Dr K Mace, Dr M Ronshaugen
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
University of Manchester Supervisors: Dr Kimberly Mace, Dr Matthew Ronshaugen. A*STAR Supervisor: Chin Yan Lim (IMB).
Myeloid cells are comprised primarily of macrophages and granulocytes. These cells play a critical role in maintaining skin health in both steady-state conditions and in response to injury. This project focuses on how ageing impacts myeloid cell behaviour in skin, and how these changes impact resident cells types, particularly epidermal cells. Preliminary data has demonstrated that epidermal cells play a significant role in the inflammatory response in the skin and the communication between myeloid cells and epidermal cells is critical to efficient tissue repair and regeneration. Ageing-related changes to myeloid cells are poorly understood, but we propose a skew towards more pro-inflammatory subsets of myeloid cells present in skin may reflect changes to gene expression programmes controlled by epigenetic factors.
Characterisation of myeloid cells subsets in ageing skin will be performed to provide a framework for the project. Analyses of bone marrow-derived stem and progenitor cells from young and old mice will be carried out and bone marrow transplants will be used to test the hypothesis that aberrant inflammation in epidermal cells is driven by ageing-related changes to myeloid cells recruited to the skin. Underlying mechanisms will be explored using RNA-sequencing and ATAC-sequencing to uncover changes to gene expression and chromatin remodelling in aged versus young. Finally, candidate molecules identified by these analyses will be further studied by manipulating their expression and/or function to rescue myeloid cell behaviour and improve wound healing in ageing skin in vivo.
Funding Notes
This project is available to UK/EU candidates. Funding covers fees (UK/EU rate) and stipend for four years. Overseas candidates can apply providing they can pay the difference in fees and are from an eligible country. Candidates will be required to split their time between Manchester and Singapore, as outlined on www.manchester.ac.uk/singaporeastar.
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
References
Alsadoun H, Hentges K, Mace KA (2016). Enforced expression of Hoxa3 inhibits classical and promotes alternative activation of macrophages in vitro and in vivo. J Immunol 197:872-84.
Wicks K, Torbica T, Mace KA (2014). Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound. Semin Immunol 26:341-53.
Bannon P, Wood S, Restivo T, Campbell L, Hardman MJ, Mace KA (2013). Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice. Dis Model Mech 6:1434-47.
Muñoz-Najar U, Sedivy JM (2011). Epigenetic control of aging. Antioxid Redox Signal 14(2): 241–259.
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