Rhys Grinter BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Rhys Grinter

My initial steps towards a career research in biochemistry started with an undergraduate degree at Flinders University in Adelaide. However, as a kid from a small town on Kangaroo Island, once I completed my honours year the excitement of the wider world proved stronger than that of a PhD, leading me to an extended absence from experimental science. During this 5 year period I tried my hand at a number of things including: English language teacher in Japan, process engineer at a salt mine in Western Australia and nomadic pan-Eurasian traveller. However, before too long, I felt to pull and excitement of experimental science and enrolled in a PhD at the University of Glasgow. My PhD brief was, broadly, to discover and investigate antibiotic proteins produced by Gram-negative bacterial pathogens. For this research I was blessed with a supervisor, Dr. Daniel Walker, who enthusiastically encouraged just about any experimental idea that I came up with. This led me to discover and investigate a number of different novel proteins and piece together some of the details of how they kill Gram-negative bacteria down to sub-nanomolar concentrations. I also investigated the potential of these proteins to protect plants from bacterial disease, by creating transgenic plants expressing them. One of these proteins, which I named pectocin M was produced by the plant-pathogen Pectobacterium. This protein was particularly intriguing to me as it consisted of a fusion between a cell wall degrading toxin domain and a horizontally acquired iron-containing plant-like ferredoxin. As it transpired (through a lot of experimental work), Pectobacterium has a specialized import system, which allows it to utilize plant-ferredoxin as an iron source, providing it with this vital nutrient during infection. Pectocin M, in what I think is one of the cooler tricks I’ve seen in molecular evolution, utilizes its ferredoxin domain as a Trojan horse, to import the toxin and kill its target cell. This discovery and its subsequent characterization, kindled my interested in how Gram-negative pathogens utilize TonB-dependent receptors to obtain iron from host-proteins during infection. In March 2015, commenced a Sir Henry Wellcome Fellowship in the lab of Professor Trevor Lithgow at Monash University. During this period, I studied the structure and biogenesis of the Gram negative bacterial outer-envelope. In addition, I investigated a number of TonB-dependent transporters and their associated proteins, determining their structures and their mechanisms of substrate binding, import and processing. In 2019, I moved to the lab of A/Prof Chris Greening at Monash University. In this current position I am investigating the structural and physiological mechanisms of Factor 420 biosynthesis and utilisation in Mycobacterium.

Abstracts this author is presenting: