Crypts, Villi, & Tissue Function - The Sumigray Lab at Yale School of Medicine

Transcript

• 00:07In the small intestine,
• 00:09which is the majority of
• 00:10your digestive tract, you have
• 00:12crypts and villi. So villi
• 00:14are these finger like projections
• 00:16that stick out.
• 00:17They're important for nutrient absorption.
• 00:20A crypt is the intestinal
• 00:22stem cell niche.
• 00:23It's just this cute little
• 00:25cup
• 00:26that sits in the intestine
• 00:27and the stem cells sit
• 00:28at the very bottom of
• 00:28it, and that forms during
• 00:30during development.
• 00:32What happens in a crypt?
• 00:33So many things happen in
• 00:34a crypt. The intestinal stem
• 00:35cells sit at the bottom,
• 00:37and they divide, and they
• 00:38make daughter cells, progeny, that
• 00:39can then move up the
• 00:40crypt. And once they move
• 00:41up the crypt, they're going
• 00:43to lose their ability to
• 00:44divide anymore, and they're gonna
• 00:46move into the villus, which
• 00:47are these these nutrient absorbers.
• 00:49And so every cell starts
• 00:50in a crypt, and it
• 00:51gets to the tip of
• 00:52the villus within a few
• 00:53days, and then it dies,
• 00:53and its job is done.
• 00:54And so it's a really
• 00:55fast process that's happening all
• 00:57the time.
• 01:03Our goal is to understand
• 01:04how cellular behaviors
• 01:06and function
• 01:07converge with physical forces
• 01:09to generate functional tissue, both
• 01:11in development. And then once
• 01:12you generate this structure, how
• 01:14do you maintain it? Shape
• 01:15is part of function. It's
• 01:17not just some sort of
• 01:18passive thing that happens. It's
• 01:19actually really contributing to
• 01:22how cells sense and respond
• 01:24to their environment. So we
• 01:25know that the the stem
• 01:27cells in the crypt require
• 01:28certain signals to see certain
• 01:30signals and respond to certain
• 01:31signals to both maintain
• 01:33their identity as a stem
• 01:34cell, but also to know
• 01:35when to divide. And if
• 01:37you start messing with the
• 01:38shape of that crypt, they
• 01:40see signals differently because now
• 01:41they're exposed to them differently.
• 01:43There's all this constant turnover.
• 01:45How do we actually make
• 01:46sure that cells are doing
• 01:47what they're supposed to do
• 01:48all the time? And we've
• 01:49been really discovering these new
• 01:50patterns in the intestine that
• 01:51we didn't know existed before.
• 01:53We wanna understand how do
• 01:55they contribute to the intestines
• 01:57function as this nutrient absorber.
• 02:04We're really big into microscopy.
• 02:05We do live tissue imaging
• 02:07and also three d quantitative
• 02:09microscopy
• 02:10as well as we use
• 02:11intestinal organoid models to do
• 02:13more mechanistic studies.
• 02:16We've been getting really into
• 02:17biophysics lately and understanding how
• 02:20cells are sort of sensing
• 02:22or responding to these forces
• 02:23like I said, and we
• 02:24think that tissue architecture is
• 02:25really important in that. So
• 02:26the shape of the intestine
• 02:27actually contributes
• 02:29a lot to the turnover
• 02:31of the cells or how
• 02:32they're behaving and moving. We're
• 02:32really excited about understanding how
• 02:34the biophysical principles of the
• 02:35tissue and the cellular behaviors
• 02:37can actually help us understand
• 02:38how to heal faster in
• 02:40these degenerative conditions.
• 02:47These can be really relevant
• 02:49in disease like cancer where
• 02:51you have not enough turnover
• 02:52and too much proliferation
• 02:54or in inflammatory conditions like
• 02:56IBD or even autoimmune like
• 02:58celiac where you're losing too
• 03:00many cells.
• 03:01The hope is, of course,
• 03:03can we sort of use
• 03:04these principles
• 03:05as therapeutics?
• 03:06Not to necessarily treat the
• 03:08underlying disease, but for example,
• 03:10in IBD,
• 03:11you have all of this
• 03:12inflammatory response happening, and then
• 03:14that decreases barrier function of
• 03:15your gut because you're losing
• 03:16all these cells, which then
• 03:17increases inflammation.
• 03:19If we can make the
• 03:19epithelial cells stop responding and
• 03:22actually heal and make a
• 03:23new barrier, can we actually
• 03:25dampen that inflammatory response?
• 03:28I think Yale is one
• 03:29of the most collaborative environments
• 03:30and places I've ever been.
• 03:32Yale has a really deep,
• 03:34strong history in cell biology,
• 03:36cytoskeleton,
• 03:37and also genetics
• 03:39and quantitative biology,
• 03:40allowing me to interface with
• 03:42different fields and can actually
• 03:43push our research further and
• 03:45in different directions.