Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 2.80M | Year: 2016
The cell is the universal unit of living matter, and there cannot be propagation of life without cell division. DivIDe aims to investigate the mechanisms and principles of cell division and to reproduce them in vitro with synthetic approaches. Crucial to cell division is the mitotic spindle, a structure whose main duty is the separation of chromosomes. The spindle is made of microtubules (MT), molecular motors, and MT-binding factors, some of which show astounding complexity. The mitotic spindle is the one of the cellular structures that best represents the ability of biological matter to self-organize though arrays of dynamic protein-protein interactions. It rapidly assembles when cells enter mitosis, and it disassembles, after sister chromatid separation and mitotic exit. The complexity and dynamic behaviour of the mitotic spindle captures the imagination of synthetic biologists and modellers. These molecular engineers try to understand and harness the principles of self-organization to generate new biological structures endowed with the most typical features of biological matter, the ability to harness energy to do mechanical or chemical work. The emerging discipline of synthetic biology aims to bring together modellers, physicists, and chemists, with biochemists, structural biologists and cell biologists. So does DivIDe, which will train a new generation of molecular engineers endowed with a strong basis in quantitative computational and biochemical methods, and therefore capable of addressing cellular and molecular mechanisms. Furthermore, molecular engineering harbours industrial applications, and DivIDe will continuously provide results for potential exploitation by the three SME partners. Training in management skills, conceptual and ethical thinking, communication and networking will complement the scientific offer. In summary, DivIDe will be able to teach an integrated package of skills and will train the molecular biologists of the future.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.3.3-4 | Award Amount: 7.82M | Year: 2011
ANTIFLU is to develop innovative drugs against influenza virus infections based on a novel concept that precludes the development of viral resistance and ensures efficacy against upcoming pandemic influenza strains. Viral replication is known to depend on multiple host factors. Whilst traditional anti-influenza treatments usually target viral factors, ANTIFLU will aim at drugs interfering with host-response pathways. The concept of drugs targeting human factors, established in treatment of other diseases, has yet not been sufficiently explored for treatment of viral infections, although it bears compelling advantages over conventional antiviral therapies: (i) the avoidance of viral escape mutants and (ii) the broad coverage against unprecedented viral variants. ANTIFLU aims to fully exploit this potent approach to fill critical gaps in our current treatment and prevention options against seasonal and pandemic influenza virus infections. By building upon an existing panel of potent human targets and firm knowledge derived from FP6 project RIGHT, an interdisciplinary consortium will pursue the identification and validation of small molecule ligands and inhibitory RNA molecules effective against influenza infection. Promising modulators will form the basis to generate lead molecules that will be further refined to yield clinically applicable therapeutics. Initial preclinical studies will aim at providing proof of concept in animal models, safety and toxicology profiles. They will allow initiating complete clinical trials immediately after the phase of FP7 support, thanks to the commitment already taken by investors from the private sector. The consortium includes several SMEs, internationally renowned research groups and clinical institutions with extensive experience in anti-influenza treatment and clinical trials. An already agreed common exploitation model will provide a smooth route to market and optimal use of the project results.
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-EID | Phase: MSCA-ITN-2015-EID | Award Amount: 2.56M | Year: 2016
The advent of the big data era in chemistry and the life sciences requires the development of new computational analysis methods, which are not only of scientific, but also economic relevance. Currently, the international data market already grows six times faster than the entire IT sector, and growth rates further increase. Achieving and sustaining a leadership positions in the big data arena represent critically important challenges for the EU. The economic developments in the emerging big data field are science-driven. Due to complexity and heterogeneity of biochemical and biomedical data, large-scale data exploration and exploitation are intrinsically interdisciplinary tasks. BIGCHEM positions itself at interfaces between chemistry, computer science, and the life science to provide well-structured multidisciplinary training and educate high-in-demand computational specialists capable of operating in interdisciplinary and international research and business settings. Cornerstones of BIGCHEMs curriculum include on-line lectures and periodic schools taught by internationally leading experts in chemical and life science informatics, a balanced consortium of academia, SMEs, and large industry, and an unprecedented symbiosis of academic and industrial training and application components. Accordingly, BIGCHEM is well positioned to boost multilateral collaborations between academia and industry and train scientists who are highly competitive in the international big data market. In BIGCHEMs R&D and training activities, the development and evaluation of conceptually novel methods for large-scale data analysis, knowledge extraction, and information sharing with demonstrated practical application potential take center stage. The network has a clearly defined policy for exploitation of new IP through wide involvement of target users, SMEs, and large industry facilitated by the experienced technology transfer department of the coordinators team.
Gaali S.,Max Planck Institute of Psychiatry |
Gaali S.,Lead Discovery Center GmbH |
Gaali S.,Max Planck Institute of Biochemistry
Nature chemical biology | Year: 2015
The FK506-binding protein 51 (FKBP51, encoded by the FKBP5 gene) is an established risk factor for stress-related psychiatric disorders such as major depression. Drug discovery for FKBP51 has been hampered by the inability to pharmacologically differentiate against the structurally similar but functional opposing homolog FKBP52, and all known FKBP ligands are unselective. Here, we report the discovery of the potent and highly selective inhibitors of FKBP51, SAFit1 and SAFit2. This new class of ligands achieves selectivity for FKBP51 by an induced-fit mechanism that is much less favorable for FKBP52. By using these ligands, we demonstrate that selective inhibition of FKBP51 enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice. Our findings provide the structural and functional basis for the development of mechanistically new antidepressants.
