Research team

Laboratory of cell biology and histology

Expertise

The interfaculty research group ‘Cell Biology and Histology’ which I am leading, has the responsibility to enlarge the core facility ‘Biomedical microscopic imaging’ and to support the community of the university concerning microscopic imaging. Available services/expertise: - scientific and technical support in setting up new experiments belonging to the expertise of the core facility, and aid with interpretation of the results - technical and scientific support of researchers and students at the different microscopy systems of the core facility, including image recording, -processing and -analysing. Apart from the above-mentioned technical expertises, my main scientific expertise relates to cell biology and histology in general ant to functional morphology of the respiratory, gastrointestinal and cardiovascular system with focus on the autonomic innervation and neuro-immune interactions.

High resolution structure determination of therapeutically relevant proteins as a means to validate an affinity grid for cryo-electron microscopy. 01/07/2021 - 30/06/2022

Abstract

Cryo-electron microscopy (cryo-EM) has evolved tremendously over the last five years, thereby becoming a promising method to gain high-resolution structural information on proteins with a relevance in human (patho)physiology (e.g., cancer, host-pathogen interactions, and neuropathologies). This rapid evolution has sparked the interest of pharmaceutical companies in cryo-EM, since obtaining detailed structural information on proteins yields better insights into their function, which can be used to develop novel and/or better pharmaceuticals. However, as a result of its success, several inefficiencies within the cryo-EM workflow have emerged, especially related to sample preparation. Novel technologies have been proposed to optimize these, but these new techniques (i) often address only a single step within the overall workflow, (ii) are incompatible with other novel protocol/procedures or (iii) are difficult to implement by non-expert users. In a previous PoC study we developed a novel type of affinity grid that can be used for on-grid protein purification. Furthermore, market interviews have revealed that the introduction of this technology is best achieved through a service for protein structure determination (including a workflow from protein sample to protein structure) rather than simply providing the technology as such. The aim of this follow-up PoC is to validate the technology by resolving different protein structures using this grid technology and meanwhile establishing a service pipeline for high-resolution protein structure determination. This will illustrate the value of the grids towards potential customers (Pharma, Biotech) and investors.

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IMARK. Network for image-based biomarker discovery and evaluation 01/01/2021 - 31/12/2026

Abstract

IMARK capitalizes on the deeply rooted expertise in biomedical imaging at the University of Antwerp to push the boundaries of precision medicine. By resolving molecular and structural patterns in space and time, IMARK aims at expediting biomarker discovery and development. To this end, it unites research groups with complementary knowledge and tools that cover all aspects of imaging-centred fundamental research, preclinical validation and clinical evaluation. IMARK harbours high-end infrastructure for electron and light microscopy, mass spectrometry imaging, magnetic resonance imaging, computed tomography, positron emission tomography and single-photon emission computed tomography. Moreover, IMARK members actively develop correlative approaches that involve multiple imaging modalities to enrich information content, and conceive dedicated image analysis pipelines to obtain robust, quantitative readouts. This unique blend of technologies places IMARK in an excellent position as preferential partner for public-private collaborations and offers strategic advantage for expanding the flourishing IP portfolio. The major application fields of the consortium are neuroscience and oncology. With partners from the Antwerp University Hospital and University Psychiatric Centre Duffel, there is direct access to patient data/samples and potential for translational studies.

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Interactive and intelligent cellomics platform. 01/05/2020 - 30/04/2024

Abstract

Crucial insights in cell and developmental biology have been gained by virtue of live cell imaging technology. Along with a growing complexity of cellular models and the finesse with which they can be genetically engineered, comes a demand for more advanced microscopy. In brief, modern comprehensive cell systems research (cellomics) requires light-efficient, intelligent and interactive imaging modalities. To address this shared need, our consortium has identified a state-of-the art platform that allows ultrafast, yet minimally invasive imaging of small to medium-sized biological samples (from single cells to organoids) at high resolution, so as to capture dynamic events that range in timescale from voltage fluctuations to successive cell divisions. To only focus on those events that are truly of interest, and thereby boost throughput, the system is equipped with online image recognition capabilities. Finally, to allow targeted perturbations such as local damage induction or optogenetic switching, small regions can be selectively illuminated in the field of view. With this level of control, it will become possible to interrogate (sub-)cellular processes with unprecedented detail. The platform readily finds applications in diverse frontline research fields including neuroscience, cardiovascular research and infectious diseases, rendering it an indispensable asset for the applicants, the microscopy core facility and the University of Antwerp.

