PhD: Underlying mechanisms of DLB

Funded PhD at University of Nottingham studying astrocyte glycosaminoglycans and alpha synuclein aggregation in dementia with Lewy bodies.

Background: Dementia with Lewy bodies (DLB) is an age-related neurodegenerative disease, often misdiagnosed with Alzheimer’s diseases (AD), affecting around 15-20% of all people living with dementia. DLB presents aggregation of alpha-synuclein protein as its main pathological hallmark. There are currently no effective treatment for DLB, and limited diagnostic biomarkers to distinguish DLB from AD. Therefore, there is an urgent need to better understand the underlying mechanisms of DLB.

Glycosaminoglycans (GAGs) such as heparan sulfate (HS) have been directly linked to protein aggregation in neurodegenerative diseases such as AD and Parkinson’s disease. Previous work from our team demonstrated that astrocytes (the most abundant cells of the brain and major producers of GAGs) secrete different GAG profiles in AD. Together, this suggests a contribution of GAGs in neurodegenerative diseases.

Hypothesis: We will test how changes in GAGs from astrocytes contribute to DLB, especially to alpha-synuclein aggregation.

Aims: We will:

1. Uncover how the GAGs secreted by astrocytes are affected in DLB and how changes in astrocytes-secreted GAGs impact the overall GAG composition of the brain of people diagnosed with DLB.
2. Investigate whether blood-circulating GAGs secreted by astrocytes (especially as cargos of  extracellular vesicles) can be used as potential diagnostic biomarkers for DLB.
3. Explore how artificially modulating GAGs/HS levels impacts alpha-synuclein aggregation and DLB.

Methods: Astrocytes carrying mutations associated with DLB or treated with HS mimetics or lacking GAG-modulating enzymes (e.g. Naglu) will be used as model systems. Composition of GAGs secreted by astrocytes (from astrocytes in culture or from blood samples from people diagnosed with DLB) and in postmortem brain tissue will be determined by ToF-SIMS. As positive controls, we will use postmortem brain tissue from people living with Sanfilippo syndrome, a syndrome that can also present alpha-synuclein aggregates and HS accumulation.

Potential impact: Longer-term, findings from this project will be translated into new prognostic biomarkers or HS-targeting therapeutic options for DLB (similar to what is currently actively being developed for Sanfilippo syndrome).

Supervisory team: This project is a collaboration between the University of Nottingham and University of Newcastle. The student will be based at the University of Nottingham Biodiscovery Institute, a world-leading hub of interdisciplinary research excellence, visiting  co-supervisor’s laboratory in Newcastle to validate key findings in postmortem brain tissue (available locally). This project is part of the Lewy Body Dementia Doctoral Training Network funded by the Alzheimer’s Society.

We are looking for a highly motivated candidate with a keen interest in dementia who wants to be part of the next generation of DLB researchers. Successful applicants will have home UK fees paid and receive a stipend. We welcome applications from home students. We are unable to support students requiring international fees.

Application criteria:

• A minimum of upper second-class honours degree from an undergraduate course (or equivalent) in a STEM based subject.
  A MSc or MRes degree and/or experience in industry in a relevant STEM based subject.
  Wet-lab experience (>1 year expected)

How to apply:

Email one combined pdf (labelled as “Your name_DLB DTP”) to Dr Mattéa Finelli (mattea.finelli@nottingham.ac.uk) with email’s subject as “Application for DLB DTP project” including all documents listed below:

• Cover letter (one-page maximum, Arial 11 font, 1” all margins) explaining your motivation to do a PhD, in particular in the field of neurosciences/DLB, and your longer-term career vision after PhD.
• Research statement (2-page maximum, Arial 11 font, 1” all margins) with details of research, relevant experience, technical expertise, research interests.
• Academic CV which should include:  Degree title and discipline of study; Details of your research project, internship, and relevant work experience; Training courses attended, technical and professional skills; Any other relevant experience.
• Academic transcripts.
• Names and email addresses of 3 academic referees (ideally one being your current supervisor)

Deadline: 31st January 2026, 5pm GMT.

Enquiries: Project Enquiries to supervisor Dr Mattéa Finelli (mattea.finelli@nottingham.ac.uk)

For information about the DTP, please contact the LBD DTN manager LBDDTN@newcastle.ac.uk

University of Nottingham: Our University is a supportive, inclusive and caring community, and we encourage applications from a diverse range of backgrounds.  Ranked among the UK’s top 20 universities and in the world’s top 100 (QS World University Rankings 2026), the University of Nottingham offers a PhD experience that combines research excellence with real-world impact. You’ll be taught by academics who are experts in their field, at a university known for its pioneering research – from the birthplace of the MRI scanner to Nobel Prize-winning discoveries. For the fifth year running, more of our graduates are in highly skilled employment than any other UK university (HESA Graduate Outcomes 2021–2025). With careers support for life and strong employer links, we’ll help you build a future without limits. Nottingham is the third most targeted UK university by leading graduate employers (High Fliers 2024), with global connections to companies like JP Morgan, ASOS, Unilever, GSK, and Deloitte. Ranked in the top 10 for student life (UniCompare 2026), our award-winning campuses are home to students from over 150 countries. With an amazing range of sports clubs and societies, plus the vibrant city of Nottingham on your doorstep, you’ll find plenty of ways to connect and thrive.