ERC FUNDED PROJECTS

The scientific goal of the proposal is to answer central questions related to diffeomorphism groups of manifolds of dimension 2 and 3, and to their deformation invariant analogs, the mapping class groups. While the classification of surfaces has been known for more than a century, their automorphism groups have yet to be fully understood. Even less is known about diffeomorphisms of 3-manifolds despite much interest, and the objects here have only been classified recently, by the breakthrough work of Perelman on the Poincar\'e and geometrization conjectures. In dimension 2, I will focus on the relationship between mapping class groups and topological conformal field theories, with applications to Hochschild homology. In dimension 3, I propose to compute the stable homology of classifying spaces of diffeomorphism groups and mapping class groups, as well as study the homotopy type of the space of diffeomorphisms. I propose moreover to establish homological stability theorems in the wider context of automorphism groups and more general families of groups. The project combines breakthrough methods from homotopy theory with methods from differential and geometric topology. The research team will consist of 3 PhD students, and 4 postdocs, which I will lead.

724 992 €

Start date: 2009-11-01, End date: 2014-10-31

Over the past 150 years, many of the greatest questions in physics, spanning astronomical dimensions to quarks, have addressed how particles can emerge in continuous fields. In this highly exploratory project, we will open a window into the behavior and control of some of the least explored and most puzzling objects in nanomagnetism: three-dimensional (3D) magnetic solitons (MSs). These are spatially localized stable magnetization textures that have particle-like properties and are expected to move and interact in 3D in magnetic crystals and heterostructures in a similar manner to ordinary particles. Until now, their theoretical study has been restricted to simple models, while the experimental study of individual 3D MSs is nearly unexplored as a result of their deep-sub-micron size and a current lack of suitable characterization techniques. We bring together four complementary research groups with expertise in theoretical descriptions of magnetism, device physics and magnetic characterization with high spatial and temporal resolution. Methodological breakthroughs by the partners will enable new fundamental theoretical and experimental insights into the nucleation, stability, dynamics and transport of 3D MSs, which are predicted to be influenced strongly by their nontrivial topology. Particular attention will be paid to the manner in which 3D MSs can be controlled and manipulated dynamically. This project will open the field of 3D magnetization textures at the nanoscale to fundamental science,with a view to enabling disruptive applications. 3D MSs are foreseen to play the role of information carriers that can move freely in any spatial direction and to offer a key advance over conventional 2D magnetization textures. Results from the project will provide guidelines for their use in applications that include magnetic storage technology and neuromorphic information processing systems and enable the realization of pervasive new 3D device concepts.

11 880 356 €

Start date: 2020-07-01, End date: 2026-06-30

Homologous recombination (HR) is a conserved DNA double-strand breaks (DSB) repair pathway that uniquely uses an intact DNA molecule as a template. Genome-wide homology search is carried out by a nucleoprotein filament (NPF) assembled on the ssDNA flanking the DSB, and whose product is a “D-loop” joint molecule. Beyond accurate DSB repair, this capacity of HR to spatially associates homologous molecules is also harnessed for homolog pairing in meiosis. The goal of “3D-loop” is to tackle two long lasting conundrums: the fundamental homology search mechanism that achieves accurate and efficient identification of a single homologous donor in the vastness of the genome and nucleus, and how this mechanism is adapted for the purpose of homologs attachment in meiosis. I overcame the main hurdle to study these core steps of HR by developing a suite of proximity ligation-based methodologies and experimental systems to physically detect joint molecules in yeast cells. It revealed elaborate regulation controlling D-loop dynamics and a novel class of joint molecules. This proposal builds upon these methodologies and findings to first address basic properties of the homology sampling process by the NPF and the role of D-loop dynamics, with the long-term goal to establish a quantitative framework of homology search in mitotic cells (WP1). Second, the meiosis-specific regulation of homology search leading to homolog pairing likely integrates chromosomal-scale information. Genome re-synthesis and engineering approaches will be deployed to (i) achieve a quantitative and dynamic cartography of the cytological and molecular events of meiosis over a large chromosomal region, (ii) probe cis-acting regulations at the chromosomal scale, and (iii) revisit the molecular paradigm for crossover formation (WP2). We expect this project to shed light on the fundamental process of homology search and its involvement in the chromosome pairing phenomenon lying at the basis of sexual reproduction.

1 499 779 €

Start date: 2020-01-01, End date: 2024-12-31

Predicting clinical response to novel and existing anticancer drugs remains a major hurdle for successful cancer treatment. Studies indicate that the tumor ecosystem, resembling an organ-like structure, can limit the predictive power of current therapies that were evaluated solely on tumor cells. The interactions of tumor cells with their adjacent microenvironment are required to promote tumor progression and metastasis, determining drug responsiveness. Such interactions do not form in standard research techniques, where cancer cells grow on 2D plastic dishes. Hence, there is a need to develop new cancer models that better mimic the physio-pathological conditions of tumors. Here, we create 3D-bioprinted tumor models based on a library of hydrogels we developed as scaffold for different tumor types, designed according to the mechanical properties of the tissue of origin. As PoC, we bioprinted a vascularized 3D brain tumor model from brain tumor cells co-cultured with stromal cells and mixed with our hydrogels, that resemble the biophysics of the tumor and its microenvironment. Our patient-derived models consist of cells from a biopsy, constructed according to CT/MRI scans, and include functional vessels allowing for patients' serum to flow when connected to a pump. These models will facilitate reproducible, reliable and rapid results, determining which treatment suits best the specific patient's tumor. Taken together, this 3D-printed model could be the basis for potentially replacing cell and animal models. We predict that this powerful platform will be used in translational research for preclinical evaluation of new therapies and for clinical drug screening, which will save critical time, reduce toxicity and significantly decrease costs generating a major societal benefit. Our platform offers a highly attractive business case, as pharmaceutical and biotech companies heavily invest in preclinical predictive tools for novel personalized drug screening strategies.

150 000 €

Start date: 2019-09-01, End date: 2021-02-28