The complex microbial ecosystem inhabiting the distal human gut, known as the gut microbiota, is inextricably linked to human health, playing central roles in maintaining host immunity, safeguarding the host against pathogens, and extracting energy from the otherwise indigestible complex carbohydrates found in dietary fibre.
Dysbiosis, an imbalance in the gut microbiota, is linked to a range of diseases, including inflammatory bowel diseases, metabolic syndrome, and Type 2 Diabetes. A growing body of evidence supports a role for microbial therapeutics, such as commercially available probiotics, in mitigating the effects of some dysbiosis-associated conditions. However, the implementation of novel, customizable therapeutics depends on the establishment of a comprehensive repository of species with known energetic requirements and ecological behaviours.
Currently we lack atomic-resolution insight into the molecular machinery required for complex carbohydrate utilization by key gut symbionts. Understanding this machinery is critical to understanding the role of carbohydrate utilization in shaping microbial communities in the human gut.
Dr. Grondin will employ structural biology in a systems-based approach, incorporating complimentary bacterial genetics and carbohydrate biochemistry to determine the atomic structures of transport protein machinery in complex with the related substrates. Comparative structure-function studies of carbohydrate-transporters, including measuring transport specificity and kinetics across substrate type and bacterial phylogeny, will delineate the role of individual complexes in fuelling microbial ecosystems. This research will provide detailed insights into the molecular mechanisms associated with the selective recognition, transport and metabolism of complex carbohydrates by the human gut microbiota. The results of will inform the development of therapeutics to address growing health concerns associated with microbiotal imbalance, such as inflammatory bowel diseases, metabolic syndrome, and Type 2 Diabetes.