Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.91M | Year: 2015
BIOPOL is an interdisciplinary European training network at the interface of cell biology, physics and engineering. BIOPOL aims specifically at the understanding of fundamental mechanochemical principles guiding cellular behaviour and function and their relevance to human disease. A new supra-disciplinary research field is emerging bringing together the fields of molecular cell biology, physics and engineering aiming at an in depth understanding of fundamental cellular mechanochemical principles. BIOPOL combines exactly this required expertise in one joint training program for young researchers. BIOPOL has assembled a unique multidisciplinary consortium bringing together top scientists from the fields of molecular/developmental cell biology, membrane physics, engineering as well as specialists from the private sector. The scientific objectives focus on understanding of fundamental mechanisms of cellular mechanosensing in health and disease, the role of external forces in cell division and mechanochemical regulation of cell polarity including tissue formation. Finally, part of BIOPOLs research program is the further development of cutting edge technologies like advanced atomic force microscopy, novel photonic tools like optical stretcher or innovative organ on a chip technology, exploiting physical cellular properties. BIOPOLs collaborative cutting edge research program is integral part of its training program provided to early stage researcher and is further translated into seven state of the art experimental training stations representing the consortiums expertise. In addition, BIOPOL has developed a 3 years modular curriculum including workshops, summerschools, Business plan competitions and conferences with a specific agenda of transferable skill training elements highly relevant for scientific communication, translational research and in particular entrepreneurship.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 14.69M | Year: 2013
Cancers are genetic disease arising from the accumulation of multiple molecular alterations in affected cells. Large-scale genomic, transcriptomic and proteomic analyses have established comprehensive catalogues of molecules which are altered in their structure and/or abundance in malignant tumors as compared to healthy tissues. Far less developed are concepts and methods to integrate data from different sources and to directly interrogate gene functions on a large scale in order to differentiate driver alterations, which directly contribute to tumor progression, from indolent passenger alterations. As a consequence, examples of successful translation of knowledge generated from omics approaches into novel clinical concepts and applications are scarce. Pancreatic cancer is a prime example of this dilemma. Representing the 4th to 5th most common cause of cancer related deaths, it is a disease with a major socioeconomic impact. Despite enormous advances in the identification of molecular changes associated with the disease, new treatment options have not emerged. Thus, 5-year survival rates remain unchanged at a dismal 6%, the lowest for all solid tumors. Using pancreatic cancer as a model disease, the goal of this integrative project is to develop novel cellular and animal models, as well as novel strategies to generate, analyze and integrate large scale metabolic and transcriptomic data from these models, in order to systematically characterize and validate novel targets for therapeutic intervention. In addition to the general tumor cell population, special consideration will be given to sub-populations of tumor-initiating cells, a.k.a. tumor stem cells. To this end, the consortium comprises i) SMEs with strong focus on technology development, ii) clinical and academic partners with extensive experience in pancreatic cancer molecular biology and management of pancreatic cancer patients, and iii) technology and data analysis experts from academic groups.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-EID | Phase: MSCA-ITN-2015-EID | Award Amount: 1.06M | Year: 2016
MIMIC is an interdisciplinary European Industrial Doctorate at the interface of cell biology, engineering and drug development. MIMIC aims to develop and improve novel organs on chips technology. This technology combines modern cell biology with microfluidics and chip-based techniques with the goal to mimic organ functionality. There is a high demand by the pharmaceutical industry for more reliable tissue models to test drug toxicity and drug efficiency at early stages of drug development. Early reliable drug testing will have a major impact on drug development costs and human health. Furthermore, ethical considerations urge for the search for alternatives to replace animal tests in drug development and basic research. Organs on chips are a new exciting possibility to closer mimic human organ functionality in vitro than conventional 2D or 3D cell cultures. Organs on chips allow both, the emulation of healthy organs as well as the emulation of specific disease conditions using corresponding engineered or patient derived human cells. Moreover, organs on chips are ideally suited for high-throughput drug screening. The EID-MIMIC will develop novel organs on chips prototypes, and validate their suitability for end-users for high throughput drug screening or basic research. MIMIC will train early stage researchers in cutting edge technologies, like novel chip based technologies e.g. cell micropatterning, soft-lithography and microfluidics technology, as well as state of the art microscopy like super resolution- and confocal spinning disc microscopy and modern genome editing techniques like CRISPR-technology. In addition, MIMIC has developed a 3 year modular curriculum including workshops on creativity and business skills, summer schools, business plan competitions and international conferences with a specific agenda of transferable skill training elements highly relevant for scientific communication, translational research and, in particular, entrepreneurship.
PubMed | Chinese National Center for Safety Evaluation for Drugs, Wyss Institute for Biologically Inspired Engineering, Massachusetts Institute of Technology, ETH Zurich and 21 more.
