Funded MSc by Research: Targeting Metabolic dysfunction-associated steatotic liver disease (MASLD)
About the Project
Funded by Tenovus Scotland (Grampian, Highlands & Islands), this project covers Home/UK tuition fees and essential research costs.
The MSc by Research programme at the University of Aberdeen is for students interested in a research-intensive master's degree. It is designed specifically to enhance your skills for a PhD or research career.
Steatotic liver disease is a rapidly growing global health problem affecting up to 2 billion people. Current treatments are limited and suboptimal, highlighting the need for improved therapies. We propose a novel approach using RNA interference (RNAi), specifically siRNA, to selectively target a key regulator of metabolism in the liver that has proven difficult to modulate with conventional drugs.
In this project, the student will develop and optimise liver-targeted siRNA molecules and evaluate their efficacy using cutting edge technologies and a comprehensive experimental pipeline. This will include in vitro characterisation in primary hepatocytes and hepatocyte cell lines to assess target engagement, efficacy, and specificity. In vivo, high-fat diet–induced obese mice will undergo detailed physiological phenotyping, including weekly body weight and adiposity measurements, as well as glucose and insulin tolerance tests. Circulating metabolic markers will be assessed to further characterise systemic dysfunction.
Liver pathology will be evaluated by measuring hepatic triglycerides biochemically, alongside histochemical and microscopic analysis of lipid accumulation and fibrosis. Molecular phenotyping will assess the expression of key regulators of hepatic lipid metabolism using qPCR and protein immunoblotting. In addition, markers of inflammation, including pro-inflammatory cytokines and macrophage markers, as well as genes involved in fibrosis and tissue remodelling, will be quantified.
Finally, therapeutic efficacy will be compared directly with the leading GLP-1 receptor agonist weight-loss drug, both as a monotherapy and in combination, to determine potential additive or synergistic benefits.
Informal enquiries are encouraged and can be directed to Dr Nimesh Mody (n.mody@abdn.ac.uk).
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