EVENT : C3BI Seminars
Logical modelling of immune cell specification and reprogramming
Speaker : Denis Thieffry, from Computational systems biology – Institut de Biologie de l’ENS Time : 02:00 pm Starting Date : 26/05/2016
Location : Retrovirus room – LWOFF (22), Institut Pasteur, Paris
Logical modelling of immune cell specification and reprogrammingBlood cells are derived from a common set of stem cells, which differentiate into more specific progenitors of erythroid, myeloid and lymphoid lineages, ultimately leading to functional cells. This ontogenesis is controlled by a complex regulatory network involving environmental signals, as well as transcriptional and epigenetic factors. Dynamical modeling of this network allows a better understanding of the control of cell fate, and to predict the effect of molecular perturbations. Using public data from molecular genetic experiments (qPCR, western blot, EMSA) or genome-wide essays (DNA-chip, ChIP-seq), we have built a comprehensive regulatory network encompassing transcription factors and signaling components involved in myeloid (macrophages and neutrophils) and lymphoid (B and T cells) development. Focusing on B cell and macrophage development, we have developed a model using a logical framework: the levels of activity of the different factors are assimilated to logical functions and their values are defined by a logical rule combining the levels of their regulators using logical operator (NOT, AND, OR). This framework enables a qualitative but nevertheless rigorous and predictive modeling of a regulatory network in the absence of quantitative data.
Our current model recapitulates several differentiation and experiments, including cytokines induced differentiation of common progenitors, pro-B cell reprogramming into macrophages induced by ectopic expression of transcription factors, and the effect of reported gene knock-downs. Tentatively, our model can be further use to design novel reprogramming experiments.
Due to security policy in Institut Pasteur, please register before if you plan to come to this meeting