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Metabolic control of T cell function

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Current research interests in Sarah Dimeloe’s lab focus on the metabolism and interlinked immune function of T lymphocytes in health and disease.

T lymphocytes are a key component of the immune system and comprise two subsets: CD4+ T cells, which co-ordinate immune responses against infections or cancers and CD8+ T cells, which can kill infected or cancerous cells of the body, as well as producing important cytokines (messenger molecules). Following an immune response, “memory” populations of both of these cell types remain in the body, surveying for reappearance of a threat, to which they are able to rapidly respond, in order to protect us.

Dr Dimeloe’s previous research has identified a key signal instructing the required changes in metabolism in order for CD4+ T cells to coordinate an immune response. Dr Dimeloe additionally worked to define the key metabolic traits of memory T cells that enable them to perform their specialised role. For example, Dr Dimeloe identified that memory CD4+ T cells have large and complex mitochondria, enabling them to survive in, and patrol oxygen-poor environments like peripheral tissues of the body. She also contributed to work identifying that memory CD8+ T cells are metabolically “primed” to rapidly respond to threats.

Dr Dimeloe’s research in Birmingham is now focused on how these “normal” metabolic functions are dysregulated in disease, and importantly, if such perturbations can be targeted to restore optimal T cell function and protection from disease. Specifically, Dr Dimeloe is investigating changes in the use of key nutrients by T cells during their development and in disease states. Additionally, she working to identify components of diseased tissues that may subvert T cell metabolism and interlinked immune function and delineate the mechanisms involved, with the aim of discovering potential therapeutic targets. One experimental approach that Sarah is using to ask these questions is to perform high-resolution metabolic tracing analyses, by working together with the Metabolic Tracer Analysis Core (MTAC) facility at the University of Birmingham.

Person Specification
Applicants should have a strong background in cell biology and experience of immunology is desirable. They should have a commitment to research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.

Informal enquiries should be directed to Dr Sarah Dimeloe, email

To be considered for this studentship, please send the following documents to Viktorija Ziabliceva, email :

• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.

Funding Notes

Self-funded applications only.

References

T-cell metabolism governing activation, proliferation and differentiation; a modular view. Dimeloe S, Burgener AV, Grählert J, Hess C. Immunology. 2017 Jan;150(1):35-44 (Review Article) PMID: 27479920
http://onlinelibrary.wiley.com/doi/10.1111/imm.12655/full/

Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function. Balmer ML, Ma EH, Bantug GR, Grählert J, Pfister S, Glatter T, Jauch A, Dimeloe S, Slack E, Dehio P, Krzyzaniak MA, King CG, Burgener AV, Fischer M, Develioglu L, Belle R, Recher M, Bonilla WV, Macpherson AJ, Hapfelmeier S, Jones RG, Hess C. Immunity. 2016 Jun 21;44(6):1312-24 PMID: 27212436
http://www.cell.com/immunity/fulltext/S1074-7613(16)30105-4

Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy. Pisarsky L, Bill R, Fagiani E, Dimeloe S, Goosen RW, Hagmann J, Hess C, Christofori G. Cell Rep. 2016 May 10;15(6):1161-74. PMID: 27134168
http://www.cell.com/cell-reports/fulltext/S2211-1247(16)30441-7

The Immune-Metabolic Basis of Effector Memory CD4+ T Cell Function under Hypoxic Conditions. Dimeloe S, Mehling M, Frick C, Loeliger J, Bantug GR, Sauder U, Fischer M, Belle R, Develioglu L, Tay S, Langenkamp A, Hess C. J Immunol. 2016 Jan 1;196(1):106-14 PMID: 26621861
http://www.jimmunol.org/content/196/1/106.long

Complement Regulates Nutrient Influx and Metabolic Reprogramming during Th1 Cell Responses. Kolev M, Dimeloe S, Le Friec G, Navarini A, Arbore G, Povoleri GA, Fischer M, Belle R, Loeliger J, Develioglu L, Bantug GR, Watson J, Couzi L, Afzali B, Lavender P, Hess C, Kemper C. Immunity. 2015 Jun 16;42(6):1033-47 PMID: 26084023
http://www.cell.com/immunity/fulltext/S1074-7613(15)00222-8

Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch. Gubser PM, Bantug GR, Razik L, Fischer M, Dimeloe S, Hoenger G, Durovic B, Jauch A, Hess C. Nat Immunol. 2013 Oct;14(10):1064-72
PMID: 23955661
https://www.nature.com/articles/ni.2687

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