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  Bioherbicides: A focus on identifying the mode of action of natural flavonoids


   School of Biological Sciences

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  Prof R S B Williams, Prof Gerhard Leubner  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Developing new, more environmentally friendly herbicides provides a key goal for agricultural companies aiming to improve global food security. Understanding the molecular mechanisms of potential herbicides is essential for this goal. This project will employ a simple, tractable model system to investigate the molecular targets and mechanisms of a new class of herbicides relating to myrigalone A, a rare hormone-derivative and phytotoxic flavonoid that provides a ‘natural’ alternative to current synthetic herbicides. Characterising the mode of action of myrigalone A and related compounds will likely provide a new mode of action for the next generation of eco-friendly herbicides.
This project will employ the social amoeba, Dictyostelium discoideum, as a research model. Using this system, molecular studies will improve our understanding of the targets and mechanism of myrigalone_A and related compounds. Through genetic screens, potential direct targets for the compounds will be identified, and both acute and chronic mechanisms will be analysed at a biochemical level. The chemical functionality of myrigalone-related compounds on cell function will also be assessed. These studies will therefore improve our understanding of the molecular basis of this potential new generation of herbicides.
The research will encompass a broad range of cell and molecular techniques including cell culture, mutant library screening, DNA cloning and plasmid construction, fluorescence microscopy, and biochemical assays. Discoveries regarding the targets and mechanism of action of myrigalone A and related compounds will then be translated to plant models. The project will therefore lead to a better understanding of the mechanism(s) of action of myrigalone-related compounds in agricultural use.
The project will be based in the laboratory of Prof Robin SB Williams (see here) providing expertise in the model system and research procedures, and in a close collaboration with Prof Gerhard Leubner (see here; and www.seedbiology.eu; and here) providing expertise in myrigalone A and translation to plant system.

This will be an extremely competitive program and applications are requested from outstanding undergraduate students in their final year of their degree or Masters graduates. Applicant will be expected to have some experience with molecular cell biology.
CASE Industrial Placement: The three month-CASE placement will be at Syngenta’s International Research Stations in the UK or Switzerland. The placement will provide experience and training it the applied research and methods relevant to the project’s topics. The timing of this is flexible, and will be either one or two blocks placed strategically in the initial and middle phase of the PhD project.



Funding Notes

The four year funded studentship (BBSRCDTP iCASE) covers stipend at the standard Research Council rate, research costs and tuition fees at the UK/EU rate, and is available for UK and EU students.

References

Some references from the Williams laboratory:
- Cocorocchio et al (2018) Disease Models and Mechanisms 11, dmm032375.
- Augustin et al (2017) Lancet Neurology, Lancet Neurology, 17 (1), 84–93
- Williams & Bate (2017) Neuropharmacology, 128: 54-62
- Otto, Sharma & Williams (2016) Journal of Alzheimer's disease 52(4):1177-87
- Frej et al (2016) Molecular and Cellular Biology, 36(10):1464-79
- Cocorocchio et al (2016) ALTEX, 33(3):225-36.
- Zuckermann et al (2016) British Journal of Pharmacology, 172(22):5306-17
- Chang et al (2015) Brain, 139(2):431-43
- Waheed et al (2013) British Journal of Pharmacology, 171(10):2659-70
- Robery et al (2013) Journal of Cell Science, 126(23):5465-76

Some references from the Leubner laboratory:
- Sperber et al (2017) Nature Communications, 8:1868
- Steinbrecher & Leubner (2017) Journal of Experimental Botany, 68: 765-783
- Lenser et al (2016) Plant Physiology, 172:1691-1707
- Graeber et al (2014) Proc Natl Acad Sci USA, 111:E3571-80
- Voegele et al (2012) Journal of Experimental Botany, 63: 5337-5350

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