PROJECT
Structure-based design of new herbicides
With 3D information about the structure of plant proteins, it is possible to use computers to find completely new herbicides
Weeds are a major issue for agriculture, responsible for a $2.5 billion annual loss in agricultural production. Herbicides control weeds and are vital for ‘no-till’ agriculture that reduces soil erosion, but this widespread use has resulted in serious herbicide resistance issues.
There is therefore an urgent need for the discovery of new herbicides with new modes of action. There are at present about 24 modes of action and resistance has evolved against almost all of them. Research has intensified recently and a couple of herbicides (aclonifen, cinmethylin) have been rediscovered with new modes of action and the truly novel tetflupyrolimet is nearing release, but apart from these cases, all ‘new’ releases for the last 30 years have been reformulations of compounds already in use.
Our lab has found many new plant target proteins that are ‘druggable’ modes of action. Making these potential target proteins in E. coli and progressing them to biochemical assays and obtaining 3D structural information opens a range of project possibilities.
- Make potential herbicide target proteins in E. coli, progress them to biochemical assays and attempts to obtain their 3D structural information. For targets that structural information is in hand, ab initio design approaches akin to target-first approaches in pharmaceutical drug design will be used. Large-scale docking experiments will suggest lists of binding compounds, which are ordered tested and optimised.
Main project goal:
- To create completely new herbicides with new modes of action
For more background information see the suggested readings below.
- Suggested readings
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- Maxime G. Corral Joel Haywood Luca H. Stehl Keith A. Stubbs Monika W. Murcha Joshua S. Mylne (2018). Targeting plant DIHYDROFOLATE REDUCTASE with antifolates and mechanisms for genetic resistance. The Plant Journal, 94 (4), 727-742.
- Michael D. Wallace, Nidda F. Waraich, Aleksandra W. Debowski, Maxime G. Corral, Anthony Maxwell, Joshua S. Mylne and Keith A. Stubbs (2018). Developing ciprofloxacin analogues against plant DNA gyrase: a novel herbicide mode of action. Chemical Communications, 54, 1869-1872.
- Maxime G. Corral Julie Leroux Dr. Stefan Tresch Dr. Trevor Newton Dr. Keith A. Stubbs Dr. Joshua S. Mylne (2017). Exploiting the Evolutionary Relationship between Malarial Parasites and Plants To Develop New Herbicides. Angewandte Chemie, 56 (33), 9881-9885.
- Maxime G. Corral, Julie Leroux, Keith A. Stubbs & Joshua S. Mylne (2017). Herbicidal properties of antimalarial drugs. Scientific Reports, 7 (45871).
Research team leader: Associate Professor Joshua Mylne
I'm a geneticist and biochemist who has worked broadly in plant genetic engineering, developmental genetics, epigenetics and peptide biochemistry; I am in the School of Molecular Sciences at UWA where I founded my lab in 2013. My research has included studies in protein evolution, biosynthesis and (in close collaboration with synthetic organic chemist Keith Stubbs) increasingly been on herbicide development and target discovery.
Collaborations and Funding
- Associate Professor Keith Stubbs, UWA
- Professor Charlie Bond, UWA
- Associate Professor David Ascher, University of Melbourne
- If this and novel herbicide targets sounds interesting to you, get in touch!
Funding:
- ARC Discovery Project DP190101048 “Putting new herbicide targets on the table” Mylne, Stubbs, Haywood, Maxwell; $516,000, 2019-2021
- Nexgen-UWA Herbicide Partnership, Industry Project, 2019-2021 (sum undisclosed)
How to apply
Interested in becoming part of this project? Complete the following steps to submit your expression of interest:
Step 1 - Check criteria
General UWA PhD entrance requirements can be found on the Future Students website.
Requirements specific to this project:
- Molecular biology or biochemistry experience is desirable, but a projects could also be tailored to someone with a more chemistry-heavy background.
Step 2 - Submit enquiry to research team leader
Step 3 - Lodge application
After you have discussed your project with the research team leader, you should be in a position to proceed to the next step of the UWA application process: Lodge an application. Different application procedures apply to domestic and international students.
Scholarships
- Scholarship specific to this project
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- Grains Research & Development Corporation (GRDC) Research Scholarship, a top up scholarship to the value of 75% of the base RTP plus $5,000 p.a. travel plus $10,000 p.a. operating budget
- Domestic students
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All domestic students may apply for Research Training Program and University Postgraduate Awards (UPA) scholarships.
The Australian Government's Endeavour Awards and Scholarships are available to Australian applicants for study in participating countries and regions.
- International students
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A range of scholarships are available from international organisations and governments. The full list, organised by country, is available on the Future Students website.
In addition, all international students may apply for International Research Training Program scholarships.
The Australian Government's Endeavour Awards and Scholarships are available to international applicants from participating countries and regions.
- Indigenous students
- Indigenous students are encouraged to apply for Indigenous Postgraduate Research Supplementary Scholarships.
- Forrest Foundation scholarships
- All international and Australian students who wish to study towards the degree of Doctor of Philosophy (PhD) at The University of Western Australia may apply for Forrest Scholarships.
- Prestigious postgraduate research scholarships
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Prestigious postgraduate research scholarships support graduate research training by enabling students of exceptional research promise to undertake higher degrees by research at the University.
New collaboration to help fight growing herbicide resistance
Researchers at The University of Western Australia have teamed up with Queensland-based plant healthcare company Nexgen Plants to help combat Australia’s growing herbicide resistance problem. Associate Professor Joshua Mylne from UWA’s School of Molecular Sciences said the partnership would enable the development of innovative new solutions and discovery of more effective herbicide target proteins.
Read moreMylne Lab Research - Plant Biological Chemistry
In close collaboration with the Stubbs lab and guidance from AHRI, our lab is discovering chemically new herbicides and exploring new possible modes of action.
Read moreHerbicide Discovery & Development
Thanks to genetic resistance to many of the most popular herbicides, the need for new ones is greater than ever. Come help be part of the solution!
Read more
