Division of Theoretical Systems Biology
Prof. Dr. Thomas Höfer
The Division of Theoretical Systems Biology pursues multidisciplinary research to understand how biological function emerges from interacting components - molecules within a cell and cells within an organism. Our work is essentially collaborative and characterized by a tight interplay between experimentation, data analysis and mathematical modeling. We dissect the molecular switches that regulate the proliferation and differentiation of T lymphocytes and thus orchestrate adaptive immune responses. The second focus of the division is on growth-factor signaling and cell-cycle control. We study the interplay of these processes in human tumor models to understand how therapy resistance arises from synergistic oncogene action. From both strands of work common principles at the systems level are emerging. Our work aims at identifying the functional behavior of molecular networks in the cell and at quantifying the control exerted by individual components to inform novel therapeutic approaches.
A key challenge of quantitative biology is to understand the interplay between molecular modules - such as those controlling the induction and maintenance of expression of master transcription factors for cell fate - and genome-wide programs that mediate coordinated cell function.
Rand, U., Rinas, M., Schwerk, J., Nöhren, G., Kröger, A., Kály-Kullai, K., Flossdorf, M., Hauser, H., Höfer, T. & Köster, M. (2012). Multi-layered cellular stochasticity and paracrine amplification shape the type-I interferon response. Mol. Syst. Biol., 8:584
Luijsterburg, M.S., von Bornstaedt, G., Gourdin, A.M., Politi, A.Z., Moné, M.J., Warmerdam, D.O., Goedhart, J., Vermeulen, W., van Driel, R. & Höfer, T. (2010). Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair. J. Cell Biol. ,189, 445-463
Busse, D., de la Rosa, M., Hobiger, K., Thurley, K., Floßdorf, M., Scheffold, A. & Höfer, T. (2010). Competing feedback loops shape IL-2 signaling between helper and regulatory T cells in cellular microenvironments. Proc. Natl. Acad. Sci. USA, 107, 3058–3063
Schulz, E., Mariani, L., Radbruch, A. & Höfer, T. (2009). Sequential polarization and imprinting of T-helper type 1 differentiation by interferon-? and interleukin-12. Immunity, 30, 678-688