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Institute of Ophthalmology Three-Year PhD Studentship

1 April 2022

PhD Title: Molecular mechanisms of lysosome-mitochondria membrane contact sites and their role in mitochondrial dysfunction

PhD studentship

PhD Description

UCL Department / Division: UCL Institute of Ophthalmology
Duration of Studentship: Three years from autumn 2022

Supervisor(s): Dr Emily Eden

We are offering a full-time, three-year PhD studentship to study communication between lysosomes and mitochondria and their coupled dysfunction in disease. Lysosomes and mitochondria are critical regulators of cellular metabolism and are both dysfunctional in several degenerative diseases including Age-related Macular Degeneration (AMD) and Niemann Pick type C (NPC). AMD is a complex and multifactorial disease that is the leading cause of vision loss amongst the elderly. In contrast, NPC is a rare, but devastating, hereditary childhood disorder that, on a cellular level, is characterised by the accumulation of lipid-rich material inside cells. Similarly, in early AMD, before vision loss even begins, lipid-rich material accumulates in cells at the back of the eye. There is currently no treatment for the most common "dry" form of AMD and a need for more effective treatments for NPC.

AMD and NPC are both associated with the accumulation of lipid-rich, lysosome-derived material and mitochondrial dysfunction.  How the interplay between these two organelles is involved in regulating cellular homeostasis is not well understood, but membrane contact sites, where neighbouring organelles are in close apposition, are gaining attention as coordinators of functional crosstalk between organelles.  We identified expanded contact sites between closely apposed lysosomes and mitochondria in cellular models of NPC. Using NPC as a model of intracellular lipid accumulation, this project aims to elucidate how lysosome:mitochondria contact sites are regulated and their contribution to mitochondrial dysfunction.
The project will involve a wide range of cell and molecular biology techniques and the student will also gain training and expertise in extensive microscopy use.

Applicants should hold, or expect to receive, a minimum upper-second class degree or equivalent in an associated subject such as biomedical science, neuroscience or life science. A Master’s degree or previous lab-based research experience is desirable. 

Duties and Responsibilities 

The successful candidate is expected to:

  • Complete BioID screens to identify novel regulators of lysosome:mitochondria contact sites.
  • Generate cell lines stably expressing heterodimerization constructs to artificially tether lysosome:mitochondria contact sites.
  • Establish if reducing contact between lysosomes and mitochondria can alleviate mitochondrial dysfunction in cellular models of disease.
  • Use confocal and electron microscopy and appropriate data analysis methods
  • Have input into project direction and experimental design
  • Maintain current knowledge of relevant literature
  • Organise the data of the project and maintain appropriate laboratory records and prepare progress reports.
  • Participate in lab meetings.
  • Prepare the results of the project for publication in peer-reviewed journals.
  • Collaborate with colleagues as an effective team member.
  • Travel for collaborations and other meetings or conferences.
  • Contribute to the overall activities of the research team, department and be aware of UCL policies 

Person Specification 

  • A BSc in a relevant biosciences subject 
  • Interest in degenerative disease 
  • Interest in microscopy
  • Experience/understanding of cell and molecular biology 
  • Ability to work collaboratively and as part of a team 
  • Commitment to UCL’s policy of equal opportunity and the ability to work harmoniously with colleagues and students of all cultures and backgrounds 

Informal enquiries should be made to Dr Emily Eden (e.eden@ucl.ac.uk).

How to apply

Applicants should submit an application to the Research Degrees Manager (ioo.pgr@ucl.ac.uk). You will be required to submit a CV, a covering letter outlining motivation, interest, and suitability for this project, and contact details for two academic referees.

Enquiries relating to the application process should be sent to the Research Degrees Manager (ioo.pgr@ucl.ac.uk).

Shortlisted candidates will be contacted directly for interview. 

The successful candidate is expected to start in September/October 2022.

Funding Notes

This studentship is funded for three years by UCL and includes UK UCL PhD tuition fees, laboratory costs and an annual salary stipend starting at £20,000.

Eligibility

The full studentship (tuition fees and salary stipend) is eligible to all UK nationals and some EU nationals depending on their settlement status.

Application deadline

22 April 2022 at 11:59pm