ERC FUNDED PROJECTS

A key synthetic challenge of widespread interest in chemical science involves the creation of well-defined 2D functional materials that exist on a length-scale of nanometers to microns. In this ambitious 5 year proposal we aim to tackle this issue by exploiting the unique opportunities made possible by recent developments with the living crystallization-driven self-assembly (CDSA) platform. Using this solution processing approach, amphiphilic block copolymers (BCPs) with crystallizable blocks, related amphiphiles, and polymers with charged end groups will be used to predictably construct monodisperse samples of tailored, functional soft matter-based 2D nanostructures with controlled shape, size, and spatially-defined chemistries. Many of the resulting nanostructures will also offer unprecedented opportunities as precursors to materials with hierarchical structures through further solution-based “bottom-up” assembly methods. In addition to fundamental studies, the proposed work also aims to make important impact in the cutting-edge fields of liquid crystals, interface stabilization, catalysis, supramolecular polymers, and hierarchical materials.

2 499 597 €

Start date: 2018-05-01, End date: 2023-04-30

The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research. The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation. The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event. Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.

1 489 823 €

Start date: 2017-03-01, End date: 2022-02-28

Optical bioimaging is limited by visible light penetration depth and stability of fluorescent dyes over extended periods of time. Surface enhanced Raman scattering (SERS) offers the possibility to overcome these drawbacks, through SERS-encoded nanoparticle tags, which can be excited with near-IR light (within the biological transparency window), providing high intensity, stable, multiplexed signals. SERS can also be used to monitor relevant bioanalytes within cells and tissues, during the development of diseases, such as tumours. In 4DBIOSERS we shall combine both capabilities of SERS, to go well beyond the current state of the art, by building three-dimensional scaffolds that support tissue (tumour) growth within a controlled environment, so that not only the fate of each (SERS-labelled) cell within the tumour can be monitored in real time (thus adding a fourth dimension to SERS bioimaging), but also recording the release of tumour metabolites and other indicators of cellular activity. Although 4DBIOSERS can be applied to a variety of diseases, we shall focus on cancer, melanoma and breast cancer in particular, as these are readily accessible by optical methods. We aim at acquiring a better understanding of tumour growth and dynamics, while avoiding animal experimentation. 3D printing will be used to generate hybrid scaffolds where tumour and healthy cells will be co-incubated to simulate a more realistic environment, thus going well beyond the potential of 2D cell cultures. Each cell type will be encoded with ultra-bright SERS tags, so that real-time monitoring can be achieved by confocal SERS microscopy. Tumour development will be correlated with simultaneous detection of various cancer biomarkers, during standard conditions and upon addition of selected drugs. The scope of 4DBIOSERS is multidisciplinary, as it involves the design of high-end nanocomposites, development of 3D cell culture models and optimization of emerging SERS tomography methods.

2 410 771 €

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

Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.

2 496 216 €

Start date: 2013-06-01, End date: 2018-05-31

Antibiotics have contributed to a tremendous increase in human well-being, saving many millions of lives. However, antibiotics become obsolete the more they are used as selection pressure promotes the development of resistant bacteria. The World Health Organization has proclaimed antibiotic resistance as a major global threat to public health. Today, 700,000 deaths per year are due to untreatable infections. To win the battle against antibiotic resistance, new policies affecting the supply and demand of existing and new drugs must be designed. I propose new research to identify and evaluate feasible and effective demand-side policy interventions targeting the relevant decision makers: physicians and patients. ABRSEIST will make use of a broad econometric toolset to identify mechanisms linking antibiotic resistance and consumption exploiting a unique combination of physician-patient-level antibiotic resistance, treatment, and socio-economic data. Using machine learning methods adapted for causal inference, theory-driven structural econometric analysis, and randomization in the field it will provide rigorous evidence on effective intervention designs. This research will improve our understanding of how prescribing, resistance, and the effect of antibiotic use on resistance, are distributed in the general population which has important implications for the design of targeted interventions. It will then estimate a structural model of general practitioners’ acquisition and use of information under uncertainty about resistance in prescription choice, allowing counterfactual analysis of information-improving policies such as mandatory diagnostic testing. The large-scale and structural econometric analyses allow flexible identification of physician heterogeneity, which ABRSEIST will exploit to design and evaluate targeted, randomized information nudges in the field. The result will be improved rational use and a toolset applicable in contexts of antibiotic prescribing.

