We are interested in understanding how biophysical mechanisms constrain development in the forming vertebrate nervous system. We study morphogen signaling using single molecule methods and live imaging in the living zebrafish embryo, and our wish is to understand how fundamental laws of physics constrain the dynamics of morphogen action and the resulting patterning processes.
Our lab is interested in studying the underlying principles of self-organization in biological structures. We currently use the metaphase spindle—the protein machinery responsible for segregating the chromosomes into the daughter cells during cell division—from Xenopus laevis egg extract and the zebrafish embryo as model systems to understand the architecture, force generation and scaling of spindles; and chromatin organization in the interphase nucleus. To dissect these processes we combine theory, cell biology, custom build microscopes and biophysical perturbations such as laser ablation.
The general interest of our group is to understand the mechanisms by which cells collectively organize to form complex patterns and morphologies in developing tissues. How does collective behavior emerge in cell assemblies? How do mechanical processes like cell adhesion or force generation influence tissue organization? And how are these mechanical processes linked to the chemical signals that orchestrate tissue development? We address these questions by combining genetics with live imaging, quantitative image analysis and biophysical approaches using the fruit fly Drosophila melanogaster as a model organism. Moreover, in collaborations with physicist and mathematicians, we use our quantitative data to build computational models of tissue organization.
Our lab is interested in the development and the application of novel optical techniques to investigate molecular transport in cell biology and nanotechnology. Building on our experience in single molecule biophysics and in the in vitro reconstruction of subcellular mechano-systems we study cooperative effects in motor transport and cell motility. Moreover we aim to apply biomolecular motor systems in a synthetic, engineered environment for the generation and manipulation of nanostructures. Thereby, our main emphasis is on the development of methods to control the nano-transport sytems by external signals in a spatio-temporal manner. Towards this end we investigate novel biotemplate-based nanostructuring techniques and fabricate smart composite surfaces, where active enzymes are embedded in stimuli-responsive polymer layers.
What controls tissue size and shape? It has long been clear that morphogen gradients emanating from organizer regions regulate the amount and orientation of growth and couple it to morphogenesis and tissue patterning. Our goal is to understand how morphogens regulate patterns of cellular metabolic and mechanical properties, and how tissue size and shape emerges from the collective interactions of these constituent cells. We approach the problem with cell biological, biochemical, biophysical, and quantitative imaging tools, and work with physicists to develop multiscale models that explore the logic of development.
Structural transitions of biomolecules underlie an overwhelming variety of cellular functions. They allow integrating chemically and topologically diverse processes into a regulated network of physico-chemical interactions between macromolecules. Whereas X-ray diffraction provides a snapshot of a static macromolecular structure under crystalline condition, we aim at observing molecular switching processes under native-like conditions and in real time by spectroscopic methods. In combination with CD-spectroscopy and calorimetry, we use infrared spectroscopy as a label-free technique to achieve atomic resolution of conformational transitions on a millisecond to second time scale to address questions that cannot be answered by crystallography, such as the role of dynamic lipid protein interactions in signaling by G-protein coupled receptors or in ion translocation by metal-transporting ATPases. The dynamics of the hydration shell reorganization in these processes is a fundamental physical process that has attracted our attention as it contributes to both structure and energetics of proteins in the complex environment of a biological phase boundary. It has led us to develop novel infrared and fluorescence-based techniques for dynamic analyses of H-bond networks to reach at structurally and energetically consistent descriptions of biomolecular switching and metal binding events in proteins and DNA.
Our group establishes a new approach to cell mechanics characterizing cells as an actively prestressed material. Unlike inanimate matter, cells contain molecular force generators that produce active contractile stresses in the cellular material. In cell mechanical probing, the contribution of these active stresses contribute to cellular force response and constitute a cellular tool to self-adjust its material properties. A central aim of our group is to reveal active and passive contributions to an effective cellular shear modulus of the cell. We combine experimental and theoretical work.
