Dissecting mechanisms of gene control in the vertebrate acute phase response

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My research program, which explores how genes are regulated, is grounded in basic biological questions that apply to all organisms. In particular, my lab is focused on the non-coding regions of the vertebrate genome that are bound by transcription factors. Transcription factors are proteins that bind to DNA and regulate the expression of genes. By experimentally determining transcription factor-DNA interactions, RNA expression, chromatin accessibility, and long-range chromatin interaction in healthy tissues or cells from different vertebrate species, we are addressing fundamental questions in evolutionary biology including: 1) What are the relative contributions of protein-coding and non-protein coding changes in DNA to the evolution of new traits? and 2) How is tissue-specific gene regulation maintained during evolution? ******The specific objectives of this research is to study gene regulatory mechanisms underlying a rapid response made by healthy livers when faced with stress and noxious stimuli and injury. This response has been called the acute-phase response (APR). Many aspects of the APR have been conserved in vertebrates and this conservation also extends to invertebrates. In addition to conserved APR genes, many species-specific APR genes have been observed. There is surprisingly little known about how changes in gene regulation have shaped the APR during evolution. ******By studying the evolution of the APR we will identify a core set of mammalian APR genes and gain specific insight into the mechanisms that control them. We will identify target APR genes in liver cells (hepatocytes) isolated from four vertebrate species. We will generate original transcription factor binding and chromatin accessibility maps of the APR in these species. We will test the extent to which conserved regulatory regions are the important for the APR and identify genome innovations which have modified the APR in a specific species. Overall, this work will allow us to make new discoveries regarding the evolution of vertebrate gene control. Knowing the conserved and species-specific components of the APR will be potentially valuable for veterinary medicine and agriculture. Our multidisciplinary training research program will result in training highly qualified personnel in bioinformatics and genomics.**