Jack Christopher Leo
Bacterial virulence and protein secretion: My main area of interest is bacterial pathogenesis, focusing especially on adhesion and other virulence functions mediated by autotransporter proteins of Gram-negative bacteria. These proteins are large, non-fimbrial rod-like surface molecules which mediate adhesion to both biotic and abiotic surfaces, but also promote autoagglutination and serum resistance, and yet others have enzymatic activities. These proteins are also self-contained secretion systems (hence the name autotransporter), in that they are able to transport the extracellular portion of the protein autonomously across the outer membrane. The long-term aim of this research is to understand three aspects of autotransporter-mediated pathogenesis: 1) the mechanisms and mechanics of the autotransporter virulence functions, 2) the biogenesis of autotransporters and 3) regulation of virulence functions and gene expression. All three steps are potential sites for intervention to prevent adhesion to host tissues, and thus host colonisation and infection. Understanding the molecular mechanisms leading to adhesion could allow for the rational design of novel antimicrobials. To understand these phenomena, I use a wide array of different techniques, including classical microbiological methods, molecular genetics, recombinant protein production and purification (including membrane proteins), microplate-based adhesion assays (ELISA and similar), biochemical methods, biophysical techniques (isothermal titration calorimetry, surface plasmon resonance, spectroscopic techniques), structural biology methods (protein crystallisation, X-ray crystallography, nuclear magnetic resonance spectroscopy), microscopy and bioinformatics. .
Biological nanoparticle formation: Under certain conditions, bacteria are able to reduce heavy metal ions into metallic nanoparticles at the cell surface. These nanoparticles have unusual electronic, magnetic and catalytic properties that are of interest in industry (electronics, chemical catalysts). I aim to find out how the bacteria form these nanoparticles and which biochemical pathways are involved.