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Multidimensional analysis of the nervous system in health and disease (µNeuro). 01/01/2020 - 31/12/2025

Abstract

Neuropathological research is an interdisciplinary field, in which imaging and image-guided interventions have become indispensable. However, the rapid proliferation of ever-more inquisitive technologies and the different scales at which they operate have created a bottleneck at the level of integration, a) of the diverse image data sets, and b) of multimodal image information with omics-based and clinical repositories. To meet a growing demand for holistic interpretation of multi-scale (molecule, cell, organ(oid), organism) and multi-layered (imaging, omics, chemo-physical) information on (dys)function of the central and peripheral nervous system, we have conceived μNEURO, a consortium comprising eight established teams with complementary expertise in neurology, biomedical and microscopic imaging, electrophysiology, functional genomics and advanced data analysis. The goal of μNEURO is to expedite neuropathological research and identify pathogenic mechanisms in neurodevelopmental and -degenerative disorders (e.g., Alzheimer's Disease, epilepsy, Charcot-Marie-Tooth disease) on a cell-to-organism wide scale. Processing large spatiotemporally resolved image data sets and cross-correlating multimodal images with targeted perturbations takes center stage. Furthermore, inclusion of (pre)clinical teams will accelerate translation to a clinical setting and allow scrutinizing clinical cases with animal and cellular models. As knowledge-hub for neuro-oriented image-omics, μNEURO will foster advances for the University and community including i) novel insights in molecular pathways of nervous system disorders; ii) novel tools and models that facilitate comprehensive experimentation and integrative analysis; iii) improved translational pipeline for discovery and validation of novel biomarkers and therapeutic compounds; iv) improved visibility, collaboration and international weight fueling competitive advantage for large multi-partner research projects.

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High-resolution slide scanner for digital histopathological phenotyping in health and disease. 01/01/2020 - 31/12/2021

Abstract

Digital pathology involves high-speed, high-resolution digital acquisition of images representing entire stained tissue sections from glass slides and allows them to be viewed directly in much the same way as standard microscopy. While this creates a permanent record of histological slide data and facilitates data sharing with collaborators, importantly, it allows analysis, quantification and objective pathological assessment of entire tissue samples, which is now current practice in pre-clinical and clinical research. We propose to acquire a high-resolution whole-slide scanner, notably absent at UA, not only to facilitate research at the promotors' groups, but virtually any research group performing basic, pre-clinical or clinical research at UA involving histopathology. We firmly believe that acquisition of such a digital scanner will help research groups at UA to stay competitive in biomedical research, facilitate and forge scientific and industrial collaborations at UA and beyond, and generate important industrial revenues.

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Development of next-generation 3D brain organoids for the study and modulation of immunemediated neurodegeneration in cerebrovascular disease. 01/01/2018 - 31/12/2022

Abstract

Developing novel neuroprotective and/or immune-modulating therapeutic strategies for almost every neurological disease or trauma requires, both for academia and pharmaceutical industry, the existence of robust in vitro cell culture models to mimic disease-associated pathological events. Unfortunately, a complex interplay between multiple central nervous system (CNS) cell types and multiple cell types from the body's peripheral immune system, cannot be easily recapitulated by currently used 2-dimensional (2D) co-culture assays. It is exactly therefore that successful pre-clinical experimental efficacy has proved to be very difficult to translate into clinical benefit, and as a consequence there is an increasing gap in knowledge and progress between bench and bed side. One highly promising novel approach to improve the predictive power of in vitro human neuro-immune research consists in developing modular 3D brain organoids that resemble brain tissue at the structural, cellular and functional level. Within this project we aim to develop and optimize a new method for generating isogenic 3D brain organoids, comprising human pluripotent stem cell (hPSC)-derived neurons, astrocytes and microglia. Furthermore, hPSC-derived astrocytes and endothelial cells will be used to create a blood-brain-barrier model for physical separation of hPSC-derived macrophages from the generated human 3D brain organoids. Together, this integrated cell system will represent a powerful new 3D human neuro-immune cell culture paradigm. Within this multidisciplinary IOF-SBO project, the methodological approach to generate 3D brain organoids, combined with the experience in the field of clinical research and the availability of patient samples, is truly unique and will - in first instance - highly contribute to the field of in vitro cerebrovascular disease modelling and treatment validation. Furthermore, our aims to install an integrated 3D brain organoid technology platform at the University of Antwerp, will - given the current scientific and economic interests – allow for both short-term and long-term valorisation of our combined efforts, with both intellectual (PhD-theses, A1 publications) as well as financial (contract research) revenues.

