Gene Essentiality Lab

Traver Hart, Ph.D.

A systems lab at the interface
of computational and experimental biology

Focusing on genetic screens in mammalian cell lines, we seek to decipher the complex web of relationships that governs how eukaryotic cells process information, respond to their environments, and transform into cancer. As part of The University of Texas MD Anderson Cancer Center, we also search for emergent vulnerabilities of tumor cells, and we collaborate extensively with preclinical and clinical researchers to translate these findings into new therapeutic opportunities

We are hiring! Postdoctoral opportunities available in systems biology and complex genetics.
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Research

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Cells from different tissues have different genetic dependencies, but all share a common set of "core fitness genes" that are required for proliferation. We use this difference between core and context essentials to guide our estimates of screen quality and gene classification, and to identify tumor-specific pathways and targets

Genes with correlated knockout fitness profiles across a diverse set of screens usually operate in the same biological process or biochemical pathway.

Integrating genes (nodes) with correlated knockout fitness profiles (edges) into a network -- see this webpage's background for an example -- reveals clusters of functionally related genes and the cell lines where they are essential.

We use approaches like these to ask fundamental biological questions about the hierarchical organization of the cell, and to guide the development of new technologies to address the blind spots in our data.

See the paper (Kim et al.) here

One such blind spot is functional buffering by paralogs, where a single gene knockout shows no phenotype in a CRISPR/Cas9 screen because a closely related gene shoulders the burden.

We used the enCas12a system to perform targeted double knockouts of selected paralogs. By measuring genetic interaction between the gene pairs, we were able to identify dozens of synthetic lethals. For example, in the Cop9 signalosome complex, most subunits are essential but the COPS7A/B genes encode proteins that can substitute for each other.