Job Opportunities

Job Opportunities

PhD studentship in Molecular Cell Biology

School of Biological Sciences Royal Holloway University of London

Application closing date: 01/03/2018

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

A 4 year, BBSRC iCASE PhD studentship, open to UK/EU students only.

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; and here providing expertise in myrigalone A and translation to plant system.

Key words: Agriculture, biochemistry, cell biology, Dictyostelium discoideum, flavonoids, food security genetics, models systems, molecular biology, natural products.

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.

PhD studentship: The studentship (BBSRCDTP iCASE) covers stipend at the standard Research Council rate (ca. £17k per year), research costs and tuition fees at the UK/EU rate, and is available for UK and EU students.

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

For further enquiries, please email Prof. Robin Williams

Application and a description of the application procedure available at: Online application

Prof. Robin SB Williams

Professor of Molecular Cell Biology
Head of Centre for Biomedical Sciences
Royal Holloway
University of London
Egham, Surry
TW20 0EX, UK
Ph: + 44 (0) 1784 276162; Fax: + 44 (0) 1784 414224

(posted February 02, 2018)

PhD thesis project: Molecular mechanisms of integration site selection by Dictyostelium retrotransposons

Friedrich-Schiller-Universität Jena

Laboratory of Prof. Dr. Thomas Winckler

Mobile elements are obligate genomic parasites that amplify as selfish DNA and play important roles in driving the evolution of their hosts. Retrotransposons amplify by reverse transcription of RNA intermediates and integration of the resulting DNA copies at new locations of their host’s genomes. In gene-dense genomes, mobile elements are confronted with high selective pressure to amplify without compromising host fitness, and therefore develop strategies to transpose to “safe” sites that limit direct damage to the host genome. We are interested to evaluate how D. discoideum retrotransposons recognize tRNA genes as integration sites. We follow the working hypothesis that protein interactions between retrotransposon-derived proteins and tRNA gene-specific transcription factors mediate targeted integration.

In the PhD project the successful candidate will characterize integration site selection by the non-long terminal repeat retrotransposon TRE5-A upstream of tRNA genes. In vivo chromatin immunoprecipitation will be combined with Illumina sequencing (ChIP-seq) to evaluate whether sites of TRE5-A integration coincide with RNA polymerase III complexes. To analyze the influence of local chromatin structure upstream of tRNA genes on TRE5-A integration, we use nucleosome profiling (MNase-seq), comparing D. discoideum wildtype and a particular mutant in which TRE5-A retrotransposition is compromised. Further, an in vivo tRNA gene targeting assay with genetically tagged TRE5-A retrotransposons will be established to directly test requirements of protein interactions between the retrotransposon and its target sites.

Selected reading:
T. Spaller, M. Groth, G. Glöckner & T. Winckler (2017). TRE5-A retrotransposition profiling reveals putative RNA polymerase III transcription complex binding sites on the Dictyostelium extrachromosomal rDNA element. PLoS ONE 12(4): e0175729
T. Spaller, E. Kling, G. Glöckner, F. Hillmann & T. Winckler (2016). Convergent evolution of tRNA gene targeting preferences in compact genomes. Mob. DNA 7, 17
A. Schmith, T. Spaller, F. Gaube, Å. Fransson, B. Boesler, S. Ojha, W. Nellen, C. Hammann, F. Söderbom & T. Winckler (2015). A host factor supports retrotransposition of the TRE5-A population in Dictyostelium cells by suppressing an Argonaute protein. Mob. DNA 6, 14 (PubMed)
T. Winckler, J. Schiefner, T. Spaller & O. Siol (2011). Dictyostelium transfer RNA gene-targeting retrotransposons - Studying mobile element-host interactions in a compact genome. Mob. Genet. Elements 1(2), 145-150
O. Siol, T. Spaller, J. Schiefner & T. Winckler (2011). Genetically tagged TRE5-A retrotransposons reveal high amplification rates and authentic target site preference in the Dictyostelium discoideum genome. Nuc. Acids Res. 39(15), 6608-6619

Prof. Dr. Thomas Winckler
Friedrich-Schiller-Universität Jena
Institut für Pharmazie
Lehrstuhl für Pharmazeutische Biologie
Semmelweisstraße 10
07743 Jena
Tel. 03641 949841
Fax: 03641 949842


(posted January 04, 2018)

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