Harvard Catalyst Profiles

Our lab works on gut commensal organisms that benefit host metabolism. We have recently discovered through clinical/translational studies that certain gut microbes can improve host metabolism by decreasing appetite. The mechanism, soon to be published, involves microbial synthesis of bioactive lipids that induce GLP-1 production by the host gut. Excitingly, we are now also on the verge of being able to knockdown genes in these key commensal organisms through CRISPR technology. Up to now, there are no known ways of editing the genomes of these microbes. The summer project would involve designing and engineering constructs that would enable genome editing. The longterm goal of this project would be to design microbiome therapeutics that treat and prevent obesity and obesity-related diseases. The student would be working directly with the PI (Jason Zhang, MD PhD), a pediatric gastroenterologist at BCH, and his team at both BCH and MIT.

The gut microbiome is strongly associated with obesity, though the mechanisms by which it controls host weight are not fully characterized. We performed a clinical translational study in which 200 healthy children underwent a comprehensive set of eating behavior assessments as well as stool metagenomic sequencing to assess their gut microbiome. The student taking on this project would need a strong bioinformatic background, with experience in Python and/or R and preferably with some skills in multivariate statistics and machine learning, though the latter is not strictly necessary. The student would perform multivariate analyses to determine which microbes are associated with healthy and unhealthy eating behaviors in children. There is also an opportunity for a very experienced student to explore new AI-based methodologies to analyze our highly-dimensional dataset.