Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - ENLIGHT-TEN (European Network linking informatics and genomics of helper T cells)

Teaser

\"The mission of ENLIGHT-TEN is to provide cross-disciplinary training in T cell immunology and big data analysis in order to train a new generation of researchers to exploit the power of emerging technological platforms.Using these emerging technological platforms to...

Summary

\"The mission of ENLIGHT-TEN is to provide cross-disciplinary training in T cell immunology and big data analysis in order to train a new generation of researchers to exploit the power of emerging technological platforms.

Using these emerging technological platforms to understand and manipulate T cell responses is critical to therapeutic intervention in a wide-range of immune-mediated pathologies. The use of immunotherapy to increase anti-tumor responses has recently gained considerable attention, and suppressing the immune response to ameliorate autoimmunity is an equally important goal.

To manipulate T cell responses in a way that brings maximum therapeutic benefit, it is necessary to generate a detailed understanding of precisely how T cells activate and differentiate following antigen encounter. Recent years have revolutionised our view on CD4+ helper T cell differentiation, with a growing recognition that it is far more complex and plastic than we previously appreciated. In addition, we now realise that diverse extrinsic cues (e.g. nutrient availability, oxygen concentrations, salt balance, the microbiome) play an even bigger role than we anticipated in guiding T cell differentiation. Thus, there are many more T cell fates that we previously realised, and many more factors that influence fate choice.

At the same time, the technologies available to study cell identity have changed dramatically. The new era of sequencing technologies has facilitated data gathering on an unprecedented scale and this has been accompanied by the emergence of novel gene-editing technologies such as CRISPR/Cas9. Thus, the tools available for the understanding of biological processes have advanced significantly, and the field is embarking on a new era of high dimensional data collection and tailored gene manipulation.

One of the challenges created by rapid advance of sequencing technologies is the gulf between the labs that have expertise in T cell functional biology and those that are equipped to handle \"\"big data\"\". The aim of ENLIGHT-TEN is to train a cohort of early stage researchers (ESRs) to be comfortable in both areas: to have an in-depth understanding of functional T cell immunology alongside the capacity to generate and process large data sets. Thereto, ENLIGHT-TEN has developed a cross-disciplinary, high-quality educational programme to provide all its PhD students with specialist high-level research training, a broad scientific skill set and experience in both academic and industrial working environments. We are ideally placed to provide a broad cross-disciplinary training that will empower trainees to rapidly take advantage of evolving technologies and apply them to biological problems. By the end of the project, all PhD students will possess combined expertise in T cell immunology as well as acquisition and interpretation of large data sets, positioning them to take immediate advantage of new big data-generating technologies as they emerge.\"

Work performed

ENLIGHT-TEN is an ITN aiming at high-dimensional analysis of CD4+ T cell differentiation, stability and function. The objectives are to:
1. Integrate cross-disciplinary technologies to generate a new view of helper T cell differentiation fates
2. Understand the pathways controlling flexibility between different helper T cell fates with a view to manipulating these choices therapeutically
3. Apply this understanding to immune-mediated pathologies (autoimmunity, atopy) allowing us to define T cell differentiation and plasticity in disease with unprecedented resolution
4. Foster a new generation of enthusiastic young researchers able to analyse next-generation-sequencing data and to implement novel concepts of T cell biology into biomedical applications

During this reporting period ENLIGHT-TEN achieved the following results:

Objective 1: WP1 “Early stages in the career of a T cell” and WP4, “-omics and bioinformatic”, which combine wet lab and bioinformatic methods to better understand T cell differentiation fates contribute to this objective. WP1 successfully delivered D1.1, “single-cell RNA-seq time course data”, D1.2 “Transcriptomes and epigenomes of Treg populations from human thymi and tonsils” as well as D1.4 “data mining of single cell transcriptomes”. Also MS1 due in this reporting period “Transcriptomics and epigenomics of human Treg cell populations” has been reached. In this reporting period, WP4 successfully delivered D4.1, a regulatory feature database as well as its related MS9. In addition, MS10, “first data integration” has been reached.

The work leading towards objective 2, understanding the flexibility between different helper T cell fates is led by WP2 “Plasticity and reprogramming of differentiated T cells” and WP4, “-omics and bioinformatic”. For WP2 no deliverables have been scheduled for this reporting period. MS4 “first bioinformatics of reprogrammed T cells” has been achieved.

For objective 3, WP3 “Immunopathologies caused by dysregulated T cells” applied the results of the aforementioned WPs as well as own data with support of WP4 “-omics and bioinformatic”. WP3 successfully delivered D3.1 “Transcriptional control of CD80 and CD86” as well as MS6 “isolation of T cell subsets form tonsils” and milestone MS7 “RNA-seq on T cells activated with or without CD28”.

Objective 4, is a joined effort of the scientific WPs mentioned above with a strong coordinating activity of WP5 “Training”. WP5 has reached D5.1 “organisation of summer schools”, D5.2 “Certificates for ESRs on completion of various courses” and D5.3 Personal Career Development Plans (PCDP) and thesis committee reports.

Final results

ENLIGHT-TEN will generate impact by
1. Enhancing research- and innovation-related human resources, skills, and working conditions to realise the potential of individuals and to provide new career perspectives and by
2. structuring doctoral/early-stage research training at the European level and to strengthening European innovation capacity

Regarding “enhancing research- and innovation-related human resources the ESRs benefit from a plethora of training opportunities (see also section 1.2.5 of the periodic report) and the intense networking amongst each other and with ENLIGHT-TEN PIs. Thus, the ESRs of ENLIGHT-TEN will acquire the skills to i) excel in different working environments (universities, industry and research institutes) and ii) fill the existing gulf between ‘wet-bench’ disciplines and computational approaches. The latter is particularly relevant since there is a high demand in both the academic sector as well as pharmaceutical companies for researchers to be able to analyse, integrate and exploit the constantly growing ‘big data’.

The project also contributes to “structuring doctoral/early-stage research training”. One example for a durable training partnership across Europe is the fact that the ENLIGHT-TEN partner EBI will continue to offer the jointly developed course “Data resources and bioinformatics tools for immunologists”. In addition, the foundation for cooperation beyond the ITN funding period has been successfully initiated: The ENLIGHT-TEN members together with additional European key opinion leaders received an award of the European Federation of Immunological Societies (EFIS) for a study group called T_CELL_CONNECT_EUROPE thus maintaining the interaction of this group beyond the lifetime of ENLIGHT-TEN.

Website & more info

More info: http://www.enlight-ten.eu.