Molecular modelling for development of vaccines against microbial disease
Associate Professor Michelle Kuttel will present the School of IT Colloquium with a seminar entitled, "Molecular modelling for development of vaccines against microbial disease".
Vaccination against microbial diseases is increasingly important for prevention of disease as antibiotic resistance rises. Glycoconjugate vaccines, which are composed of microbial surface carbohydrates linked to carrier proteins, have proven extremely successful in preventing disease caused by Streptococcus pneumoniae, Neisseria meingitidis and other bacteria. However, bacterial and fungi typically have many strains (or serotypes) and manufacturers of vaccines must select the specific serotypes to be included in the vaccine carefully to ensure both maximum coverage and y affordability. However, the mechanisms involved in cross-protection across serotypes remain poorly understood: where vaccines have been developed, disease caused by non-vaccine serotypes is on the rise, despite expectation that specific antigens would provide protection against similar non-vaccine strains.
Carbohydrates are complex molecules with extreme variation in their structure and shape (conformation). Slight changes in the structure of bacterial carbohydrates (of a residue type or linkage position) can change the molecular conformation enough to prevent binding of carbohydrate antigens to antibodies, enabling the bacterium to evade the host immune response. As current experimental methods have very limited ability to probe carbohydrate structure in solution, molecular simulations have proven to provide valuable insight into both the conformation and dynamics of the highly flexible carbohydrates.
In this talk Michelle will discuss our project to use molecular simulations to inform the development of effective carbohydrate vaccines.
Michelle is an Associate Professor in the CS Department at UCT. My research activities lie in the broad area of Computational Science, specifically in Computational Glycochemistry, software for Astronomy, High Performance Computing and scientific visualisation.