ERC FUNDED PROJECTS

"Computational chemistry is playing an increasingly important role for research in the pharmaceutical industry, oils & plastic, and materials development. Simulation and high-throughput screening can be orders of magnitude cheaper than experiments in the early stages of drug design. The ERC project preceding this application has developed several new techniques that make it orders-of-magnitude more efficient to calculate free energies from simulations rather than approximate docking screening. We have already had great academic success, but the requirement of large computer clusters or access to the Folding@Home network makes it difficult to implement in industry. To address this, we have developed a new framework for peer-to-peer distributed computing combined with Markov state models (called “Copernicus”) to be presented at Supercomputing’11. Copernicus completely removes the need to deal with single simulations, and allows users to specify workflows - directly on their laptop - in terms of free energy calculations or sampling of complex processes such as protein folding. Workflows are transparently uploaded to a server and split into distributed calculation workunits (e.g. in a company), computer clusters, but also cloud computing to deal with peaks in usage. The results are again transparently moved to the user’s machine. This provides a clear competitive advantage in terms of efficiency, and it removes all investment and support costs related to high-performance computing. This is of course not limited to molecular simulation, and in addition to the pharmaceutical track we want to investigate usage in the financial industry. We have just submitted a patent application for the dynamic data flow network that makes the peer-to-peer usage possible, but we would need a programmer to turn the research-level code into a working proof-of-concept for high-throughput screening applications in the pharmaceutical industry and another person to work on business development."

122 600 €

Start date: 2012-08-01, End date: 2013-07-31

BioNLight has been designed to investigate the prospective of commercially exploiting our multimodal nanoparticle technology in the biological imaging market. The introduction of this technology will open up an entirely-new window of molecular imaging possibilities, thereby supporting advances in biology, drug discovery & development and diagnostics. Funded by ERC, Prof. Brunsveld and colleagues have developed modular nanoparticles that exactly address the needs of the molecular imaging field. These nanoparticles of organic nature can be produced in a reproducible one-step method by self-assembly in water. The result is a highly-robust and biocompatible nanoparticle that can be modulated to emit any desirable colour frequency with long-term emission and high photostability. Moreover, they can be functionalised with multiple ligands thanks to great control over surface functionality and can be prepared not only for fluorescent studies, but also for other imaging technologies. In practise this implies that the technology platform can be used to advance a wide range of in-vitro and in-vivo assays and to visualise yet-uncovered processes. It is the objective of BioNLight to select the most interesting applications for commercialisation and to build up a prospectus that can be used to convince future customers of the practicability and the imaging power of our technology platform. Besides, we aim to construct a sound business model and strategy for commercialisation. This will be done by external validation of the nanoparticles by industry followed by final optimisation, by means of an extensive market study, by building a strong IP position and by setting up a business plan with detailed financial feasibility projections. The ERC Proof of Concept Grant will enable us to take the ERC Starting Grant results to a sound business proposition.

149 990 €

Start date: 2012-08-01, End date: 2013-07-31

In this project we will develop a broadly applicable signal amplification system that relies on chemical catalysis for biosensing purposes. In preliminary experiments it was demonstrated that the functionalization of two oligonucleotides with triphenyl phosphine ligands and their hybridization on a target DNA strand produced a very efficient catalyst for the dehalogenation of an iodinated boron dipyrromethane (BODIPY) dye. The removal of the iodine transforms the non-fluorescent chromophore into a highly fluorescent dye. In this way, a single hybridization event results in more than 1000 fluorescent reporters and extremely low detection limits of 10 fM were successfully realized. Herein it is planned to extend this concept of signal amplification to commercially relevant technologies like Enzyme Linked Immunosorbent Assays (ELISAs) or DNA microarrays. For that purpose different ligands will be synthesized and the reactivity as well as the spectral range of the BODIPY reporters will be varied. These experimental efforts, therefore, represent a broadening of our existing proof of concept experiments. Besides this experimental work, we will write up a business plan to commercialize our technology and receive further funding like seed grants or venture capital. There is a strong need in the in vitro diagnostic industry to fabricate improved analytical tests to detect new disease markers at low concentrations. With the catalytic signal amplification system several of these needs can be fulfilled. Due to the broad applicability of our technology platform it is envisioned to found a spin-off company that acts as service provider for the diagnostic industry.

150 000 €

Start date: 2012-04-01, End date: 2013-03-31

"Cisplatin is a platinum-based complex used widely as a chemotherapeutic drug. However, due to its limitations, including narrow activity range and severe side effects, other transition metal complexes are investigated as antitumorur agents. Titanium complexes that previously reached clinical trials showed fair activity, and were mainly limited by rapid decomposition in water, within minutes. Titanium complexes of diamino bis(phenolato) (""salan"") ligands studied in our laboratory under the ERC grant demonstrate extremely high stability for up to weeks in water solutions. Importantly, they have shown great potency as anti-tumour agents towards a number of cells in vitro. Their activity exceeds that of cisplatin by up to two orders of magnitude. In particular, halogenated compounds at specific positions demonstrate a combination of exceptional hydrolytic stability and particularly high cytotoxicity, and are covered in a patent application. In addition, minor effect on regular cells was observed. As the titanium has been previously shown based on in vivo testing to be significantly less toxic than platinum, (and is commonly found in food and cosmetics), several pharmaceutical companies expressed interest in our compounds. However, in vivo activity and some mechanistic insights (required for FDA approval) are fundamental for allowing commercialization. Therefore, we propose to conduct a series of experiments that will bring this research to a more ""mature"" level suitable to be undertaken by pharmaceutical companies. These include in vivo testing on mice to establish safety and activity towards different cells and by different administration techniques, including IV. Additionally, as solubility is an issue, different formulations will be assessed. Basic mechanistic studies will include evaluating potential interaction with DNA. All these studies are not covered by the ERC grant, and will be conducted in collaboration with a biologist expert in cancer research."

149 599 €

Start date: 2012-03-01, End date: 2013-05-31