Investigating the role of alveolar macrophage metabolic reprogramming in pathogenesis of progressive pulmonary fibrosis.

Progressive Pulmonary Fibrosis (PPF) is a devastating condition which causes worsening breathlessness and disability, with a high mortality rate. Macrophage metabolic reprogramming and dysfunction are implicated in PPF pathogenesis, however the mechanisms remain unclear. The aim of this studentship will be to determine the role of extracellular vesicles in mediating macrophage dysfunction and reprogramming in PPF. The objectives will be to characterise the function and metabolic profile macrophages from PPF patients, determine the biological effect of extracellular vesicles on macrophages in vitro and using ex-vivo human lung slice models of fibrosis, and determine whether these effects can be reversed. This is an exciting and highly topical project, which could identify new therapeutic targets for PPF. A range of translational research skills will be taught, including flow cytometry, fluorescence microscopy, qPCR, Luminex, Seahorse metabolic profiling, macrophage functional assays, electron microscopy, mass spectrometry proteomics, microRNA profiling, digital spatial transcriptomics, and Western blotting. This project benefits from access to human lung tissue from surgical resections; the student will learn how to isolate primary macrophages from tissue, and use precision-cut lung slices in models of pulmonary fibrosis. The student will work collaboratively with an integrated team of discovery scientists and translational clinical academics.

Dr Mahida is an Associate Professor in the Birmingham Acute Care Research (BACR) group, one of the core themes of the Institute of Inflammation and Ageing at the University of Birmingham (https://www.birmingham.ac.uk/staff/profiles/inflammation-ageing/mahida-rahul.aspx). His translational research focuses on the role of inflammatory pathways, extracellular vesicles and macrophage dysfunction in the pathogenesis of acute and chronic respiratory diseases. The group’s aim is to develop novel immunomodulatory therapies to promote the resolution of pulmonary inflammation and fibrosis.

The Institute of Inflammation and Ageing is embedded within the University Hospitals Birmingham NHS Trust, which hosts the largest single-site ICU in Europe and one of the largest regional Interstitial Lung Diseases services in the UK. This enables access to large patient cohorts for clinical, translational and data based studies.

Applicants should have a first or upper second-class degree in a relevant scientific discipline, and who are self-funded or have typically applied for, or secured funding for their studies from their government, employer or associated charitable organisations. Applicants with research experience and/or Master’s degree should apply directly to the Institute of Inflammation and Ageing for a 3 or 4 year full-time PhD –

https://www.birmingham.ac.uk/postgraduate/courses/research/med/inflammation-ageing. This route requires applicants to submit a drafted research proposal.

Applicants will need to submit the following documentation during the application process.

• Detailed CV, including your nationality and country of birth;

• Covering letter highlighting your research experience/capabilities and why you wish to undertake a PhD in the team;

• Names and addresses of two referees;

• Copies of your degree certificates with transcripts written in English;

• Evidence of your proficiency in the English language, if applicable.

• Evidence of scholarship application/funding or independent funding.

ADDITIONAL INFORMATION

University of Birmingham offers pre-sessional English Language courses through the Birmingham International Academy – https://www.birmingham.ac.uk/international/bia/presessional/index.aspx

For additional information on postgraduate studying at University of Birmingham please click – https://www.birmingham.ac.uk/study/postgraduate

For additional information on research at the College of Medical and Dental Sciences please click – https://www.birmingham.ac.uk/research/activity/mds/index.aspx

For additional information on research within the Birmingham Acute Care Research Group please click – https://www.birmingham.ac.uk/research/inflammation-ageing/acute-care-research.aspx

Funding notes:

Applicants are invited from self-funded or scholarship-funded graduates ONLY

Applicants will be self-funded or will have typically applied for, or secured funding for their studies from their government, employer or associated charitable organisations.

Overseas graduates require IELTs of 6.5 overall.

Applying directly to the Institute of Inflammation and Ageing for either a 3 or 4 year full-time PhD – https://www.birmingham.ac.uk/postgraduate/courses/research/med/inflammation-ageing.aspx.

Applying to the 4 year Integrated Doctoral Training Programme in Life Sciences for Health, which combined a MRes and PhD – https://www.birmingham.ac.uk/postgraduate/pgr/idtp/index.aspx.