ERC FUNDED PROJECTS

Cell volume regulation is crucial for any living cell because changes in volume determine the metabolic activity through e.g. changes in ionic strength, pH, macromolecular crowding and membrane tension. These physical chemical parameters influence interaction rates and affinities of biomolecules, folding rates, and fold stabilities in vivo. Understanding of the underlying volume regulatory mechanisms has immediate application in biotechnology and health, yet these factors are generally ignored in systems analyses of cellular functions. My team has uncovered a number of mechanisms and insights of cell volume regulation. The next step forward is to elucidate how the components of a cell volume regulatory circuit work together and control the physicochemical conditions of the cell. I propose construction of a synthetic cell in which an osmoregulatory transporter and mechanosensitive channel form a minimal volume regulatory network. My group has developed the technology to reconstitute membrane proteins into lipid vesicles (synthetic cells). One of the challenges is to incorporate into the vesicles an efficient pathway for ATP production and maintain energy homeostasis while the load on the system varies. We aim to control the transmembrane flux of osmolytes, which requires elucidation of the molecular mechanism of gating of the osmoregulatory transporter. We will focus on the glycine betaine ABC importer, which is one of the most complex transporters known to date with ten distinct protein domains, transiently interacting with each other. The proposed synthetic metabolic circuit constitutes a fascinating out-of-equilibrium system, allowing us to understand cell volume regulatory mechanisms in a context and at a level of complexity minimally needed for life. Analysis of this circuit will address many outstanding questions and eventually allow us to design more sophisticated vesicular systems with applications, for example as compartmentalized reaction networks.

2 247 231 €

Start date: 2015-07-01, End date: 2020-06-30

"This proposal aims at strengthening the connections between more fundamentally oriented areas of mathematics like algebra, geometry, analysis, and topology, and the more applied oriented and more recently emerging disciplines of discrete mathematics, optimization, and algorithmics. The overall goal of the project is to obtain, with methods from fundamental mathematics, new effective tools to unravel the complexity of structures like graphs, networks, codes, knots, polynomials, and tensors, and to get a grip on such complex structures by new efficient characterizations, sharper bounds, and faster algorithms. In the last few years, there have been several new developments where methods from representation theory, invariant theory, algebraic geometry, measure theory, functional analysis, and topology found new applications in discrete mathematics and optimization, both theoretically and algorithmically. Among the typical application areas are networks, coding, routing, timetabling, statistical and quantum physics, and computer science. The project focuses in particular on: A. Understanding partition functions with invariant theory and algebraic geometry B. Graph limits, regularity, Hilbert spaces, and low rank approximation of polynomials C. Reducing complexity in optimization by exploiting symmetry with representation theory D. Reducing complexity in discrete optimization by homotopy and cohomology These research modules are interconnected by themes like symmetry, regularity, and complexity, and by common methods from algebra, analysis, geometry, and topology."

2 001 598 €

Start date: 2014-01-01, End date: 2018-12-31

A major challenge in contemporary traffic and transportation theory is having a comprehensive understanding of pedestrians and cyclists behaviour. This is notoriously hard to observe, since sensors providing abundant and detailed information about key variables characterising this behaviour have not been available until very recently. The behaviour is also far more complex than that of the much better understood fast mode. This is due to the many degrees of freedom in decision-making, the interactions among slow traffic participants that are more involved and far less guided by traffic rules and regulations than those between car-drivers, and the many fascinating but complex phenomena in slow traffic flows (self-organised patterns, turbulence, spontaneous phase transitions, herding, etc.) that are very hard to predict accurately. With slow traffic modes gaining ground in terms of mode share in many cities, lack of empirical insights, behavioural theories, predictively valid analytical and simulation models, and tools to support planning, design, management and control is posing a major societal problem as well: examples of major accidents due to bad planning, organisation and management of events are manifold, as are locations where safety of slow modes is a serious issue due to interactions with fast modes. This programme is geared towards establishing a comprehensive theory of slow mode traffic behaviour, considering the different behavioural levels relevant for understanding, reproducing and predicting slow mode traffic flows in cities. The levels deal with walking and cycling operations, activity scheduling and travel behaviour, and knowledge representation and learning. Major scientific breakthroughs are expected at each of these levels, in terms of theory and modelling, by using innovative (big) data collection and experimentation, analysis and fusion techniques, including social media data analytics, using augmented reality, and remote and crowd sensing.

2 458 700 €

Start date: 2015-11-01, End date: 2020-10-31

For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.

2 500 000 €

Start date: 2009-01-01, End date: 2013-12-31