Our research vision focuses on unravelling the structural mechanisms by which pathogenic species attack their eukaryotic hosts. Diseases caused by bacteria, viruses, fungi and protozoa represent major challenges to humanity and its activities, impacting on quality of life, economic performance and food/water security. The long coexistence between microorganisms and higher eukaryotes has fine tuned their relationships. Cells sense and respond to their environment through molecular interactions that are often controlled by secreted proteins and complexes. These interactions are extremely complex and dynamic, but they are fundamental to disease progression, asymptomatic carriage and eventual elimination. It therefore comes as no surprise that these organisms have developed remarkable armouries of molecular systems for the trafficking of molecules across the outer-membrane and exchanging signals with their host. These processes are initiated by the specific recognition of host components by elaborate surface receptors, while secreted molecules enable the manipulation of cellular pathways from either outside or inside host cells. The molecular details of the transport, assembly and interactions of these pathogenic factors and the subsequent unravelling of disease processes are only just emerging. The follow research questions will be addressed:
o How do microbial pathogens transport and construct extracellular components and assemblies?
o How do they use these systems to recognise target ligands, host cells surfaces and other microbial cells?
o How do they modulate signalling pathways within their hosts and other pathogens?
Our approach engages multi-disciplinary and complementary methods that aim to marry biological insight with quantitative data. In addition to employing a diverse array of molecular and structural tools, we are developing new nuclear magnetic resonance (NMR) methods to assist in mapping molecular flexibility and interactions in large assemblies. Studying cellular communication processes used by pathogenic microorganisms not only provides insights into disease pathways, it illuminates fundamental cell biology in higher eukaryotes. Our work also provides a foundation for future research and translational activities, such as providing new paths towards therapeutic intervention and diagnosis. Also, studying the pathogen frontline provides opportunities for the development of new tools and reagents for manipulating eukaryotic cells for investigating basic human biology.