© Third Infinity 2017
9th - 11th October 2017 in Göttingen, Germany 3rd Conference on Physics of Biological and Complex Systems Presenting Third Infinity 2017, a conference organized by the doctoral candidates of the International Max Planck Research School - Physics of Biological and Complex Systems (IMPRS-PBCS). This conference aims to bring together young researchers and leading scientists working on complex systems from the three fundamental perspectives: theory, experiments and simulations.

Reinhard Jahn

Department of Neurobiology Max Planck Institute for Biophysical Chemistry, Göttingen, Germany Keynote Speaker Research of our group focuses on two major goals. First, we aim at arriving at a molecular description of vesicle docking and membrane fusion at the level of defined protein-protein and protein-membrane interactions and the associated conformational changes. In this regard, the SNARE proteins that function as fusion catalysts take center stage. We primarily use in- vitro approaches involving biochemical and biophysical methods, with the aim of isolating and characterizing partial reactions involved in the fusion pathway. In addition, we study fusion of endosomes which is less complex than the highly regulated neuronal exocytosis and thus more suitable for unravelling conserved molecular principles. The second goal is aimed at arriving at a better understanding of the question: how are synaptic vesicles filled, within seconds, with thousands of neurotransmitter molecules? This step is critical for neurotransmission, but of all steps is the least well understood. Several years ago we have developed a quantitative molecular model of synaptic vesicles, providing a solid foundation for quantitative work. Neurotransmitter uptake is mediated by specific transporters in the vesicle membrane that draw the energy for transport from an electrochemical proton gradient across the vesicle membrane. We want to understand how osmotic and charge balance is maintained during transport and how the transporters manage to remain operational while vesicular solute composition undergoes dramatic changes.

Eugene Terentjev

Biological and Soft Systems, Cavendish Laboratory University of Cambridge, UK How Cells Feel: Physical Mechanisms of Mechanosensitivity Sensors are the first element of the pathways that control the response of cells to their environment. After chemical, the next most important cue is mechanical, and protein complexes that produce or enable a chemical signal in response to a mechanical stimulus are called mechanosensors. There is a sharp distinction between sensing an external force (or pressure/tension applied to the cell) and sensing the mechanical stiffness of the environment. We call the first mechanosensitivity of the 1st kind, and the latter - mechanosensitivity of the 2nd kind. There are two variants of protein complexes that act as mechanosensors of the 2nd kind: producing either a one-off or a reversible action. The latent complex of TGF - beta is an example of the one - off action: on the release of active TGF - beta signal, the complex is discarded and needs to be replaced. In contrast, the focal adhesion kinase (FAK) in a complex with integrin is a reversible mechanosensor, which initiates the chemical signal in its active phosphorylated conformation, but can spontaneously return to its closed folded conformation. We examine the physical mechanism of mechanosensitivity of the 2nd kind, using TGF- beta and FAK as two practical examples, finding how the rates of conformation changes depend on the substrate stiffness and the pulling force applied from the cell cytoskeleton.

Marco Mongillo

Molecular Cardiology The Venetian Institute of Molecular Medicine, Italy Optogenetic Investigation of Sympatho-cardiac Coupling Prof. Dr. Marco Mongillo is an assistant professor at the University of Padova, in the Department of Biomedical Sciences. He also holds the position of group leader at the Venetian Institute of Molecular Medicine in Padova. His group focuses on the Autonomic Control of Cardiac Function and is devoted to improving the basic understanding of the mechanisms that regulate intercellular communication between autonomic neurons and the cardiomyocytes. The lab employs techniques ranging from molecular and cell biology, confocal calcium and cAMP imaging, to ex vivo morphometric analyses using both fluorescence and electron microscopy. Most of our research projects benefit from ongoing collaborations with other groups within the VIMM and other European laboratories. In short, we aim to define the disease mechanism in stress-induced genetic arrythmias, understand the role of sympathetic innervation in the triggering of cardiac arrhythmias, and investigate emerging roles of the cardiac SNS in controlling myocardial structure. In addition, an independent project aims to identify new signaling pathways regulating mitochondrial function upon adrenergic activation in cardiomyocytes. This research line is being carried out and led by Dr. Giulietta Di Benedetto, a senior research scientist hosted in the group.

Neel S. Joshi

Hansjörg Wyss Institute for Biologically Inspired Engineering School of Engineering and Applied Science, Harvard University, USA Programmable Biofilm-based Materials from Engineered Curli Nanofibers The significant role of biofilms in pathogenicity has spurred research into preventing their formation and promoting their disruption, resulting in overlooked opportunities to develop biofilms as a synthetic biological platform for self-assembling functional materials. My research group has developed Biofilm-Integrated Nanofiber Display (BIND) as a strategy for the molecular programming of the bacterial extracellular matrix material by genetically appending peptide domains to the amyloid protein CsgA, the dominant proteinaceous component in Escherichia coli biofilms. These engineered CsgA fusion proteins are secreted and extracellularly self-assemble into amyloid nanofiber networks that retain the functions of the displayed peptide domains. We have shown the use of BIND to confer diverse artificial functions to the biofilm matrix, such as nanoparticle biotemplating, substrate adhesion, covalent immobilization of proteins or a combination thereof. Our current efforts are focused on further developing this basic concept of BIND – in situ, microbially fabricated materials – and tailoring it for use in engineered probiotic bacteria and for bioremediation applications.

