Periodic Reporting for period 1 - ENLIGHT-TENplus (European Network Linking Informatics and Genomics of Helper T cells in Tissues)
Reporting period: 2021-03-01 to 2023-02-28
More recent findings suggest that chronicity of autoimmune diseases largely depends on the reactivation of tissue-resident memory T (TRM) cells that reside in almost all tissues of the body. Therefore, TRM cells represent the target for the development of precision diagnostic and therapeutic strategies for autoimmune diseases.
TRM cells are strongly influenced by the ‘conditioning’ in the tissue. In healthy settings, this conditioning tailors the immune response to the precise need for organ-specific defence, however, in patients with chronic autoimmune diseases environmental conditioning may modulate an ongoing tissue-resident memory response to unexpectedly trigger pathology. Very often, the molecular factors controlling the tissue-specific conditioning as well as reactivation of TRM cells in the context of autoimmunity are incompletely understood as the interaction of the TRM cells with their microenvironment is extremely complex. As a consequence, there is a pressing need to apply cellular immunology and -omics approaches to TRM cells derived from steadystate and autoimmune conditions in order to better understand their identity and function, and to fully harness their therapeutic potential.
However, a crucial missing link in the current research environment is the lack of qualified individuals who possess the cellular & molecular immunology skills to recognise and define important scientific questions amenable to -omics approaches and also the bioinformatic expertise to interrogate and interpret the resulting Big Data appropriately. As a consequence, large datasets can be acquired on particular TRM cell populations, but not utilised optimally because of insufficient expertise in bioinformatics.
The aim of ENLIGHT-TEN+ (European Network Linking Informatics and Genomics of Helper T cells in Tissues comprising TEN European countries) is to train a cohort of early-stage researchers (ESRs) who have an in-depth understanding of T cell immunology and also expertise in bioinformatic processing of large datasets.
ENLIGHT-TEN+ has the following major objectives:
- Integrate cross-disciplinary and highly innovative technologies to generate a novel view of tissue-resident T cells and understand the microenvironmental cues & molecular factors shaping their unique functional properties with unprecedented resolution
- Apply this understanding to immune-mediated pathologies allowing us to selectively manipulate tissue-resident T cells in autoimmune disease
- Foster a new generation of enthusiastic young researchers able to analyse Big Data and implement novel concepts of T cell biology into biomedical applications
In the two already completed summer schools, the ESRs gained deeper knowledge on T cell immunology and have been introduced to data resources and bioinformatic tools to analyse diverse types of Big Data sets related to T cells.
In addition, ESRs have been learning various technologies relevant to their projects, i.e. multi-colour flow cytometry, working with murine models, different in vivo and in vitro techniques, detailed bioinformatics methods (e.g. programming in R), and imaging.
They have started to generate and analyse different types of omics data to address their scientific questions. Furthermore, the development of new bioinformatic tools to analyse Big Data in the context of TRM cells in autoimmune diseases has been initiated.
Furthermore, by combining interactions of different scientific ‘wet-bench’ disciplines and computational approaches through a network of academic and non-academic partners, ENLIGHT-TEN+ creates a unique working platform for multidisciplinary research education. This training will produce confident and highly competent researchers with a broad expertise in T cell and computational biology. In secondments and events planned in various European countries, ESRs will become familiar with cultural work-related aspects and will prepare them for the possibility of careers throughout Europe.