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 aim of this project is to develop a diffraction based transmission X-ray microscope, d-TXM, for non-destructive structural characterization of polycrystalline materials such as metals, ceramics, semiconductors, dust, soil and rocks, and for R&D applications in e.g. the energy-, electronics- and environmental sectors. Uniquely, d-TXM will be able to visualise the grains inside 100 micrometer thick specimens with a spatial resolution of 10-30 nm. Up to a thousand grains may be mapped simultaneously in three dimensions with respect to morphology, phase, orientation and local stress-state. Furthermore, the method will be sufficiently fast to enable the acquisition of 3D movies of the time evolution of the structure in nano-materials and components during synthesis, processing or operation. During the last decade the applicant pioneered and matured a set of X-ray based methods for 3D studies of polycrystals on the micrometre scale. For this achievement, he is recognized as a worldwide leading figure in X-ray instrumentation for structural materials, situated at a nodal point between materials, X-ray physics, applied mathematics and crystallography. The underlying vision of d-TXM is similar to this past work, but in terms of optics the microscopy approach is radically different and the spatial resolution will be two orders of magnitude better. In this project, the scientific potential will be demonstrated by means of applications to selected issues in metallurgy. Being able to directly observe the evolution of the individual crystalline elements, our understanding of processes such as plasticity and phase evolution can be greatly enhanced. Dissemination to other fields will take place via an advisory board of future users and a workshop. Continuity of the project is ensured by the technique being implemented at the European Synchrotron Research Facility.

2 499 860 €

Start date: 2012-10-01, End date: 2017-09-30

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

Aptamers are single-stranded oligonucleotides which are able to target peptides, proteins, small molecules or live cells by virtue of their well-defined three-dimensional shapes. Aptamers are typically generated by evolution of specific sequences against a given target by in vitro evolution using the process known as SELEX. Progress of this field with respect to drug development has so far been hampered by the relative large size and poor biostability of evolved aptamers composed of unmodified nucleotides, necessitating tedious and extensive post-SELEX truncation and modification approaches. LNA (locked nucleic acid) is a prominent nucleotide modification which is in the process of revolutionizing gene silencing and RNA detection. LNA however has never been included in de novo aptamer evolution. EVOLNA is an ambitious but coherent research program with the objective of transforming the field of aptamer technology. The vision is to enable evolution of aptamers that per se possess most of the desired properties, thereby alleviating the need for extensive post-SELEX procedures. This will be realized by combining the unique properties of LNA with innovative methods for LNA aptamer evolution. LNA aptamer technology is envisioned to enable evolution of aptamers displaying maximum chemical diversity, minimum size and high biostability. The developed strategies will be applicable not only towards evolution of therapeutic aptamers, which will be the main subject of this program, but also towards evolution of aptamers for biosensing, diagnostic and imaging applications. The program is at the very frontier of biotechnology research and spans the areas of chemistry, molecular biology and drug research.

2 497 720 €

Start date: 2011-04-01, End date: 2016-03-31