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The peripheral component of neurodegeneration: uptake and transmission of amyloid proteins in the enteric nervous system. 01/01/2018 - 31/12/2021

Abstract

Since a few years, evidence is growing that a disease process affecting the central nervous system (CNS) can also involve its enteric counterpart (ENS) and vice-versa. Indeed, various neurodegenerative disorders are accompanied or even preceded by gastrointestinal malfunctions. This relationship is well-documented for prion diseases and Parkinson's disease, but has not yet been scrutinized for Alzheimer's disease (AD), a devastating neurodegenerative disorder that is typified by a progressive and debilitating cognitive decline. A defining feature of AD is the accumulation of misfolded amyloid-beta peptides. Considering that the CNS and ENS are highly interconnected, the gut microbiome produces amyloids that can cross-seed polymerization, and inflammation promotes amyloid build-up, it is highly conceivable that the gut is a vulnerable node for amyloid-driven degeneration. Yet, the mechanisms underlying cellular processing of amyloids in the ENS are poorly characterized. Hence, with this research project, we will investigate the entry routes, spreading behaviour and cellular effects of microbial and host-derived amyloid proteins in the ENS. Using innovative imaging technologies and well-defined molecular characterization methods, this work will provide a solid basis for refining the gut-brain axis theory in the context of AD and will open novel avenues for both fundamental and clinical research with relevance for a broad range of proteopathic neurodegenerative diseases.

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The peripheral component of neurodegeneration: response to and transmission of host-derived and microbial amyloid proteins in the enteric nervous system. 01/01/2018 - 31/12/2021

Abstract

Alzheimer's disease (AD) currently affects 1 in 9 individuals over 65 years of age but its prevalence will only rise against the background of a steadily greying population. With no cure currently available and diagnosis relying on the assessment of late-stage cognitive decline, it is imperative that novel early medical entry points are explored through original fundamental research. Recent insights suggest that the gut may be a vulnerable node for amyloid-driven neurodegeneration. That is why we want to define the origin, entry routes and spreading behaviour of amyloid proteins in the enteric nervous system (ENS). Using innovative imaging technologies and well-defined molecular analyses, we will shed light on a novel gut-brain relationship with relevance for future (pre-)clinical research. As the gut represents a unique, minimally invasive window to assess neuropathology, our work may spark the development of early biomarkers that directly report on disease progression in AD-patients. Moreover, confirming the notion that microbial-derived amyloids could represent a putative trigger for pathology may cause a paradigm shift for AD therapy."

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Lab-on-a-chip for cryo-EM (LOCEM). 01/10/2019 - 30/09/2021

Abstract

The general purpose of this project is the development of an optimized prototype of the total lab-on-a-chip for cryo-EM, i.e. a cryo-EM affinity grid in combination with a microfluidic chip. The latter will enable the purification of bioparticles (i.e. proteins) which will then be loaded on a cryo-EM affinity grid.

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Development of an affinity grid for cryo-electron microscopy enabling protein structure determination. 01/04/2019 - 31/10/2020

Abstract

Cryo-electron microscopy (cryo-EM) has evolved tremendously over the last five years, thereby becoming a promising method to gain high-resolution structural information on therapeutically relevant proteins involved in cancer, bacterial or viral infections, or neuropathologies. This rapid evolution has sparked the interest of pharmaceutical companies in cryo-EM, because protein structure information may yield better insights into the functioning of proteins, which can be used to develop better drugs. However, as a result of its success several inefficiencies within the cryo-EM workflow have emerged, especially related to sample preparation. Novel technologies have been proposed to optimize these, but these new techniques (i) often address only a single step within the overall workflow, (ii) are incompatible with other novel solutions or (iii) are difficult to implement by non-expert users. The objective of this PoC study is to revive affinity grids, electron microscopy grids that can be used for on-grid protein purification, and a potential solution to bypass some of the existing bottlenecks. by introducing novel recent developments in nanotechnology. The novel grid will be part of a larger international initiative aimed at developing an integrated workflow for highthroughput cryo-EM.

