报告题目：Logical modelling of haematopoietic cell fate specification

报告人： Dr. Denis THIEFFRY，法国巴黎高师系统生物学教授

主持人：  翁杰敏 教授

报告时间：9月7日 10:00（周五）

报告地点：闵行生命科学学院大楼534报告厅

报告人简介：Denis THIEFFRY，法国巴黎高师系统生物学教授。1993年获得布鲁塞尔自由大学博士学位，之后先后在墨西哥国立自治大学、德国克斯-普朗克研究所、比利时根特大学做博士后研究，2000至2010年任法国地中海大学生物信息学教授。已在国际学术期刊上发表100多篇论文，担任Biosystems、PLoS Computational Biology等杂志编辑。

报告内容简介：Logical modelling constitutes a flexible framework to build qualitative predictive models, which can be readily analysed or simulated as such, and potentially used as scaffolds to build more quantitative (continuous or stochastic) models. We use Multi-valued Decision Diagrams to implement (multi-level) logical updating rules in the modelling software GINsim  (for Gene Interaction Network simulation) . This representation enabled the development of efficient algorithms for the identification of stable states, or yet to identify specific (positive or negative) regulatory circuits involved in specific dynamical properties (e.g., multiple attractors or sustained oscillations). To cope with larger molecular networks, we have implemented a flexible reduction method conserving the attractors of the original model into our software GINsim. Furthermore, we have delineated an incremental, compositional strategy to build large models by combining logical models for simpler regulatory modules. Recently, these methodological developments have been applied to the differentiation of T-helper cells into different subtypes, depending on activation by antigen presenting cells and on micro-environment (combinations of cytokines) (for another recent modelling study related to neuro-development). In collaboration with Thomas Graf (Center for Genomic Regulation, Barcelona, Spain), we are currently developing a  model accounting for the differentiation of common lymphocyte/myoloid progenitors into lymphocyte and macrophage progenitors.  Furthermore, this model recapitulates the reprogramming of T or B lymphocyte precursors into macrophages upon induced expression of the transcription factors CEBPa or CEBPb. Finally, this model can be used to simulate the behaviour of the system in novel situations, e.g. in the presence of combinations of perturbations such as gene knockouts or ectopic expressions.