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PhD Studentship: Macrophage scavenger receptor regulation of lipids in atherosclerosis

Employer
Global Academy Jobs
Location
United Kingdom
Closing date
Jan 24, 2018

Job Details

Details

Obesity is characterised by elevated plasma lipid levels and a chronic, systemic inflammation. This syndrome is reaching pandemic proportions in Europe and beyond and is a major risk factor for a number of chronic diseases, including cardiovascular disease, type 2 diabetes. In addition, a rapidly increasing body of literature supports its importance in the development and progression of cancer.

The liver and adipose are two key organs involved in regulating plasma lipid homeostasis; their normal function is disrupted in obesity. An increasing body of recent evidence demonstrates that tissue resident innate immune cells, including macrophages, play a key role in the regulation of metabolic function in these tissues, both under homeostatic conditions and in obesity. In addition, tissue macrophages are at the centre of regulating the development of atherosclerosis; a process that is driven by altered lipid homeostasis.

Macrophages readily engulf lipoprotein particles from their tissue environment and also efflux surplus cholesterol, aided by a range of scavenger receptors expressed on their cell surface. However, regulatory mechanisms that control scavenger receptor expression in macrophages are only partially understood.

The current project builds on a previous body of work in our laboratory examining the ability of macrophages to uptake and efflux lipoprotein particles under different inflammatory conditions. These results led us to hypothesise that alterations in cholesterol handling are key in shaping tissue macrophage function and that the expression of various scavenger receptors is regulated in a coordinated fashion.

This PhD project will define the mechanisms for scavenger receptor regulation using a combination of computational and experimental approaches. We will define joint upstream regulators of scavenger receptors by bioinformatic analysis of published and in-house transcriptomic datasets and will test these predictions experimentally in monocyte and bone marrow derived macrophage model systems. Finally, we will test whether pharmacological or genetic alterations of the newly identified regulators of scavenger receptor expression may provide a clinically useful approach to regulate lipid metabolism in vivo.

 

Funding Notes

The Faculty Scholarships for Medicine, Dentistry & Health cover fees and stipend at Home/EU level. Overseas students may apply but will need to fund the fee differential between Home and Overseas rate from another source.

Company

Global Academy Jobs works with over 250 universities worldwide to promote academic mobility and international research collaboration. Global problems need international solutions. Our jobs board and emails reach the academics and researchers who can help.

"The globalisation of higher education continues apace, driving in turn the ongoing development of the global knowledge economy, striving for solutions to the world’s problems and educating a next generation of leaders and contributors."

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