Grant: Project Grant

Humans, like all other animals, evolved to be able to survive periods of starvation, in part by creating stores in periods of plenty. However in these days of easy food availability, periods of starvation are near to non-existent and the trend is to store much more that is used. These constant over-feeding can lead to obesity and health problems, including diabetes, and metabolic syndrome and cancer. At the level of the cell, two major proteins are involved in the fine regulation between responses to nutrient availability and starvation. These proteins are called AMPK and mTOR and have opposite responses. When one is activated the other is inhibited and vice versa. There needs to be a fine delicate control of their activities for the proper responses to nutrients or their absences. This happens in part through the actions of other proteins called FLCN and FNIPs. In this proposal, we want to study how exactly FLCN and FNIPs regulate the switch from a state of nutrient excess to a state of starvation and vice versa by understanding their interactions with AMPK and mTOR. We propose to do this in both conditions of using cells grown in petri dishes and in a mouse model system for a metabolic disease. The major goal is to better understand what happens in normal condition to then be better able to understand detect the specific problems in cases of metabolic disease so that eventually new approaches to treatment can be found.