how this regulatory information is interpreted by transcription factors to produce the temporal and spatial patterns of gene expression underlying major biological processes. We do not understand how specific combinations of cis-regulatory elements give rise to specific patterns of transcription, and we do not understand what physical and sequence features of promoters and enhancers enable regulatory elements to distinguish themselves within the vast landscape of the genome. 

To understand how regulatory sequence is interpreted by the cell, we require systems-level, biophysical models that describe how transcription factor concentration, affinity, cooperativity, and competition convert sequence information into specific patterns of gene expression. With such biophysical models in hand, we will better understand the physical basis of transcriptional programs in development, cell division, and differentiation, and we will improve our ability to predict the effects of non-coding genetic variation on disease risk and progression. These models will lead to better interpretation of the results of high-throughput genome occupancy experiments such as ChIP-seq, and they will strengthen our ability to identify functional regulatory elements in the genome. A biophysical understanding of cis-regulation will also enable us to rationally engineer transcriptional circuits for health, agricultural, and energy applications.  In my work, I use quantitative and high-throughput data together with physical models to understand the biophysical basis of cis-regulatory logic.

Recent writings (my full CV is here)

** Co-first authorship

White, MA, Myers, CA, Corbo, JC, and Cohen, BA. A massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks. Submitted, Feb. 2013.

White, MA, Parker, DS, Barolo, S, and Cohen, BA. A model of spatially restricted transcription in opposing gradients of activators and repressors. Molecular Systems Biology 8:614 (2012). Link

White, M. “A Genome-Sized Media Failure”, The Huffington Post, Sept. 13, 2012. Link

White, MA. Evolution and Robots. Science 337 294-295 (2012). Link

White, MA 500 Million Years of Pain. The Good Men Project, October 10, 2011. Link

Parker, DS**, White, MA**, Ramos AI, Cohen BA, Barolo S. The cis-regulatory logic of Hedgehog gradient responses: key roles for Gli binding affinity, competition, and cooperativity. Science Signaling 4, ra38 (2011). Link

See accompanying Perspective: Whitington T, Jolma A, Taipale J.  Beyond the balance of activator and repressor. Science Signaling 4, pe29 (2011). Link