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Ubiquitin-dependent signalling pathways in ageing


   Department of Biomedical Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Project Overview

Unravelling the molecular and cellular mechanisms of ageing to improve human health across the whole lifespan is a central aim of biomedical research. Ageing is characterised by a general functional decline of cells with increased risk of disease. The major aim of our research is to identify the molecular mechanisms and signalling events that may interfere with the ubiquitination system, leading to dysfunctional cells and tissues, and accelerated ageing. Our previous work has shown that deubiquitinating enzymes (DUBs) are involved in the preservation of different compartments, organelles, or degradation of dysfunctional proteins of the cytoplasm (1-5). Deubiquitinating enzymes are emerging as critical regulators of the stability, activity, complex formation, and intracellular localisation of a wide variety of proteins. Consequently, DUBs play key regulatory roles in a multitude of processes, and their dysfunction is linked to various human diseases. Despite intensive research there is only little known about the potential function of DUBs’ maintenance of the ageing proteome. 

This project aims to identify the role of DUBs in regulation of healthy ageing. Regardless of their importance, most DUBs are uncharacterised, and their substrate specificity is largely unknown. The age-related impairment of ubiquitin-dependent proteolysis results in enhanced accumulation of damaged proteins and organelles which can lead to loss of cell integrity, tissue degeneration and can also shorten lifespan. On the other hand, direct ubiquitination of distinct lifespan regulators also actively influences the life expectancy of different organisms (1-5). 

Using combined bioinformatics, molecular, cellular and organismal approaches we will investigate the action of deubiquitinating enzymes safeguarding the ageing proteome and we will suggest interventions to improve human health. 

Kevei group 

The Kevei group is focusing on investigating ageing and ageing related diseases using the Nematode Caenorhabditis elegans model organism and cellular models. The research group is currently composed of 3-4 PhD students and post-doctoral scientists, plus masters and undergraduate students. The research group benefits from the collaborative research environment of the University of Reading Agriculture, Food and Health theme and from UK-based and international collaborations. 

School of Biological Sciences, University of Reading: 

The University of Reading, located west of London, England, provides world-class research education programs. The University’s main Whiteknights Campus is set in 130 hectares of beautiful parkland, a 30-minute train ride to central London and 40 minutes from London Heathrow airport.   

Our School of Biological Sciences conducts high-impact research, tackling current global challenges faced by society and the planet. Our research ranges from understanding and improving human health and combating disease, through to understanding evolutionary processes and uncovering new ways to protect the natural world. In 2020, we moved into a stunning new ~£60 million Health & Life Sciences building. This state-of-the-art facility is purpose-built for science research and teaching. It houses the Cole Museum of Zoology, a café and social spaces.  

In the School of Biological Sciences, you will be joining a vibrant community of ~180 PhD students representing ~40 nationalities. Our students publish in high-impact journals, present at international conferences, and organise a range of exciting outreach and public engagement activities.  

During your PhD at the University of Reading, you will expand your research knowledge and skills, receiving supervision in one-to-one and small group sessions. You will have access to cutting-edge technology and learn the latest research techniques. We also provide dedicated training in important transferable skills that will support your career aspirations. If English is not your first language, the University's excellent International Study and Language Institute will help you develop your academic English skills. 

The University of Reading is a welcoming community for people of all faiths and cultures. We are committed to a healthy work-life balance and will work to ensure that you are supported personally and academically. 

Eligibility: 

Applicants should have a minimum of a UK Upper Second (2:1) undergraduate degree (or equivalent) in biology or a strongly-related discipline. Applicants will also need to meet the University’s English Language requirements. We offer pre-sessional courses that can help with meeting these requirements. 

How to apply: 

Submit an application for a PhD in Biomedical Sciences at http://www.reading.ac.uk/pgapply

Further information: 

http://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/PhD/sbs-phd.aspx 

Enquiries: 

Dr. Eva Kevei, email:  

Please see Dr Kevei’s profile: 

Dr Eva Kevei – University of Reading 


Funding Notes

We welcome applications from self-funded students worldwide for this project.
If you are applying to an international funding scheme, we encourage you to get in contact as we may be able to support you in your application.

References

References
Herzog LK, Kevei É, Marchante R, Böttcher C, Bindesbøll C, Lystad AH, Pfeiffer A, Gierisch ME, Salomons FA, Simonsen A, Hoppe T, Dantuma NP. The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy. Aging Cell. 2020 Jan;19(1):e13051.
Kevei, E. & Hoppe, T. (2014) Ubiquitin sets the timer: impacts on aging and longevity, Nature structural & molecular biology. 21, 290-2.
Kevei, E., Pokrzywa, W. & Hoppe, T. (2017) Repair or destruction-an intimate liaison between ubiquitin ligases and molecular chaperones in proteostasis, FEBS letters. 591, 2616-2635.
Tawo, R., Pokrzywa, W., Kevei, E., Akyuz, M. E., Balaji, V., Adrian, S., Hohfeld, J. & Hoppe, T. (2017) The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover, Cell. 169, 470-482 e13.
Kuhlbrodt, K., Janiesch, P. C., Kevei, E., Segref, A., Barikbin, R. & Hoppe, T. (2011) The Machado-Joseph disease deubiquitylase ATX-3 couples' longevity and proteostasis, Nat Cell Biol. 13, 273-81.

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