PhD Studentship: Analysing Somatic Mitochondrial DNA Alterations in Single Neurons of Lewy Body Dementia Patients to Understand Cell-type Variation and Related Plasticity

Closing Date
4 Mar 2019
Address
Neuroscience, University of Sussex
Duration
Fixed term for 42 months

A Ph.D. studentship (42 months) is available from August 2019 under the supervision of Dr. Ilse Pienaar, Department of Neuroscience, School of Life Sciences, University of Sussex.

Deadline: 4 March 2019

Brief description of the project:

Lewy Body Dementia (LBD) comprises the second most common dementing neurodegenerative syndrome in the elderly after Alzheimer’s disease. Different neuronal-types show different vulnerabilities towards undergoing neuronal death and forming intraneuronal proteinaceous (α-synuclein) inclusions during LBD, requiring a step-change towards studying individual cells from precise brain regions. This project will explore the extent of somatic mitochondrial DNA (mtDNA) damage between different neuronal populations taken from post-mortem LBD brains compared to controls. The project will further correlate mtDNA variations with patients’ clinical features. This single-cell approach is experimentally optimal, since if mtDNA changes are present in a neuronal subpopulation, their expression under disease conditions might go unnoticed against a heterogeneous cell population background. The expected information will be essential for designing improved cell-based therapies that limit drugs’ off-target actions, contrasting to therapies that target cells globally. Following this phase of the project, the work will then focus on assessing the potential of novel mitochondria targeting drugs to reverse neuronal death and α-synuclein aggregation, using patient-derived induced pluripotent stem cells (iPS).

The work will be conducted in state-of-the-art laboratories at the University of Sussex and will be supervised by Drs. Ilse Pienaar and Matt Neale from Sussex and Dr. Joanna Elson from Newcastle University. Apart from learning skills relating to human brain anatomy, the histological processing of post-mortem brain tissue and single-neuron genetic/molecular analysis, the successful applicant will also learn specialist molecular biology techniques and gain in-depth bioinformatics skills. In addition, the project offers a chance to engage in a drug discovery programme and learn lab skills relating to drug screening and drug target optimisation.

For further details and/or an informal discussion, contact the lead investigator, Dr. Ilse Pienaar, at email: I.S.Pienaar@susesx.ac.uk. Contact Julie Carr for application enquiries (J.L.Carr@sussex.ac.uk).

Please submit a formal application using our online application system at http://www.sussex.ac.uk/study/phd/apply, including a CV, degree transcripts and certificates, statement of interest and names of two academic referees.

On the application system use Programme of Study – PhD Genome Stability.

Please make sure you include the project title and Supervisor’s name with your statement of interest on the application form.

This School funded position, which covers fees and a stipend at standard RCUK rates, is open to Home / EU applicants. Ideal candidates will have a strong background in neuroscience/experimental psychology with additional experience of molecular biology/bioinformatics. Eligible applicants will have recently received an MSc and/or a First or high 2:1 BSc in a relevant subject. Candidates for whom English is not their first language will require an IELTS score of 6.5 overall, with not less than 6.0 in any section.

For more information and to apply, click here

Contact Details

Dr. Ilse Pienaar: I.S.Pienaar@susesx.ac.uk
Julie Carr: J.L.Carr@sussex.ac.uk