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Interrogating the role of vascular microenvironments during T cell development


Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences

About the Project

Keywords: Vascular Niche, T Cells, Thymus, Adaptive Immunity, Angiogenesis
Themes: Immunology, Vascular Biology, Stem Cell Biology

Studentship code - KTPSAK

The Project: The thymic microenvironment harbours a hierarchical system of lymphoid/T cell progenitors and supports T cell development which is crucial for generation of adaptive immune diversity. Recent studies hint towards the involvement of blood vessels during T cell development but little is known about the cellular and molecular mechanisms. Our preliminary data indicates that niche microenvironments in thymus may regulate thymic function. Here, this project aims to gain mechanistic insights into the role of vascular niche microenvironments in regulating T cell development. This project will employ a powerful combination of new cutting-edge techniques including single cell sequencing and advanced 3D imaging, to interrogate the role of vascular niches during T cell development. This interdisciplinary project to provide insights into the novel function/s of the vasculature and may provide a strategy to boost immune response by manipulation of vasculature.

Training and Career Opportunities: Student will be based at the Kennedy Institute of Rheumatology, which is a world-renowned research centre, housing basic and clinician scientists working on diverse aspects of immunology and inflammation. In addition to variety of cell and molecular biology techniques, student will be trained to utilize multiple cutting-edge technologies to tackle this interdisciplinary project at the frontiers of immunology, vascular, developmental and stem cell biology. In addition to the lab and departmental meetings, seminar programme and journal clubs, student will attend national and international scientific conferences where she/he will be expected to present the research findings. Student will have the opportunity to attend career events and workshops.

The application guide and form is found online and the DPhil will commence in January 2021.

Application Guide

University of Oxford
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References

Kusumbe AP, Ramasamy SK, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507: 323-328.

Choudhuri K, Llodrá J, Roth EW, Tsai J, Gordo S, Wucherpfennig KW, Kam LC, Stokes DL, Dustin ML (2014) Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 6;507(7490):118-23.

Ramasamy SK, Kusumbe AP, Wang L, Adams RH (2014) Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature 507: 376-380.

Kusumbe AP, Ramasamy SK, Itkin T, Mae M, Langen U, Betsholtz C, Lapidot T, Adams RH (2016) Age-dependent modulation of vascular niches for haematopoetic stem cells. Nature 532: 380-384

Amit Singh, Vimal Verriah, Pengjun Xi, Vimal Veeriah, Sara G. Romeo, Saravana K Ramasamy, Anjali P Kusumbe (2019) Angiocrine signals regulate quiescence and therapy resistance in bone metastasis, JCI Insight Jul 11;4(13)

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