1 498 920 €

Start date: 2019-01-01, End date: 2023-12-31

The clinical success of anticancer and antiviral vaccines often requires the use of an adjuvant, a substance that helps stimulate the body’s immune response to the vaccine, making it work better. However, few adjuvants are sufficiently potent and non-toxic for clinical use; moreover, it is not really known how they work. Current vaccine approaches based on weak carbohydrate and glycopeptide antigens are not being particularly effective to induce the human immune system to mount an effective fight against cancer. Despite intensive research and several clinical trials, no such carbohydrate-based antitumor vaccine has yet been approved for public use. In this context, the proposed project has a double, ultimate goal based on applying chemistry to address the above clear gaps in the adjuvant-vaccine field. First, I will develop new improved adjuvants and novel chemical strategies towards more effective, self-adjuvanting synthetic vaccines. Second, I will probe deeply into the molecular mechanisms of the synthetic constructs by combining extensive immunological evaluations with molecular target identification and detailed conformational studies. Thus, the singularity of this multidisciplinary proposal stems from the integration of its main objectives and approaches connecting chemical synthesis and chemical/structural biology with cellular and molecular immunology. This ground-breaking project at the chemistry-biology frontier will allow me to establish my own independent research group and explore key unresolved mechanistic questions in the adjuvant/vaccine arena with extraordinary chemical precision. Therefore, with this transformative and timely research program I aim to (a) develop novel synthetic antitumor and antiviral vaccines with improved properties and efficacy for their prospective translation into the clinic and (b) gain new critical insights into the molecular basis and three-dimensional structure underlying the biological activity of these constructs.

1 499 219 €

Start date: 2017-03-01, End date: 2022-02-28

Amorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents. Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels – DNA cells – with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing. In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities. The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.

2 157 698 €

Start date: 2016-06-01, End date: 2021-05-31

Rates of domestic violence and the relative risk of premature death for women are higher in sub-Saharan Africa than in any other region. Yet we know remarkably little about the economic forces, incentives and constraints that drive discrimination against women in this region, making it hard to identify policy levers to address the problem. This project will help fill this gap. I will investigate gender discrimination from two complementary perspectives. First, through the lens of economic history, I will investigate the forces driving trends in women’s relative well-being since slavery. To quantify the evolution of well-being of sub-Saharan women relative to men, I will use three types of historical data: anthropometric indicators (relative height), vital statistics (to compute numbers of missing women), and outcomes of formal and informal family law disputes. I will then investigate how major economic developments and changes in family laws differentially affected women’s welfare across ethnic groups with different norms on women’s roles and rights. Second, using intra-household economic models, I will provide new insights into domestic violence and gender bias in access to crucial resources in present-day Africa. I will develop a new household model that incorporates gender identity and endogenous outside options to explore the relationship between women’s empowerment and the use of violence. Using the notion of strategic delegation, I will propose a new rationale for the separation of budgets often observed in African households and generate predictions of how improvements in women’s outside options affect welfare. Finally, with first hand data, I will investigate intra-household differences in nutrition and work effort in times of food shortage from the points of view of efficiency and equity. I will use activity trackers as an innovative means of collecting high quality data on work effort and thus overcome data limitations restricting the existing literature

1 499 313 €

Start date: 2018-08-01, End date: 2023-07-31

Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication. Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations. The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications. Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications. The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.

1 968 709 €

Start date: 2015-08-01, End date: 2020-07-31