Large-scale nutrigenetics and genomics in a tractable metazoan model

Description of work to be performed at Northwestern University (Andersen lab): We will contribute to all three Specific Aims. To complete Aim 1, we will grow 96 divergent C. elegans strains for extraction of RNA and metabolites in three biological replicates. These samples will be processed for Illumina RNA-sequencing and sent to the Schroeder lab for metabolite profiling. To complete Aim 2, we will aid in narrowing the defined quantitative trait locus (QTL)t o a small number of candidate genes by constructing near-isogenic lines and CRISPR/Cas9 genome-edited strains. Additionally, we will grow 12 divergent C. elegans strains in the presence of heavy propionate for extraction of RNA and metabolites in three biological replicates. These samples will be processed for Illumina RNA-sequencing and sent to the Schroeder lab for metabolite profiling. To complete Aim 3, we will identify gene candidates for genome-editing to validate metabolite QTL. Then, we will use our existing equipment and pipeline to generate genome-edited strains and send these strains to the Walhout and/or Schroeder groups for measurement of metabolite levels. Explicit tasks will include but will not be limited to: •Collect samples of 96 wild C. elegans isolates •Measure gene expression of 96 wild C. elegans isolates and 12 divergent priopionate wild isolates •Construct near-isogenic lines and genome-edited strains