We seek to identify algorithms of life that confer robustness and resilience in biological systems, using tools from nonlinear dynamics, stochastic processes and information theory. How do cells and tissues compute information, or self-organize into functional structures, in light of noise and an ever fluctuating environment? Our focus is on cell motility and motility control, including decision making of motile cells during navigation, as well as the self-organized pattern formation, e.g. of cellular force generators and biological transport networks inside tissues. For these projects, we closely collaborate with biologists and experimental physicists. We aim at quantitative theoretical descriptions of biological dynamics, which are calibrated by experimental data and make testable predictions, thus providing an interface between theory and experiment.
Morphogenesis refers to the generation of form in Biology. We are interested in bridging physical mechanisms from molecular scales to cell and tissue scales, to understand how an unpatterned blob of cells develops into a fully structured and formed organism. We combine theory and experiment, and investigate force generation on multiple scales. At the level of cells an tissues we study how the actomyosin cell cortex self contracts, reshapes and deforms, and how these morphogenetic activities couple to regulatory biochemical pathways. At the level of molecules we investigate force generation and movement of individual molecules of RNA polymerases in the context of gene expression and transcriptional proofreading
Cells are the basic functional entities of multicellular, biological systems. They can be seen as little machines that have particular physical properties, which enable them to navigate their 3D physical environment and fulfil their biological functions. We investigate these physical - mechanical and optical - properties of living cells and tissues using novel photonic, microfluidic and biophysical tools to test their biological importance. We are also interested in how cells sense the mechanical properties of their environment and how that feeds into their function - especially in the development and pathologies of the central nervous system. Our ultimate goal is the transfer of our findings to medical application in the fields of improved diagnosis and prognosis of diseases and novel approaches in regenerative medicine.
Our aim is to understand how epithelial tissue forms de novo. The transition of progenitor stem cells into a polarized epithelium is a fundamental process during embryogenesis and the formation of many organs. Our approach is to use 3D cell culture organoids as model systems to dissect the underlying mechanisms of cell polarization and differentiation during this transition. The long-term goal is to integrate cell adhesion, cortical flows and membrane trafficking into a model which describes the transition process as a self-organizing system. To characterize the transition from cells to tissue we use optical microscopy (from STED to SPIM) in combination with genetic engineering. We complement this by reconstitutions of self-organization on artificial membranes and controlled cell adhesion assays.
We are interested in studying cell polarity, centrosome assembly and microtubule dynamics. Currently, the main goal of the lab is to understand how cells form non-membrane bound compartments. Using a combination of genetics and physics, we have discovered that a principle underlying the organization of many of these compartments is liquid-liquid phase separation. We study these compartments both in vivo and in vitro, using reconstitution methods. We primarily use C. elegans as a model system, but we complement this with studies in human iPS cells.
Biological Physics at PKS focuses on the theoretical study of active processes in cells and
tissues. We develop concepts and methods to understand principles that govern the organization
of cellular processes and the morphogenesis of tissues. To this end approaches from statistical
physics of non-equilibrium systems and from non-linear dynamics are very important. Key to our
work are close collaborations with experimental groups, in particular, at the Max Planck Institute
of Molecular Cell Biology and Genetics, Dresden.
Our research addresses one of the retinas most surprising, but least investigated characteristics, its optical architecture: since the sensitive portions of the photoreceptor cells are found on the back of the vertebrate retina, light needs to travel through several layers of living neuronal tissue prior to detection. What is usually regarded as being a problem of neuronal activity is complemented from the perspective of optics, focusing on one key question: how does the retina deal with incident light?
For this we are using custom design microscopy to gain a detailed understanding of how optical constrains shape retinal development, from the overall architecture down to the level of the chromatin organization. Apart from its importance for the initiation of the visual process, light propagation in neuronal tissues is also key to the optical observation of brain activity over large scales. The experimental side of this research is accompanied by theoretical approaches and computer modeling.
Further interests of our lab address reaction-diffusion systems of pattern formation, and the origin of life.
Cryo-transmission electron microscopy (cryo-EM) is a powerful technology that can be used to reveal the three-dimensional architecture and the assembly of macromolecular machines, organelles and cells. We use cryo-EM and electron tomography to reveal the structural basis of flagella and cilia assembly, as well as motility. The assembly takes place at the distal tip of the cilium and the transport of ciliary proteins from the cell body to the tip is mediated by the intraflagellar transport (IFT) machinery. We currently study the assembly of the cilium by investigating the detailed 3D structure, the molecular arrangement, the protein composition, and the dynamics of the ciliary tip complex and of the IFT trains.
