MSc by Research: Targeted protein degradation in plants – developing “Green PROTACs” for functional analysis of lethal genes

Climate change is one of the biggest threats to global food production, leading to unpredictable weather patterns and geographical migration of pathogens. As sessile organisms, plants must respond to a changing environment in situ and have developed complex systems of perception and response to mitigate against environmental stress. Understanding the function of these proteins is crucial to informing breeding and crop development programs to mitigate against climate change, emerging pathogens, food insecurity and fresh water shortage.  

Functional studies of plant genes and their proteins is often hampered by lethal phenotypes when genes are mutated or severe mutant phenotypes prevent examination of plant life stages or processes of interest. Historically, these genes have proved almost impossible to study at a functional level. In animal systems the emergence of Proteolysis Targeting Chimeras (PROTACs), that selectively degrade a protein of interest through the artificial recruitment of ubiquitin ligases, has proved to be powerful tool for functional determination. However, PROTACs have not been established in plants. This project aims to bring this powerful technology to the study of plant proteins, enabling otherwise impossible research questions to be addressed.  

Based on exiting BromoTAG work at Dundee (Bond et al., J. Med. Chem. 2021, 64, 20, 15477–15502) we have synthesised a range of PROTACs that will recruit plant ubiquitin ligases to proteins of interest. The aims of this project are to characterise these PROTACs for the ability to direct degradation of proteins in plants and, where necessary, collaborate with chemists to improve uptake or activity. This is an interdisciplinary biotechnology project, co-supervised by Prof Alessio Ciulli, primarily providing skills in plant molecular biology, protein biochemistry and plant transformation, but necessitating close working with structural biologists and chemists. You will join a diverse and collaborative lab with opportunities for a wide range transferrable skills training. Recent ~£65 million investment in the Advanced Plant Growth Centre and International Barley Hub ensure that cutting edge plant growth facilities are available, in addition to the world leading biochemical, molecular, structural, chemical and proteomic expertise and facilities at Dundee.  

For further details and informal discussion prospective students are strongly encouraged to contact Dr Piers Hemsley ([Email Address Removed]) before submitting an application.  

Please see our website for further details on the programme:

Life Sciences MSc by Research MSc by Research (Postgraduate) : Study : University of Dundee

Please note before submitting your application that you must list your top three project choices in the Research Proposal section of the application form.

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