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Biomedical subjects

Markus Kollmann

Publications and source records attributed to Markus Kollmann.

4 recordsLinked to original sources

Design principles of a bacterial signalling network.

Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations. Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population. Our results suggest that this pathway has evolved to show an optimal chemotactic performance while minimizing the cost of resources associated with high levels of protein expression. Moreover, the underlying topological design principles compensating for intercellular variations seem to be highly conserved among bacterial chemosensory systems.

Adaptation, Physiological↗

Computational processing and error reduction strategies for standardized quantitative data in biological networks.

High-quality quantitative data generated under standardized conditions is critical for understanding dynamic cellular processes. We report strategies for error reduction, and algorithms for automated data processing and for establishing the widely used techniques of immunoprecipitation and immunoblotting as highly precise methods for the quantification of protein levels and modifications. To determine the stoichiometry of cellular components and to ensure comparability of experiments, relative signals are converted to absolute values. A major source for errors in blotting techniques are inhomogeneities of the gel and the transfer procedure leading to correlated errors. These correlations are prevented by randomized gel loading, which significantly reduces standard deviations. Further error reduction is achieved by using housekeeping proteins as normalizers or by adding purified proteins in immunoprecipitations as calibrators in combination with criteria-based normalization. Additionally, we developed a computational tool for automated normalization, validation and integration of data derived from multiple immunoblots. In this way, large sets of quantitative data for dynamic pathway modeling can be generated, enabling the identification of systems properties and the prediction of targets for efficient intervention.

Algorithms↗

Single-file diffusion of colloids in one-dimensional channels.

We study the diffusive behavior of colloidal particles which are confined to one-dimensional channels generated by scanning optical tweezers. At long times t, the mean-square displacement is found to scale as t(1/2), which is expected for systems where single-file diffusion occurs. In addition, we experimentally obtain the long-time, self-diffusive behavior from the short-time collective density fluctuations of the system as suggested by a recent analytical approach [Phys. Rev. Lett. 90, 180602 (2003)].

Journal Article↗

Single-file diffusion of atomic and colloidal systems: asymptotic laws.

We present a general derivation of the non-Fickian behavior for the self-diffusion of identically interacting particle systems with excluded mutual passage. We show that the conditional probability distribution of finding a particle at position x(t) after time t, when the particle was located at x(0) at t=0, follows a Gaussian distribution in the long-time limit, with variance 2W(t) approximately t(1/2) for overdamped systems and with variance 2W(t) approximately t for classical systems. The asymptotic behavior of the mean-squared displacement, W(t), is shown to be independent of the nature of interactions for homogeneous systems in the fluid state. Moreover, the long-time behavior of self-diffusion is determined by short-time and large-scale collective density fluctuations.

Journal Article↗