This grant proposal is for an F32, three-year postdoctoral fellowship. The research proposed is in the fields of evolutionary genetics and cell biology. The methods proposed for this research include bioinformatics, genomics, and analysis of signatures of selection, molecular genetics, microscopy and biochemistry. I propose utilizing a novel approach to understanding the fates of duplicate genes at the subcellular level. I plan to combine the power of genomic analysis of duplicate genes with subcellular colocalization studies of fluorescently tagged paralogs. I will use the amount of overlap in signal of paralog fusions to gauge the overlap in function between both intra- and interspecies paralogs. The use of gene families involved in membrane trafficking, whose protein determinants act in a spatially specific manner, will allow me to correlate function with subcellular localization. The relatively recent whole genome duplications and species radiation within the Paramecium aurelia species complex, combined with a high degree of synteny between Paramecium genomes, offer a powerful genomic system in which to conduct this analysis. This work will further the understanding of both the evolutionary causes and the functional consequences of the evolution of duplicate genes, which has implications for evolutionary genetics as well our understanding of basic eukaryotic cell biology.
This research will lead to a better understanding of subcellular functions, specifically membrane trafficking mechanisms, and their evolutionary causes. Studying the proteins involved in membrane trafficking pathways utilizing this cross-disciplinary approach promises to yield novel insights into basic cellular activities, which also has broad implications for our understanding of such cellular disruptions as host-pathogen interactions and cancer.
|Bright, Lydia J; Gout, Jean-Francois; Lynch, Michael (2017) Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species. Mol Biol Cell 28:1101-1110|