Conformation and cross-reactivity
Comparing antigen structures to understand why vaccination against one bacterial serotype may, or may not, provide protection against another.
Research
Computational insight for carbohydrate vaccine science
I use molecular modelling to investigate the conformations and interactions of microbial surface carbohydrates - structures that are central to infection, immunity and the development of antimicrobial vaccines.
The central question
How does molecular shape influence immune recognition?
Many pathogenic bacteria are surrounded by flexible capsular polysaccharides or O-antigens. These molecules help pathogens evade host defences, but they can also be targeted by vaccine-induced antibodies.
My research connects carbohydrate sequence and chemical modification to three-dimensional conformation, epitope presentation and immune cross-reactivity. The goal is to provide mechanistic evidence that can help explain vaccine performance and inform the design of broader, more effective and more affordable vaccines.
This work sits at the intersection of computer science, chemistry, glycobiology and vaccine development. It combines molecular dynamics simulation, carbohydrate force fields, high-performance computing and close comparison with structural and immunological experiments.
Primary research programme
Carbohydrate antigens and vaccine cross-protection
Closely related pathogens can display similar carbohydrate antigens, yet the antibodies generated against one serotype do not always protect against another. Molecular modelling helps reveal when antigen pairs adopt comparable conformations, when structural decorations expose or mask epitopes, and when flexibility alters conjugation or immune recognition.
The programme has examined vaccine-relevant carbohydrates from organisms including Streptococcus pneumoniae, Shigella flexneri, Neisseria meningitidis, Haemophilus influenzae, Streptococcus suis, Salmonella enterica and Moraxella catarrhalis.
Research questions
From molecular detail to vaccine behaviour
Structural decorations
Investigating how O-acetylation, glucosylation and related chemical changes alter polysaccharide rigidity, epitope presentation and functional immune responses.
Force fields and molecular simulation
Evaluating the computational models used for carbohydrates, including the role of partial atomic charges in maintaining experimentally plausible conformations.
Fungal carbohydrate antigens
Modelling fungal polysaccharides, including the capsule of Cryptococcus neoformans, to understand conformation, epitope presentation and potential vaccine targets.
Research infrastructure
Tools for building and sharing carbohydrate knowledge
Research software and structured data are integral to the programme, making specialist methods more accessible and reusable.
CarbBuilder
Software for rapidly generating three-dimensional models of complex oligo- and polysaccharides from primary structure descriptions, including large and branched structures.
Learn about CarbBuilderSugarDB
A user-centred repository for bacterial carbohydrate primary structures, with carbohydrate-specific search, immediate dataset overviews and automatic glycan structure diagrams.
Visit SugarDBSelected recent outcomes
A sustained programme of collaborative vaccine research
Studies addressed a newly identified pneumococcal serotype 20C, the immunological role of O-antigen decorations in Salmonella enterica, and synthetic Moraxella catarrhalis glycoconjugates.
Conformational comparison of Pasteurella multocida capsular polysaccharides extended the programme's analysis of structurally related antigens.
Work connected molecular conformation with pneumococcal serogroup 10 epitopes, serotype 15 cross-functional immunity, and improved understanding of carbohydrate force fields.
The sabbatical research programme produced seven published papers and consolidated collaborations across academic vaccine research and industry.
Collaboration
Interdisciplinary by design
A long-standing collaboration with Professor Neil Ravenscroft in UCT Chemistry combines molecular modelling with NMR-based structural characterisation of carbohydrate antigens. The broader programme has also involved academic, public-research and pharmaceutical collaborators internationally, bringing simulation together with synthesis, vaccine formulation and immunological evaluation.