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


   Institute of Inflammation and Ageing

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  Dr Rahul Mahida, Dr A Scott, Dr D Parekh  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Additional supervisor Dr Amanda Tatler, University of Nottingham

Informal enquiries should be directed to the lead project supervisor [Email Address Removed]

Person Specification

Applicants should have a strong background in biological sciences. They should have a commitment to research in lung disease / immunology and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject. Other key criteria include:

  • A willingness to learn and apply new scientific techniques.
  • An ability to analyse information and communicate effectively.
  • An ability to work well within a team and independently when required.
  • Previous experience with cell culture or flow cytometry is desirable, but not essential.

Project details

Progressive Pulmonary Fibrosis (PPF) is a devastating lung condition, which causes worsening breathlessness, disability, and early mortality. Early studies have implicated macrophage metabolic reprogramming and dysfunction in PPF pathogenesis. Extracellular Vesicles (EVs) have also been shown to transport pro-fibrotic cargo (including microRNAs) in models of PPF.

The aim of this studentship will be to determine the role of extracellular vesicles in mediating macrophage dysfunction and metabolic reprogramming in PPF. The objectives will be: 1) to characterise the functional and metabolic profile of macrophages from PPF patients; 2) to determine the biological effect of extracellular vesicles on PPF patient macrophages and on human lung slice models of fibrosis; 3) to determine whether these effects can be reversed.

This is an exciting and 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, Seahorse metabolic profiling, macrophage functional assays, microRNA profiling, extracellular vesicle characterisation and human lung slice models. This project benefits from access to PPF patient samples and human lung tissue from surgical resections. You will work within an integrated collaborative research team of discovery scientists and clinical academics in the Institute of Inflammation and Ageing.

How to apply

Please click on the institution website where you will be taken to the MRC AIM website which contains full information as well as the application forms. Please ensure your application is submitted by the deadline of midday (GMT) Friday 12 January 2024 as late applications will not be considered.

Biological Sciences (4)

Funding Notes

This is a fully funded studentship provided by the Medical Research Council.
If you are successful, you will receive a stipend (currently £18,622 per year for 2023/24) and a tuition fee waiver for 4 years.
Successful candidates will also receive an allowance for a laptop, a travel and conference allowance and an allowance for laboratory/PhD running costs.

References


1. Simpson T, Barratt SL, Beirne P, et al. The burden of progressive fibrotic interstitial lung disease across the UK. The European respiratory journal. 2021;58(1).
2. Xie N, Cui H, Ge J, et al. Metabolic characterization and RNA profiling reveal glycolytic dependence of profibrotic phenotype of alveolar macrophages in lung fibrosis. American journal of physiology Lung cellular and molecular physiology. 2017;313(5):L834-l44.
3. Mahida RY, Scott A, Parekh D, et al. Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome. Frontiers in Medicine. 2021;8(1669).
4. Mahida RY, Matsumoto S, Matthay MA. Extracellular Vesicles: A New Frontier for Research in Acute Respiratory Distress Syndrome. American journal of respiratory cell and molecular biology. 2020;63(1):15-24.
5. Virga F, Cappellesso F, Stijlemans B, et al. Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation. Science advances. 2021;7(19).
6. Sato S, Chong SG, Upagupta C, et al. Fibrotic extracellular matrix induces release of extracellular vesicles with pro-fibrotic miRNA from fibrocytes. Thorax. 2021;76(9):895-906.
7. Alsafadi HN, Staab-Weijnitz CA, Lehmann M, et al. An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices. American journal of physiology Lung cellular and molecular physiology. 2017;312(6):L896-l902.

Where will I study?

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