PhD studentship - protein degradation in plant development

When the beginning marks the end: Roles for the N-end rule pathway of protein degradation in plant development and stress-response

Details

Proteins are major functional components of cells, and regulation of their stability is essential for controlling responses and developmental outputs across kingdoms. Targeted protein degradation (proteolysis) is especially important in plants, and controls almost all aspects of their life - for example, the sensing of most plant hormones and many environmental signals is reliant on protein degradation. Therefore, increasing our understanding of the mechanisms regulating protein stability is a major aim for plant science, because such studies will identify new targets for enhancing yield and improving stress-resilience to ensure future food security.

The ‘N-end rule’ is a specific pathway for protein degradation that targets proteins for destruction based on their N-terminal amino acid (see Gibbs et al. 2014 Trends in Cell Biology). This pathway has previously been shown to be important in plants for: (1) sensing low oxygen stress (hypoxia), a situation that frequently occurs during floods (Gibbs et al. 2011 Nature), and; (2) sensing nitric oxide (NO), a gaseous molecule that regulates developmental transitions and environmental responses in plants (Gibbs et al. 2014 Molecular Cell). More recently, we have linked this pathway to the regulation of a protein that controls long-term epigenetic responses to the environment by modifying chromatin, and we are also investigating a new ‘branch’ of the system that has previously been characterised in yeast and animals based on N-terminal acetylation of proteins. Currently, our work in these areas is supported by a BBSRC New Investigator grant and an ERC-STG grant.

Despite its emergence as a major regulator of plant signal transduction, our knowledge of the range of protein targets and cellular processes regulated by the N-end rule pathway in plants is currently limited. A PhD project in my lab would be focussed on one of several key areas of study relating to the N-end rule pathway in plants:

(i) Investigating the role of protein degradation via the N-end rule pathway in controlling the epigenome, and its subsequent effects on development and environmental responsiveness.

(ii) Investigating links between N-terminal acetylation and protein stability in plants, by functionally characterising the enzymes involved, identifying protein targets, and linking the pathway to plant growth and stress-responses.

(iii) Using synthetic biology approaches to engineer new signalling pathways by artificially coupling proteins to the N-end rule pathway and assessing the effects on protein stability and plant behaviour.

The majority of our work is carried out in the genetic model plant Arabidopsis, with the eventual aim of this research being to translate key findings into crop species, such as barley or rice. The research will be largely molecular based and may also include ‘omics’ approaches (such as ChIP-Seq and proteomics). The PhD candidate will therefore gain expertise in a wide range of cutting edge and transferable techniques.

References:
Gibbs DJ, Lee SC, Isa NM, Gramuglia S, Fukao T, Bassel GW, Correia CS, Corbineau F, Theodoulou FL, Bailey-Serres J, Holdsworth MJ (2011) Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants. Nature. 479(73):415-8.

Gibbs DJ, Isa NM, Movahedi M, Lozano-Juste J, Mendiondo GM, Berckhan S, Marín-de la Rosa N, Vicente Conde J, Sousa Correia C, Pearce, SP, Bassel GW, Hamali B, Talloji P, Tomé DFA, Coego A, Beynon J, Alabadí D, Bachmair A, León J, Gray JE, Theodoulou FL, Holdsworth MJ (2014) Nitric oxide sensing in plants is mediated by proteolytic control of Group VII ERF transcription factors. Molecular Cell. 53(3): 369-379

Gibbs, DJ (2015) Emerging functions for N-terminal protein acetylation in plants. Trends In Plant Science. 20(10): 599-601

Gibbs DJ*, Bacardit J, Bachmair A, Holdsworth MJ* (2014) The eukaryotic N-end rule pathway: conserved mechanisms and diverse functions. Trends in Cell Biology. http://dx.doi.org/10.1016/j.tcb.2014.05.001 ;