Analysis of signalling response functions underlying switch-like cellular decisions

Research Project
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01.04.2010
- 31.03.2013

Dynamical systems biology aims at explaining the behaviour of cellular molecular networks with the help of mathematical models. To understand the behaviour of the whole system it is desirable to understand quantitatively how each individual network component modulates the activity of its interaction partners within the living cell, an action described by response functions. The transmission of information along the network links is bounded by basal interactions and saturation at the lower and higher ranges of signal intensities, respectively. Secondly, the strength of interaction determines the intensity the input signal has to pass to generate the desired output. Thus, the dynamic range and the interaction strength define the limits of information transmission, while the ranges of the signalling frequency and amplitude reveal how a network link is exploited. Consecutive steps in pathways can utilize different values for the above parameters. The mutual relation of these values delimits the types of behaviours a network topology can generate. This proposal focuses on how the response functions of steps in a signalling pathway are aligned to optimally operate switches in different regulatory networks, including a metabolic, a cell-fate and cell-cycle network. Cellular switches are fundamental to promote short- or long-term decisions between different functional states of a cell. The first part of the proposal explores how yeast cells integrate signals elicited by glucose and galactose to switch between high and low galactose utilization states. The second part explores whether a transcriptional switch underlies the meiotic developmental transition. The third part explores how oscillatory expressions of cell cycle regulators are aligned to optimize the G1 / S cell cycle switch in order to prevent genomic instability. The above analysis requires the quantitative measurements of the relevant pathways without the interference from pleiotropic cellular signals. This will be achieved by substituting parts of the networks with synthetic genetic elements so that specific responses can be extracted. Our results will reveal principles of pathway alignment and provide design principles and tools for cell and tissue engineering, for which efficient cell differentiation and genomic stability are essential.

Collaborations & Cooperations

2013 - Participation or Organization of Collaborations within own University

Dr. Alex Schmidt, Biozentrum, Research cooperation

2013 - Participation or Organization of Collaborations on an international level

Tatiana Marquez Lago, Okinawa Institute of Science and Technology, Research cooperation

Members (1)

Attila Becskei

Principal Investigator

Research Groups

Mechanisms controlling gene regulatory networks