ERC FUNDED PROJECTS

The use of renewable feedstocks by the chemical industry is fundamental due to both the depletion of fossil resources and the increasing pressure of environmental concerns. Biomass can act as a sustainable source of organic industrial chemicals; however, the establishment of a renewable chemical industry that is economically competitive with the present oil-based one requires the development of new processes to convert biomass-derived compounds into useful industrial materials following the principles of green chemistry. To achieve these goals, developments in several fields including heterogeneous catalysis are needed. One of the ways to accelerate the discovery of new potentially active, selective and stable catalysts is the massive use of computational chemistry. Recent advances have demonstrated that Density Functional Theory coupled to ab initio thermodynamics, transition state theory and microkinetic analysis can provide a full view of the catalytic phenomena. The aim of the present project is thus to employ these well-tested computational techniques to the development of a theoretical framework that can accelerate the identification of new catalysts for the conversion of biomass derived target compounds into useful chemicals. Since compared to petroleum-based materials-biomass derived ones are multifuncionalized, the search for new catalytic materials and processes has a strong requirement in the selectivity of the chemical transformations. The main challenges in the project are related to the high functionalization of the molecules, their liquid nature and the large number of potentially competitive reaction paths. The requirements of specificity and selectivity in the chemical transformations while keeping a reasonably flexible framework constitute a major objective. The work will be divided in three main work packages, one devoted to the properties of small molecules or fragments containing a single functional group; the second addresses competition in multiple functionalized molecules; and third is dedicated to the specific transformations of two molecules that have already been identified as potential platform generators. The goal is to identify suitable candidates that could be synthetized and tested in the Institute facilities.

1 496 200 €

Start date: 2010-10-01, End date: 2015-09-30

Each year millions of animals undertake remarkable migratory journeys, across oceans and through hemispheres, guided by the Earth’s magnetic field. The cellular and molecular basis of this enigmatic sense, known as magnetoreception, remains an unsolved scientific mystery. One hypothesis that attempts to explain the basis of this sensory faculty is known as the magnetite theory of magnetoreception. It argues that magnetic information is transduced into a neuronal impulse by employing the iron oxide magnetite (Fe3O4). Current evidence indicates that pigeons employ a magnetoreceptor that is associated with the ophthalmic branch of the trigeminal nerve and the vestibular system, but the sensory cells remain undiscovered. The goal of this ambitious proposal is to discover the cells and molecules that mediate magnetoreception. This overall objective can be divided into three specific aims: (1) the identification of putative magnetoreceptive cells (PMCs); (2) the cellular characterisation of PMCs; and (3) the discovery and functional ablation of molecules specific to PMCs. In tackling these three aims this proposal adopts a reductionist mindset, employing and developing the latest imaging, subcellular, and molecular technologies.

1 499 752 €

Start date: 2014-04-01, End date: 2019-03-31

Signal transduction in biology relies on the transfer of information across biomolecules by concerted conformational changes that cannot currently be characterized experimentally at high resolution. In CONCERT we will develop a method based on the use of nuclear magnetic resonance spectroscopy in solution that will provide very detailed descriptions of such changes by using the information about structural heterogeneity contained in a parameter that is exquisitely sensitive to molecular shape called residual dipolar coupling measured in steric alignment. To show how this new method will allow the study of information transfer we will determine conformational ensembles that will report on the intra and inter-domain concerted conformational changes that activate the androgen receptor, a large allosteric multi-domain protein that regulates the male phenotype and is a therapeutic target for castration resistant prostate cancer, the condition suffered by prostate cancer patients that have become refractory to hormone therapy, the first line of treatment for this disease. To complement the structural information obtained by nuclear magnetic resonance and, especially, measure the rate of information transfer across the androgen receptor we will carry out in a collaborative fashion high precision single molecule Förster resonance energy transfer and fluorescence correlation spectroscopy experiments on AR constructs labelled with fluorescent dyes. In summary we will develop a method that will make it possible to describe some of the most fascinating biological phenomena, such as allostery and signal transduction, and will, in the long term, be an instrument for the discovery of drugs to treat castration resistant prostate cancer, a late stage of prostate cancer that is incurable and kills ca. 70.000 European men every year.

1 950 000 €

Start date: 2015-07-01, End date: 2020-06-30

After decades of truly transformative advancements in single molecule (bio)physics and surface science, it is still no more than a vision to predict and control macroscopic phenomena such as adhesion or electrochemical reaction rates at solid/liquid interfaces based on well-characterized single molecular interactions. How exactly do inherently dynamic and simultaneous interactions of a countless number of interacting “crowded” molecules lead to a concerted outcome/property on a macroscopic scale? Here, I propose a unique approach that will allow us to unravel the scaling of single molecule interactions towards macroscopic properties at adhesive and redox-active solid/liquid interfaces. Combining Atomic Force Microscopy (AFM) based single molecule force spectroscopy and macroscopic Surface Forces Apparatus (SFA) experiments CSI.interface will (1) derive rules for describing nonlinearities observed in complex, crowded (water and ions) and chemically diverse adhesive solid/liquid interfaces; (2) uniquely characterize all relevant kinetic parameters (interaction free energy and transition states) of electrochemical and adhesive reactions/interactions of single molecules at chemically defined surfaces as well as electrified single crystal facets and step edges. Complementary, (3) my team and I will build a novel molecular force apparatus in order to measure single-molecule steady-state dynamics of both redox cycles as well as binding unbinding cycles of specific interactions, and how these react to environmental triggers. CSI.interface goes well beyond present applications of AFM and SFA and has the long-term potential to revolutionize our understanding of interfacial interaction under steady state, responsive and dynamic conditions. This work will pave the road for knowledge based designing of next-generation technologies in gluing, coating, bio-adhesion, materials design and much beyond.

1 499 750 €

Start date: 2016-07-01, End date: 2021-06-30