The Kiel University is a university in the city of Kiel, Germany. It was founded in 1665 as the Academia Holsatorum Chiloniensis by Christian Albert, Duke of Holstein-Gottorp and has approximately 24,000 students today. The University of Kiel is the largest, oldest, and most prestigious in the state of Schleswig-Holstein. Until 1864/66 it was not only the northernmost university in Germany but at the same time the 2nd largest university of Denmark. Wikipedia.
News Article | May 8, 2017
In a recent study in Human Molecular Genetics, researchers from VIB and KU Leuven led by prof. Philip Van Damme, reveal a novel function for progranulin in lysosomes: it acts as chaperone of the lysosomal protease cathepsin D. The results were obtained in collaboration with Prof. Paul Saftig from the University of Kiel. Prof. Philip Van Damme (VIB-KU Leuven/University Hospital Leuven): "Our findings suggest that dysfunction of lysosomal enzymes such as cathepsin D can contribute to neuronal dysfunction caused by progranulin deficiency in diseases such as frontotemporal dementia. These are important new insights in our search for solutions." Frontotemporal dementia or FTD is the second most common form of early onset dementia, after Alzheimer's Disease, characterized by neuronal loss in the frontal and anterior temporal lobes. It generally affects people in their mid 40's to mid 60's leading to severe changes in behavior or language problems. Behavioral changes include, but are not limited to, apathy and disinhibition, which eventually prohibit the patient's ability for normal social interaction. Patients can also display different language problems leading to semantic dementia or primary progressive aphasia. Currently, there is no treatment available for this disease, limiting the prognosis of FTD patients to 6-8 years after symptom onset. In almost half of the patients, the disease runs in the family. Mutations in the gene encoding progranulin are one of the most frequent causes and result in a 50% loss of functional progranulin protein. Efforts to model the human disease in mice have been disappointing as the full knockout of progranulin leads to a mild phenotype without neurodegeneration. Previous studies have shown that progranulin can stimulate neuronal survival and neurite outgrowth in cultures. These findings led to the hypothesis that neurodegeneration in FTD patients might occur due to a reduced trophic support for neurons. An in vivo paradigm of facial nerve crush injury was used to study the neurotrophic effects of progranulin in more detail. The recovery from such injury was delayed in the absence of progranulin and reintroduction of human progranulin in these mice could completely rescue this deficit, indicating that axonal regeneration after nerve injury depends specifically on the presence of progranulin. Using newly generated microglial and neuronal specific progranulin knockout mice, it was show that basal progranulin expression is mainly neuronal and that only neuronal progranulin deletion drives the axonal outgrowth deficit. A transcriptomics approach to identify possible mediators of the observed effects pointed towards the lysosomal aspartic protease cathepsin d (CTSD) as the most upregulated gene in progranulin knockout mice. A direct interaction between the two proteins was established. In the brains of aged progranulin knockout mice, the relative CTSD activity was reduced. By adding progranulin, the proteolytic activity of CTSD could be stimulated in a dose-dependent manner. Progranulin was shown to bind to CTSD and prevented its heat induced degradation. The interaction between GRN and CTSD proved to be necessary for the recovery after facial nerve injury, linking the neurotrophic effects of GRN to a lysosomal chaperone function on CTSD. Note: Philip Van Damme and Sander Beel are part of the VIB-KU Leuven Center for Brain & Disease Research
Agency: European Commission | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016
This project is the second in the series of EC-financed parts of the Graphene Flagship. The Graphene Flagship is a 10 year research and innovation endeavour with a total project cost of 1,000,000,000 euros, funded jointly by the European Commission and member states and associated countries. The first part of the Flagship was a 30-month Collaborative Project, Coordination and Support Action (CP-CSA) under the 7th framework program (2013-2016), while this and the following parts are implemented as Core Projects under the Horizon 2020 framework. The mission of the Graphene Flagship is to take graphene and related layered materials from a state of raw potential to a point where they can revolutionise multiple industries. This will bring a new dimension to future technology a faster, thinner, stronger, flexible, and broadband revolution. Our program will put Europe firmly at the heart of the process, with a manifold return on the EU investment, both in terms of technological innovation and economic growth. To realise this vision, we have brought together a larger European consortium with about 150 partners in 23 countries. The partners represent academia, research institutes and industries, which work closely together in 15 technical work packages and five supporting work packages covering the entire value chain from materials to components and systems. As time progresses, the centre of gravity of the Flagship moves towards applications, which is reflected in the increasing importance of the higher - system - levels of the value chain. In this first core project the main focus is on components and initial system level tasks. The first core project is divided into 4 divisions, which in turn comprise 3 to 5 work packages on related topics. A fifth, external division acts as a link to the parts of the Flagship that are funded by the member states and associated countries, or by other funding sources. This creates a collaborative framework for the entire Flagship.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-01-2016 | Award Amount: 16.02M | Year: 2017
