ERC FUNDED PROJECTS

All levels of life entail cooperation and conflict. Genes cooperate to build up a functional genome, which can yet be undermined by selfish genetic elements. Humans and animals cooperate to build up societies, which can yet be subverted by cheats. There is a long-standing interest among biologists to comprehend the tug-of-war between cooperation and conflict. Recently, research on bacteria was successful in identifying key factors that can tip the balance in favour or against cooperation. Bacteria cooperate through the formation of protective biofilms, cell-to-cell communication, and the secretion of shareable public goods. However, the advantage of bacteria being fast replicating units, easily cultivatable in high numbers, is also their disadvantage: they are small and imperceptible, such that measures of cooperation typically rely on averaged responses across millions of cells. Thus, we still know very little about bacterial cooperation at the biological relevant scale: the individual cell level. Here, I present research using the secretion of public goods in the opportunistic human pathogen Pseudomonas aeruginosa, to tackle this issue. I will explore new dimensions of bacterial cooperation by asking whether bacteria engage in collective-decision making to find optimal group-level solutions; whether bacteria show division of labour to split up work efficiently; and whether bacteria can distinguish between trustworthy and cheating partners. The proposed research will make two significant contributions. First, it will reveal whether bacteria engage in complex forms of cooperation (collective decision-making, division of labour, partner recognition), which have traditionally been associated with higher organisms. Second, it will provide insights into the evolutionary stability of cooperation – key knowledge for designing therapies that interfere with virulence-inducing public goods in infections, and the design of stable public-good based remediation processes.

1 994 981 €

Start date: 2016-09-01, End date: 2021-08-31

We aim to understand host cell entry of enveloped viruses at molecular level. A crucial step in this process is when the viral membrane fuses with the cell membrane. Similarly to cell–cell fusion, this step is mediated by fusion proteins (classes I–III). Several medically important viruses, notably dengue and many bunyaviruses, harbour a class II fusion protein. Class II fusion protein structures have been solved in pre- and post-fusion conformation and in some cases different factors promoting fusion have been determined. However, questions about the most important steps of this key process remain unanswered. I will focus on the entry mechanism of bunyaviruses by using cutting-edge, high spatial and temporal resolution bio-imaging techniques. These viruses have been chosen as a model system to maximise the significance of the project: they form an emerging viral threat to humans and animals, no approved vaccines or antivirals exist for human use and they are less studied than other class II fusion protein systems. Cryo-electron microscopy and tomography will be used to solve high-resolution structures (up to ~3 Å) of viruses, in addition to virus–receptor and virus–membrane complexes. Advanced fluorescence microscopy techniques will be used to probe the dynamics of virus entry and fusion in vivo and in vitro. Deciphering key steps in virus entry is expected to contribute to rational vaccine and drug design. During this project I aim to establish a world-class laboratory in structural and cellular biology of emerging viruses. The project greatly benefits from our unique biosafety level 3 laboratory offering advanced bio-imaging techniques. Furthermore it will also pave way for similar projects on other infectious viruses. Finally the novel computational image processing methods developed in this project will be broadly applicable for the analysis of flexible biological structures, which often pose the most challenging yet interesting questions in structural biology.

1 998 375 €

Start date: 2015-04-01, End date: 2020-03-31

"This proposal concentrates on Quantum Chromodynamics (QCD) in its least well understood "final frontier": the high energy limit. The aim is to treat the formation of quark gluon plasma in relativistic nuclear collisions together with other high energy processes in a consistent QCD framework. This project is topical now in order to fully understand the results from the maturing LHC heavy ion program. The high energy regime is characterized by a high density of gluons, whose nonlinear interactions are beyond the reach of simple perturbative calculations. High energy particles also propagate nearly on the light cone, unaccessible to Euclidean lattice calculations. The nonlinear interactions at high density lead to the phenomenon of gluon saturation. The emergence of the "saturation scale", a semihard typical transverse momentum, enables a weak coupling expansion around a nonperturbatively large color field. This project aims to make progress both in collider phenomenology and in more conceptual aspects of nonabelian gauge field dynamics at high energy density: 1. Significant advances towards higher order accuracy will be made in cross section calculations for processes where a dilute probe collides with the strong color field of a high energy nucleus. 2. The quantum fluctuations around the strong color fields in the initial stages of a relativistic heavy ion collision will be analyzed with a new numerical method based on an explicit linearization of the equations of motion, maintaining a well defined weak coupling limit. 3. Initial conditions for fluid dynamical descriptions of the quark gluon plasma phase in heavy ion collisions will be obtained from a constrained QCD calculation. We propose to achieve these goals with modern analytical and numerical methods, on which the P.I. is a leading expert. This project would represent a leap in the field towards better quantitative first principles understanding of QCD in a new kinematical domain."

1 935 000 €

Start date: 2016-10-01, End date: 2021-09-30

Advances in technology and methodology over the last decade, have enabled the study of galaxies to the highest redshifts. This has revolutionized our understanding of the origin and evolution of galaxies. I have played a central role in this revolution, by discovering that at z=2, when the universe was only 3 Gyr old, half of the most massive galaxies were extremely compact and had already completed their star formation. During the last five years I have led a successful group of postdocs and students dedicated to investigating the extreme properties of these galaxies and place them into cosmological context. Combining a series of high profile observational studies published by my group and others, I recently proposed an evolutionary sequence that ties together the most extreme galaxies in the universe, from the most intense dusty starburst at cosmic dawn, through quasars: the brightest sources in the universe, driven by feedback from supermassive black holes, and galaxy cores hosting the densest conglomerations of stellar mass known, to the sleeping giants of the local universe, the giant ellipticals. The proposed research program will explore if such an evolutionary sequence exists, with the ultimate goal of reaching, for the first time, a coherent physical understanding of how the most massive galaxies in the universe formed. While there is a chance the rigorous tests may ultimately reveal the proposed sequence to be too simplistic, a guarantied outcome of the program is a significantly improved understanding of the physical mechanisms that shape galaxies and drive their star formation and quenching

1 999 526 €

Start date: 2015-09-01, End date: 2021-02-28