4 year BBSRC CASE PhD Studentship - The role of intermediary metabolism in skin ageing and interplay between inflammation and senescence

Project Summary:

Ageing skin is associated with increased senescence loss of regenerative potential and diminished function. We propose that (a) intrinsic and extrinsic ageing of dermal fibroblasts promote a switch from glycolytic to OXPHOS metabolism in keratinocytes (b) this results in increased ROS and inflammation which promote changes in skin thickness and barrier function, extracellular matrix (ECM) production and impaired hair growth. (c) Changes in skin metabolism due to intrinsic and extrinsic ageing impact on the ability of skin to respond to UV and oxidative stress promoting further ageing.

The overarching aim is to provide a rationale for modulating keratinocyte metabolism as a strategy for promoting healthy ageing. This proposal aims to explore the impact of fibroblasts on keratinocyte metabolism using both neonatal, intrinsically aged and senescent fibroblasts both in 2D and 3D skin model systems. Using arrange of techniques including transcriptomics, seahorse extracellular flux analysis and metabolomics approaches using LC-MS/MS. We aim to dissect the interplay between aged and senescent fibroblasts and keratinocytes and how this may contribute to skin ageing phenotypes. We will be particularly interested to ask how aged fibroblasts impact on keratinocyte metabolism and how this relates to changes in keratinocyte function. We will use a range of technical approaches outlined above and sophisticated 3D systems to model complex in vivo relationships and examine the role of metabolism in skin ageing.

This project is in partnership with Unilever R&D and incorporates an industrial training placement. Extensive training will be provided in siRNA technology, high-throughput screening, 3D organotypic culture, and high content image analysis. The combination of diverse strengths from each party involved provides a chance for a novel way of investigating ageing.

Supervisors:

Academic: Prof. Mike Philpott & Dr. Cleo Bishop Centre for Cell Biology and Cutaneous Research (CBCR), Blizard Institute and Dr Katiuscia Bianchi Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University London.
Industry: Dr David Messenger, Unilever

Applications:

Interested applicants are encouraged to contact Prof. Mike Philpott ([Email Address Removed]) in advance of the deadline.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in biology, biochemistry, genetics or a related biological/medical science area. Previous experience of some of the techniques referenced above would be an advantage, as would a related Masters qualification.

Further information about the Blizard Institute can be found here: www.blizard.qmul.ac.uk

Further information about Barts and The London School of Medicine can be found here: www.smd.qmul.ac.uk