| Date |
Sep 8, 2017 |
| Speaker |
Jie Liang, Professor, Department of Bioengineering, University of Illinois at Chicago, USA
|
| Title |
Computational modeling of cellular fate: control of stochastic networks and 3D chromsome folding
|
| Abstract |
Genome sequences provide the overall genetic blueprint of cells, but
cells possessing the same genome can exhibit diverse phenotypes.
There is a multitude of mechanisms controlling cellular epigenetic
states and the behavior of cells. Among these, networks of
interacting molecules, often under stochastic control, can exhibit
different landscapes of phenotypic states. In addition, chromosome
folding in three-dimensional space provides another important control
mechanism for selective activation and repression of gene expression.
We describe recent progress towards understanding and modeling these
phenomena. We first discuss an optimal state enumeration algorithm
and the ACME (accurate chemical master equation) method for solving
the discrete chemical master equation (dCME) underlying stochastic
networks. We show how exact time-evolving probabilistic landscapes can
be computed without Gillespie simulation or Fokker-Planck/Langevin
approximations, how a priori error bound for the steady state can be
constructed without trial simulations. We also show how to
characterize multi-stability, epigenetic states, first-passage time of
rare events, and the robustness of decision networks from computed
probability landscape. We then describe the nC-SAC model of 3D
chromosome folding, and how chromosome conformation capture data can
be accounted for, including the scaling rules of chromatin, through
the spatial confinement of the cell nucleus. We further demonstrate
that both inter- and intra-chromsome organization, as well as
gathering of fragile sites of budding yeast can be explained by
confinement and nuclear landmarks. We then give examples on how novel
mechanisms of promoter-enhancer interactions and gene regulation in
alpha globin can revealed through our ensemble models of chromatins.
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