About the Project
Programmed Cell Death (PCD) is a process that is critical to all organisms for development and defence against pathogens. The process of PCD in plants does not mirror what has been described in animal apoptosis and represents a novel alternative pathway still to be fully discovered. In particular, major animal regulators such as the Bcl2 family and the caspase family are absent from plants genomes. Unravelling the molecular mechanism of plant PCD has implications for the understanding of PCD evolution in eukaryotes and for biotech applications in plants.
We have new and strong genetic evidence that cathepsinB (CathB) is mediating PCD in plants and we have identified this protease as a key component to manipulate PCD in target plant species. Our aim is to understand how CathB mediates PCD with a view to manipulate the process to develop improved plant strains for the industrial biotechnology. For this, we need to identify proteins that are substrates of CathB and which are expected to mediate its function. Specific objectives are: 1) Identify CathB protein substrates using a robust proteomic approach called TAILS that identifies neo-N-termini generated by proteases; 2) Define the CathB cleavage signature and validate selected CathB substrates in vitro and in vivo; 3) Understand the function of cleavage by CathB for at least one substrate using a combination of non-cleavable substrates made by site-directed mutagenesis, of activated substrate over-expression, of knock-out line, as appropriate for the predicted consequences of the cleavage.
Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Funding Notes
This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
References
1. Ge, Y., Cai, Y.M., Bonneau, L., Rotari, V., Danon, A., McKenzie, E.A., McLellan, H., Mach, L. and Gallois, P., 2016. Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis. Cell death and differentiation, 23(9), p.1493.
2. Cai, Y.M., Yu, J., Ge, Y., Mironov, A. and Gallois, P., 2018. Two proteases with caspase‐3‐like activity, cathepsin B and proteasome, antagonistically control ER‐stress‐induced programmed cell death in Arabidopsis. New Phytologist, 218(3), pp.1143-1155.
3. Zhang, H., Gannon, L., Hassall, K.L., Deery, M.J., Gibbs, D.J., Holdsworth, M.J., van der Hoorn, R.A., Lilley, K.S. and ., 2018. N‐terminomics reveals control of Arabidopsis seed storage proteins and proteases by the Arg/N‐end rule pathway. New Phytologist, 218(3), pp.1106-1126.
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