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University of Pittsburgh, Uchida, Justus Liebig University, Glorioso Iii and Grandi | Date: 2017-06-28

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

Justus Liebig University | Date: 2017-02-15

The invention relates to an ion drive for a spacecraft, in particular for a satellite, comprising a reservoir with fuel; an ionization chamber connected to the reservoir; a generator for producing an electrostatic, magnetostatic and/or electromagnetic field the interior of the ionization chamber, wherein the field is suitable for ionizing the fuel; and a charge-carrier acceleration system for producing an electric field suitable for accelerating the ionized fuel, wherein the fuel contains a diamondoid. Moreover, the invention relates to a spacecraft comprising an ion drive, a method for operating an ion drive and the use of diamandoid as fuel for an ion drive.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.87M | Year: 2017

CircRTrain focuses on circular RNAs (circRNAs), a new large class of single-stranded RNAs with covalently closed ends. CircRNAs have only very recently attracted high general interest and become the focus of an increasing number of publications: recent discoveries through sequencing technology and computational analyses have revealed the widespread existence of circRNAs in animal cells. Particularly in neural tissues, circRNA expression is high, dynamic, and evolutionarily conserved. In aging animal brains the expression of certain circRNAs is strongly elevated, suggesting connections to age-related diseases. The study of circRNAs thus emerges as a novel topic with highest importance for the understanding of such diverse conditions as neurodegenerative diseases, aging, and cancer. Moreover, the highly stable expression and their presence in human blood and exosomes make circRNAs attractive biomarker candidates. The overall aims of circRTrain are to 1. Elucidate the biogenesis and function of circRNAs; 2. Define their role in diseases; 3. Exploit their potential as biomarkers and for medical applications; and 4. Combine cutting-edge technologies and disciplines. Understanding circRNAs and exploring their medical relevance requires to integrate various technologies (sequencing, single-molecule and whole-organism imaging, RNA knockdown/delivery, CRISPR/CAS9), disciplines (biochemistry, computational biology, genetics), model systems (worm, fly, mouse, human) and medical applications (biomarkers, new therapeutic strategies). CircRTrain will combine these diverse approaches and industrial technologies by training 15 early stage researchers (ESR) at two SMEs and seven academic partners, which are all leaders in their respective fields. Additionally, cooperation with four partner organizations, circRNA devoted conferences, winter- and summer schools will extend training for the ESRs, sustaining the critical number of young talented professionals in the field.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-06-2016 | Award Amount: 6.00M | Year: 2017

Natural epidemics and outbreaks of emerging viral epidemics are growing problems internationally. The general aim of the CCHFVaccine project is to develop and deliver a vaccine, which can significantly increase our capacity to control the situation of Crimean Congo Haemorrhagic fever (CCHF) disease on a global basis. The proposed work program on CCHF virus aims to build a multidisciplinary research network, able to deliver vaccine candidates, methods and procedures eligible for clinical trials, with a special focus on prevention. Thanks to the background, unique facilities and tools available among the consortium participants, CCHFVaccine will deliver tools for countering the threat of this infection in Europe and endemic areas of the world. This work program will attempt to fill gaps in CCHFV virus research on immunology and vaccinology. To achieve this overall aim, an intensive work plan will be put in place with the following specific objectives: i) to produce vaccine candidates, ii) to bring several unique animal models into front line vaccine research, iii) to validate and bring the most promising vaccine candidates to clinical trials, iv) to ensure that an immune mediated protection is adequately understood, v) to perform clinical trials at Phase I and ensure a strategy for the effective deployment and utilization in resource-poor countries, and vi) to link this project to public health bodies, NGOs and vaccine companies. The proposed CCHFVaccine project will succeed in bringing together selected competitive advantages such as: operating capacity with appropriate facilities (state-of-the-art BSL-4s) and the only animal BSL-4 -with capacity to challenge domestic animals in Europe, highly experienced researchers in the development and evaluation of vaccine candidates, authorities and entities of human and animal health, clinical samples from endemic countries, and an international network proven to be functional by the previous EU-funded CCHFever and EDENext.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.10M | Year: 2017

