Erica D. Sonnenburg, Ph.D.

RESEARCH INTEREST

Bacteroides thetaiotaomicron (Bt), a Gram-negative obligate anaerobe and prominent human intestinal symbiont, boasts expanded families of environmental-sensing proteins that far outnumber those in previously sequenced bacteria. Many of these sensors are adjacent in the genome to another expanded family of genes, the polysaccharide-degrading glycoside hydrolases, suggesting they detect and rapidly respond to changes in the nutrient environment rendering them critical to Bt's success in the highly competitive and dynamic gut ecosystem. Deciphering the mechanisms by which Bt senses its external environment and coordinates an appropriate response is paramount to understanding the success of Bacteroides in the mammalian GI tract.
I study a member of the family of novel signaling proteins called the hybrid two-component system. Hybrid two-component proteins are transmembrane proteins that span the inner membrane of Bt and contain a putative periplasmic sensor domain and three intracellular domains: a histidine kinase domain, a response regulator domain, and an AraC-type DNA binding domain. Comparison of sequences between paralogs shows that the periplasmic sensor domain is highly divergent relative to the well-conserved intracellular portion, indicating that a plethora of periplasmic signals may be sensed via this novel family. Using a variety of techniques such as gnotobiotic mouse models, transcriptional profiling with GeneChip technology, mass spectrometry based profiling, yeast two hybrid screening, and structural biology approaches, I hope to elucidate the molecular mechanisms of nutrient sensing and glycoside hydrolase regulation in Bt.

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