BE Seminar: Modeling complex phenotypes supported by gene regulatory networks by Dr. Tomas Gedeon

Speaker: Dr. Tomas Gedeon
Date: 13th March
Time: 4.00 PM
Venue: TCS Smart X Building, Classroom 03 – (G F – 12)

Title: Modeling complex phenotypes supported by gene regulatory networks

Abstract: Gene regulatory networks with more than a 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 the parameters of a gene network model.

The mathematical challenge is to develop methods to describe, search, and analyze the behavior of models across large sets of parameters. He will illustrate the use of the techniques that we developed, which are based on combining discrete Boolean approaches with differential equations models, on three problems:

The first problem studies a problem where naive CD4+ cells differentiate into Th1, Th2, Th17, and Treg subsets which mutually inhibit each other. in their model, they compare the prevalence, across all parameters, of a fully differentiated cell type to a cell type that combines characteristics of two of the four types. They find that such a type of hybrid occurs
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.

The second problem concerns the ability of the same cell cycle network in yeast to support two phenotypes: (a) regular cell cycle, and (b) endocycling, where the cell duplicates the genome but does not go through mitosis. Endocycling can be induced experimentally by knocking down mitotic cyclin and they use the data to show that, indeed, a single network in different parameter regimes, can support these different phenotypes.

The third problem concerns the gap gene network in Drosophila. Maternal gradients provide cell-specific input into the gap gene network along the head-to-tail axis. They investigate if this varying input, interpreted as varying specification of parameters of the gap gene network, is sufficient to explain different states that the network reaches in different segments, which lays down the segmentation plan for the animal.

If interest and time remain, He will explain a bit of the mathematics that allows us to do this type of analysis.

About the Speaker: Dr. Tomas Gedeon is a Professor of Mathematics at Montana State University who specializes in mathematical modeling of biological systems, especially those arising in cellular and molecular biology. His most recent interest is to develop new methods to understand the behavior of gene regulatory networks with applications to apply understanding of cell cycle and behavior of developmental networks across time and space. He obtained his undergraduate degree from Comenius University in his native Slovakia in 1989 and a PhD in Mathematics from Georgia Institute of Technology in 1994.