ERC Consolidator Grant
ERC Consolidator Grants are awarded to researchers with between 7 and 12 years of experience post-PhD with a strong research proposal and a promising scientific track record. Funding is provided for up to five years to allow the investigator to establish their independence by building a research team. Up to 2 million euro may be awarded to an individual investigator. It is a highly prestigious grant designed to support cutting edge research. In 2017, Professor David Finlay was a recipient of this award, which is being used to investigate nutrients as key determinants of DC-induced CD8 T cell responses.
ERC Proof of Concept Grant
ERC Proof of Concept grants are awarded to investigators who have previously been supported by ERC to maximise the potential value of discoveries arising from existing projects. The value of this grant is up to 150,000 euro. Professor David Finlay was a recipient of this award in January 2023. The 4Dplus_MetaFlux project will focus on measuring metabolic fluxes in single cells in vivo.
Dendritic Cell-Nutrient Project
The Finlay research group are conducting research at the forefront of the immunometabolism field and were the first to characterize cellular metabolic pathways in Natural Killer (NK) cells to show the different way in which they metabolize glucose. They also showed that glucose controls signal transduction pathways in Dendritic cells (DC) to inhibit DC functions and to limit the induction of CD8 T cell responses
mTORC1 is a key metabolic regulator in many immune cells. It promotes glycolysis in response to glucose stimulation. mTORC1 signalling is shown to be shut off in dendritic cells when glucose availabililty is limited, which leads to enhanced induction of T cells responses by the antigen presenting dendritic cells.
QUAS-R: Glutamine Uptake Assay
Our lab, alongside collaborators Dr. Linda Sinclair from the University of Dundee and Dr. Sander van Kasteren from Leiden University, have developed a flow cytometry assay which allows for rapid, sensitive, and quantitative measurement of SLC1A5-mediated uptake, which is used to interrogate the transport capacity of the complex immune subpopulations within the thymus, at a single cell resolution previously unreachable. This assay is a significant addition to the single-cell metabolic toolbox required to decode the metabolic landscape of complex immune microenvironments. Find it here at: https://www.cell.com/cell-reports/pdfExtended/S2211-1247(23)00839-2
Highlights
- Bioorthogonal amino acids AHA and HPG are transported by SLC1A5, a key glutamine transporter.
- Click chemistry targeted fluorophores report SLC1A5 transport with single cell resolution.
- HPG uptake in vivo by immune cells, visualised by ex vivo fluorophore conjugation.
- An assay to report glutamine uptake of individual cells in complex immune microenvironments.
4Dplus MetaFlux project
The aim of 4D+ meta flux is to provide a method to interrogate multiple metabolic parameters of different cell types with single cell resolution. The project is enabled by harnessing and developing novel metabolic probes to measure different metabolic nutrient uptakes such as amino acids, fatty acids and glucose. Through the use of click chemistry and novel metabolic probes we can understand the differences in nutrient uptake in complex immune microenvironments such as the lymph node and spleen. Applying this technology to health and disease we can interrogate the metabolic heterogeneity in environments such as the tumor to understand the distribution of nutrients and how certain pathways can be targeted to enhance anti-tumor immunity and immune cell functions through metabolism.