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Our research is focused on functional and structural characterization of an unusual class of transcription factors that regulate polysaccharide utilization in Bacteroides. Dietary fiber is an important carbon source for gut bacteria and it impacts the composition of the gut microbiome. In Bacteroides, dozens of gene clusters encoding protein systems necessary for metabolism of specific complex carbohydrates are colocalized into polysaccharide utilization loci, or PULs. Many PULs are regulated by Hybrid Two-Component Systems (HTCSs) in which the transmembrane sensor histidine kinase and response regulator transcription factor of canonical TCSs are fused into a single protein. HTCS regulation is central to the important balance between degradation of dietary fiber and host glycans that form the intestinal mucus layer.