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| Former group members Jakub Jędrak, Ph. D., postdoctoral researcher, jjedrak [AT] ichf.edu.pl Piotr Wiącek, student, University of Warsaw Maciej Ślot, student, University of Łódź |
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| Our publications Click here to see the list of our publications |
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Completed projects:
Evolution of gene regulation as a stochastic
process: Savageau's demand theory, cost of regulation and
noise
However, in recent years, with the advent of systems biology and its tools, new studies began to appear, questioning the universality of the theory and extending it with new criteria. Since even a genetically uniform population of cells is subject to random fluctuations in gene expression, a phenotypic diversity exists in such a population. We want to see how taking into account the costs of regulation and random fluctuations in the concentrations of transcription factor complements the classic Savageau’s demand rules? The project is theoretical – we use the tools of statistical physics and the theory of stochastic processes – but it may deliver experimentally testable predictions and can encourage biologists to carry out new types of evolutionary experiments, focusing on the role of randomness in gene expression. In the long term, understanding the evolution of phenotypic diversity is crucial in the struggle against bacterial resistance to antibiotics, one of the most pressing problems of modern medicine. Click here for more information about the project
7.2013-7.2015: Polish Ministry of Science Iuventus Plus
grant 0501/IP1/2013/72Theoretical study of conditions for precise gene regulation in a 2-gene cascade with autoregulation 
In [A.
Ochab-Marcinek, M. Tabaka, PNAS, 2010] we studied a
theoretical model of gene expression in the simplest
possible gene regulatory system: a two-step cascade
with noncooperative binding of transcription factors.
Such a system is deterministically monostable. We have
shown that in this system bimodal gene expression is
still possible: The reaction of binding of
transcription factors to DNA acts as a nonlinear noise
filter that transforms the unimodal distribution of
transcription factors over the cell population into the
bimodal distribution of proteins produced from the
regulated gene. We have found a simple method based on
geometric construction that allows one to predict the
onset of bimodality. These findings may explain the
experimentally observed bimodal response of cascades
controlled by the tetracycline repressor. In the current project, we extend our study to more complex regulatory motifs. We want to find the conditions for precise gene regulation in these systems. Click here for more information about the project  12.2011-
12.2014: National Science Center SONATA grant no.
2011/01/D/ST3/00751Transition from nano- to macroviscosity in diffusion of nanoparticles in a crowded environment: Theoretical and experimental study of the depletion layer effect 
Gene expression strongly depends on the rate constants
of biochemical reactions, such as e.g. transcription
factor + DNA. A small variation in these rates may
dramatically change the gene expression. Therefore, in
order to design genetic circuits having desired
properties, biotechnologists have to know exactly the
rates of reactions that control gene expression. In
biochemistry, a standard reaction rate analysis is
usually done in vitro, in a buffer of viscosity of
water. However, in vivo, in a crowded environment of
high viscosity, biochemical reactions are usually
limited by diffusion, and their rates may differ by
several orders of magnitude from those expected based
on the standard measurements. Moreover, many
biochemical reactions in living cells are
diffusion-limited. If the diffusion of molecules in a
crowded environment differs from that expected based od
in vitro experiments, then also the rates of
biochemical reactions may be quite different from in
vitro predictions.
In this project, we study (both theoretically and experimentally) the transition from the nanoscopic to macroscopic diffusion in a crowded environment. In particular, we study the effect of the less crowded depletion layer around the diffusing nanoparticle. The depletion layer affects the speed of diffusion in different length scales: The motion of the nanoparticle is faster within the less crowded layer and slower on longer distances. We want to experimentally measure the depletion layer thickness, to understand theoretically the dependence of that thickness on the particle size and other factors. Next, we want to understand how the rates of biochemical reactions, especially those involved in gene regulation, are affected by this non-uniform diffusion. The experimental methods we use are: dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS). Click here for more information about the project |
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The
“demand theory”, formulated by the M.A. Savageau in the
70s, explains the evolution of positive or negative gene
regulation by the frequency of demand for a given protein
and sensitivity of genes to mutations.