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Project website

Purchase scanning electron microscope 01/01/2018 - 31/12/2018

Abstract

This project comprises the purchase of a new scanning electron microscope for studying surface features of biomedical samples and replaces the SEM515 (purchased in 1987). The new instrument allows examination of samples both at low and high vacuum conditions.

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The study of the possible interactions between human Mas-related G Protein-coupled receptors. 15/07/2017 - 14/07/2018

Abstract

Mas-related G-Protein coupled receptors (Mrgpr's) have a putative role in sensory processes, including itch and pain. Previous studies on Mrgpr's in intestinal inflammatory conditions revealed marked expressional changes in them, specifically in sensory neurons of enteric nervous system (ENS). The fact that most of Mrgpr's are still classified as orphan, has hampered the study of their functions and regulatory mechanisms. This project develops novel approaches to explore the function of Mrgpr despite their current orphan status and explores protease-linked activation mechanisms of these Mrgprs. MrgprE and MrgprF are of special interest since these receptors are co-expressed in both enteric plexusses (myenteric and submucosal), and co-regulated in Schistosoma mansoni and TNBS-induced ileitis murine models. Mouse and human MrgprE and MrgprF are orthologous, and ongoing studies on gut biopsies in our laboratory confirm expression of MrgprE and MrgprF in the human gastrointestinal tract. This has prompted us to elucitade the interaction of human (h-) MrgprE and MrgprF. Therefore, we employed various biophysical and biochemical techniques including a novel luciferase complementation technique (NanoBiT), Bioluminescence resonance energy transfer (BRET), Fluorescence resonance energy transfer (FRET) and co-immunoprecipitation to validate our hypothesis. Results gave concrete evidence of h-MrgprE/h-MrgprF heteromerization, as well as h-MrgprE and h-MrgprF homomerization respectively. Over the last decade examples of GPCR's homo- and hetero-merizations are increasing at accelerating pace. Homo- and heteromeric states of GPCR's modulate the signal transductions capabilities and, therefore, regulate G-protein-dependent or -independent signalling associated with them. Nevertheless, biophysical tools used for detecting homo- and heteromerization of GPCR's account only for the oligomerization state but do not define their affinity and the competition among interacting partners for oligomerization. Therefore, there is need of novel protein-protein interaction (PPI) tools to ascertain affinity and competition among GPCR's. Starting from our obtained results, we are developing a quantitative NanoBiT assay, which will expand the current PPI tools and provide a better tool to study affinity, competition, biased agonism and transient protein interactions.

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Modular confocal microscopy platform with light sheet illumination. 01/05/2016 - 30/04/2020

Abstract

The application concerns an innovative microscopy platform for visualizing cells, tissue specimen and living small model organisms in three dimensions at unprecedented speed and with excellent resolution and contrast. As a unique feature, the platform is equipped with a light-sheet module, which is based on an orthogonal configuration of laser-generated, micrometer-thin plane illumination and sensitive one-shot detection. Seamless integration with confocal modalities enables imaging the same sample from the micro- to the mesoscale. The device has a broad application radius in the neurosciences domain inter alia for studying neurodegeneration and -regeneration (e.g. whole brain imaging, optogenetics); but it also has direct utility in various other fields such as cardiovascular research (e.g. plaque formation and stability), plant developmental research (e.g. protein localization during plant growth) and ecotoxicology (e.g. teratogenicity and developmental defects in zebrafish). Furthermore, its modular construction will enable adaptation and targeted expansion for future imaging needs.

