Department of Genetics
Simches Research Building, CPZN 7250
185 Cambridge Street
Boston, MA 02114
Lab Members: 20 postdoctoral fellows, 2 graduate students, 2 technicians, 1 project manager
Visit my lab page here.
Our lab uses C. elegans molecular genetics and genomics to study miRNA and RNAi pathways as well as mechanisms of aging and toxin surveillance. Using genetic and RNA interference approaches, we have identified many genes that positively or negatively regulate RNAi and microRNA pathways. These genes reveal the trajectory of siRNAs and miRNAs as they target mRNAs, as well as components that may be developed as drug targets to enhance RNAi in mammals. In the aging projects, we discovered that an insulin-like signaling pathway controls C. elegans metabolism and longevity. We have used full genome RNAi libraries to explore the complete set of genes that regulate aging and metabolism. Current research attempts to weave these lists of aging regulatory genes into pathways that assess and regulate metabolic tempo and mode, repair and regeneration, and protective and degenerative pathways.
Our genetic analysis of the C. elegans response to gene inactivations that increase longevity and to natural chemical toxins that target similar pathways has revealed a complex genetic pathway for xenobiotic detection, aversion, and detoxification. The human homologues of the genes we identify promise to explain how humans respond appropriately and inappropriately to drugs, or activate drug detoxification pathways in the absence of a triggering drug, perhaps inducing a false endocrine state of poisoning. Variation in xenobiotic detection and response pathways may be the cause of diseases as diverse as anorexia nervosa and migraine. The drug or essential gene inactivations in C. elegans inhibit feeding and induce an aversive program. The endocrine state of these aversively stimulated animals may be homologous to the endocrine state of humans who feel unwell. As we seek genetic suppressors of this aversive behavior, an endocrinology of feeling ill would emerge.
We are developing protocols and instruments that use PCR primers corresponding to universal sequence elements of the 16S RNA gene to search for diverse microbes that may cause diseases unsuspected to be due to pathogens and microbes from extreme environments. One long term goal of this project is to send a robotic thermal cycler with these primers to Mars in search of microbial life that is ancestrally related to life on Earth.
For a complete listing of publications click here.
Last Update: 8/14/2012