Biophysical Chemistry Group
Anna Ochab-Marcinek, Ph.D. (dr hab.)
 
  Institute of Physical Chemistry
Polish Academy of Sciences

ul. Kasprzaka 44/52
01-224 Warsaw
Poland
office: 201
phone: +48 22 343 3399
e-mail: ochab [AT] ichf.edu.pl

My home page


Jakub Jędrak, Ph.D.
Postdoctoral researcher
office: 201
phone: +48 22 343 3399
e-mail: jjedrak [AT] ichf.edu.pl
 
Marcin Rubin, B.Sc.
Assistant
office: 201
phone: +48 22 343 3399
e-mail: mrubin [AT] ichf.edu.pl
 
Maciej Ślot
M. Sc. student, University of Łódź


Our publications

Click here to see the list of our publications


Student internships available

Email me for details: ochab@ichf.edu.pl



Current project:

Evolution of gene regulation as a stochastic process: Savageau's demand theory, cost of regulation and noise
Sonata Bis 6 project no. 2016/22/E/ST2/00558, financed by the National Science Centre

 

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.

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 will 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.



Completed projects: 

7.2013-7.2015: Polish Ministry of Science Iuventus Plus grant 0501/IP1/2013/72
Theoretical 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/ST3/00751
Transition 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