Mathematical modeling of homeostasis and oncogenesis in mature T cells
In this project we apply mathematical modelling techniques to consistently explain processes that potentially lead to malignant transformations of T cells. Specifically, we establish a mathematical framework, which allows to study effect of cellular interactions of multiple T-cell receptor(TCR)-specific clones on the expansion and/or control of malignant T-cell clones. Based on the modelling work, we will be able to derive experimentally testable predictions, addressing particular regulatory mechanisms, but also proposing potential therapeutic strategies to treat T-cell related malignancies.
Phenomenon which motivated the modelling work (Figure from Gerdes et al., Front. Immunol. 2013)
The modelling approach is a central component to link the experimental efforts within CONTROL-T and to achieve a quantitative, scale-bridging understanding of proliferation and survival of mature T-cell clones in the normal homeostatic and in the malignant situation. Beyond the mathematical modelling, our group also supports the bioinformatical and statistical analysis of next generation sequencing data to identify genetic lesions that are potentially related to the malignant transformation of T cells.
Simulation results. Abundance of healthy and pre-leukemic T cells for two different situations. Top: In the oligo-clonal situation, i.e. number of different TCR-specific clones (M=33) below a critical threshold, the healthy T cells are outcompeted by the (malignant( pre-leukemic T cells. Bottom: In case of a more poly-clonal situation, i.e. number of different TCR-specific clones (M=66) above a critical threshold, the pre-leukemic T cells can be controlled. For details see Diebner et al. J. Theor. Biol. 2016.
Involved scientists
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Hans Diebner
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Matthias Kuhn
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Ingo Roeder
Publications
Funding
DFG (RO3500/4-1) within the DFG research group FOR1961 „Control-T“