ERC FUNDED PROJECTS

"We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."

1 996 126 €

Start date: 2014-04-01, End date: 2019-09-30

The project’s overall target is to arrive at a fundamental understanding of electrolyte thermodynamics and thus enable the engineering of a new generation of useful, physically sound models for electrolyte solutions. These models should be general and applicable to a very wide range of conditions so that they can be potentially used for a wide range of applications. Electrolyte solutions are present almost anywhere and find numerous applications in physical sciences including chemistry, geology, material science, medicine, biochemistry and physiology as well as in many engineering fields especially chemical & biochemical, electrical and petroleum engineering. In all these applications the thermodynamics plays a crucial role over wide ranges of temperature, pressure and composition. As the subject is important, a relatively large body of knowledge has been accumulated with lots of data and models. However, disappointingly the state-of-the art thermodynamic models used today in engineering practice are semi-empirical and require numerous experimental data. They lack generality and have not enhanced our understanding of electrolyte thermodynamics. Going beyond the current state of the art, we will create the scientific foundation for studying, at their extremes, both “primitive” and “non-primitive” approaches for electrolyte solutions and identify strengths and limitations. The project is based on the PI’s many years of experience in thermodynamics. The ambition is to make new advances to clarify major questions and misunderstandings in electrolyte thermodynamics, some remaining for over 100 years, which currently prevent real progress from being made, and create a new paradigm which will ultimately pave the way for the development of new engineering models for electrolyte solutions. This is a risky, ambitious and crucial task, but a successful completion will have significant benefits in many industrial sectors as well as in environmental studies and biotechnology.

2 500 000 €

Start date: 2019-09-01, End date: 2024-08-31

Over the past decade, epigenetic phenomena have taken centre stage in our understanding of gene regulation, cellular differentiation and human disease. DNA methylation is a prevalent epigenetic modification in mammals, which is brought about by enzymatic transfer of methyl groups from the S-adenosylmethionine (SAM) cofactor by three known DNA methyltransferases (DNMTs). The most dramatic epigenomic reprogramming in mammalian development occurs after fertilization, whereby a global loss of DNA methylation is followed by massive reinstatement of new methylation patterns, different for each cell type. Although DNA methylation has been extensively investigated, key mechanistic aspects of these fascinating events remain obscure. The goal of this proposal is to bridge the gap in our understanding of how the genomic methylation patterns are established and how they govern cell plasticity and variability during differentiation and development. These questions could only be answered by precise determination of where and when methylation marks are deposited by the individual DNMTs, and how these methylation marks affect gene expression. To achieve this ambitious goal, we will metabolically engineer mouse cells to permit SAM analog-based chemical pulse-tagging of their methylation sites in vivo. We will then advance profiling of DNA modifications to the single cell level via innovative integration of microdroplet-based barcoding, precise genomic mapping and super-resolution imaging. Using this unique experimental system we will determine, with unprecedented detail and throughput, the dynamics and variability of DNA methylation and gene expression patterns during differentiation of mouse embryonic cells to neural and other lineages. This project will give a comprehensive, time-resolved view of the roles that the DNMTs play in mammalian development, which will open new horizons in epigenomic research and will advance our understanding of human development and disease.

2 499 875 €

Start date: 2017-09-01, End date: 2022-08-31

A new class of devices exploiting Fano resonances and with important applications in information technology is suggested. Typically, the resonance of a system is described by a frequency and a lifetime, leading to a Lorentzian lineshape function. If the system instead involves interference between a discrete resonance and a continuum, a Fano lineshape appears with fundamentally different characteristics. Here, the Fano resonance is used to make a novel integrated mirror, enabling realization of Fano lasers, Fano switches and quantum Fano devices. These devices challenge well-accepted paradigms for photonic devices. The goals of the project are to demonstrate a laser with modulation bandwidth greatly exceeding all existing lasers; a nanolaser with linewidth three orders of magnitude smaller than existing nanocavity lasers; and a switch that operates at femtojoule energies and provides gain. Such devices are important for realizing high-speed optical interconnects and networks between and within chips. An increasing fraction of the global energy consumption is being used for data communication, and photonics operating at very high data rates with ultra-low energy per bit has been identified as a key technology to enable a sustainable growth of capacity demands. Existing device designs, however, cannot just be scaled down to reach the goals for next-generation integrated devices. The Fano mirror will also be used to demonstrate control at the single-photon level, which will enable high-quality on-demand single-photon sources, which are much demanded devices in photonic quantum technology. These devices all rely on the unique properties of the Fano mirror, which provides a new resource for ultrafast dynamic control, noise suppression and ultra-low energy operation. Using photonic crystal technology the project will achieve its goals in a concerted effort involving development of new theory, new nanofabrication techniques and advanced experiments.

2 500 000 €

Start date: 2019-09-01, End date: 2024-08-31