ERC FUNDED PROJECTS

In order to tackle some of the prime societal challenges of this century, science has to urgently provide effective tools addressing the redesign of chemical value chains through the exploitation of novel, bio-based raw materials, and the discovery and implementation of more resource-efficient production platforms. Nature will inevitably play a pivotal role in the imminent transformation of industrial strategies, and the recent bioeconomy approaches can only be regarded as initial step towards a sustainable future. Operating at the interface between chemistry and life sciences, my ABIONYS will fundamentally challenge the widely held distinction separating chemical from biosynthesis, and will deliver the first proof-of-concept where abiotic reactions act as productive puzzle pieces in biosynthetic arrangements. On the basis of our previous ground-breaking discoveries on artificial enzyme functions, I will create a significantly extended toolbox of biocatalysis modules by applying protein-based interpretations of synthetically crucial but non-natural reactions i.e. transformations that are in no way biosynthetically encoded in living organisms. My research will exploit these tools in multi-enzyme cascades for the preparation of complex organic target structures, not only to highlight the great synthetic potential of these approaches, but also to lay the groundwork for in vivo implementations. Eventually, the knowledge gathered from enzyme discovery and cascade design will enable to create an unprecedented class of bioproduction systems, where the genetic incorporation of artificial enzyme functions into recombinant microbial host organisms will yield tailor-made cellular factories. Combining classical organic synthesis strategies with the power of modern biotechnology, ABIONYS is going to transform the way we synthesize complex and functional building blocks by allowing us to encode organic chemistry thinking into living production platforms.

1 995 707 €

Start date: 2020-11-01, End date: 2025-10-31

The human microbiome has been increasingly in the focus of research for its importance in human health and disease. Yet, the viruses (phages) infecting these microbiota have gained much less attention. The majority of phages reside integrated in the genomes of their microbial hosts as so called lysogenic prophages. Often, these prophages encode important toxins and other virulence related factors that, while they are beneficial to their microbial hosts, may be detrimental for the infected human. Prophages can be induced under certain conditions to resume a lytic lifestyle resulting in the production of virus particles and often in the destruction of the host cell. Frequently, however, phage induction also leads to increased production of virulence factors. In this project, we aim to uncover small molecules modulating phage induction. We will explore to what extent microbial metabolites of human microbiota act as native triggers or inhibitors of phage induction and shape the complex interspecies interactions in the microbiome. The corresponding phage inducing or dysregulating metabolites will be isolated to elucidate their chemical structure and unveil their molecular targets. We will develop chemical tools to dissect and interrogate the responsible mechanisms and finally develop customized synthetic modulators that allow us to achieve control over the activity of phage-microbe systems with specific medical relevance. The integrated approach of the CAPSID project will provide first comprehensive insights into the chemistry of microbe-phage interactions and allow to assess its role for infectious diseases and its potential for customized treatment of microbial pathogens.

1 992 240 €

Start date: 2020-10-01, End date: 2025-09-30

Since the discovery in the nineteenth century, carbonylation chemistry has found broad applicability in chemical industries and become now a key technology for bulk and fine chemical synthesis. Despite its substantial toxicity, carbon monoxide (CO) is commonly used as carbonyl source causing considerable safety issues, particularly when used on bulk scale. The replacement of this hazardous gas with more benign surrogates would be highly desirable, and recent ideas focus on the valorisation of carbon dioxide as abundant, non-toxic and renewable carbon resource. However, few industrial processes utilise carbon dioxide as a raw material, and potent catalysts are required to overcome its thermodynamic and kinetic barrier. In this regard, ionic liquids show considerable potential as cooperative media as they can solubilise large concentrations of carbon dioxide but also strongly interact and activate carbon dioxide. This project focuses on the photocatalytic reduction of carbon dioxide in ionic liquids and its successive conversion into carbonyl compounds. Several goals need to be realised, including fundamental studies and optimisation of the ionic liquid co-catalysed photocatalytic reduction of carbon dioxide to produce CO under mild conditions (Goal 1). The reactivity of formed CO in supercritical carbon dioxide with various organic substrates needs to be explored (Goal 2) before finally developing a streamlined and continuous process for the direct formation of carbonyl compounds from carbon dioxide (Goal 3). I envision that the photocatalytic activation of carbon dioxide in combination with the positive features of tailored ionic liquids as co-catalysts may overcome problems currently associated with carbon dioxide utilisation, eventually replacing the long-standing bastion of CO-based carbonylation chemistry with novel solutions.

1 963 515 €

Start date: 2021-01-01, End date: 2025-12-31

Advanced ceramics are often combined with metals, polymers or other ceramics to produce structural and functional systems with exceptional properties. Examples are resistors and capacitors in microelectronics, piezo-ceramic actuators in car injection devices, and bio-implants for hip joint replacements. However, a critical issue affecting the functionality, lifetime and reliability of such systems is the initiation and uncontrolled propagation of cracks in the brittle ceramic parts, yielding in some cases rejection rates up to 70% of components production. The remarkable “damage tolerance” found in natural materials such as wood, bone or mollusc, has yet to be achieved in technical ceramics, where incipient damage is synonymous with catastrophic failure. Novel “multilayer designs” combining microstructure and architecture could change this situation. Recent work of the PI has shown that tuning the location of “protective” layers within a 3D multilayer ceramic can increase its fracture resistance by five times (from ~3.5 to ~17 MPa∙m1/2) relative to constituent bulk ceramic layers, while retaining high strength (~500 MPa). By orienting the grain structure, similar to the textured and organized microstructure found in natural systems such as nacre, the PI has shown that crack propagation can be controlled within the textured ceramic layer. Thus, I believe tailored microstructures with controlled grain boundaries engineered in a layer-by-layer 3D architectural design hold the key to a new generation of “damage tolerant” ceramics. This proposal outlines a research program to establish new scientific principles for the fabrication of innovative ceramic components that exhibit unprecedented damage tolerance. The successful implementation of microstructural features (e.g. texture degree, tailored internal stresses, second phases, interfaces) in a layer-by-layer architecture will provide outstanding lifetime and reliability in both structural and functional ceramic devices.

1 985 000 €

Start date: 2019-05-01, End date: 2024-04-30