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.

As part of this project the successful PhD applicant will:
  • 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.

 

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

Collaborators:

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)

Handshake


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 applicationDifferent application procedures apply to domestic and international students.


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