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Characterising human metalloproteome to disrupt metal toxicity induced neurodegeneration (Ref: SF20/APP/SOUNDARARAJAN)


Project Description

Metal accumulation and biometal dyshomeostasis in the nervous system leads to loss of neuronal function. In neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s Disease, and Huntington’s disease the metal toxicity triggers oxidative stress, alteration in key proteins concentrations, protein aggregation and deranged enzyme activity amongst other changes. A systematic understanding of the metalloproteome deregulation that accompany these molecular alterations is necessary to treat the neurodegenerative disorders at an early stage. Therefore, this project will focus on elucidating the molecular mechanisms of various metals including Zinc and Cadmium based toxicities that lead to neurodegeneration.

The University provides an interdisciplinary environment, underpinned by
state-of-the-art core services with emphasis on Proteomics, metabolomics, laser micro dissection, multimodal assay platforms. The research investigation will use molecular biology, content imaging, chemical biology and proteomics approaches to elucidate the underlying molecular mechanisms that lead to neuronal dysfunction. The completion of the study will help us develop tools for successfully disrupting loss of neuronal function and reversing disease progression.

Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
• Applicants cannot apply for this funding if currently engaged in Doctoral study at Northumbria or elsewhere.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed and the reasons you consider yourself suited to the project. Applications that do not include the advert reference (e.g. SF20/…) will not be considered.

Deadline for applications: 1st July for October start, or 1st December for March start
Start Date: October or March

Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality.

Please direct enquiries to Dr Meera Soundararajan ([email protected])

Funding Notes

Please note, this is a self-funded project and does not include tuition fees or stipend; the studentship is available to Students Worldwide. Fee bands are available at View Website . A relevant fee band will be discussed at interview based on project running costs.

References

Understanding Miro GTPases: Implications in the Treatment of Neurodegenerative Disorders.
Kay L, Pienaar IS, Cooray R, Black G, Soundararajan M.
Mol Neurobiol. 2018 Sep;55(9):7352-7365.

Proteomics and bioinformatics analyses identify novel cellular roles outside mitochondrial function for human miro GTPases.
Kay LJ, Sangal V, Black GW, Soundararajan M.
Mol Cell Biochem. 2019 Jan;451(1-2):21-35.

Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism.
Peters DT, Kay L, Eswaran J, Lakey JH, Soundararajan M.
Int J Mol Sci. 2018 Dec 2;19(12) pii: E3839.

Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition. Soundararajan M, Roos AK, Savitsky P, Filippakopoulos P, Kettenbach AN, Olsen JV, Gerber SA, Eswaran J, Knapp S, Elkins JM. Structure. 2013 Jun 4;21(6):986-996.

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