Being able to clarify the atomistic dynamics of molecular collisions and chemical reactions has been a central research goal for decades. For reactions of charged particles in particular, the importance of quantum dynamics is barely understood, as quantum state-resolved experiments beyond total cross section measurement are very challenging and most theoretical descriptions still rely on quasi-classical approaches. In particular, quantum scattering resonances, known by now to be relevant in a few well-studied neutral molecule reactions, have never been observed for ion-molecule collisions up to now. In the past years we have spearheaded research on crossed-beam reactive scattering of ions with neutral molecules. Our measured differential scattering cross sections could provide detailed insight into the dynamics of polyatomic reactions and allowed us to discover several new reaction mechanisms. In this project, we propose a novel experimental approach to achieve a multifold improved resolution for the scattering images, which will allow us to answer several key questions: Which product quantum states are populated in molecular ions that are produced in three- and four-atom reactions? How do quantum scattering resonances influence the collision dynamics and the product state distribution? Which momentum vector correlations govern the three-body break-up in ion-neutral reactions and which transition states are responsible for these dynamics? How are ionic reactions contributing to the radiation damage of biological molecules in cells? Our proposed experimental approach can answer these questions and will thereby reach a new domain for the investigation of ion-molecule reactions with unprecedented quantum state control for three- and four-atom reactions and highly differential insight into polyatomic reactions.

The realization of the first total syntheses of the two marine natural products waixenicin A and xenibellol A is the aim of this proposal. For this purpose, a N-heterocyclic carben (NHC)-catalyzed bicyclization shall be employed as key transformation. Both target structures are members of the Xenia diterpenoids family and exhibit cytotoxicity against human cancer cell lines. Despite these highly desirable, promising biological properties and unique structural features, therapeutic applications have been prevented by the circumstance that no synthetic access has been achieved until this day. Using retrosynthetic pattern recognition, we realized that the central fused lactone motif (of both natural products) could be efficiently accessed via a recently reported NHC-catalyzed bicyclization reaction. This organocatalytic methodology enables a rapid creation of molecular complexity and, therefore, its application to these total syntheses should save time and other resources. If a therapeutic potential can be corroborated, a synthetic access would provide this family of Xenia diterpenoids (or their derivatives) as possible anticancer drugs. As a result, this project could potentially lead to an improvement of medical care for future cancer patients, thereby also addressing a UN sustainable development goal.

The rapid advancement in quantum technologies for the experimental control of isolated many-body quantum systems calls for the design of new proposals to probe synthetic states of matter in quantum simulators. Topological quantum matter represents the "holy grail" for quantum scientists as it stands out for its exotic properties and numerous applications in quantum computation. This research proposal aims to develop a theoretical framework for the systematic construction of topological quantum spin liquids suited for realization in Rydberg atom arrays. Combining the Applicant's expertise in topological phases of many-body systems and the Host's mastery of quantum optics, the goal of this project is to envision novel topologically ordered states of matter and devise their implementation in Rydberg atom-based quantum simulators.

Women with germline mutations in the BRCA1 genes face a 40-fold increased risk of developing breast and ovarian cancer. As a result, and due to a lack of other options, many women with a BRCA1 mutation choose to undergo drastic risk reducing surgery (removal of both breasts, ovaries and Fallopian Tubes) when they are still very young. Drugs currently recommended for prevention of breast cancer, such as tamoxifen or aromatase inhibitors, do not prevent those cancers with the poorest prognosis, such as triple negative breast cancer. Methods to prevent breast and ovarian cancers in these women are therefore a critical unmet medical need. We and others have identified progesterone as one of the key drivers for triple negative breast cancer development. We have shown that progesterone is consistently elevated during the luteal phase of the menstrual cycle in BRCA1 mutation carriers compared to women without such a mutation, and preliminary data point to progesterone receptor antagonists, such as mifepristone, as a promising class of drugs for primary prevention. Clinical trials of primary cancer prevention are extremely challenging due to the time-gap between the start of the cancer-preventive treatment and the primary endpoints (i.e., cancer incidence and cancer death). Current tools do not predict the likelihood of future cancer development with sufficient accuracy to be used to determine the preventive efficacy of a new treatment. We have developed DNA methylation markers reflecting tissue age and cell type that are increased in cancer tissue as well as in normal tissue from women with a BRCA1 mutation and could be used to monitor preventive efficacy. Clinical trials are now required to further investigate the use of antiprogestins for the prevention of breast and ovarian cancer. This ERC Proof of Concept grant aims to bring consensus among the scientific, patient and regulatory/ethical communities regarding the design and conduct of an initial clinical trial.