ERC FUNDED PROJECTS

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

Many questions in science, policy making and everyday life are of a causal nature: how would changing A influence B? Causal inference, a branch of statistics and machine learning, studies how cause-effect relationships can be discovered from data and how these can be used for making predictions in situations where a system has been perturbed by an external intervention. The ability to reliably make such causal predictions is of great value for practical applications in a variety of disciplines. Over the last two decades, remarkable progress has been made in the field. However, even though state-of-the-art causal inference algorithms work well on simulated data when all their assumptions are met, there is still a considerable gap between theory and practice. The goal of CAFES is to bridge that gap by developing theory and algorithms that will enable large-scale applications of causal inference in various challenging domains in science, industry and decision making. The key challenge that will be addressed is how to deal with cyclic causal relationships ("feedback loops"). Feedback loops are very common in many domains (e.g., biology, economy and climatology), but have mostly been ignored so far in the field. Building on recently established connections between dynamical systems and causal models, CAFES will develop theory and algorithms for causal modeling, reasoning, discovery and prediction for cyclic causal systems. Extensions to stationary and non-stationary processes will be developed to advance the state-of-the-art in causal analysis of time-series data. In order to optimally use available resources, computationally efficient and statistically robust algorithms for causal inference from observational and interventional data in the context of confounders and feedback will be developed. The work will be done with a strong focus on applications in molecular biology, one of the most promising areas for automated causal inference from data.

1 405 652 €

Start date: 2015-09-01, End date: 2020-08-31

The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.

1 999 375 €

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

Plants secrete metabolites to communicate with other organisms in their rhizosphere. An exciting example of rhizosphere signalling molecules are the strigolactones. These are used by the friends of plants, the arbuscular mycorrhizal fungi, for host detection but also by their enemies, root parasitic plants. Furthermore, they have an endogenous signalling function, as a plant hormone that regulates shoot branching and root architecture. I postulate that this dual positive and negative signalling role of the strigolactones is the result of a paradigm: enemies of plants recruit molecules that are essential to the plant as cues. This paradigm has two important implications: 1) other plant-produced signalling molecules known to be abused by plant enemies likely have another, beneficial essential function in plants and 2) the involvement of multiple, positive and negative, biological functions exerts a selective pressure on these signalling molecules that results in the evolution of diversity in structure and biological specificity. In the project proposed here I will address implication 1) using an innovative approach in a new area by setting out to discover a new signalling role for plant parasitic cyst nematode hatching stimulants and I will investigate implication 2) by studying how biological specificity in strigolactones and hatching stimulants is mediated by the creation of structural diversity and the concomitant changes in perception, in parasitic plants and nematodes. This work will shed light on the significance of structural diversity in signalling molecules and the co-evolution of perception and may result in the discovery of a new class of signalling molecules in plants. It will also provide the fundamental knowledge enabling biotechnological and agronomical applications to optimise colonisation by AM fungi and plant development, and control parasitation by root parasitic plants and cyst nematodes.

2 498 674 €

Start date: 2015-12-01, End date: 2020-11-30