Decoding the physiology and pathology of ROCO proteins: Multifunctional hubs of cellular signal transduction

About the Project

Project overview:

This project explores the function of evolutionarily conserved ROCO proteins - large enzymes with critical roles in coordinating intracellular signalling pathways. In humans, three of the four ROCO proteins are characterised by a unique combination of two enzymatic activities, GTPase and kinase, within a single polypeptide. The project will focus on these ROCO proteins, Leucine-Rich Repeat Kinase 1 (LRRK1), Leucine-Rich Repeat Kinase 2 (LRRK2), and Death-Associated Protein Kinase 1 (DAPK1), all implicated in human diseases. Pathogenic mutations in LRRK2 can cause Parkinson’s disease, characterised by motor dysfunction due to the death of specific neurons in the brain. LRRK1, though less studied, is involved in bone metabolism and is associated with osteopetrosis, a disease with excessive bone growth and density. DAPK1 is implicated in cell death and cancer. Despite their biomedical significance, the regulatory mechanisms and physiological roles of these proteins remain poorly understood.

To investigate the roles of ROCO proteins, the project will combine in vivo studies in the nematode Caenorhabditis elegans, carrying mutations in the orthologous DAPK-1 and LRK-1 proteins, with in vitro analyses using cellular models. In C. elegans, DAPK-1 and LRK-1 regulate key processes such as tissue integrity, immune response, neuronal maintenance, and stress resistance. Complementary experiments in cellular models will explore conserved signalling mechanisms and the interplay between kinase and GTPase domains. By integrating cellular and whole-organism approaches, this research aims to uncover fundamental principles of signal transduction mediated by multi-activity proteins. The findings will provide insights into basic biology and human health, with direct relevance to neurodegeneration, metabolism, cancer, and healthy ageing, while also informing future therapeutic strategies.

The Cogo group is a newly established research group within the vibrant scientific community at the University of Reading, utilising C. elegans and cellular models to investigate aging and neurodegeneration. The lab is part of a lively network of national and international collaborators.

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 good degree (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. With a commitment to improving diversity in science and engineering, we encourage applications from underrepresented groups.

How to apply:

Submit an application for a PhD in Biomedical Sciences via our online application system.

Further information:

https://www.reading.ac.uk/biological-sciences/research

Enquiries:

Dr Susanna Cogo, email: s.cogo@reading.ac.uk

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.