The Bhagirath Singh Early Career Award in Infection and Immunity 2024 Recipient
Kirk Bergstrom
In our bodies, the mucus produced by special cells in the colon wall, called "goblet cells, plays a crucial role in keeping our gut healthy. When this mucus doesn't work well, it can lead to inflammatory bowel disease (IBD), which affects many Canadians. In mice (which have colons similar to people), we've seen that a specific protein, called "Muc2", is needed for this mucus to work. Muc2 forms a "firewall", stopping harmful microbes from invading the gut lining to cause inflammation. Until recently, scientists thought the goblet cells in the last part of the colon (e.g. rectum) made most of this mucus, but our research in mouse models shows it's actually goblet cells in the first part of the colon (the proximal colon) that do most of the work by secreting lots of Muc2 that shields the lower colon and rectum from inflammation. We think a similar process is happening in humans too. However, we're still not sure exactly how these goblet cells in the first part of the colon work or how we can use them to treat IBD. Based on our early findings, we believe these cells can sense microbes in the gut using special receptors, and that boosting their mucus production with a safe drug could help treat chronic colitis. To test this, we have three main goals: 1. Figure out which sensors these proximal goblet cells use to survey the gut bacteria and respond through mucus secretion, and whether these sensors are found in special goblet cell "flavors" (subtypes), since they are so diverse; 2. See if we can safely increase mucus production in goblet cells to help treat colitis in mice; and 3. Find out what our own human proximal goblet cells are doing by studying "miniguts", which come from and secrete mucus like a human colon, but are cultured in a dish. We're collaborating with experts from around the world to make sure we cover all aspects of this research. We hope that by understanding how goblet cells work, we can find new ways to treat IBD and improve gut health.
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