Molecular Arms Races Shape the Evolution and Function of Antiviral Proteins

Wednesday, June 21, 2023 | 2:00 to 3:00 p.m. ET

Harmit Malik, Ph.D.

Professor and Associate Director, Basic Sciences Division

Fred Hutch

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Dr. Harmit Malik studies genetic conflict, the competition between genes and proteins with opposing functions that drives evolutionary change. His research could have implications for a range of diseases, from HIV to cancer. As part of this work, his team developed an approach for identifying genes that divide one species from another, which could help solve the riddle of how new species evolve. Dr. Malik also studies the evolutionary processes that drive our body’s interactions with viruses, including contemporary scourges like HIV as well as ancient viruses whose fossils litter our genome. With Hutch colleagues, he has characterized the rapidly evolving interface between proteins on human cells and viruses that make us sick. This work has highlighted surprising deviations from “textbook” models of these interactions, and it is revealing gene variants that could influence our susceptibility to infection.

Summary

The Malik lab 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). We are interested in understanding these "molecular arms races" and how they drive recurrent genetic innovation, from the perspective of both evolutionary biology and human disease. Malik and his colleagues have used an evolutionary lens to dissect and discover both primate antiviral as well as viral adaptation strategies. This lecture will describe how we use evolution-guided mutagenesis approaches to dissect and enhance the function of antiviral proteins.

Objectives:

• Explain how rapid evolution alters binding specificities between host and viral proteins.

• Describe how mutational resilience may provide an evolutionary edge to antiviral proteins despite being locked in arms races with rapidly evolving viruses.

• Demonstrate how rapid evolution and combinatorial mutagenesis can be used as a guide to enhance antiviral specificities against target viruses.