Molecular mechanisms controlling CTL killing: from genes to secretion (360G-Wellcome-217100_Z_19_Z)

£3,292,176

The aim of my research is to understand the molecular mechanisms that control cytotoxic T lymphocyte (CTL) polarized secretion and killing. In a recent screen of single gene deletion mice we identified novel genes that are required for CTL killing and implicate important roles for organelles including mitochondria and peroxisomes. During the course of these studies we also developed advanced (high-throughput) assays for CTL killing and a detailed map of events leading to CTL secretion. Our specific aims over the next five years will be to (i) Identify the roles of the newly discovered genes, and the organelles they implicate, in CTL killing using a combination of biochemical, genetic and high-resolution imaging approaches. (ii) Determine how transcriptional control fine-tunes CTL killing, combining gene deletion and cell biological approaches (eg micro-patterning) with single cell transcriptomics to ask how CTL modulate their responses in order to modulate their killing. (iii) Broaden the range of genetic diseases for studying CTL function and make use of emerging genomic data to identify new causal genes in immunodeficiency. With the combination of genetic and cell biological approaches that we take, we aim to bridge the current gap between genes and function in CTL.

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Grant Details

Amount Awarded 3292176
Applicant Surname Griffiths
Approval Committee Science Interview Panel
Award Date 2019-07-16T00:00:00+00:00
Financial Year 2018/19
Grant Programme: Title Principal Research Fellowship Renewal
Internal ID 217100/Z/19/Z
Lead Applicant Prof Gillian Griffiths
Partnership Value 3292176
Planned Dates: End Date 2024-09-01T00:00:00+00:00
Planned Dates: Start Date 2019-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England