Unravelling fibroblast-macrophage crosstalk in the lung and its role in inflammation and extracellular matrix remodelling

Fibroblasts are the most abundant cells within the tissue stroma. These cells are probably best known for their roles in synthesising and regulating the extracellular matrix (ECM), a 3D scaffold of molecules that provides architectural tissue support and influences tissue biology. However, fibroblasts can also influence immune responses either directly through production of immune mediators such as cytokines/chemokines, or indirectly through their ability to shape the ECM environment. Conversely, immune cells can produce molecules such as growth factors that regulate fibroblast functions. There is increasing lines of evidence demonstrating that fibroblasts and macrophages (immune cells that play important roles in inflammation and ECM remodelling) can directly communicate with each other to influence the tissue microenvironment and the balance between health and disease.

In the lung, technologies such as single cell RNAseq and imaging has revealed different fibroblast populations exist phenotypically and spatially within the tissue. During pulmonary fibrosis it is clear that macrophages can produce factors that stimulate fibroblasts to turn on production of the ECM. However, in diseases like asthma where ECM remodelling around the airway is a key feature of disease, the communication between specific fibroblast and macrophage subsets is less clear. Equally whether molecules produced by fibroblasts are important for activating macrophages to influence ECM remodelling in the lung is poorly understood. Dissecting fibroblast-macrophage interactions and the specific molecules involved in crosstalk will help identify unique approaches to target aberrant ECM remodelling in asthma a serious chronic disease that effects over 5 million people in UK, with 3 people a day dying from asthma related complications.

Aim: This PhD project will investigate how communication between fibroblasts and macrophages can influence pulmonary ECM remodelling in asthma

Objectives:

1. Characterise phenotype and location of fibroblasts in the lungs during homeostasis and allergic airway pathology focussing on immune-regulatory molecules
2. Utilise ex vivo precision cut lung slices to investigate macrophage and fibroblast communication
3. Determine whether the ECM composition, stiffness and structure of the lung influences fibroblast-macrophage dynamics

To address these questions, we will use a combination of in vivo, sophisticated ex vivo cultures and in vitro assays alongside a wide range of techniques including flow cytometry, imaging, cell culture and molecular biology techniques including RNASeq. The student will directly work with the supervisory team and labs and have the opportunity to develop and shape this project. This is an exciting opportunity to learn cutting-edge skills, develop critical thinking and transferable skills within a supportive and diverse lab environment.

You can see more information about the lab’s interests here. For informal enquires please get in touch - [Email Address Removed]

Candidate Background

The student should be enthusiastic and highly motivated with strong problem solving skills ideally with experience in immunology, cell biology or molecular biology. You should have a 1^st or 2:1 from a Bachelor’s degree in biomedical/biological sciences, immunology, cell biology or related field. Experience in the following areas would be an advantage: flow cytometry, bioinformatic analysis of large datasets, imaging, microscopy, lung pathology.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

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APPLICATION PROCEDURE

• Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
• You should apply for Medical Sciences (PhD) to ensure your application is passed to the correct team for processing.
• Please clearly note the name of the supervisor and project title on the application form. If you do not mention the project title and the supervisor on your application, it will not be considered for the studentship.
• Your application must include: A personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.
• Please note: you DO NOT need to provide a research proposal with this application
• General application enquiries can be made to [Email Address Removed]