Doctoral Candidate Position 16 - University of Oxford, UK

The effects of inflammation in the human Parkinson's disease brain

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Description of project

This post provides an exciting opportunity to join a multidisciplinary research team funded by Marie Sklodowska-Curie Doctoral Network (BICEPS) to investigate the role of inflammation in Parkinson's disease (PD). Decades of research into PD have fallen short in fully comprehending its mechanisms, leaving us without a cure. Current treatments merely alleviate symptoms temporarily, but are unable to impede the progression of the disease. Clearly, PD research has hit a wall, and new approaches are needed. Recent discoveries of the involvement of the peripheral immune system in PD have sparked a ground-breaking proposition that PD must be considered a systemic disease with an immune response involving both brain and periphery. Thus, to revolutionize PD research, we must shift away from the neuro-centric approach of past decades and extend our focus to studying the immune system outside the brain. Furthermore, recent advancements, such as systems biology and artificial intelligence (AI)-driven data mining, diagnosis, and drug development, hold significant promise for advancing PD research.
The BICEPS network includes 15 participants from the European academic institutions, startup companies, and established pharmaceutical firms including University of Oxford. The primary objective is to train a new generation of PD researchers with interdisciplinary expertise in these fields. This ambitious goal will be realized through an intensive training program that encompasses cutting-edge methodologies, encourages innovation, nurtures transferable skills, and provides immersive, hands-on research experiences. Thereby, the BICEPS network aims to shape the future of PD research by adopting a fresh perspective and expediting the development of diagnostics and therapies for PD, with a particular focus on the immune system. The project in University of Oxford will focus on studying the effects of inflammation specifically in the human Parkinson's disease brain and is led by Professor Laura Parkkinen from the Nuffield Department of Clinical Neurosciences who also directs the Oxford brain bank. Prof Parkkinen's research group is combining expertise in translational neuropathology, molecular biology, protein chemistry, genetics and computational biology to investigate mechanisms and develop drug targets and biomarkers for two main neurodegenerative disorders, Alzheimer's disease and PD. The main objective of this current project is to deconvolute the neuroinflammation with pathological hallmarks of human PD brain and progression of disease using high-throughput, AI-driven digital tools, proteomics, and transcriptomic profiling.

Responsibilities

You will;
Use digital pathology and deep learning algorithms that allow a robust, reproducible and high-throughput quantitative assessments of both protein aggregates and neuroinflammatory profile in a large, well-characterised PD cohort (~500 brains) to examine the relationship of inflammatory responses to the progression of PD-related pathology and progression of disease (e.g. onset, duration of disease, motor symptoms, dementia).
Use proteomics to examine cytokines, chemokines and angiogenesis-related or other inflammation-associated molecules in brain samples representing different progressive stages of PD pathology and also examine these same markers in the matching blood samples in order to determine if these can be used as biologically-relevant biomarkers.
Use spatial transcriptomics to elucidate the molecular determinants and interactions that drive these neuro-immune cellular responses across the landscape of the human PD brain.

Essential selection criteria

Desirable selection criteria

Pre-employment screening

If you are offered the post, the offer will be subject to standard pre-employment checks. You will be asked to provide: proof of your right-to-work in the UK; proof of your identity; and (if we haven't done so already) we will contact the referees you have nominated. You will also be asked to complete a health declaration so that you can tell us about any health conditions or disabilities for which you may need us to make appropriate adjustments. Please read the candidate notes on the University's pre-employment screening procedures.

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