Prothena Biosciences Ltd and University of Munster | Date: 2017-01-18
The present application provides evidence that a combined blockade against alpha-4 integrin and MCAM is more effective than against either molecule alone. In consequence, the invention provides methods of combination treatment in which both an antagonist of alpha-4 integrin and an MCAM antagonist are administered to a subject having or at risk of multiple sclerosis or other autoimmune disease.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.08M | Year: 2017
For the selective and effective incorporation of oxygen into biological molecules (oxygenation reaction), several enzyme types have evolved in nature. They catalyse crucial reactions in various metabolic routes. The chemistry feasible with these biocatalysts is unrivalled when compared with conventional chemical methods. Therefore, these oxygenating enzymes are very promising tools in biotechnological approaches. However, when compared with other enzyme classes, such as hydrolases, oxygenases are still in their infancy considering their biotechnological potential. To fully exploit the catalytic power of oxygenases, several hurdles have to be taken for which a higher level of knowledge on these enzymes is needed while also technical aspects have to be solved. The European Training Network (ETN) OXYTRAIN is a joint academic/non-academic training initiative supporting the convergence of biochemistry, enzyme engineering and biotechnology. The consortiums mutual goal is developing a new generation of innovative and entrepreneurial early stage researchers (ESRs) to satisfy the need for knowledge and skills to produce and apply oxidative enzymes. This will be achieved by setting up a network and intersectoral programme in which multiple disciplines will be integrated and exploited. By bringing together 7 academic beneficiaries that are experts in the field of individual oxygenase groups, the network will provide perfect conditions for cross-fertilization of knowledge, while the 3 industrial beneficiaries and 5 partner organisations will add to the consortium by translating the generated knowledge into real industrial applications, such as textiles, pharmaceuticals and biorefineries.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.89M | Year: 2017
The network Collective effects and optomechanics in ultra-cold matter (ColOpt) will train early-stage researchers (ESR) in fundamental science and applications in the areas of cold atom and quantum physics, optical technologies and complexity science to promote European competiveness in emergent quantum technologies. It consists of nine academic nodes and three companies from six European countries, supported by two partners in Brazil and the USA, five further non-academic partners and one public-private partnership. Collective, nonlinear dynamics and spontaneous self-organization are abundant in nature, sciences and technology and of central importance. Building on this interdisciplinary relevance, a particular novelty of ColOpt is the integration of classical and quantum self-organization. The research program focuses on collective interactions of light with laser-cooled cold and quantum-degenerate matter. We will explore innovative control of matter through optomechanical effects, identify novel quantum phases, enhance knowledge of long-range coupled systems and advance the associated trapping, laser and optical technologies, establishing new concepts in quantum information and simulation. ColOpt combines cutting-edge science with training in complex instrumentation and methods to the highest level of technical expertise, both experimentally and theoretically, and fosters the development of transferable skills and critical judgement. Each ESR will be exposed to a broad spectrum of experimental, theoretical and industrial environments, to obtain core competence in one of them and the collaborative experience and skills to thrive in a truly international and intersectorial framework. ESRs will develop the capabilities to analyse and understand complex interactions, and will gain awareness of societal and entrepreneurial needs and opportunities. Taken together, this will enable them to excel in a variety of sectors of our diverse and rapidly changing society.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.83M | Year: 2017
ES-Cat will use directed evolution as a tool to reproduce Natures remarkable ability to generate molecular machines - in particular enzymes that perform at levels near perfection. Instead of seeing rational and combinatorial approaches as alternatives, we combine them in this network to achieve a smarter and more efficient exploration of protein sequence space. By harnessing the forces of Darwinian evolution and design in the laboratory we want to (i) screen large and diverse libraries for proteins with improved and useful functions, (ii) optimize existing proteins for applications in medicine or biotechnology and (iii) provide a better understanding of how existing enzymes evolved and how enzyme mechanisms can be manipulated. This Network brings together leading academic and industrial groups with diverse and complementary skills. The range of methodologies represented in ES-Cat allows an integrated approach combining in silico structural and sequence analysis with experimental high-throughput screening selection methods (phage-, ribozyme and SNAP display, robotic liquid handling, lab-on-a-chip/microfluidics) with subsequent systematic kinetic and biophysical analysis. This integration of methods and disciplines will improve the likelihood of success of directed evolution campaigns, shorten biocatalyst development times, and make protein engineering applicable to a wider range of industrial targets. It will also train the next generation of creative researchers ready to fill roles in tailoring enzymes and other proteins for industrial application in synthetic biology efforts to move towards a bio-based economy, rivaling advances that are being made in the US and allowing the EU economy to harvest its evident socio-economic benefits.
Wencel-Delord J.,University of Strasbourg |
Glorius F.,University of Munster
Nature Chemistry | Year: 2013
The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry. © 2013 Macmillan Publishers Limited.