Lead Discovery Center GmbH | Date: 2013-02-27
The present invention relates to a CDK9 inhibitor, especially a selective CDK9 inhibitor, for use in treating, ameliorating and/or preventing midline carcinoma. Also corresponding methods for treating, preventing or ameliorating midline carcinoma are subject of the present invention. Preferably, NUT midline carcinoma is treated with the CDK9 inhibitors in accordance with the present invention.
Lead Discovery Center GmbH | Date: 2013-09-04
The present invention relates to pyrazolo[1,5-a][1,3,5]triazine derivatives and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of infectious diseases, including opportunistic diseases, immunological diseases, autoimmune diseases, cardiovascular diseases, cell proliferative diseases, inflammation, erectile dysfunction and stroke, and pharmaceutical compositions containing at least one of said pyrazolo[1,5-a][1,3,5]triazine derivatives and/or pharmaceutically acceptable salts thereof. Furthermore, the present invention relates to the use of said pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors for a protein kinase.
Lead Discovery Center GmbH | Date: 2013-02-27
The present invention relates to a method of selecting (a) cell(s), (a) tissue(s) or (a) cell culture(s) with susceptibility to a selective CDK9 inhibitor. Also a method for determining the responsiveness of a mammalian tumor cell or cancer cell to treatment with a selective CDK9 inhibitor is described herein. In particular, the present invention provides for an in vitro method for the identification of a responder for or a patient sensitive to a selective CDK9 inhibitor, whereby the patient is suspected to suffer from NUT midline carcinoma (NMC). The present invention also relates to a method of monitoring or predicting the efficacy of a treatment of NUT midline carcinoma (NMC), wherein treatment with a selective CDK9 inhibitor is in particular envisaged. Also the use of a (transgenic) non-human animal or a (transgenic) cell having at least one rearrangement in the NUT gene for screening and/or validation of a medicament for the treatment NUT midline carcinoma (NMC) is described. Furthermore, a kit useful for carrying out the methods described herein as well as an oligo- or polynucleotide capable of detecting rearrangements in the NUT gene are provide.
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.34M | Year: 2016
The goal of the TASPPI European Training Network (ETN) is the establishment of a highly interdisciplinary research and educational training platform for early stage scientists in the Chemical Life Sciences to overcome the inherent boundaries between academia and industry and to increase their employability in both areas. To this end we have teamed up in a consortium comprising 5 partners from industry (AstraZeneca, GlaxoSmithKline, UCB, Lead Disocvery Center, Taros Chemicals) and 6 partners from academia (Universities of Dundee, Eindhoven, Leeds, Lille, Prague, and Siena). The scientific objective of the multi-sectorial Training Network is the development and implementation of a multidisciplinary technology platform bringing together structural molecular biology, chemical biology, cell biology, synthetic chemistry, and medicinal chemistry for the identification of Small-molecule Stabilizers of Protein-Protein Interactions (PPIs) as a novel class of therapeutic agents and basic research tool compounds. With this new technological approach we aim to address a number of unmet medical needs in the areas Cancer, Neurodegenerative Diseases (Alzheimers, Parkinsons), Pulmonary Diseases, Inflammation and Metabolic Diseases (Diabetes).
Agency: Cordis | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2011-IAPP | Award Amount: 2.01M | Year: 2012
The objective of the application is the development and characterization of small molecule stabilizers of protein-protein interactions (Molecular Glues) as a novel class of biological tool compounds and potential therapeutic drugs for the treatment of cancer as well as Alzheimers and Parkinsons Disease, respectively. As biological targets we work on 14-3-3 proteins, an important class of adapter proteins that regulate a multitude of enzymes and proteins involved in the development of cancer and neurodegenerative diseases. 14-3-3 protein-protein interactions relevant in different cancers are Raf1 and YAP/TAZ. In Alzheimers and Parkinsons Disease the interaction of 14-3-3 proteins with AICD and -Synuclein are of potential therapeutic interest. The proposed project is based on the innovative approach to develop small molecules that bind selectively to the interaction surface of specific disease-related protein complexes thereby stabilizing their interaction which might lead to a beneficial therapeutic effect. This approach is complementary to todays strategy of developing inhibitors that target the active site of single enzymes and opens new possibilities to address undrugable targets. In fact, small molecule stabilizers of protein-protein-interactions have the potential to deliver a target-specific, target-oriented and more efficient modulation of the protein function than classical inhibitors. In this application, we propose two projects identifying and optimizing small molecules stabilizing 14-3-3 interactions with: 1. The cancer-relevant proteins Raf and YAP/TAZ 2. The Alzheimers and Parkinsons disease-relevant proteins AICD and -Synuclein. By stabilizing these protein-protein interactions the biological functions and biochemical properties like biochemical activity, subcellular localization and aggregation behaviour of the 14-3-3 target proteins are modulated.
Lead Discovery Center GmbH | Date: 2016-11-30
The present invention relates to methods for detection of nucleotide polymerase activity and methods of detecting compounds that modulate nucleotide polymerase activity, by detecting product formation of the nucleotide polymerase to be tested based on determination of close proximity of two labeled nucleotide probes able to bind the product of the nucleotide polymerase. It is preferred that proximity dependent energy transfer, such as frster resonance energy transfer, between said labeled nucleotide probes is determined. The invention further provides kits comprising components for carrying out the inventive methods for detection of nucleotide polymerase activity.