Michael A. White, PhDGene Regulation, Genomics, Computational Biology
Function and Specificity
The central task of genomics is to understand how the genome’s “library of specificities” (in the words of D. L. Nanney) is encoded by DNA sequence and expressed by the cellular machinery. With that foundational knowledge, we can discover how human genetic variation alters those specificities, with consequences for normal development and disease.
Specificity of Transcription Factors
Why don’t transcription factors get lost? To control gene expression, transcription factor proteins need to select their target sites from a vast genomic excess of non-functional, potential binding sites. We use a range of genomic technologies and computational strategies to understand how the photoreceptor transcription factor cone-rod homeobox (CRX) recognizes different target sites in several retinal cell types.
Functional genomics of genetic variation
We develop massively parallel functional assays to understand how both protein-coding and non-coding genetic variants affect molecular function. Our aim is to use large scale functional data to develop quantitative models that accurately predict the impact of variants on proteins and cis-regulatory elements.
Biophysical models of enhancers
We develop biophysical models of gene regulation that connect DNA sequence and transcription factor binding with gene expression levels. My current interest is to build on existing statistical thermodynamic models in order to take into account the newly recognized role of molecular condensantes in transcriptional control.
Technology development for genetic screens at single cell resolution
We are currently building a new technolgy for single cell mRNA barcoding that does not require isolation of single cells. This technology would greatly facilitate highly multiplxed genetic screens.