The SYSCID consortium aims to develop a systems medicine approach for disease prediction in CID. We will focus on three major CID indications with distinct characteristics, yet a large overlap of their molecular risk map: inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis. We have joined 15 partners from major cohorts and initiatives in Europe (e.g.IHEC, ICGC, TwinsUK and Meta-HIT) to investigate human data sets on three major levels of resolution: whole blood signatures, signatures from purified immune cell types (with a focus on CD14 and CD4/CD8) and selected single cell level analyses. Principle data layers will comprise SNP variome, methylome, transcriptome and gut microbiome. SYSCID employs a dedicated data management infrastructure, strong algorithmic development groups (including an SME for exploitation of innovative software tools for data deconvolution) and will validate results in independent retrospective and prospective clinical cohorts. Using this setup we will focus on three fundamental aims : (i) the identification of shared and unique core disease signatures which are associated with the disease state and independent of temporal variation, (ii) the generation of predictive models of disease outcome- builds on previous work that pathways/biomarkers for disease outcome are distinct from initial disease risk and may be shared across diseases to guide therapy decisions on an individual patient basis, (iii) reprogramming disease - will identify and target temporally stable epigenetic alterations in macrophages and lymphocytes in epigenome editing approaches as biological validation and potential novel therapeutic tool. Thus, SYSCID will foster the development of solid biomarkers and models as stratification in future long-term systems medicine clinical trials but also investigate new causative therapies by editing the epigenome code in specific immune cells, e.g. to alleviate macrophage polarization defects.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-18-2015 | Award Amount: 8.19M | Year: 2016
Liver cancer in the paediatric population is rare with an incidence approximately 1-1.5 per million population. The commonest tumour seen in the childhood population is hepatoblastoma (HB), usually seen in young children and infants. Much rarer (about 10% of paediatric liver cancers) is hepatocellular carcinoma (HCC), usually seen in the teenage population and sometimes associated with underlying cirrhotic liver diseases. The ChiLTERN project relates to topic PHC 18 establishing effectiveness of health care interventions in the paediatric population. The ChiLTERN project builds on a unique opportunity to undertake a comprehensive research programme linked to an ambitious global partnership which will see the single largest clinical trial (the Paediatric Hepatic International Tumour Trial - PHITT) ever undertaken in this population of patients, with several randomised questions in six subgroups of patients. ChiLTERN will allow us to move towards an era of personalised therapy in which each patient will receive the correct amount of chemotherapy and will undergo has the best surgical operation (surgical resection or liver transplant). By using both clinical and biological information, we can assign patients more accurately to risk groups based on their survival. Using genetic tests and biomarkers, we will determine those children who may be at risk of developing long term side effects (deafness, heart failure, kidney damage). In addition, biomarkers will allow us to monitor during therapy and detect toxicities early before serious damage is done so that we can adapt treatment and prevent these problems. Finally, we will be using imaging technology tools which will help our surgeons plan liver operations more safely and effectively. Ultimately ChiLTERN will allow us to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-09-2016 | Award Amount: 6.20M | Year: 2017
Due to lack of targeted interventions, compliance issues, insufficient effect sizes and a high non-responder rate to currently available interventions, there is an urgent need to develop innovative and new interventions for chronic paediatric neuropsychiatric disorders, such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Transcranial direct current stimulation (tDCS) has been shown to be an innovative, effective and safe alternative treatment approach for neuropsychiatric disorders in adults. Here, for the first time, the effect of tDCS on core neurocognitive and behavioral outcomes will be proven in children and adolescents. First, effect sizes and safety of standard tDCS in the clinical setting targeting core brain regions and disorder specific cognitive tasks will be established by three phase-IIa randomized, double blind, sham-controlled studies in ADHD and ASD. Second, the impact of brain development and age-dependent anatomical / functional features on effects of tDCS will be studied systematically using methods of modern neurophysiology, neuroimaging and electric current modeling. This involves an additional phase-I clinical trial. Third, mechanisms of tDCS on brain function will be studied, and biomarkers will be developed in order to predict individual response to standard and individualized stimulation protocols. Finally, the applicability of tDCS in children and adolescents will be improved by developing an innovative personalized home-based treatment option in combination with a telemental health service, which will be tested by a fifth, phase-IIa clinical trial. Throughout the entire project, ethical concerns of the target population will be addressed. This project opens a new avenue for the application of tDCS as an alternative treatment for a great number of chronic neuropsychiatric disorders in children and adolescents and will allow flexible integration of tDCS in the daily routine of families.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-18-2015 | Award Amount: 5.54M | Year: 2016
Each year 15 million babies are born prematurely and many suffer from respiratory failure due to immaturity of the lung and lack of control of breathing. Although respiratory support, especially mechanical ventilation, can improve their survival, it also causes severe injury to the vulnerable lung resulting in severe and chronic pulmonary morbidity lasting in to adulthood. Heterogeneity of lung aeration, resulting in areas of lung over inflation and lung collapse, plays a crucial part in the risk of mortality and morbidity due to respiratory failure. This distribution of lung aeration cannot be detected by currently available bedside monitoring tools and imaging methods. Thus, an imaging technique for continuous non-invasive bedside monitoring of infants lung function is urgently needed. In order to address this, CRADL will use EIT technology to establish a monitoring tool for interventions in the paediatric population. Electrical impedance tomography (EIT) is a non-radiative, inexpensive technique that can facilitate real time dynamic monitoring of lung aeration, and recent studies have shown that it is effective in monitoring aeration in preterm babies. CRADL will show how EIT can provide new cost effective, easy to use, respiratory management tools and clinical protocols that can be universally adopted to reduce deaths and disability in preterm babies by delivering a tool that provides continuous, non-invasive, radiation free, bedside information on regional lung aeration and ventilation during daily clinical care of (preterm) infants and children with respiratory failure. CRADL will also assess the effectiveness, efficacy and safety of such a system in guiding respiratory management and supportive care of the most common causes of paediatric respiratory failure (respiratory distress syndrome, bronchiolitis and acute respiratory distress syndrome), with the final goal of reducing short and long term adverse effects of disease and its treatment in this populat