Harmit Malik studies the causes and consequences of genetic conflicts that take place between different genomes (e.g., host-virus interactions, mitochondrial conflicts with nuclear genomes) or between components of the same genome (e.g., chromosomal competition at centromeric regions). He is interested in understanding these "molecular arms races" and how they drive recurrent genetic innovation, from the perspective of both evolutionary biology and human disease.
Rapid Evolution and Chromosomal Competition Within and Between Species
Chromosomal segregation is an essential process in all eukaryotes. Defects in this process can lead to aneuploidy (often one of the early events in tumorigenesis) as well as trisomies (such as Down syndrome). Despite the importance of this process in biology, many components of the segregation apparatus evolve unexpectedly rapidly (akin to a host-virus "arms race"). We wish to understand what evolutionary forces are driving this change, which may even lead to speciation (the process of splitting one ancestral species into two).
This project will focus on discovering the molecular basis of findings from our lab that chromosomes from closely related species of yeast outcompete each other to gain evolutionary dominance. This project is ideal a student interested in gaining hands-on experience with genetics and molecular biology as well as evolution. The student will also be exposed to several ongoing projects in the lab involving genetic conflicts between and within organisms. Training will be provided not only on the bench but also in terms of reading and presenting scientific literature.
Paleovirology: Exploiting Ancient Host-Virus Arms Races to Understand Modern-Day Susceptibility to Viral Infection
The rate of human evolution is remarkably slow when compared to the viruses that infect us. Because of this discrepancy, our immune system is fine-tuned not to the viruses that are present today, but to those that emerged in our ancient past. Our lab is interested in using lessons from these ancient infections to understand how our innate immune system works today.
We use bioinformatics, evolution, genetics, virology, and molecular biology to dissect ancient and ongoing host-virus arms races. In particular, we are interested in mechanisms by which antiviral proteins engage viruses, and strategies that permit broad-acting antiviral factors to counteract the vast and ever-changing repertoire of viral pathogens. We expect that these studies will shed light on human susceptibility to viral infection, and suggest intervention strategies based on lessons learned from ancient encounters with pathogenic viruses.
A summer project will provide a hands-on introduction to these topics to a motivated and enthusiastic student. The student should expect to be a fully engaged member of the lab and will participate in group meetings and local seminars. Training will be provided not only on the bench but also in terms of reading and presenting scientific literature.