Dr. Ulf Liebal

The way simple bacteria interact with their environment teaches us about the complexity of nature. Can we use this information to our benefit?

PhD Students (from 2007-01-01 until 2015-12-31)

Thesis title: "Regulation of the general stress response of Bacillus subtilis"

Research interest

Bacterial Stress Response: Decisions at the Organism-Environment Interface

"The way simple bacteria interact with their environment teaches us about the complexity of nature. Can we use this information to our benefit?"

To survive, bacteria have to adapt to changing environmental conditions like heat, desiccation, and starvation. They sense changes in the environment and adapt their way of life: becoming greedy with expenses, control of proper functioning of the intracellular components, preparing for dormancy.
The question we focus on is: How is the information of a challenging environment transported how is it modified on its way, how does it lead to the activation of genes and how is the signal muted?

The stress responses enable bacteria to sustain their life functions. This sheds light on the organism-environment relationship. We can use this knowledge to improve biotechnological production of chemical products as well as in the design of new therapeutics for bacterially related diseases.
We studied how a bacterium changed its way of living during the transition to starvation. We followed a particular behaviour which is only transiently activated. Why this behaviour is transient is not clear, but we could add new information about this. During that behavioural response a huge protein complex is activated that integrates the information of the stresses it receives. This complex makes decisions not unlike a computer and we tested hypotheses how the structure supports its functions.

Our results show that the stability of the protein which we used to asses the stress state of the cell is changing during stress. Proteins might generally be subject to increased turnover at the transition to starvation. We found that the computer-like stress integrating complex would not be able to perform its function if there would be weaker associations. As this complex is also used by pathogenic bacteria to activate disease related genes, knowledge about it will lead to new therapeutic drugs.

Academic background

2007 - 2015 PhD-Project
University of Rostock, Rostock/Germany
2001 - 2006 Masters Degree in Biochemistry (Dipl. Biochemiker)
Martin Luther University, Halle(Saale)/Germany
Thesis conducted at the Bioprocess Engineering Laboatory
Oulu University, Oulu/Finland

Selected publications

Simulations of Stressosome Activation Emphasize Allosteric Interactions Between RsbR and RsbT

Liebal UW, Millat T, Marles-Wright J, Lewis RJ, Wolkenhauer O (2013)

BMC Systems Biology 7:3

Proteolysis of beta-galactosidase following SigmaB activation in Bacillus subtilis

Liebal UW, Sappa PK, Millat T, Steil L, Homuth G, Völker U, Wolkenhauer O (2012)

Molecular Biosystems 8(4):1806-14

How mathematical modelling elucidates signalling in B. subtilis

Liebal UW, Millat T, de Jong I, Kuipers O, Völker U, Wolkenhauer O (2010)

Molecular Microbiology 77: 1083-1095

Integration of sensitivity and bifurcation analysis to detect critical processes in a model combining signalling and cell population dynamics

Nikolov S, Lai X, Liebal UW, Wolkenhauer O, Vera J (2010)

International Journal of Systems Science 41: 81-105

Protein diversity of the stressosome - Stress sensitivity and Response magnitude

Liebal U, Millat T, Marles-Wright J, Lewis R, Wolkenhauer O

12th International Conference on Systems Biology (ICSB), Heidelberg/Mannheim, Germany, 28 August - 1 September 2011

Venue: Heidelberg/Mannheim, Germany

Automated analysis of flow cytometry data from heterogeneous bacterial populations

Millat T, Rubenis O, Liebal U, Wolkenhauer O, de Jong I, Kuipers O

12th International Conference on Systems Biology (ICSB), Heidelberg/Mannheim, Germany, 28 August - 1 September 2011

Venue: Heidelberg/Mannheim, Germany

Protein Diversity of the Stressosome - Stress Sensitivity and Response Magnitude

Liebal UW, Millat T, Marles-Wright J, Lewis R, Wolkenhauer O

12th International Conference on Systems Biology (ICSB), Heidelberg/Mannheim, Germany, 28 August - 1 September 2011

Venue: Heidelberg/Mannheim, Germany

The dynamics of the phosphorelay and the initiation of sporulation in Bacillus subtilis - a systematic study

Millat, Liebal U, Wolkenhauer O, de Jong I, Kuipers O

11th International Conference on Systems Biology (ICSB), Edinburgh, UK, 10 October - 15 October 2010

Venue: Edinburgh, UK

Using a modelling approach to elucidate unexpected reporter gene signals for sigmaB activity in B. Subtilis

Liebal U, Sappa PK, Millat T, Steil L, Völker U, Wolkenhauer O

Conference on Systems Biology of Microorganisms, Paris, France, 22 March - 24 March 2010

Venue: Paris, France

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Use of sensitivity analysis to detect critical biochemical processes in a mathematical model linking intracellular and cell population dynamics in erythropoiesis

Lai X, Liebal U, Nikolov S, Wolkenhauer O, Vera J

The 6th Conference on Computational Methods in Systems Biology (CMSB), Rostock-Warnemünde, Germany, October 2008

Venue: Rostock-Warnemünde, Germany

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Analysis of a Model of sigB Activation Following Glucose Starvation

Liebal U, Millat T, Wolkenhauer O, Sappa PK, Steil L, Völker U

10th International Conference on Systems Biology (ICSB), Stanford, USA, 30 August -4 September 2009

Venue: Stanford, USA

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Dynamic Behavior Determines the Design Strategy of Metabolic Regulation Networks

Liebal U, Kim JR, Wolkenhauer O, Cho KH

10th International Conference on Systems Biology, Stanford, USA, 30.8.-4.09.2009

Venue: Stanford, USA

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Sensitivity Analysis based Adaptive Search-Space Reduction for Parameter Estimation Applications

Liebal U, Schmidt H

9th International Conference on Systems Biology, Göteborg (Gothenburg), Sweden, August 2008

Venue: Gothenburg, Sweden

Modelling Aspects of Stress Response mediated by sigB

Liebal UW, Hildisch H, Millat T, Völker U, Wolkenhauer O

SysMo Evaluation Conference, Bad Honnef, Germany, 1 July - 2 July 2008

Venue: Bad Honnef, Germany

Betrunkene Bakterien verraten Wissenschaftlern viel

Thiel W, Liebal UW, Vetter U, Wolkenhauer O

02.04.2012, Pressemeldung der Universität Rostock

Regulation of the general stress response of Bacillus subtilis

Liebal U

The bacterium Bacillus subtilis lives in the environmentally diverse soil habitat. Various environmental signals are sensed by the stressosome protein complex. Stimulation of the stressosome modifies its phosphorylation patterns and activates a signalling cascade that lead to protein expression changes. The thesis introduces models to study structural processes and signalling principles of the stressosome. Overall, the thesis enhances our understanding of the SigmaB-mediated general stress response and raises our awareness of the environmental integration of B. subtilis.

Defense: 4 February 2013