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Biomedical Microscopic Imaging and in-vivo Bio-Imaging (EGAMI). 01/01/2015 - 31/12/2020

Abstract

EGAMI stands for Expert Group Antwerp Molecular Imaging. Moreover, EGAMI is the mirror word of 'image'. EGAMI clusters the internationally recognized expertise in the profession of fundamental and biomedical imaging at the University of Antwerp: the Bio-Imaging Lab, the Molecular Imaging Center Antwerp (MICA), Radiology, the Laboratory for Cell Biology and Histology, and the Vision Lab (for post-processing of medical images). EGAMI's mission is providing an integrated research platform that comprises all aspects of multimodality translational medical imaging. Multimodality refers to the integration of information from the various imaging techniques. Within EGAMI, there is pre-clinical and clinical expertise and infrastructure for magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). EGAMI executes projects ranging from applied biomedical (imaging) and fundamental research to imaging methodologies. Die applied biomedical research focusses on the research fields neuro(bio)logy (i.e. development and validation of biomarkers (as well as therapy evaluation) for diseases like Alzheimer's, schizophrenia, multiple sclerosis etc.) and oncology (i.e. biomarkers for improved patient stratification and therapy monitoring). Since the pre-clinical biomedical research within EGAMI makes use of miniaturized versions of imaging equipment for humans (scanners) is it inherently translational, in other words initial findings acquired in animal experiments can be translated into clinical applications for improved diagnosis and treatment of patients ('from bench to bedside'). Beside the application of imaging in the biomedical research, EGAMI also conducts projects that aim to achieve an improvement and optimization of the imaging methodology. The expertise of the MICA (e.g. the development of new radiotracers) and of the Vision Lab (e.g. the development of image reconstruction, segmentation, and analysis algorithms) offers here the strategic platform to assemble intellectual property rights.

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Networking and strategy. 01/12/2014 - 30/11/2016

Abstract

This project represents a formal research agreement between UA and on the other hand VITO. UA provides VITO research results mentioned in the title of the project under the conditions as stipulated in this contract.

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    Centre for R&D Monitoring. (ECOOM) 01/01/2014 - 31/12/2018

    Abstract

    The mission of the Centre for R&D Monitoring (ECOOM) is to develop and consolidate a consistent and performing system of R&D and Innovation (RD&I) indicators which provides the Flemish Governement with actual and relevant statistic data for mapping and monitoring the RD&I efforts in the Flemish region. At the same time ECOOM develops a portfolio of relevant scientific research activities to support this mission. Therefore, ECOOM (1) has a series of targeted, long term task packages to map, measure and analyze the Flemish R&D and innovation potential; (2) ensures that a data management infrastructure is available to the Flemish Government containing bibliometric and technometric data and data on innovation and PhDs; (3) provides qualified staffing; (4) builds the necessary and appropriate IT-infrastructure and (5) is able to conduct ad-hoc task or projects at request of the Flemish Government. ECOOM acts as an inter-association center.

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      Project website

      Mas-related gene receptors as new mediators of gastrointestinal neuro-immune communication. 01/01/2014 - 31/12/2017

      Abstract

      The current project aims to further explore the role and regulation of Mrgs in the gastrointestinal tract. We will study the function of Mrg in neurons and mast cells using advanced microscopical and cell biological techniques. Furthermore we plan to explore the role of Mrg beyond inflammatory intestinal pathologies, i.e. to investigate the involvement of these receptors in irritable bowel syndrome. We will combine animal models with research in human tissues to study the translational potential of the findings. Ultimately, this study aims to provide insight in the role of Mrg receptors in gastrointestinal pathologies.

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      From mice to men and back. Human iPSC-derived neurons to boost Drug Discovery in Alzheimer's disease (DDIPS). 01/04/2013 - 31/03/2015

      Abstract

      This project represents a formal research agreement between UA and on the other hand private institution. UA provides private institution research results mentioned in the title of the project under the conditions as stipulated in this contract.

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      Subsidy for the support of young researchers. 01/10/2012 - 30/09/2016

      Abstract

      The funds are allocated for activities relating to the support and supervision of young researchers. The grant will be used to create a framework for and the development, implementation and strengthening of activities related to the following objectives: Training of young researchers; Career development and promotion of career prospects of young researchers; Strengthening the international orientation in the careers of young researchers."

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        Investigation of functional and structural brain abnormalities utilizing multimodal brain imaging in a neurodevelopmental animal model with relevance to schizophrenia. 01/01/2012 - 31/12/2015

        Abstract

        The current project will follow the development of neuroinflammation together with functional brain integrity and behavioural outcome in a rodent model of maternal immune activation in vivo utilising state-of-the-art multimodal imaging biomarkers.This project will generate highly novel information about the contribution of neuroinflammation to the development of schizophrenia and its consequences for the functional integrity of the brain, and eventually provide a rationale for the implementation of novel disease-modifying strategies.

