The superfamily of G protein-coupled receptors (GPCRs) includes ~800 seven-transmembrane receptors involved in diverse physiological and pathological functions. GPCRs have been named as the most successful drug targets of medicine to date, with ~30% of all drugs targeting human GPCRs. Currently, for ~150 GPCRs ligands are unknown (so called orphan GPCRs), and these are a promising source of new drug targets. The most common form of motor neuron disease, amyotrophic lateral sclerosis (ALS), is a severe, debilitating and inevitably fatal neuromuscular disorder characterised by diverse pathophysiology which currently has no disease-modifying therapies.
This PhD project will test the hypothesis that specific orphan GPCRs become dysregulated in ALS, contribute to the disease pathogenesis and can constitute promising therapeutic targets in different ALS subtypes.
The student will work within research groups in a vibrant and stimulating environment at the Sheffield Institute for Translational Neuroscience (SITraN). SITraN is a purpose-built research facility which that houses clinical and fundamental scientists from the Department of Neuroscience and the primary focus is research into neurodegenerative disorders. During the project, the student will become proficient in a number of core techniques used in translational neurodegeneration research, including bioinformatics approaches, advanced histological analysis, neuronal cell culture and work with mammalian disease models. At the first stage of the project, the student will perform data mining, integration and analysis of differential expression profiles for orphan GPCRs in ALS using public databases. This will be followed by the validation of selected candidates in CNS tissues from mouse ALS models, human post-mortem tissue and functional studies in human cultured motor neurons. Based on the results of these studies and in consultation with the project’s translational partner, 1-2 candidates for in-depth characterisation will be selected, taking into account the candidate tractability and drug discovery potential.
Please note, this project is also being advertised under our University of Sheffield Postgraduate Research Scholarships scheme.
Entry requirements:
You must fulfil the eligibility criteria listed here: https://www.sheffield.ac.uk/postgraduate/phd/scholarships/csc
How to apply:
Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying
Please clearly state the prospective main supervisor in the respective box and select Neuroscience as the department.
Deadline:
Applications close at 5pm Wednesday 26th January 2022.
Enquiries:
Interested candidates should in the first instance contact Dr Tatyana Shelkovnikova, [Email Address Removed]
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