The European Training Network DNAREPAIRMAN aims to train a new generation of innovative young scientists in cutting edge biophysical research methodology to address central questions in biology concerning the mode of action of critical molecular machines with relevance for human health. The Network consists of a highly collaborative consortium consisting of 12 participants coming from academia, industry, and the creative sector. Participating laboratories in the Network are part of established research schools within renowned research organizations and Universities, with supervisors who are experts within their respective research field, publish regularly in high-impact journals and have received EURYI and ERC awards. This environment of excellence offers a multidisciplinary PhD program to 12 young researchers (ESRs), through training in the analysis of basic chemical and physical principles that underlie the correct timing and localization of events during DNA repair. In addition training will center around method development using methodology, equipment, software and experience provided first-hand by four small technology-driven companies. Individual research projects as well as personal training plans will be implemented for each ESR, incorporating a local training program, multiple rotations within partner laboratories, exposure to the non-academic sector and Network meetings. ESRs will follow scientific workshops, courses in transferable skills, career development and entrepreneurship, and will disseminate and communicate their projects to a diverse audience in close collaboration with the creative sector. DNAREPAIRMAN will result in a new generation of mature and innovative European scientists with a thorough understanding of fundamental quantitative principles underlying biology, with experience in technique development, and affinity for the academic as well as the non-academic research setting, providing a broad and promising career perspective.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 2.86M | Year: 2017

The consolidation of the knowledge that cancer is not only a genetic, but also a metabolic disease, has led scientists to investigate the intricate metabolic plasticity that transformed cells must undergo to survive the adverse tumor microenvironment conditions, and the contribution of oncogenes and tumor suppressors in shaping metabolism. In this scenario, genetic, biochemical and clinical evidences place mitochondria as key actors in cancer metabolic restructuring, not only because these organelles have a crucial role in the energy and biosynthetic intermediates production but also because occurrence of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA has been associated to different types of cancer. TRANSMIT aims to dissect the metabolic remodeling in human cancers, placing the focus on the role of mitochondria and bridging basic research to the improvement/development of therapeutic strategies. Further, TRANSMIT fosters the communication of this emerging field to the patients and their families. To these aims, TRANSMIT will create a network of seven different countries, among which world-leading basic science and clinical centers of excellence, several industrial partners with up-to-date omics technologies, as well as non-profit foundations and associations who care for cancer patients. By creating the critical mass of scientific excellence, TRANSMIT will allow to transfer the current knowledge into the wide field of cancer research, translating scientific and technical advances into the education and training of eleven Early Stage Researchers. TRANSMIT will implement training-through-research dedicated to unravel the metabolic features of cancer, as well as to provide a full portfolio of complementary skills through the creation of a network of basic, translational and industrial laboratories, devoted to a multidisciplinary/multisectorial education of young scientists.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: COMPET-3-2016-b | Award Amount: 1.49M | Year: 2017

MINOTORs strategic objective is to demonstrate the feasibility of the ECRA technology as a disruptive game-changer in electric propulsion, and to prepare roadmaps paving the way for the 2nd EPIC call, in close alignment with the overall SRC-EPIC strategy. Based on electron cyclotron resonance (ECR) as the sole ionization and acceleration process, ECRA is a cathodeless thruster with magnetic nozzle, allowing thrust vectoring. It has a considerable advantage in terms of global system cost, where a reduction of at least a factor of 2 is expected, and reliability compared to mature technologies. It is also scalable and can potentially be considered for all electric propulsion applications, from microsatellites to space tugs. Although the first results obtained with ECRA have been encouraging, the complexity of the physics at play has been an obstacle for the understanding and development of the technology. Thus an in-depth numerical and experimental investigation plan has been devised for the project, in order to bring the technology from TRL3 to TRL5. The strong consortium is composed of academic experts to perform the research activities on ECRA, including alternative propellants, along with experienced industrial partners to quantify its disruptive advantages on the propulsion subsystem and its market positioning. ECRAs advantages as an electric thruster technology can be a disruptive force in a mostly cost-driven satellite market. It would increase European competitiveness, help develop low-cost satellite missions such as constellations, provide end-of-life propulsion, and pave the way for future emerging electric propulsion technologies. The 36 months MINOTOR project requests a total EC grant of 1 485 809 M for an experienced consortium of 7 partners from 4 countries: ONERA (FR, Coordinator), industries Thales Alenia Space (BE), Thales Microelectronics (FR), SNECMA (FR), Universities Carlos III (ES) and Giessen (GE), and SME L-up (FR).

