ACDC Seminar by Tomáš Gedeon on the 11th of June

On the 11th of June at 16.00, Tomáš Gedeon will give an Amsterdam Dynamics Seminar. We will go for drinks at Bar Boele after the talk.

The talk will take place in the Maryam seminar room (9A-46).

Title:  Modeling complex phenotypes supported by gene regulatory networks

Abstract: Gene regulatory networks with more than few genes can support different phenotypes in different conditions. These conditions may be external inputs like intercellular signaling, resource abundance or internal variability like abundance of ribosomes, RNAP or even copy number of different enzymes. The different conditions can be modeled as changes in parameters of a gene network model. The mathematical challenge is to develop methods to describe, search and analyze behavior of models across large sets of parameters. I will first describe three classes of different Boolean-like discrete models that are suited to model directed signed network dynamics and how to build exhaustive finite collections of all models that are compatible with the network. I briefly show how these collections are linked to each other and how some of them provide description of global dynamics of certain ODE systems. I will then focus on network models formed by lattices of monotone Boolean functions (MBF) and discuss the structure of those MBFs that support particular types of equilibria, as well as bistability. I will also show that the MBF dynamics does not capture all dynamics generated by ODE network models. I will then illustrate our method on a problem where naive CD4+ cells differentiate into Th1, Th2, Th17 and Treg subsets which mutually inhibit each other. We compare prevalence, across all choices of MBF models, of fully differentiated cell type to a cell type which combines characteristic of two of the four types. We find that such two-hybrid states occur more frequently. This suggests that differentiation to four types likely happens in a two step process, rather than in a single step. The model is general and conclusions may apply to other differentiation processes.

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