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