IDENTIFYING MICROBIAL MECHANISMS THAT REGULATE ANIMAL INSULIN SIGNALING

PROJECT SUMMARY
Insulin resistance and Type 2 diabetes affect nearly 10% of the population, and are on the rise. Recent evidence
suggests that human intestinal bacteria can regulate insulin release, which implies that microorganisms harbor
novel mechanisms or factors that influence insulin signaling. Identifying microorganisms and novel bacterial
mechanisms of modulating animal insulin release in vivo is very challenging in mammals because of the
extensive microbial diversity in the mammalian intestinal microbiota, and because resident microorganisms are
resistant to colonization by artificially administered isolates. I have overcome these limitations by developing a
novel, high-throughput C. elegans model for identifying bacterial isolates that regulate in vivo insulin signaling,
and demonstrated (for the first time) that environmental bacteria contain previously undiscovered, novel
mechanisms or factors for regulating animal insulin resistance. In this transformative project, I will perform the
first-ever, large-scale screen for bioactive bacteria that modify animal insulin signaling; use transposon
mutagenesis to identify those bacterial genes or factors responsible for regulating insulin signaling; and engineer
at least one human probiotic strain to express a bacterial insulin-regulating system or factor. Taken together, this
project will generate new insights into the types of bacteria that modify animal insulin signaling; the mechanisms
bacteria have evolved to do so; and provide the field with fundamentally new directions and strategies for
alleviating one of the most common and impactful human pathologies in existence.

Grant Number: 1DP2DK139569-01
NIH Institute/Center: NIH
Principal Investigator: Nicholas Burton