Lecturer: Dr. Michael Assaf
Affiliation: Racah Institute of Physics
The Hebrew University of Jerusalem
Abstract:
Cellular processes do not follow
deterministic rules; even in identical
environments genetically identical cells can
make random choices leading to different
phenotypes.
This randomness originates from
fluctuations present in the biomolecular
interaction networks. Most previous work
has been focused on the intrinsic noise (IN)
of these networks. Yet, especially for high-
copy-number biomolecules, extrinsic or
environmental noise (EN) has been
experimentally shown to dominate the
variation. Here we develop an analytical
formalism that allows for calculation of the
effect of EN on gene expression motifs. We
introduce a new method for modeling
bounded EN as an auxiliary species in the
master equation. The method is fully
generic and is not limited to systems with
small EN magnitudes. We focus our study
on motifs that can be viewed as the building
blocks of genetic switches: a non-regulated
gene, a self-inhibiting gene, and a self-
promoting gene.
The role of the EN properties (magnitude,
correlation time, and distribution), on the
statistics of interest are systematically
investigated, and the effect of fluctuations
in different reaction rates is compared. Due
to its analytical nature, our formalism can
be used to quantify the effect of EN on the
dynamics of biochemical networks and can
also be used to improve the interpretation
of data from single-cell gene expression
experiments.