MIRA: Systems genomics of complex traits - Administrative Supplements to Support Undergraduate Summer Research Experiences

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Project Summary: The genotype-phenotype map in humans is shaped by complex interactions between multiple loci and environmental factors, but the structure and function of these interactions remain poorly understood. This lack of understanding limits our ability to predict and prevent individual susceptibility to sickness and disease. These interactions can generate pleiotropic effects that confound traditional knockout approaches. Moreover, the genomic context can modulate these interactions both functionally and evolutionarily. We aim to elucidate these questions using a systems-genetics framework with three experimental paradigms in Caenorhabditis elegans and its relatives: (1) How do complex regulatory systems evolve and function? (2) What are the sources and consequences of genomic hyper diversity?, and (3) How do variation, recombination and sexual reproduction affect evolutionary responses? We will employ an integrative approach that combines genomics, single-cell analysis, microfluidic engineering, high-throughput phenotyping, genetic transformation, and computational biology. This research combines a strong functional hypothesis-testing framework with natural genetic variation to apply a systems-genetics approach that helps understand the evolution and function of complex regulatory systems that have critical implications for human health.