Expery Omollo, PhD

This organization enables rapid regulation of gene expression, but also complicates efforts to understand how individual processes influence one another inside the cell.

My research focuses on measuring these processes directly in living bacterial cells using quantitative in vivo approaches. By examining transcription, translation, and mRNA decay together rather than in isolation, my work seeks to establish general principles for how gene expression is regulated at multiple levels in bacteria.

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.

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.

Protein misfolding and aggregation underlie many neurodegenerative diseases, yet the earliest steps of these processes are difficult to observe experimentally.

In this project, I studied the folding and nucleation kinetics of amyloid-β, a peptide central to Alzheimer's disease pathology.

Using cysteine-mediated quenching of intrinsic tryptophan autofluorescence, I monitored conformational changes in denatured amyloid-β monomers in real time. This approach enabled quantitative measurements of early folding and nucleation events that precede fibril formation.

Together, this work provided insight into the initial molecular steps that drive amyloid aggregation and established experimental strategies for probing protein folding kinetics at early stages.