Dr I Pienaar, Dr M Neale
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Lewy Body Dementia (LBD) comprise 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. The work will be conducted in stat-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 and the histological processing of this, the successful applicant will also learn specialist molecular biology techniques and gain in-depth bioinformatics skills.
Lewy Body Dementia (LBD) comprise 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. The work will be conducted in stat-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 and the histological processing of this, the successful applicant will also learn specialist molecular biology techniques and gain in-depth bioinformatics skills.
How to apply:
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, English certificates (for non-UK candidates), statement of interest and names of two academic referees. On the application system use Programme of Study – PhD Neuroscience. In the funding section state that you are applying for funding.
For enquiries about the application process contact Anna Izykowska ([Email Address Removed])
For enquiries about the project contact Dr. Ilse Pienaar ([Email Address Removed])
Funding Notes
This 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 candidates 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.
References
Bury AM, Pyle A, Dexter DT, Elson JL, Hudson G & Pienaar IS (2017). Mitochondrial DNA changes in pedunculopontine cholinergic neurons in Parkinson’s disease. Annals of Neurology, 82(6):1016-1021.
Nido GS, Dolle C, Flones I, Tuppen HA, Alves G, Tysnes OB, Haugervoll K, Tzoulis C (2018). Ultradeep mapping of neuronal mitochondrial deletions in Parkinson's disease. Neurobiol Aging, 63:120-127.
Garcia-Esparcia P, López-González I, Grau-Rivera O, García-Garrido MF, Konetti A, Llorens F, et al. (2017). Dementia with Lewy Bodies: Molecular pathology in the frontal cortex in typical and rapidly progressive forms. Front Neurol, 13;8:89.
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