Rowan Walters

Using cryoEM and functional biophysics to understand the mycobacterial bd oxidase, a key enzyme in tuberculosis

About me

I obtained my integrated Masters degree in Biochemistry from the University of York. My final year project working in the Blaza lab first introduced me to microbial bioenergetics. This project involved establishing growth conditions in a model mycobacteria species (Mycobacterium smegmatis), to natively overexpress a terminal oxidase called the bd oxidase. I enjoyed the mixture of microbiology and biophysical techniques involved in this work. This and the desire to continue this work led me to apply for my PhD project.

My project

Tuberculosis is still a devastating disease, with a growing problem in multidrug resistance. Bioenergetics has recently emerged as a new target space for anti-TB agents. This involves inhibiting the cellular machinery that is used to provide energy the bacteria require. My project will focus on the bd oxidase. It allows bacteria to scavenge oxygen in low oxygen environments and possibly to break down the harmful hydrogen peroxide generated by the hosts immune system. I will use the conditions I established in my final year project to natively express and purify the bd oxidase in an active form that hopefully recapitulates its physiological activity. This preparation will then be subject to CryoEm for structural studies. I will also use pre-steady-state and steady state kinetics to clarify its activity with oxygen and hydrogen peroxide.


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