Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS

Periodic Report Summary 1 - QUANTI (Quantitative T cell Immunology)

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With the enthusiastic participation of all academic and industrial partners and associated partners, the network has recruited and trained fourteen fellows in Quantitative T cell Immunology. Network training, management and scientific events have been held in the UK, Ireland and Germany. The inaugural meeting was hosted, in August 2013, by NUI Maynooth, the first annual meeting by NUI Galway, and the midterm review meeting by DKFZ Heidelberg. A complementary skills training event and fellows' meeting have been held at the University of Leeds. The research in the different work packages has been strengthened by secondments and work package meetings.

WP1 is a collaboration between Mariona Baliu Pique (ESR), Pedro Costa del Amo (ESR) and Julio Lahoz-Beneytez (ESR), supervised by José Borghans, Becca Asquith and Christoph Niederalt at University Medical Centre Utrecht, Imperial College and Bayer Technology Services, respectively, that focusses on stable isotope labelling. Experimental and mathematical techniques developed by QuanTI partners are being used to quantify the rate at which living cells proliferate and die, with more confidence than ever before possible.

The WP2 partnership Sary El Daker (ER) and Luis de la Higuera (ESR), supervised by Antonio Freitas and Carmen Molina-París, at Institut Pasteur and the University of Leeds, is developing new experimental and mathematical models to test Antonio Freitas’ “quorum-sensing” hypothesis, an indirect feedback loop where IL-2 is produced by a sub-population of T cells and detected by a sub-population of CD4 regulatory T cells. Mathematical models of CTLA-4, a receptor expressed by T cells and regulatory T cells, binding B7-1 and B7-2 on the surface of antigen presenting cells, and its internalisation to endosomes has been developed, as a mechanism of the suppression exerted by regulatory T cells on IL-2 secreting effector T cells.

In their work for WP3, Pedro Goncalves (ER) and Benedita Rocha (INSERM) have carried out single-cell sequencing to analyse the diversity of the CD8+ T cell receptor (TCR) repertoire in naive cells and its modification during LCMV immune responses for memory T cells. The experimental methods go beyond published results, that focus on the spleen, extending the analysis to lymph nodes and bone marrow; the theoretical analysis of this data, being carried out by Marco Ferrarini (ESR supervised by Grant Lythe) at Leeds, goes beyond the current state-of-the-art in sampling and diversity analysis methodology. A new bioinformatics software package, LymAnalyzer, has been written by Yaxuan Yu (ESR) at NUI Galway (supervised by Cathal Seoighe).

Rob de Boer (supervisor) and Aridaman Pandit (ER), in WP4, have developed mathematical models of the generation of memory T cell populations. Their cutting edge theoretical methods, based on branching and stochastic processes, benefit from state-of-the-art experimental measurements, based on cellular genetic barcoding, pioneered by the Ton Schumacher (supervisor) group at the QuanTI partner NKI, and novel methods to reveal the underlying mechanisms of T cell heterogeneity being developed by Ali Can Sahillioglu (ESR).

In WP5 with Ken Duffy (supervisor) at NUI Maynooth, Harry Tideswell (ESR) has helped to develop the statistical framework required to analyse primary data from a new experimental system created in collaboration with our associated partner, the Hodgkin group at the Walter and Elisa Hall Institute of Medical Research. Giulio Predevello (ESR) has been studying the mathematics of survival analysis in order to test the Cyton Theory of adaptive immune responses on data provided by the Hodgkin group.

Melania Barile (ESR), in the Thomas Höfer (supervisor) group at DKFZ Heidelberg, has developed a deterministic model for cell population dynamics in order to quantitatively characterise adult hematopoiesis under steady state and perturbed conditions, describing in vivo time course data. Joint work with Max Löhning (supervisor) and Domonkos Varga (ESR), at QuanTI partner Charité Universitaetsmedizin Berlin, is examining the cell-to-cell variability in cytokine production. The goal is to unravel the molecular mechanisms behind individual cytokine memory of subsets of helper T cells.

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Life Sciences
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