Mechanistic characterization of quantitative trait genetics affecting cell metabolism

NIH RePORTER · NIH · R01 · $331,931 · view on reporter.nih.gov ↗

Abstract

Natural variation in DNA sequences between individuals occurs as a result of mutations over time. Variations in DNA sequence can lead to differences in the ultimate outcome, or phenotype, of the individual carrying these genetic variants. Using the model yeast Saccharomyces cerevisiae, our group has identified regions of the genome in which differences in DNA sequence result in heritable differences in the level of specific proteins that are made by genes distinct from the changed regions. Our focus is on changes to protein levels that occur independently of changes in expression of the mRNAs that code for these proteins. We will identify the specific base-pair changes in DNA sequence that are responsible to better understand the mechanisms by which changes in DNA lead to changes in the level of other proteins. Many of the proteins we found to be regulated in this way are necessary for the uptake and catabolism of glucose by cells. We will specifically identify which DNA sequences lead to different rates of glucose uptake in order to understand how glucose transporters are regulated. We will also use mass spectrometry chemical analysis to measure the contents of cells and determine whether these changes in protein level lead to changes in the growth of cells, or alternatively whether some of these differences are a way by which cells enact metabolic homeostasis.

Key facts

NIH application ID
10130565
Project number
5R01GM132238-03
Recipient
STATE UNIVERSITY NEW YORK STONY BROOK
Principal Investigator
BRUCE Bruce FUTCHER
Activity code
R01
Funding institute
NIH
Fiscal year
2021
Award amount
$331,931
Award type
5
Project period
2019-04-01 → 2024-03-31