We are interested in understanding the general design principles of how gene expression is regulated at the genomic level in multicellular organisms. This includes understanding how large-scale DNA characteristics such as patterns in non-coding sequence, gene structure, and large-scale chromosome organization influence gene expression. For example, given that a large fraction of genomes are derived from foreign DNA such as retrotransposons (~40% for the human genome), how do cells distinguish and differentially regulate the “self” and “foreign” genome? Similarly, if we consider the complete genomic sequence of an organism, what fraction of the DNA can be assigned defined function(s)?
To understand the grammar of how primary DNA sequence regulates gene expression, we use classical genetics, bioinformatics, and biological engineering in the nematode C. elegans, inspired by the nascent field of synthetic biology. We believe that quantitative, high-throughput approaches will drive insights into how gene expression is regulated in multi-cellular organisms, how developmental programs are organized, and how the primary genome sequence directs these programs. My lab therefore has a dual focus: (1) to continuously improve and develop tools for true genome-scale engineering in C. elegans, and (2) to use these tools to identify and define the functional roles of regulatory DNA in the genome.
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