Between the Genes! The Genomics of Gene Regulation.
In between the tiny sections of the human genome that code for our genes lie vast tracts of non-coding genomic DNA. Scattered throughout this non-coding DNA are enhancers, short DNA sequences that control when, where, and to what extent the genes are transcribed. Enhancers orchestrate the intricate patterns of gene expression that direct normal development and physiology in all animals. The importance of enhancers is emphasized by the fact that the majority of disease causing variants in the human genome reside not in the genes, but between the genes, where they disrupt normal gene expression, presumably by interfering with the function of enhancers.
Because of their importance in development and disease we are trying to understand the DNA sequence features that control the activity and specificity of enhancers and other cis-regulatory elements. We take a multidisciplinary approach to this problem, employing both experimental and computational approaches borrowed from Genetics, Genomics, Systems Biology, Synthetic Biology, Biophysics, Computer Science, and Statistical Physics. Ultimately we hope to produce quantitative models that accurately identify new regulatory sequences in the genome and predict the consequences of mutations in these elements. Such models will be critical tools for understanding normal development, as well as diseases caused by non-coding mutations.
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