Characterisation and chemical inhibition of a novel regulatory module controlling chloroplast protein translation
This 4 year BBSRC-CASE studentship, funded through the Midlands Integrative Biology Training Partnership (MIBTP), will be supervised by Dr Daniel Gibbs (University of Birmingham) in association with Dr Christian Noble (Syngenta).
Question: This PhD project will investigate a novel molecular mechanism controlling chloroplast ribosome biogenesis in plants, and in conjunction with project partner Syngenta will explore if this system can be chemically targeted to disrupt protein translation in this organelle.
Background: Regulation of protein biosynthesis in chloroplasts is critical for photosynthetic function and plant survival. Despite this, our knowledge of the molecular mechanisms controlling chloroplast ribosome biogenesis and mRNA translation is limited. We have identified a cytosolic E3 ubiquitin ligase that controls protein biosynthesis specifically in the chloroplast (Bailey and Gibbs, unpublished). This E3 ligase regulates production of a conserved chloroplast-targeted ‘substrate’ protein that is required for plastid ribosome biogenesis. In accordance with this, knockout mutants of the E3 ligase and/or its substrate in Arabidopsis have reduced numbers of chloroplast ribosomes, extreme hypersensitivity to chloroplast-specific translation inhibitors, severe chlorosis, and reduced growth. Both the E3 ligase and substrate are highly conserved in flowering plants, and therefore represent promising new targets for the development or identification of herbicides that disrupt chloroplast protein biosynthesis, a key priority area for Syngenta.
The project: The candidate will use a variety of molecular techniques to investigate this signalling pathway in the model plant Arabidopsis. Initially, protein-protein interaction techniques will be used to investigate the associations between these proteins. These experiments will then guide the development of a range of luminescent protein reporters that can be expressed in plants and used to monitor protein interactions and degradation rates in vivo. Plants expressing these reporters will be screened against Syngenta chemical libraries to identify compounds that disrupt E3-ligase/substrate interactions and influence substrate stability. Chloroplast ribosome activity and protein translation rates in response to chemical treatment will also be assessed. Furthermore, the candidate will develop a new ELISA-based assay to allow high throughput screening of chloroplast protein translation rates.
Skills: This project represents an exciting mix of fundamental and applied research, since it will provide new insight into how plants coordinate their chloroplast function whilst also investigating novel ways of disrupting and monitoring chloroplast translation for industrial benefit. The candidate will learn and use a range of diverse state-of-the-art molecular biology, genetic and protein biochemistry techniques. This project will therefore provide the candidate with training in a wide range of varied, important and highly transferable molecular laboratory based skills. The candidate will also profit from interactions with Syngenta, one of the largest biotech companies in the world.
To apply please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/icase/
Fully funded BBSRC-CASE studentship in association with Syngenta
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