Dr Joel Haywood

Structural biologist Dr Joel Haywood welcomes the opportunity to perform impactful research that addresses a substantial gap in our knowledge of fungicide resistance.

Q: How did you become involved in research related to antimicrobial resistance (AMR)?

Joel: After my PhD at the Institute of Microbiology in Beijing, I came to the University of Western Australia to do my first post-doc. I was interested in a particular enzyme that makes cyclic peptides, which have potential as new drug compounds. Not much was known about how the enzyme works. I solved its 3D structure, which revealed how it catalyses cyclisation.

My supervisor at the time, a plant biologist, was interested in herbicides and antimalarials and the link between the two. Antimalarials are herbicidal, and herbicides are antimalarials. That led us to ask, what other kinds of drugs are herbicidal? I screened over a thousand drugs and found that quite a few of them could kill plants. Because we knew how the drugs work in humans, we could figure out whether they used the same mode of action in plants. I worked on new herbicide discovery for three years before moving to the Centre for Crop Disease Management at Curtin University.

Weeds and microbes have very similar mechanisms of resistance, so my work on herbicides is very relevant to fungicides.

Q: You’re working on the ‘Management of Apple Scab’ project, part of the SAAFE Monitoring Program. What does your work involve?

Joel: Not much is known about AMR in Venturia inaequalis, the fungus that causes apple scab. Farmers have no way of knowing whether they have resistance or which fungicides are no longer effective. They need more information.

The WA Department of Primary Industries and Regional Development (DPIRD) has sent us around 250 samples of apple scab from different farms all over Australia. I’ll take the samples, grow them up, then test them against a range of fungicides. If a fungal strain is resistant, it will survive.

In collaboration with DPRID, we will sequence the genes of the resistant strains and discover the mutations that cause resistance. This will also tell us how prevalent the AMR genes are throughout Australia and help us design probes for the rapid detection of resistance.

Q: How is structural biology relevant to this project?

Joel: Usually resistance is caused by mutations in the active site of a protein, which prevent the fungicide from binding but still allow the protein to carry out its normal function. Looking at the protein structure helps us to understand what’s happening – an important part of monitoring resistance.

In the future, we can use structural biology for solutions as well. If you know the protein structure, you can rationally design a compound to fit into the mutated protein or design novel proteins to target the fungus. But that's blue sky research. First, we need to do the translational research that has a direct impact for farmers.

Q: What part of your work is the most exciting?

Joel: Finding out things that were not known is always exciting. Whatever kind of research you do, that's what keeps you going. It doesn't come along often though! But when you discover something new and you can tell people about it, it's worth it.