Benjamin Doughty

Understanding the genetic basis for diseases and complex traits remains an open problem in human genetics, a task made complicated by the fact that most are caused by tens to thousands of different mutations spread across the genome. The majority of these mutations don’t affect protein-coding genes, but rather fall in regions of DNA known as enhancers, regulatory sequences that control when and how much genes are expressed. Currently, we lack an equivalent “genetic code” for enhancers and consequently cannot predict the effect of non-coding mutations. I will use a combination of single-molecule genomics, in vitro biochemistry, and high-throughput genome engineering to determine at scale how genetic variation can affect enhancer function. This will not only reveal basic principles underlying the sequence determinants of gene regulatory elements, it will also uncover the mechanisms behind how previously-identified mutations mediate disease risk.