Modesto Orozco

Molecular Modelling and Bioinformatics Group Barcelona Institute for Research in Biomedicine, Spain DNA: A Complex Multi-scale Problem DNA is a crucial player in life and is one of the molecules with the largest potential in biomedical and bio-technical applications. Unfortunately, investigating DNA is extremely complex due to the need to simultaneously study small (Å-scale) behavior and large, macroscopic (meter-scale) systems. This multi -scale nature generates a multi-physics problem, as the level of calculations used to represent Å-scale systems (nucleobases) are not applicable to studying meter-long systems (the entire chromatin). This talk will summarize our recent advances in the multiscale simulation of DNA, from the electron to the chromosome.

Ben Schuler

Department of Biochemistry and Department of Physics University of Zürich, Switzerland Probing the Structure, Dynamics, and Function of Disordered Proteins with Single-molecule Spectroscopy Single-molecule spectroscopy provides a versatile way of quantifying distance distributions and dynamics in biomolecules on length scales of nanometers and timescales down to nanoseconds. I will illustrate the methodological basis of the experiments and the power of polymer physics as a framework for understanding the physical properties of unfolded and intrinsically disordered proteins over a wide range of conditions. Finally, I will focus on the surprising observation of two highly charged intrinsically disordered proteins that bind each other with high affinity but without forming any structure, thus indicating an important role for such polyelectrolyte complexes in biology.

Miriam Osterfield

Green Center for Systems Biology University of Texas Southwestern Medical Center, USA Three-dimensional Epithelial Morphogenesis in Drosophila Evolution: Theme and Variations Epithelial morphogenesis refers to the biological process in which a flat sheet of epithelial cells is transformed into a three-dimensional tissue. Epithelial morphogenesis is essential for the formation of many organs during embryonic development, including the neural tube, lungs, and kidneys. Initially, when epithelial sheets are still flat, they are patterned so that different regions of the sheet express different gene products. Our work focuses on how these patterns of gene expression influence cellular properties, and how patterns of cellular properties collectively drive changes in tissue shape. We are using the eggshell appendages of the fruitfly Drosophila melanogaster as a model system for studying epithelial morphogenesis. These appendages are formed and shaped by epithelial tubes, and their formation is highly amenable to analysis using genetics, imaging, computational modeling, and evolutionary comparisons.

Carl Modes

Network Complexity and Systems Biophysics Max Planck Institute of Molecular Cell Biology and Genetics, Dresden Extracting Hidden Hierarchies in Complex Spatial Biological and Physical Networks Natural and man-made transport webs are frequently dominated by dense sets of nested cycles. The architecture of these networks -- the topology and edge weights -- determines how efficiently the networks perform their function. Yet, the set of tools that can characterize such a weighted cycle-rich architecture in a physically relevant, mathematically compact way is sparse. In order to fill this void, this seminar presents a new characterization that rests on an abstraction of the physical `tiling' in the case of a two dimensional network to an effective tiling of an abstract surface in space that the network may be thought to sit in. Generically these abstract surfaces are richer than the plane and upon sequential removal of the weakest links by edge weight, neighboring tiles merge and a tree characterizing this merging process results. The properties of this characteristic tree can provide the physical and topological data required to describe the architecture of the network and to build physical models. This new algorithm can be used for automated phenotypic characterization of any weighted network whose structure is dominated by cycles, such as, for example, mammalian vasculature in the organs, the root networks of clonal colonies like quaking aspen, and the force networks in jammed granular matter. In particular this seminar will also present some progress in the analysis of both neurovasculature and force networks chains.

Hartmut Wekerle

Emeritus Director Max Planck Institute of Neurobiology, Munich, Germany Multiple Sclerosis and the Gut Flora: A Bacterial Bioreactor Fuels Brain Autoimmunity The group of Hartmut Wekerle seeks to understand the early events that trigger brain-specific autoimmune responses such as those associated with Multiple Sclerosis (MS). Robust evidence indicates that MS is triggered by an autoimmune attack against brain myelin and neurons by self-reactive T and B cells. While these otherwise dormant cells are normal components of the healthy immune repertoire, accidental activation in the periphery causes them to mount an attack against their target tissue. This sudden activation occurs within the gut-associated lymphatic tissue as a result of an interaction between auto-reactive T cells and components of the commensal microbiota. The activated autoimmune T cells first travel through peripheral immune organs where they are tuned to pass through the microvascular blood-brain barrier. This talk will focus largely on data primarily based on experimental models of brain autoimmunity, but will also include updates on ongoing experimental work in the field.