Research Projects in The Churchill Group and Korstanje Group:
My postdoctoral work is focused on studying aging as a complex trait under the joint mentorship of Ron Korstanje and Gary Churchill as part of The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging. The bulk of this work is aimed at applying genome-scale statistical techniques to identify novel genetic players in longevity determination and the regulation of age-dependent changes in target of rapamycin (TOR) signaling and insulin/IGF-1-like signaling (IIS), two central aging pathways.
To achieve this aim I employ two primary strategies. In the first, I am using quantitative trait loci (QTL) analysis to identify loci associated with either longevity or pathway specific markers of TOR signaling and IIS in F2 intercross or diversity outbred (DO) mouse populations. Genetic mapping techniques that are being developed in the Churchill lab in the DO mouse population allow for high-precision QTL mapping, possibly to single-gene resolution.
In the second strategy, I use comparative genetics to select strong genetic candidates for evolutionarily conserved factors in determining longevity. Meta-analysis of published human and mouse genome-wide association studies allowed us to generate an initial list of longevity-associated genes. I then narrow the list by selecting only genes for which orthologous gene display a clear effect on aging in the nematode, Caenorhabditis elegans, thus leveraging the relatively fast and inexpensive techniques available to modify gene expression and assess life span in worms. I then return to mammals, examining the impact of altering expression of genes on the refined candidate list on life span and other age-associated phenotypes using mouse models.