Project description DEENESFRITPL Insight into the stemness of memory lymphocytes Immunological memory can provide life-long protection against recurrent infections. Scientists of the EU-funded project SCIMAP have previously shown that single memory T cells can maintain immunological memory through a mechanism of self-renewal conventionally encountered in stem cells. The scope of SCIMAP is to identify the precise T cell subset that harbours such stemness during chronic infections and answer whether stem cell-like features are present also in NK cells. To achieve this, researchers will utilise cellular barcoding to track the fate of single T and NK cells in vivo and long-term continuous imaging to monitor their development in vitro. The project has the potential to identify new molecular targets and immunotherapeutic strategies for the treatment of infection or malignancy. Show the project objective Hide the project objective Objective Almost two decades ago it was first proposed that immunological memory may depend on stem cell-like mechanisms, enabling individual antigen-specific T and B cells to generate progeny that contains short-lived effectors as well as long-lived memory cells. To test this capacity, I have in the past developed a stringent set of single cell-based approaches, which allowed me to show that single CD8+ and CD4+ T central memory cells harbour the capacity to self-renew and generate a diverse offspring of effector cells, but also, show immense variation in executing these essential functions upon activation.Thus, even physiological immune responses to infection appear not to harness the full protective potential available in every antigen-specific lymphocyte. To better understand the regulatory principles underlying this single-cell derived variation, in the context of classical T-cell memory, T-cell exhaustion and memory-like NK cell responses, I developed novel fate mapping technologies such as ‘single-cell colour barcoding’ and ‘single-cell RNA barcoding’. I will now integrate these approaches with single-cell RNA sequencing, genetic reporter systems and continuous live-cell imaging, to answer three fundamental questions in immunobiology:1) Do exhausted T-cell responses to chronic infection and adaptive-like immune responses of NK cells also rely on the stem cell-like potential of individual cells? 2) Do single-cell-derived T and NK cell families enter the memory or memory-like exhausted compartment on a direct road or through de-differentiation, after passing through an early effector state? And 3) how is the development of these T and NK cell families influenced by their founding members’ fundamental cellular properties, such as asymmetric cell-division, quorum sensing and cell-cycle speed? Answering these questions will help to identify new molecular targets and therapeutic strategies to enhance or reinvigorate protective immunity against infection or malignancy. Fields of science engineering and technologymaterials engineeringcolorsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNA Keywords T-cell memory NK cell memory T-cell exhaustion stemness single-cell fate-mapping single cell RNA sequencing RNA velocity LCMV MCMV Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-STG - ERC STARTING GRANTS Call for proposal ERC-2020-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution TECHNISCHE UNIVERSITAET MUENCHEN Net EU contribution € 1 499 236,00 Address Arcisstrasse 21 80333 Muenchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 236,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all TECHNISCHE UNIVERSITAET MUENCHEN Germany Net EU contribution € 1 499 236,00 Address Arcisstrasse 21 80333 Muenchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 499 236,00
