Research

We focus on the physics of bacterial systems. At the level of single molecules we investigate the mechanism of force generation in bacteria. How are directed movement and force generated at the molecular scale? How do multiple motors coordinate? How do interbacterial forces govern biofilm structure? We are particularly interested in bacterial motors involved in motility and horizontal gene transfer. At the population level, we have recently started investigating the evolutionary significance of these molecular motors. What are costs and benefits of horizontal gene transfer? How fast do newly acquired genes spread through a structured population? In our group, physicists, biologists, and biochemists work in close collaboration using a combination of tools from nanotechnology, image analysis, and molecular biology.

Background: Horizontal gene transfer

Background: Type IV pili

 

 

Force generation by bacterial type IV pili

Type IV pili are among the most wide-spread bacterial surface appendages. They are multifunctional polymers that mediate adhesion, motility, biofilm formation, and horizontal gene transfer. By depolymerization, type IV pili generate very high forces, exceeding 150 pN. We have developed biophysical tools for characterizing the dynamics and force generation of single pili. Currently, we are investigating the molecular mechanism of high force generation. This project involves joint forces from molecular biology and nanotechnology. [more ...]

Coordination of type IV pilus motors

Many bacterial species use type IV pili for moving on surfaces. The pili act like grappling hooks undergoing cycles of polymerization, adhesion to the surface, and subsequent retraction. During retraction, the cell body moves towards the point of attachment. We have shown that multiple pili cooperate through a tug-of-war mechanism to generate bacterial movement. Currently, we are looking at the role of force generation of pili to understand bacteria switching from moving as individuals to the aggregation of bacterial colonies and biofilms. [more ...]

Molecular mechanism of DNA uptake during transformation

Bacterial gene transfer constitutes an important medical problem since antibiotic resistance and virulence traits are transferred between bacteria. In a process called transformation, bacteria take up naked DNA from the environment. The first step to transformation is the transport of DNA through the cell envelope. Macromolecular translocation through nanometer-sized pores is a ubiquitous theme in cell biology and a challenging problem in physics. For efficient transport, we suggest, that a molecular machine pulls the DNA molecule through the cell envelope. We are using a combination of single molecule techniques and genetic manipulations for deciphering the molecular mechanism of DNA import. [more ...]

Bacterial interaction forces shape biofilms

Communities of bacterial cells can live together embedded within a slime-like molecular matrix as a biofilm. This allows the bacteria to hide from external stresses. A single bacterium can replicate itself and develop into a biofilm, and over time the bacterial cells in specific regions of the biofilm will start to interact with their neighbors in different ways. These interactions occur via structures on the surface of the bacterial cells, and the differences in these interactions resemble those that occur as cells specialize during the development of animal embryos. In this project, we address the question how differential interaction forces between bacteria govern the local structure and global morphology of the biofilm. In the long term, we want to understand how bacterial interaction forces impact on bacterial fitness under benign conditions and under external stress.

Horizontal gene transfer in bacterial biofilms

Biofilms are considered ideal reaction chambers for horizontal gene transfer and development of multi-drug resistance. The rate at which genes are exchanged within biofilms and the factors that govern the exchange rate are unknown. We are quantifying the acquisition of double-drug resistance by gene transfer between bacteria with single resistances. We found that intact biofilms enable efficient gene exchange. The spreading of beneficial double-resistant transformants is strongly dependent on biofilms architecture, since bacteria within it exhibit a higher antibiotic tolerance. We propose that while biofilms help generate multi-resistant strains, selection may take place mostly after dispersal from the biofilm. [more ...] 

Cost and benefit of bacterial transformation

Bacterial transformation enables bacteria to exchange genetic information and can therefore speed up adaptive evolution. However, it is unclear under which conditions the benefit of transformation outweighs its cost. The goal of this project will be to experimentally quantify the costs and benefits of transformation in Neisseria gonorrhoeae. In the long run, this project will contribute to our understanding of how recombination has evolved and is stably maintained. [more ...]

Phenotypic heterogeneity as a strategy for speeding up adaptive evolution at a minimal cost

Bacillus subtilis shows phenotypic variability in the stationary growth phase. In particular, a well-defined fraction of isogenic cells differentiates into the state of competence for transformation. Various regulators controlling this competent fraction have been identified but a full understanding of the benefit of having such a defined fraction has yet to be found. We address the question of whether this type of behavior, population differentiation and competence development, is optimal to speed up adaptation while minimizing the cost of competence development. [more ...]