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2016 | Award Amount: 1.07M | Year: 2017
Space is the foundational characteristic of visual perception and we generally perceive it as continuous and uniform. Behavioural measurements and the properties of our sensory systems however, demonstrate that this is an illusory situation and our percept is constructed by the brain. One example is our lack of awareness of the blind spot that exists in each eye. Space is non-uniformly represented in the visual brain and this representation is dynamically influenced by motor behaviour, in particular by eye movements. The PLATYPUS consortium will investigate the dynamic nature of spatial sensation and perception, focussing on the continuous mutual interaction of motor behaviour and perception. Our research objectives integrate human behavioural and cutting edge non-human primate electrophysiological research techniques and focus on translation of basic into applied research. Focussing on the adaptive nature of vision and action, strategies to perturb and probe perceptual space and geometry will allow measurement of spatial and geometrical perception in humans and the representation of such in non-human primates. This research will extend to applications for people wearing progressive lenses which distort action and space perception, patients with a blind area in their visual field and for virtual reality technology development. PLATYPUS researchers will grow existing and establish new collaborative teams, sharing research techniques, knowledge and mentoring between established and with upcoming researchers in academia and industry. Individuals will benefit from intense scientific and career development training while institutions will benefit from the exchange of state-of-the-art techniques. The ultimate outcome will be increased understanding of the continuously updating neural construction of space and the production of assistive technologies for people needing corrective lenses, with ocular or visual discontinuity and for the growing virtual reality industry.
Herter J.M.,University of Munster
Blood | Year: 2013
Integrin activation is essential for the function of leukocytes. Impaired integrin activation on leukocytes is the hallmark of the leukocyte adhesion deficiency syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. In inflammation, leukocytes collect different signals during the contact with the microvasculature, which activate signaling pathways leading to integrin activation and leukocyte recruitment. We report the role of P-Rex1, a Rac-specific guanine nucleotide exchanging factor, in integrin activation and leukocyte recruitment. We find that P-Rex1 is required for inducing selectin-mediated lymphocyte function-associated antigen-1 (LFA-1) extension that corresponds to intermediate affinity and induces slow leukocyte rolling, whereas P-Rex1 is not involved in the induction of the high-affinity conformation of LFA-1 obligatory for leukocyte arrest. Furthermore, we demonstrate that P-Rex1 is involved in Mac-1-dependent intravascular crawling. In vivo, both LFA-1-dependent slow rolling and Mac-1-dependent crawling are defective in P-Rex1(-/-) leukocytes, whereas chemokine-induced arrest and postadhesion strengthening remain intact in P-Rex1-deficient leukocytes. Rac1 is involved in E-selectin-mediated slow rolling and crawling. In vivo, in an ischemia-reperfusion-induced model of acute kidney injury, abolished selectin-mediated integrin activation contributed to decreased neutrophil recruitment and reduced kidney damage in P-Rex1-deficient mice. We conclude that P-Rex1 serves distinct functions in LFA-1 and Mac-1 activation.
Sorokin L.,University of Munster
Nature Reviews Immunology | Year: 2010
The advent of in situ immunology and intravital analyses of leukocyte movement in tissues has drawn attention to the previously neglected extracellular matrix (ECM) and its role in modulating immune cell behaviour in inflamed tissues. The ECM exists in different biochemical and structural forms; both their individual components and three-dimensional ultrastructure impart specific signals to cells that modulate basic functions that are important for the early steps in inflammation, such as immune cell migration into inflamed tissues and immune cell differentiation. In chronically inflamed tissues, aberrant ECM expression and fragments of the ECM that are derived from tissue-remodelling processes can influence immune cell activation and survival, thereby actively contributing to immune responses at these sites. © 2010 Macmillan Publishers Limited. All rights reserved.
Studer A.,University of Munster
Angewandte Chemie - International Edition | Year: 2012
This Minireview highlights recent developments in radical trifluoromethylation reactions. The trifluoromethyl group belongs to the privileged moieties in medicinal chemistry. Many drugs and drug candidates contain a trifluoromethyl substituent. Also in agrochemicals, the CF3 moiety often appears. The present article addresses the radical trifluoromethylation of alkenes and arenes mainly focussing on recent achievements. However, important earlier work in this field is also covered. A privileged moiety, the CF3 substituent can be found in many drugs, drug candidates, and agrochemicals. This Minireview highlights recent developments in the radical trifluoromethylation of alkenes and arenes. Important older contributions are also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Agency: European Commission | Branch: H2020 | Program: ERC-STG | Phase: ERC-2016-STG | Award Amount: 1.49M | Year: 2017
Infinite one-dimensional structures with a metallic main chain of short metal-metal contacts have attracted considerable attention in the field of materials science for many decades due to their excellent optical properties and remarkable dichroism and electrical (semi)conductivity. These materials suffer, however, from decomposition prior to melting and low solubility and processability. The strategy of introducing alkyl side chains of different nature in the past two decades proved to be particularly successful towards better soluble materials or gels with implications in optoelectronics. However, this comes at the price of reduced bulk conductivities leading in some cases to electrical insulators due to the perturbation of the metal-metal contacts. In this proposal, a Systems Chemistry approach will be introduced to create unprecedented supramolecular copolymers that are anticipated to exhibit: a) high solubility, reversibility and stability in organic solvents and water and, b) short metal contacts involving either positively and negatively charged metal ions of the same nature (Pt2\/Pt2-) or dissimilar metal centres (Pd(II)/Pt(II) and Ag(I)/Au(I)) with equivalent coordination geometry. To achieve this goal, ligands with an extended aromatic surface for pi-stacking supported by complementary non-covalent interactions have been selected to bring suitable metal ions in close proximity. This can be summarized in three approaches. 1) Optimization of the geometrical complementarity between the interacting ligands; 2) Introduction of hydrogen bonding and electrostatic complementarity between side groups, and 3) Exploiting weak interactions between geometrically equivalent electron rich and electron poor units. The extent of metal-metal interactions can be ultimately controlled by introducing suitable light switchable groups. This concept is expected to provide access to novel, highly-ordered materials with rich photophysical and semiconductive properties.