Genetic Conflicts Drive The Unexpected Rapid Evolution Of Essential Chromatin Proteins

Prof. 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). A significant area of research in the Malik lab is the study of rapid evolution in genes involved in essential cellular processes such as chromatin organization and chromosome segregation. Together with Steven Henikoff, he proposed the 'centromere-drive' model, which posits that unusual genetic conflicts during female meiosis drive the unexpectedly rapid evolution of centromeric DNA and proteins, which in turn may provide a basis of postzygotic reproductive isolation between recently diverged species. He is also interested in the hypothesis that genetic conflicts during male meiosis may explain the unexpectedly rapid evolution of sperm chromatin proteins. Using in vivo gene swap studies guided by evolution, he is testing these hypotheses using Drosophila as a model.

About Harmit Malik, PhD

Harmit Singh Malik is an evolutionary biologist renowned for uncovering how genetic conflicts and evolutionary “arms races” between genomes shape fundamental cellular processes and host–pathogen interactions. He is a Howard Hughes Medical Institute Investigator and professor in the Basic Sciences Division at Fred Hutchinson Cancer Center in Seattle, where he leads a research program centered on the causes and consequences of genetic conflict. Malik grew up in India and earned his undergraduate degree in chemical engineering from the Indian Institute of Technology Bombay before moving to the United States for graduate school. He completed his PhD in molecular evolutionary biology at the University of Rochester, where his work on retrotransposons showed that these “selfish” genetic elements were already present in ancestral lineages rather than being recently acquired, as with viruses, thereby reshaping prevailing ideas about their origins. He joined Fred Hutch for postdoctoral research on centromeres with Steven Henikoff and subsequently established his own lab, focusing on how rapidly evolving genetic elements might drive speciation, genome stability, and disease susceptibility. Malik is best known for helping to develop the centromere-drive model, which explains how “selfish” centromeres can bias their transmission during female meiosis, thereby driving the rapid evolution of centromeric DNA and its associated proteins. His lab has been a major force in paleovirology, using viral “fossils” in animal genomes to reconstruct ancient host–virus arms races and to understand why genes involved in chromosome segregation, innate immunity, and mitochondrial biology often evolve unusually quickly. Across these projects, his group uses evolution-guided approaches to identify rapidly evolving genes, link signatures of positive selection to mechanisms, and illuminate how conflicts between genes, genomes, and pathogens influence both disease and the origin of new species. Malik’s contributions have been recognized with many prestigious honors. He received the Presidential Early Career Award for Scientists and Engineers (PECASE), the Vilcek Prize for Creative Promise in Biomedical Science for his work on genetic conflict, and the Eli Lilly and Company Research Award from the American Society for Microbiology. He was appointed an HHMI Investigator, elected to the American Academy of Arts and Sciences and the National Academy of Sciences, and awarded the Genetics Society of America’s Edward Novitski Prize for creative, paradigm-shifting work on chromosome biology and evolution. He has also received the McDougall Mentoring Award at Fred Hutch.

Registration is free, but required at: https://tinyurl.com/2rw8n7bt

Sponsored by the Center for Physical Genomics and Engineering, the Cancer and Physical Sciences Program at the Robert H. Lurie Comprehensive Cancer Center, and NIH Grants T32GM142604 and U54CA268084

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Mechanometabolic Control of Cell Behavior

Abstract

To move, cells must utilize ATP to fuel the cellular contractility and forces that sustain migration, however very little is known about how the metabolic state of a cell affects its ability to migrate and vice versa. In this talk, I will describe my lab’s efforts to understand the forces driving cell movements in the tumor microenvironment and the energy required for movement. Combining tissue engineering approaches, mouse models, and patient samples, we create and validate in vitro systems to understand how cells navigate the tumor stroma environment to identify novel targets of cancer metastasis. Microfabrication and native biomaterials are used to build mimics of the paths created and taken by cells during metastasis. Using these platforms, we have described a role for a balance between cellular energetics, cell and matrix stiffness, and confinement in determining migration behavior. Moreover, we have extended this work into investigating the intersection of diabetes and the diabetic tissue microenvironment with tumor progression, showing that mechanical changes in the tissue due to diabetes can promote cancer. Overall, our work has demonstrated key mechanical drivers of metastasis within the tissue microenvironment.

Bio

Cynthia Reinhart-King is the John W. Cox Professor and Department Chair in the Department of Bioengineering at Rice University. Before joining Rice, she was a University Distinguished Professor in Biomedical Engineering and Cell and Developmental Biology at Vanderbilt University, where she also served as Senior Associate Dean for Research in the School of Engineering. She obtained undergraduate degrees in Chemical Engineering and Biology at MIT and her PhD at the University of Pennsylvania in the Department of Bioengineering. Her lab’s research interests are cell and tissue mechanobiology in cancer and atherosclerosis. She was awarded the Rita Schaffer Young Investigator Award, the inaugural Mid-Career Award, and the Herb Voigt Service Award from the Biomedical Engineering Society, an NSF CAREER Award, the Sonny Yau ‘72 Excellence in Teaching Award, the Cornell University Cook Award and the Zellman Warhaft Award from the Cornell College of Engineering, the Vanderbilt Chancellor’s Award for Research and the Edward J. White Service Award from the Vanderbilt University School of Engineering. She is a fellow of the Biomedical Engineering Society, the American Institute for Medical and Biological Engineering (AIMBE), and the International Academy of Medical and Biological Engineering, and she was an inaugural New Voices Fellow of the National Academies of Science, Engineering and Medicine. She served as a standing member of the NIH CMT study section panel, an elected Board Member of AIMBE, Secretary and Elected Board member of BMES, and Chair of the Diversity and Inclusion Committee of AIMBE. She is the current Past-President of the Biomedical Engineering Society.

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