Expery Omollo, PhD

Damon Runyon Postdoctoral Fellow · MIT

I am a Biochemist and Systems Biologist working to understand how bacteria coordinate transcription, translation, and RNA decay to control gene expression.

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About

I am a Damon Runyon Postdoctoral Fellow in Gene-Wei Li's lab in the Department of Biology at MIT and the Howard Hughes Medical Institute (HHMI). I joined the lab in 2024 and am currently training as a Systems Biologist. My work uses in vivo assays to monitor transcription, translation, and RNA decay as they occur at the same time inside cells.

I completed my PhD in Biochemistry at the University of Wisconsin-Madison in 2023 in Robert Landick's lab. During my PhD, I used in vitro biochemical assays and cryo-electron microscopy (cryo-EM) to study how elongating RNA polymerase pauses and terminates transcription and how transcription factors regulate this pausing and termination.

I obtained my BS in Biochemistry and Molecular Biology from Michigan State University in 2020. As an undergraduate, I worked with Lisa Lapidus and Lisa Tiemann to study nucleation and folding kinetics of amyloid-beta monomers to understand the early stages of amyloid fibril formation in Alzheimers patients.

Each of these projects is described in more detail in the Research section. Thank you for visiting my site and for your interest in my work.

Research

Transcription-Translation Coupling in bacteria

I study how RNA polymerase, ribosomes, and the mRNA degradasome stay coordinated during gene expression to ensure accurate control of protein output.

More to come soon.

Regulation of RNA polymerase elongation by NusG

NusG is a conserved transcription factor found in all life. This work, published in Molecular Cell (2023), explains how one protein can produce opposite outcomes in different species.

During transcription elongation, RNA polymerase transitions between an active elongating state, and an inactive paused state.

While in elemental paused state, RNA polymerase pausing can be further stabilized by formation of a pause hairpin inside the exit channel.

Our findings showed that NusG shifts the balance between active and paused RNA polymerase depending on the species.

In Mycobacterium tuberculosis, NusG stabilizes a paused RNAP whereas in E. coli, it stabilizes active elongation.

These results provide a blueprint for drug design against Mycobacterium tuberculosis NusG.

Mechanism of intrinsic transcription termination

This work, published in Nature (2023), provides snapshots of how intrinsic termination occurs across all RNA polymerases.

During transcription elongation, RNA polymerase gets a signal to slow down (pause momentarily) at U7 and U8 of the uracil tract.

This pre-termination pausing allows the nascent RNA to fold onto itself and form secondary structures.

Once RNA polymerase is paused, the exit channel widens to accomodate the nucleating terminator hairpin. This causes RNAP to swivel.

For RNA to be released, the terminator hairpin has to complete forming, which is only possible after the -10 and -9 bases in the upstream DNA bubble rewind. These two processes happen concurrently.

After terminator hairpin completion, RNA is released first and the binary RNAP-DNA complex survives.

This is consistent with biochemical evidence that shows terminated RNAP can remain associated with and slide on DNA after RNA release.

Kinetics of Amyloid-β monomer folding and fibril nucleation

Monitored the folding and nucleation kinetics of denatured amyloid-β monomers using cysteine-mediated quenching of tryptophan autofluorescence.

Publications

1. Delbeau M.*, Omollo E.O.* et al. (2023). Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis . Molecular Cell. *Equal contribution.
2. You L., Omollo E.O., et al. (2023). Structural basis for intrinsic transcription termination . Nature.
3. Omollo E.O. (2023). Role of NusG, NusA, and nascent RNA structures in regulating transcription elongation and termination . PhD disertation. University of Wisconsin-Madison.

Education

University of Wisconsin–Madison
PhD in Biochemistry
2020 - 2023

Michigan State University
BS in Biochemistry & Molecular Biology/Biotechnology
Graduated with Honors
2016 - 2020

Contact

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