Aashiq H. Kachroo, PhD.
PhD (Indian Institute of Science, Bangalore, INDIA)
PDF (The University of Texas at Austin, Austin, TX, USA)
Engineering complex biological processes in simplified cells
The most deeply evolutionarily conserved human genes encode essential cellular machinery whose failures are linked to diverse diseases, from cancer to cardiovascular disease. Recent systematic studies have discovered extensive genetic polymorphism in these genes yet studying how these variations contribute to cellular function and overall human health remains a challenge. Our group is interested in studying these conserved human genes along with many of their variants, by systematically humanizing yeast cells, replacing each of the essential yeast genes in turn by its human version. The resulting strains will serve as new physical reagents for studying the human genes in a simplified organismal context, opening up simple high-throughput assays of human gene function, analyzing the impact of human genetic variation on gene function, the screening and repurposing of drugs and the rapid determination of mechanisms of drug resistance. Our work will illuminate fundamental principles of evolution, providing direct measurements of whether or not human and yeast genes have retained their ancestral functions over a billion years of evolutionary divergence.
Photo credit: Aashiq H. Kachroo
3. Cannon B*, Kachroo AH*, Jarmoskaite I, Jayaram M, Russell R. Hexapeptides that inhibit processing of branched DNA structures induce a dynamic ensemble of Holliday junction conformations. J Biol Chem. 2015 Sep 11;290(37):22734-46. PMID: 26209636;PMCID: PMC4566245. (link)