Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Signalling pathways that control T cell metabolism and T cell fate

Funder Wellcome Charity-funded
Recipient organisation University of Dundee
Funding £4.0M
Period Oct 2017 — Oct 2022

In plain English

AI plain-English summary

T cells rewire their internal chemistry when they encounter an infection, and this lab will map the molecular switches that control that metabolic transformation. The problem is that T cells do not simply fight pathogens—they also decide whether to become aggressive killers, long-lived memory cells, or exhausted cells that stop working. The molecular signals that guide these fates remain poorly understood, particularly how the supply of oxygen, glucose, and iron alters T cell behaviour. Without this map, efforts to improve immunotherapies or vaccine responses rely on trial and error. This is fundamental science. The researchers will systematically trace how specific enzymes—PHD2, AMPKa1, OGT, SHP-1, SHP-2, PTEN, and SHIP1—translate environmental cues into changes in T cell metabolism, protein networks, and gene activity. If successful, the work will provide a wiring diagram of T cell decision-making. That knowledge could eventually help researchers design more durable immune responses in cancer immunotherapy, improve vaccine efficacy in older adults, or prevent the T cell exhaustion that undermines chronic infection control. Past fundamental mapping of immune signalling pathways has directly enabled checkpoint inhibitor drugs and CAR-T cell therapies.

View original technical description
The laboratory will map how antigen receptor, cytokine and environmental signals integrate to control the function of T lymphocytes. We will comprehensively define signaling pathways that maintain T cell metabolism, transcriptional and proteomic landscapes. Specifically, we will comprehensively delineate the molecular details of how changing the supply of oxygen, glucose and iron impact on T cell signal transduction pathways and T cell phenotype. We will explore the ability of the Prolyl hydroxylase domain protein PHD2 and the transcription factor NFIL3 to link oxygen sensing to the control of T cell function. We will define how glucose fueled signaling pathways including those mediated by AMP-activated Protein Kinase alpha1 (AMPKa1) and the O-GlcNAc transferase (OGT) control T cell fate. We will comprehensively map how the protein tyrosine phosphatases SHP-1 and SHP-2 regulate protein phosphorylation networks in T cells and how they modulate T cell proteomes and T cell function. We will also characterize signaling pathways mediated by Phosphatidylinositol 3,4,5-trisphosphate PI-3,4,5-P(3) and define how the lipid phosphatases PTEN and SHIP1 shape T cell metabolism and T cell function. These experiments will map and define the molecular processes that determine T cell fate outcomes.

View the original record at the funder ↗

Researchers

Doreen Cantrell (EPMC Awardee)

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Original classification

Principal Research Fellowship Renewal

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.