Grant: Project Grant

Mucus is produced by colonic goblet cells and is comprised of sticky, sugar covered mucin proteins. Mucus plays two different, yet critical roles in our colons. First, mucus lines the inner surface of the colon, forming a dense barrier that prevent microbes from escaping the colon. Above this barrier, there is a second, loose outer layer of mucus that is heavily colonized by microbes that use it as a food source. For decades, it was believed that all goblet cells in the colon produced barrier mucus, and that the outer, loose mucus formed through microbe-driven degradation of the barrier mucus. We now hypothesize that the barrier and loose forms of mucus are actually distinct types of mucus, produced by spatially separated goblet cell populations. Moreover, we hypothesize that it is goblet cells in the middle region of the colon that are the primary source of barrier mucus. We plan to define the basis for these differences in mucus function by growing mini-guts from the middle, proximal and distal regions of the colon, and studying the mucus they produce at the protein, sugar and functional level. We will also study how barrier mucus production in the middle colon is regulated by microbe-host interactions, including when the colon is first colonized by beneficial bacteria, and also when the host is infected by dangerous bacterial pathogens, which can trigger a rapid increase in mucus production as a way of protecting the host's colonic mucosa.