Can macrophage polarization modulate fibroblast behaviour?

• MRC
• Reference Code: CL061

Details:

Name of the supervisor(s)
Dr L Borthwick, Fibrosis Lab, Institute of Cellular Medicine (ICM) 

Professor A Fisher, Fibrosis Lab, Institute of Cellular Medicine (ICM) 

Dr F Oakley, Fibrosis Lab,  Institute of Cellular Medicine (ICM) 

Sponsor
Medical Research council (MRC).

Duration of the award
4 year integrated MRes/PhD (Immunobiology) or 3 year PhD if applicant has a suitable Masters Degree.

Project description
Dysregulated repair leading to fibrosis is a pathological hallmark of several chronic inflammatory lung diseases causing major morbidity and mortality. However, no effective therapies to limit or reverse fibrosis in the lung have been identified highlighting the need for a better understanding of the mechanisms driving fibrosis.

The macrophage is a key effector cell in tissue injury. Macrophages demonstrate remarkable plasticity and change phenotype in response to their microenvironment. Classically activated macrophages (CAMφ) are a vital component of host defence, secreting high levels of pro-inflammatory cytokines and their activation is tightly controlled because they can lead to tissue damage. Alternatively activated macrophages (AAMφ) promote wound healing by secretion of extra-cellular matrix but may be detrimental to the host if their matrix-enhancing activity is dysregulated. Interestingly, selective depletion of macrophages revealed distinct macrophages populations associated with injury and recovery phases of inflammatory scarring. However the direct effect of CAMφ and AAMφ on the activation of human lung fibroblasts remains poorly understood.

This studentship will investigate the potential of CAMφ and AAMφ to change human lung fibroblast behaviour. The effect on inflammatory and fibrotic responses in fibroblasts from normal or diseased lung will be assessed. In addition, by blocking key signaling pathways in fibroblasts and cytokines/growth factors released from macrophages, we will attempt to identify novel targets to block macrophage dependent fibroblast activation.

Value of the Award and Eligibility
Depending on how you meet the MRC’s eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees at the UK/EU rate and an annual stipend of £13,590 (2012/13). A partial award covers fees at the UK/EU rate only.

Person Specification

Candidates must have or expect to obtain a first-class or upper-second-class BSc Honours degree or a Masters degree (Merit or Distinction) in a relevant subject.

How to Apply
You must complete the University’s postgraduate application form. Select “Doctor of Philosophy (Medical Sciences) – cellular medicine” as the programme of study. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CL061.

Closing date for applications
Prompt application is advised as this post is only available until a suitable candidate is appointed.

Further Information
For further details, please contact:
Dr L Borthwick
E-mail: lee.borthwick@ncl.ac.uk