Type: Journal Article | Journal: ALTEX | Year: 2016
The recent advent of microphysiological systems - microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro - is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-six experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 5.10M | Year: 2015
Common mechanisms and pathways in Stroke and Alzheimers disease. It has long been recognized that stroke and (Alzheimers Disease) AD often co-occur and have an overlapping pathogenesis. As such, these two diseases are not considered fellow travelers, but rather partners in crime. This multidisciplinary consortium includes epidemiologists, geneticists, radiologists, neurologists with a longstanding track-record on the etiology of stroke and AD. This project aims to improve our understanding of the co-occurrence of stroke and AD. An essential concept of our proposal is that stroke and AD are sequential diseases that have overlapping pathyphysiological mechanisms in addition to shared risk factors. We will particularly focus on these common mechanisms and disentangle when and how these mechanisms diverge into causing either stroke, or AD, or both. Another important concept is that mechanisms under study will not only include the known pathways of ischemic vasculopathy and CAA, but we will explore and unravel novel mechanisms linking stroke and AD. We will do so by exploiting our vast international network in order to link various big datasets and by incorporating novel analytical strategies with emerging technologies in the field of genomics, metabolomics, and brain MR-imaging.
Wevers N.R.,Mimetas Inc. |
de Vries H.E.,VU University Amsterdam
Tissue Barriers | Year: 2016
The microvasculature of the brain forms a protective blood-brain barrier (BBB) that ensures a homeostatic environment for the central nervous system (CNS), which is essential for optimal brain functioning. The barrier properties of the brain endothelial cells are maintained by cells surrounding the capillaries, such as astrocytes and pericytes. Together with the endothelium and a basement membrane, these supporting cells form the neurovascular unit (NVU). Accumulating evidence indicates that the supporting cells of the NVU release a wide variety of soluble factors that induce and control barrier properties in a concentration-dependent manner. The current review provides a comprehensive overview of how such factors, called morphogens, influence BBB integrity and functioning. Since impaired BBB function is apparent in numerous CNS disorders and is often associated with disease severity, we also discuss the potential therapeutic value of these morphogens, as they may represent promising therapies for a wide variety of CNS disorders. © 2016 Taylor & Francis Group, LLC.
Oedit A.,Leiden University |
Oedit A.,Netherlands Metabolomics Center |
Vulto P.,Leiden University |
Vulto P.,Netherlands Metabolomics Center |
And 7 more authors.
Current Opinion in Biotechnology | Year: 2015
The Lab-on-a-Chip concept aims at miniaturizing laboratory processes to enable automation and/or parallelization via microfluidic chips that are capable of handling minute sample volumes. Mass spectrometry is nowadays the detection method of choice, because of its selectivity, sensitivity and wide application range. We review the most interesting examples over the last two-and-a-half years where the two techniques were used for bioanalytical applications. Furthermore, we discuss the merits and limitations of such hyphenated systems. We inventorize the reported applications and approaches. We see an ongoing trend towards chip-based liquid chromatography-mass spectrometry usage and small volume analysis applications, particularly in the field of proteomics where bottom-up approaches profit from chip-based technologies and hyphenation with complex cell cultures. © 2014 The Authors Published by Elsevier Ltd.
Mimetas Inc. | Date: 2015-11-03
Scientific, optical measurement and inspection apparatus and instruments for producing, growing and studying biological tissues; laboratory apparatus for the production and culture of cells and tissues, and research into cells, tissues and organs. Research, design and development of microfluidic products for use in scientific research laboratories in the medical, chemical, pharmaceutical and veterinary fields; research, design and development of cells, tissues and organs for use in scientific research laboratories in the medical, pharmaceutical, cosmetic, surgical, dental and veterinary field; development and research into biological tissues and organs models; scientific and industrial research and for health care services. Medical and pharmaceutical services, including services for the diagnosis of disorders of the human body, development of tissue and organ models, development of personalized diagnostic tests, to determine the effects and side effects of drugs and potential drugs; information services relating to pharmaceutical services provided via online computer networks; medical care services in the field of hygiene, beauty; providing information in the field of diagnostics; providing medical information to medical professionals on patients with artificially produced biological tissues and organs from a website; health information, namely, providing information about products and services via global computer networks for health; medical analysis for the diagnosis and treatment of persons.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-02-2015 | Award Amount: 6.00M | Year: 2015
The overall objective of this project is to identify novel drug candidates capable of slowing down the progression of neurodegeneration in the subset of Parkinsons disease (PD) patients with overt mitochondrial dysfunction. Multi-modal phenotypic characterisation of cohorts of monogenic PD patients with overt mitochondrial dysfunction will be used as an anchor for the discovery of two extreme cohorts of idiopathic PD patients: with and without detectable mitochondrial dysfunction. A suite of personalised in vitro, in vivo, and in silico models will be generated using induced pluripotent stem cells (iPSCs) from selected subjects and controls. An industrial quality 3D microfluidic cell culture product, specifically designed for the culture of iPSC-derived dopaminergic neurons, will be developed for use in a morphological and bioanalytical screen for lead compounds reduce mitochondrial dysfunction. By monitoring motor behaviour and in situ striatal neurochemistry at high temporal resolution, the in vivo response to lead compounds will be characterised in humanised mouse models with striatally transplants of iPSC-derived dopaminergic neurons derived from PD patients. Personalised computational models of dopaminergic neuronal metabolism and mitochondrial morphology will be developed. These in silico models will be used to accelerate drug development by prioritising pathways for metabolomic assay optimisation, stratifying idiopathic PD patients by degree of mitochondrial dysfunction, predicting new new targets to reduce mitochondrial dysfunction and mechanistic interpretation in vitro and in vivo experimental results. SysMedPD unites a highly experienced multidisciplinary consortium in an ambitious project to develop and apply a systems biomedicine approach to preclinically identify candidate neuroprotectants, for the estimated 1-2 million people worldwide who suffer from PD with mitochondrial dysfunction.