We combine expertise from computer science, mathematics, physics and biology in order to develop and apply computational methods for the study of spatiotemporal biological processes in 3D. We exploit the unifying framework of particle methods for numerical simulation, image analysis, and model identification. Since computational biology comes with a unique set of challenges, from complex geometric shapes to non-equilibrium processes, we develop and apply novel computational methods in a targeted co-design approach with the ultimate mission of understanding the algorithms of tissue formation.
Our lab is curious about nature and its huge pool of molecular machines. We are studying these in vitro to understand their chemo-mechanical and enzymatic activities using fluorescence- and force-based single-molecule techniques. In particular, we are interested in DNA interacting enzymes that are involved in DNA replication and recombination. Furthermore, we are studying how cytosolic and membrane proteins find their tertiary structure and loose it in the process of protein degradation. To this end, we are developing novel tools and techniques based on optical and mechanical manipulation combined with fluorescence based single-molecule FRET studies.
We are interested to find clues on how spatial constraints dictate cellular behavior and function. For this purpose we use micropatterning and strain engineering to encapsulate single living cells into on-chip transparent tubular micro-architectures.
We also generate new micro-biorobots, which are remotely controllable. The combination of a biological power source (e.g. a spermatozoon) and a microdevice (e.g. a magnetic microtube) is a compelling approach for fascinating future applications such as assisted in-vivo artificial fertilization.
Polymers are most important molecules in living systems and an essential component of materials ranging from packing to smart surfaces and applications of synthetic polymers in contact with living matter. Our group at the Leibniz-Institute of Polymer Research Dresden (IPF) is studying the physical properties of polymers using theoretical concepts and computer simulations. The long-chain nature, flexibility, architectural diversity and the multitude of possible forms of interactions and self-organization in polymer systems is a challenge for analytical approaches and demands for the development of new computational algorithms. Very important for our research is the close collaboration with experimental groups. Our research interests in the field of bio-functional polymers concerns in particular the interactions of polymers with lipid membranes and bio-functional polymer gels.
Biology is well equipped in exploiting a large number of out of equilibrium processes to support life. A complete understanding of these mechanisms is still in its infancy due to the complexity and number of the individual components involved in the reactions. However, a bottom up approach allows us to replicate key biological processes using a small number of basic building blocks. This methodology has the added advantage that properties and characteristics of the artificial cell can be readily tuned and adapted. Working between biophysics, materials science and synthetic biology, we reimagine and translate the physical phenomena which drive out of equilibrium processes in cells into novel, robust and dynamic systems for synthetic biology applications.
We are interested in the collective dynamics and self-organization of distributed systems exhibiting multiple feedback. We combine and develop theoretical concepts from Nonlinear Dynamics, Graph Theory and Statistical Physics, Applied Mathematics and computational tools to understand mechanisms underlying collective phenomena in biological and engineered systems. Our research focus is on the dynamics of networked systems. Application areas include distributed biological computing, structure function relations in biological networks and the dynamics of biological and engineered flow networks.
In order for the cell to function properly, proteins must be robust to both changes in their environment and errors made during their synthesis. At the same time, proteins also need to be able to evolve novel functions to survive on long evolutionary timescales. The very same processes, i.e. genetic and phenotypic mutations, generate the diversity that leads to functional innovations and broken proteins, ultimately resulting in novel organisms, diseases and, in some cases, extinction. We aim to define and quantify the phenotypic plasticity of a protein, and to identify the compensatory mechanisms that buffer otherwise deleterious mutations. We wish to reveal the evolutionary potential of latent phenotypes to create novel functions and to influence gene-disease associations.
We apply and develop methods of statistical physics to get a better understanding of multicellular dynamics and self-organization. In close collaboration with our experimental colleagues we work on various problems ranging from motility of individual bacterial cells to the formation and growth of bacterial colonies called biofilms, dynamics of chromosome pairing in meiosis, and phenomenon of genome activation during the early embryo development. Analytical frameworks of stochastic processes, population dynamics, and, of course, random walks are our favorite tools to address these exciting questions of biological physics.