Prof Ethan Goddard, Lab Head | WEHI Researcher Profile

Q: 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.

Q: 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.

Q: 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.

About

The Goddard-Borger laboratory studies the glycobiology of human diseases and works towards the development of new therapeutics using techniques in chemical, structural and molecular biology. Our research is highly collaborative, leading us to work closely with leading scientists at the institute, across Australia and around the world. This provides an excellent interdisciplinary training environment for students and postdoctoral researchers.

Education

Grants and funding

Publications

Selected publications from Prof Ethan Goddard

Bloch JS, John A, Mao R, Mukherjee S, Boilevin J, Irobalieva RN, Darbre T, Scott NE, Reymond J-L, Kossiakoff AA, Goddard-Borger ED, Locher KP. Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. Nature Chemical Biology. 2023;19(5):10.1038/s41589-022-01219-9

Lopaticki S, McConville R, John A, Geoghegan N, Mohamed SD, Verzier L, Steel RWJ, Evelyn C, O’Neill MT, Soler NM, Scott NE, Rogers KL, Goddard-Borger ED, Boddey JA. Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission. Nature Communications. 2022;13(1):10.1038/s41467-022-32076-8

Sharma M, Lingford JP, Petricevic M, Snow AJD, Zhang Y, Järvå MA, Mui JW-Y, Scott NE, Saunders EC, Mao R, Epa R, da Silva BM, Pires DEV, Ascher DB, McConville MJ, Davies GJ, Williams SJ, Goddard-Borger ED. Oxidative desulfurization pathway for complete catabolism of sulfoquinovose by bacteria. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(4):10.1073/pnas.2116022119

Mao R, Xi S, Shah S, Roy MJ, John A, Lingford JP, Gäde G, Scott NE, Goddard-Borger ED. Synthesis of C‑Mannosylated Glycopeptides Enabled by Ni-Catalyzed Photoreductive Cross-Coupling Reactions. Journal of the American Chemical Society. 2021;143(32):10.1021/jacs.1c05567

John A, Järvå MA, Shah S, Mao R, Chappaz S, Birkinshaw RW, Czabotar PE, Lo AW, Scott NE, Goddard-Borger ED. Yeast- and antibody-based tools for studying tryptophan C-mannosylation. Nature Chemical Biology. 2021;17(4):10.1038/s41589-020-00727-w

Järvå MA, Lingford JP, John A, Soler NM, Scott NE, Goddard-Borger ED. Trefoil factors share a lectin activity that defines their role in mucus. Nature Communications. 2020;11(1):10.1038/s41467-020-16223-7

Järvå MA, Dramicanin M, Lingford JP, Mao R, John A, Jarman KE, Grinter R, Goddard-Borger ED. Structural basis of substrate recognition and catalysis by fucosyltransferase 8. Journal of Biological Chemistry. 2020;295(19):10.1074/jbc.ra120.013291

Lopaticki S, Yang ASP, John A, Scott NE, Lingford JP, O’Neill MT, Erickson SM, McKenzie NC, Jennison C, Whitehead LW, Douglas DN, Kneteman NM, Goddard-Borger ED, Boddey JA. Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts. Nature Communications. 2017;8(1):10.1038/s41467-017-00571-y

Speciale G, Jin Y, Davies GJ, Williams SJ, Goddard-Borger ED. YihQ is a sulfoquinovosidase that cleaves sulfoquinovosyl diacylglyceride sulfolipids. Nature Chemical Biology. 2016;12(4):10.1038/nchembio.2023

Goddard-Borger ED, Stick RV. An Efficient, Inexpensive, and Shelf-Stable Diazotransfer Reagent: Imidazole-1-sulfonyl Azide Hydrochloride. Organic Letters. 2007;9(19):10.1021/ol701581g