ERC FUNDED PROJECTS

Hundreds of millions of people suffer from obesity and diabetes worldwide. These diseases diminish both life quality and expectancy and new treatment strategies are desperately needed. One possible approach is to target the calorie-burning and glucose-consuming functions of brown and beige adipose tissue (B/BAT). Previous attempts to harness the therapeutic potential of B/BAT have largely focused on the β-adrenergic class of G protein-coupled receptors (GCPRs). Unfortunately, these methods are hindered by adverse cardiovascular side effects linked to adrenergic activation. Therefore, uncovering non-adrenergic alternatives to exploit B/BAT for treating metabolic disease holds the potential for enormous societal and economic benefit. Here, we propose the activation of one such non-adrenergic GPCR on B/BAT as a means to treat obesity and diabetes. We identified this GPCR from a screen of B/BAT receptors performed in my ERC Starting Grant project, aCROBAT. We found that treating brown adipose cells with the peptide ligand for this GPCR increased oxygen consumption. We recognized the therapeutic potential after observing that ligand administration in vivo lowered bodyweight and improved insulin sensitivity in obese mice. However, the resources required to develop this discovery into a tangible innovation extend beyond the scope of aCROBAT. Consequently, I’m applying for an ERC PoC grant for critical support to take the initial steps to commercial application. Specifically, we seek to strengthen our IP position by developing patentable, longer-lived analogues of the ligand. Importantly, we will test these lead compounds head-to-head and in combination with current treatment options. We have assembled a team of experts to address key aspects from peptide design and pharmacology to IPR strategy and commercial development. Combined with our validated in vitro and in vivo testing platforms, we are ideally poised to maximize innovation potential.

149 986 €

Start date: 2017-10-01, End date: 2018-08-31

State-of-the-art simulations and observations highlight the self-organization of convective clouds. Our recent work shows two aspects: these clouds are capable of unexpected increase in extreme precipitation when temperature rises; interactions between clouds produce the extremes. As clouds interact, they organize in space and carry a memory of past interaction and precipitation events. This evidence reveals a severe shortcoming of the conventional separation into "forcing" and "feedback" in climate model parameterizations, namely that the "feedback" develops a dynamics of its own, thus driving the extremes. The major scientific challenge tackled in INTERACTION is to make a ground-breaking departure from the established paradigm of "quasi-equilibrium" and instantaneous convective adjustment, traditionally used for parameterization of "sub-grid-scale processes" in general circulation models. To capture convective self-organization and extremes, the out-of-equilibrium cloud field must be described. In INTERACTION, I will produce a conceptual model for the out-of-equilibrium system of interacting clouds. Once triggered, clouds precipitate on a short timescale, but then relax in a "recovery" state where further precipitation is suppressed. Interaction with the surroundings occurs through cold pool outflow,facilitating the onset of new events in the wake. I will perform tailored numerical experiments using cutting-edge large-eddy simulations and very-high-resolution observational analysis to determine the effective interactions in the cloud system. Going beyond traditional forcing-and-feedback descriptions, I emphasize gradual self-organization with explicit temperature dependence. The list of key variables of atmospheric water vapor, temperature and precipitation must therefore be amended by variables describing organization. Capturing the self-organization of convection is essential for understanding of the risk of precipitation extremes today and in a future climate.

1 314 800 €

Start date: 2018-07-01, End date: 2023-06-30

Progress within many contemporary or emergent technologies, including photovoltaics, single-photon light sources, and plasmonics, depends crucially on our ability to control the interactions between light and matter. The complexity of the light-matter interactions has made the development of photonic materials a slow, expensive, and empirical-based science. Of particular importance are the detrimental non-radiative processes mediated by defects and phonons that lead to efficiency losses in photovoltaics, reduce the quantum efficiency of single-photon emitters, and cause Ohmic losses in the metallic components of plasmonic devices. LIMA will develop ground breaking methods for calculating non-radiative relaxation rates in real materials from first principles. These will be used to evaluate key performance parameters such as photo-carrier lifetimes and plasmon propagation lengths and thus facilitate a realistic computational assessment of the application potential of photonic materials. In terms of materials, LIMA will focus on the emergent class of atomically thin two-dimensional (2D) materials. The possibility of combining different 2D materials into van der Waals heterostructures (vdWHs) provides a unique platform for controlling light-matter interactions with atomic scale precision. Multi-scale methods for predicting quasiparticle band structures of general, incommensurable vdWHs will be developed and used to design novel photonic materials with tailored light dispersion and multi-junction solar cells with high absorption and low thermalization losses. High-throughput computational screening will be used to identify novel color centers in 2D materials with potential to act as single-photon sources with high quantum yield and narrow linewidths, which are urgently needed by leading quantum technologies. The possibilities of controlling the color centers via strain engineering and light management will be explored in close collaboration with experimentalists.

1 951 354 €

Start date: 2018-04-01, End date: 2023-03-31

The goals are: 1) to develop a universal laboratory-based 4D X-ray microscope with potentials in the broad field of materials science and beyond; 2) to advance metal research by quantifying local microstructural variations using the new 4D tool and by including the effects hereof in the understanding and modelling of industrially relevant metals. Today, high resolution 4D (x,y,z,time) crystallographic characterization of materials is possible only at large international facilities. This is a serious limitation preventing the common use. The new technique will allow such 4D characterization to be carried out at home laboratories, thereby wide spreading this powerful tool. Whereas current metal research mainly focuses on average properties, local microstructural variations are present in all metals on several length scales, and are often of critical importance for the properties and performance of the metal. In this project, the new technique will be the cornerstone in studies of such variations in three types of metallic materials: 3D printed, multilayered and micrometre-scale metals. Effects of local variations on the subsequent microstructural evolution will be followed during deformation and annealing, i.e. during processes typical for manufacturing, and occurring during in-service operation. Current models largely ignore the presence of local microstructural variations and lack predictive power. Based on the new experimental data, three models operating on different length scales will be improved and combined, namely crystal plasticity finite element, phase field and molecular dynamics models. The main novelty here relates to the full 4D validation of the models, which has not been possible hitherto because of lack of sufficient experimental data. The resulting fundamental understanding of the inherent microstructural variations and the new models are foreseen to be an integral part of the future design of metallic materials for high performance applications.

2 496 519 €

Start date: 2018-10-01, End date: 2023-09-30