Bollenbach Group

Cells ranging from those in the tissues of multi-cellular organisms to single-celled microbes respond to signals in the environment by modifying the expression of their genes. While recent technological advances have enabled us to measure and manipulate such gene expression responses genome-wide, little is known about the high-level capabilities and limitations of the genetic circuits that control these responses. Our long term goal is to gain a deeper, more quantitative understanding of the relation between the signals present in the cell’s environment and the information processing and other events which they trigger inside cells. In particular, we aim to identify general principles that capture key properties of gene regulatory responses. To this end, we combine quantitative experiments, often based on fluorescence measurements in single cells or entire populations, with theoretical approaches from physics. Whenever possible we measure and interpret numbers, rather than pictures or qualitative effects.

Contact
Tobias Bollenbach
Institute of Science and Technology Austria (IST Austria)
Am Campus 1
A – 3400 Klosterneuburg

Phone: +43 (0)2243 9000-4101
E-mail: tobias.bollenbach@ist.ac.at

CV and publication list

Bollenbach Group website

Assistant
Nicole Hotzy

Phone: +43 (0)2243 9000-1032
E-mail: nicole.hotzy@remove-this.ist.ac.at

Open Positions
We are continuously looking for outstanding postdocs. Physicists with an interest in biological systems, molecular biologists, and biochemists are particularly encouraged to apply. If you are interested in joining our interdisciplinary lab, please send your application (incl. CV, publication list, 3 reference letters) to e-mail. Exceptional students interested in doing a PhD in our lab are welcome to get in touch with me directly, but should also apply directly at the IST Austria Graduate School.

Team

• Guillaume Chevereau, Postdoc
• Karin Mitosch, PhD Student
• Andreas Piehler, Student Intern

Selected Projects

• Cellular responses to conflicting signals
  Cells are often faced with the simultaneous presence of multiple signals that individually elicit opposite gene expression responses. How do cells resolve such gene regulatory conflicts? We use fluorescent reporters, time-lapse microscopy combined with microfluidics, and a state-of-the-art robotic system to reveal how the bacterium Escherichia coli and the budding yeast Saccharomyces cerevisiae respond to combinations of antimicrobial drugs. Antimicrobials are important drugs for the treatment of infectious diseases. They are often used in combination, making them a particularly relevant example.
• Antibiotic resistance and drug combinations
  The rapid rise of antibiotic resistance is a serious concern for public health, in particular since the discovery of new antibiotics has essentially come to a halt. How can this looming crisis be averted? We aim to find new ways of combining drugs and other compounds to minimize or even prevent the evolution of drug resistance. As a prerequisite we aim to elucidate the underlying causes of drug interactions such as synergism and antagonism.
• Theoretical models of bacterial growth
  Even though the main cellular targets of many drugs are known, their effects on cell physiology and growth are often hard to rationalize. Are there quantitative laws governing bacterial growth in the presence of antibiotics? We develop a theoretical framework to describe bacterial growth and gene regulation. Of particular interest in these models is the regulation of cellular stress response and drug resistance systems. We use the toolbox of dynamical systems theory and statistical physics to analyze these models and perform experiments to test our predictions directly.
• Optimization of gene regulatory responses
  Optimality has been suggested to be a key design principle of biological systems. But to what extent are cellular responses really optimized for a functional goal? To address this question, we systematically measure and synthetically manipulate gene expression responses. We focus on single-celled bacteria and fungi where the maximization of cell survival and growth is a plausible, clearly defined, and experimentally quantifiable functional goal.
• Theoretical models of animal development
  We are interested in cell differentiation, communication between cells by secreted signaling molecules, and other key processes in the development of higher organisms such as fruit flies and mice. How do signaling molecules move through cells and tissues? How do cells accurately detect and respond to such signals? We build physics-inspired theoretical descriptions of cellular processes and compare them to experimental data using quantitative image analysis. We collaborate with developmental cell biology and bio-imaging labs to quantify key parameters of animal development and thus improve our understanding of these fascinating phenomena.

Selected Publications

• Bollenbach, T. and Kishony, R. (2011). Resolution of gene regulatory conflicts caused by combinations of antibiotics. Molecular Cell 42, 413-25.
• Plachta, N., Bollenbach, T., Pease, S., Fraser, S.E., and Pantazis, P. (2011). Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nature Cell Biology 13, 117-23.
• Bollenbach, T., Quan, S., Chait, R., and Kishony, R. (2009). Nonoptimal microbial response to antibiotics underlies suppressive drug interactions. Cell 139, 707-718.
• Kicheva, A.*, Pantazis, P.*, Bollenbach, T.*, Kalaidzidis, Y., Bittig, T., Jülicher, F., and González-Gaitán, M. (2007). Kinetics of morphogen gradient formation. Science 315, 521-525.
• Bollenbach, T., Kruse, K., Pantazis, P., González-Gaitán, M., and Jülicher, F. (2005). Robust formation of morphogen gradients. Physical Review Letters 94, 018103.

*equal contribution

Career

• Jun 2005 – PhD in theoretical Physics, Max Planck Institute for the Physics of Complex Systems, Dresden
• Jul to Aug 2005 – Guest scientists at the University of Tokyo, Japan
• Sep 2005 to Jul 2006 – Postdoctoral fellow, Max Planck Institute for the Physics of Complex Systems, Dresden
• Aug 2006 to Oct 2010 – Postdoctoral fellow, Department of Systems Biology, Harvard Medical School, Boston

Selected Distinctions

• Member of the Young Academy ("Junge Akademie") at the German National Academy of Sciences Leopoldina and the Berlin-Brandenburg Academy of Sciences and Humanities (2011)
• Feodor Lynen Fellowship of the Alexander von Humboldt-Foundation (2007-2009)
• Fellowship of the German National Scholarship Foundation (‘Studienstiftung des deutschen Volkes’) (PhD 2003-2005, student 2000-2002)