Probability of event-free survival (pEFS) in pediatric T-cell lymphoblastic lymphoma is about 80%, whereas survival in relapsed patients is very poor. No stratification criteria have been established so far. Recently, activating NOTCH1 mutations were reported to be associated with favorable prognosis, and loss of heterozygosity at chromosome 6q (LOH6q) was reported to be associated with increased relapse risk. The current project was intended to evaluate the prognostic effect of these markers. Mutations in hot spots of NOTCH1 and FBXW7 were analyzed in 116 patients. Concerning LOH6q status, 118 patients were investigated, using microsatellite marker analysis, in addition to an earlier reported cohort of 99 available patients. Ninety-two cases were evaluable for both analyses. All patients were treated with T-cell lymphoblastic lymphoma-Berlin-Frankfurt-Münster group (BFM)-type treatment. LOH6q was observed in 12% of patients (25/217) and associated with unfavorable prognosis (pEFS 27% ± 9% vs 86% ± 3%; P < .0001). In 60% (70/116) of the patients, NOTCH1 mutations were detected and associated with favorable prognosis (pEFS 84% ± 5% vs 66% ± 7%; P = .021). Interestingly, NOTCH1 mutations were rarely observed in patients with LOH in 6q16. Both prognostic markers will be used as stratification criteria in coming Non-Hodgkin Lymphoma-BFM trials.

Marschall R.,Justus Liebig University
Advanced Functional Materials | Year: 2014

The formation of semiconductor composites comprising multicomponent or multiphase heterojunctions is a very effective strategy to design highly active photocatalyst systems. This review summarizes the recent strategies to develop such composites, and highlights the most recent developments in the field. After a general introduction into the different strategies to improve photocatalytic activity through formation of heterojunctions, the three different types of heterojunctions are introduced in detail, followed by a historical introduction to semiconductor heterojunction systems and a thorough literature overview. Special chapters describe the highly-investigated carbon nitride heterojunctions as well as very recent developments in terms of multiphase heterojunction formation, including the latest insights into the anatase-rutile system. When carefully designed, semiconductor composites comprising two or three different materials or phases very effectively facilitate charge separation and charge carrier transfer, substantially improving photocatalytic and photoelectrochemical efficiency. The formation of semiconductor composites, leading to multicomponent and multiphase heterojunctions, is herein reviewed. Highly active photocatalyst systems with improved charge carrier separation and charge transfer are the result, leading to significantly enhanced efficiencies. Particular interest is given to recent developments in multiphase composites © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hughes J.,Justus Liebig University
Annual Review of Plant Biology | Year: 2013

Extensive studies in both lower and higher plants indicate that plant phytochrome photoreceptors signal not only by regulating transcription in the nucleus but also by acting within the cytoplasm, the latter signaling routes acting within minutes or even seconds and also providing directional information. Directional signals seem to arise from phytochromes attached anisotropically to the plasma membrane. Neochromes-phytochrome-phototropin hybrid photoreceptors probably attached to the plasma membrane-provide this signal in various ferns and perhaps certain algae but are absent from other groups. In mosses and probably higher plants too, a subpopulation of canonical phytochromes interact with phototropins at the plasma membrane and thereby steer directional responses. Phytochromes also seem able to regulate translation in the cytoplasm. This review discusses putative phytochrome functions in these contexts. © Copyright ©2013 by Annual Reviews. All rights reserved.

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