Ethan Goddard-Borger-Projects

Ethan Goddard-Borger-Projects

Projects

Super Content: 
Leafy green vegetables

Discovering how bacteria feed on leafy green vegetables may explain how ‘good’ bacteria promote health.

The role of glycosylation in the transmission of 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.

Microscope image
Perinuclear localisation of protein within
the Plasmodium ring stage

 

Next-generation mucolytics to treat lung diseases

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.

Scientific illustration of mucin oligomerisation
Architecture of the mucin oligomers that comprise mucus

 

Unraveling excystation in Giardia lablia

Giardia lamblia is a common water-borne pathogen found all over the world. It forms resilient cysts that persist in the environment for a long time, thanks to a durable coating composed of polysaccharide and proteins. Once a cyst has been ingested and it has passed through the stomach, the parasite carefully disassembles its protective cyst wall so that it can establish an infection within the small intestine.

This project is unraveling how Giardia disassembles its protective cyst wall ­– a fascinating aspect of parasite biology that could inspire the development of new vaccines and prophylactic drugs to block transmission of giardiasis.

Scientific illustration
Homology model of a Giardia cyst-wall processing enzyme

 

Discovering new prebiotics to manage IBDs

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.

Scientific illustration
The role of SCFA in the colonic epithelium