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In this computational PhD, the student will generate methods to model the interactions between immune cells to find out key molecules involved in joints aging, homeostasis and development of pathologies. The identified pathways will be confirmed using multiplex imaging/RNAscope of synovial tissues or synovial organoids.
This project is suitable for an applicant with a background in maths, physics or computer science interest in applying computational skills to a key biomedical problem.
Recent advances in single cell transcriptomic sequencing (scRNA-Seq) allow us to define gene expression in a single cell and give us potential insight into how the neighbour cells interact.
Our recent research ( https://www.nature.com/articles/s41591-020-0939-8) revealed that inflammation and disease resolution in patients with rheumatoid arthritis stay is driven by the communication between specific subtypes of inflammatory or protective macrophages and fibroblasts. In this project, we want to generate computational methods to capture in existing scRNA-Seq data the molecules involved in these processes and extend the study to other form of arthritis, Psoriatic Arthritis that also involves skin. We will apply the developed tools to datasets from embryonic and adult healthy joints to compare how the communication changes due to ageing and disease.
The core goal of this project is to develop novel computation models to capture the communication between the immune cells at the different development stages. The interpretation of the computation model will reveal changes of communication due to disease and aging. To validate our finding, we will test the most promising pathways from the communication network in the laboratory with the aim to understand if there could be drug targets or markers for disease outcome.
The student will learn several computational around scRNA-Seq with the aim to generate novel algorithm for cell-cell interaction and should therefore have a solid computational background with an interest applying in to biological sciences. There is the opportunity to learn laboratory technics. There will be a good day-to-day support from the Otto (Computational - https://www.gla.ac.uk/researchinstitutes/iii/staff/thomasdanotto/) and Kurowska-Stolarska lab (Immunological- https://www.gla.ac.uk/researchinstitutes/iii/staff/mariolakurowska-stolarska/). Dr Alivernini will help to link the computational data to the clinical outcome.
Part of the PhD (mining the cell interactions in embryonic joints and multiplex imaging/RNAscope) is a 6-9 months stay at The Kennedy Institute Of Rheumatology at the University of Oxford with Prof Mark Cole - https://www.kennedy.ox.ac.uk/team/mark-coles.
Please contact [Email Address Removed] for further information.
This project is part of RACE, which is a collaboration between the Universities of Birmingham, Glasgow, Newcastle and Oxford, with funding and support from Versus Arthritis. The programme capitalises on the expertise of the contributing academic institutions and offers an outstanding opportunity for students to undertake excellent project-based research training within world-class research environments.
There are a five studentships available across the collaborating Institutes; please see http://www.race-gbn.org/phds/
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