Healthy human cells, cancer cells, pathogenic microbes and even viruses modify their proteins with complex sugar molecules called glycans. These structurally diverse modifications are essential for protein production, stability and function.
Our group is studying the role that glycans play in the development and progression of disease using a combination of biological and chemical techniques.
We leverage this newfound knowledge to develop novel therapeutics for the treatment of diseases as diverse as asthma, chronic obstructive pulmonary diseases (COPDs), cystic fibrosis, inflammatory bowel diseases, cancer and malaria.
Malaria remains one of the most significant problems in human health and represents a tremendous burden on the world’s poorest nations. The malaria parasites, and other apicomplexan parasites, rely on gliding motility to migrate through biological tissues and invade or emerge from host cells.
We have recently discovered that a key component of the molecular machinery involved in gliding motility is modified with an unusual glycan that, in higher eukaryotes, is essential for correct protein trafficking.
We are characterising this glycosylation pathway in collaboration with the Boddey laboratory at the institute, and developing chemical compounds that target it.
Asthma, cystic fibrosis and COPDs are characterised by the overproduction of mucus, which restricts the airways and makes it difficult for patients to breathe. Thinning this mucus to aid in its clearance, without completely ablating this protective coating of the epithelium, remains a challenging problem in the clinic.
Mucin proteins, the principle component of mucus, form complex polymeric networks to impart mucus with it high viscosity. Disrupting these intermolecular interactions is an effective means of thinning mucus.
We are collaborating with the Allan laboratory at the institute to develop a range of proteins that disrupt mucin-mucin interactions to treat diseases of the airways.
Inflammatory bowel diseases (IBDs) affect around 1 per cent of the population in the western world. Changes in the microbiota of these patients play a key role in disease progression with a notable loss of the colonic bacteria that produce short chain fatty acids (SCFAs). Microbial SCFAs nourish colonocytes, reduce epithelial barrier leakage, prime the innate immune response and potentiate the differentiation of regulatory T cells to keep autoimmune responses in check.
This project has been identifying polysaccharides in our diet that promote the growth of SCFA-producing bacteria. These could be used as supplements to aid in the management of IBDs.
We are an interdisciplinary group that uses techniques in chemical, molecular and cell biology to elucidate the roles of glycoconjugates in the development and progression of human diseases.