December 17, 2021

Rachel Keener (Duke University)

Evolution of a novel plague receptor discovered through natural human diversity

Fall 2021 Graduate Student Award in Pathogenic and Commensal Organisms

 

By leveraging natural genetic diversity in a cellular genome-wide association screen of Yersinia pestis infection, I identified a genome-wide significant non-synonymous variant in a gene belonging to the Fc receptor-like family. Based on my preliminary data, I propose this may be a previously unrecognized receptor for Y. pestis in human cells. As Y. pestis can naturally infect many animal species, I plan to investigate the evolutionary consequences of human-Y. pestis interaction on Fc receptor-like proteins along different animal lineages. Additionally, it is not yet clear what the bacterial ligand for this receptor may be. By performing co-immunoprecipitation mass spectrometry analysis, I will identify the bacterial protein necessary for the interaction. Preliminary results suggest that other closely related bacteria do not utilize this receptor, and so I will investigate the possibility that Y. pestis gained the use of the receptor through horizontal gene transfer. Overall, this project will explore the functional conservation and pathogen specificity of Fc receptor-like proteins through comparative genomics and functional assays of Y. pestis cell infection.