© Third Infinity 2017
THIRD
INFINITY
2017
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.
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.
Biomedical Physics
Max Planck Institute for Dynamics and Self-Organisation, Göttingen, Germany
Optogenetic Approaches in Cardiac Research
As a research associate, Dr. Richter is, among other things, responsible for cell culture experiments and
the multi-modal optical setup developed in her lab known as the Macroscopic Imaging Setup for
Fluorescence Investigative Tasks, or MISFIT for short.
In her capacity as a biologist, or more precisely an animal physiologist, she is strongly interested in
biophysical, molecular/genetic research and biomaterials. Beside focusing on questions on cell cultures,
she is also working on the self-organization of tissue development, which plays an important role in 3D
tissue engineering.
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.
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.
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.
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.
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.
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.