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        The role of autophagy in lethal reperfusion injury following myocardial infarction and the effect of postconditioning in relation to adiponectin plasma levels. 01/01/2011 - 31/12/2014

        Abstract

        In this study, we will investigate the role of autophagy (a cell survival and death pathway) and adiponectin (an endogenous hormone produced by fat cells) in a protective post-myocardial infarction reperfusion therapy called postconditioning. Adiponectin has protective myocardial effects that limit lethal reperfusion injury. However, patients with central obesity have low plasma levels of adiponectin, which may confound the cardioprotective properties of postconditioning.

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          Identification of functional molecular pathways in the pulmonary neuroepithelial body microenvironment: Laser capture microdissection and gene expression study. 01/01/2011 - 31/12/2011

          Abstract

          This project aims at identifying pathways that are involved in the normal function of NEBs in postnatal lungs. The NEB microenvironment will be dissected in large numbers via advanced laser capture microdissection and will be used for gene expression analysis.

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          Biomedical Microscopic Imaging and in-vivo Bio-Imaging (EGAMI). 01/02/2010 - 31/12/2014

          Abstract

          This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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          Support PhD research. 01/01/2010 - 30/09/2016

          Abstract

          This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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            VIB-Neurotrophic factors in the pathophysiology of depression: focus on VEGF (DEPVEGF). 01/01/2010 - 31/12/2011

            Abstract

            This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

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              Neuronal networks in vitro: spontaneous activity and synaptic plasticity in health and disease. 01/10/2009 - 30/09/2013

              Abstract

              This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

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              Expression of vascular adhesion molecules on endothelial progenitor cells and their relation to the homing capacity of these cells towards sites of tissue ischemia. 01/10/2009 - 30/09/2011

              Abstract

              This project proposal aims at verifying in which way the different homing signals originating from ischemic tissue lead endothelial progenitor cells - via induction of the PI3K-Akt-eNOS pathway - to express cellular adhesion molecules, which results in efficient homing, adhesion and diapedesis.

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                Centre for R&D Monitoring. (ECOOM) 01/01/2009 - 31/12/2013

                Abstract

                The mission of the Centre for R&D Monitoring (ECOOM) is to develop and consolidate a consistent and performing system of R&D and Innovation (RD&I) indicators which provides the Flemish Governement with actual and relevant statistic data for mapping and monitoring the RD&I efforts in the Flemish region. At the same time ECOOM develops a portfolio of relevant scientific research activities to support this mission. Therefore, ECOOM (1) has a series of targeted, long term task packages to map, measure and analyze the Flemish R&D and innovation potential; (2) ensures that a data management infrastructure is available to the Flemish Government containing bibliometric and technometric data and data on innovation and PhDs; (3) provides qualified staffing; (4) builds the necessary and appropriate IT-infrastructure and (5) is able to conduct ad-hoc task or projects at request of the Flemish Government. ECOOM acts as an inter-association center.

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                  Transmission Electron Microscope with cryo-ware. 19/12/2008 - 18/12/2013

                  Abstract

                  This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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                  Network rhythms and the dynamical response properties of neuronal microcircuits. (Cofinancing mandate by Francqui-fund) 01/10/2008 - 30/09/2011

                  Abstract

                  This project represents a formal research agreement between UA and on the other hand Francqui-fonds. UA provides Francqui-fonds research results mentioned in the title of the project under the conditions as stipulated in this contract.

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                    The putative effect of corticostatin and neuropeptides belonging to the CRF-family on the interaction between visceral afferents, mast cells and dendritic cells during intestinal inflammation. 01/01/2008 - 31/12/2011

                    Abstract

                    The aim of this project is (1) to verify whether CRF, UCN2 and UCN3, in addition to UCN1 and CST, also have anti-inflammatory effects on intestinal inflammation; (2) to determine, on the one hand, the effect of these neuropeptides on the neuroimmune interaction during inflammation and, on the other hand, the importance of this effect in the therapeutical effects of these neuropeptides; and (3) to examine which receptors are effectively involved in this process.

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                    Project website

                    Bidirectional communication between the enteric nervous system and elements of the immune system in inflammatory gastrointestinal disorders. 01/01/2008 - 31/12/2011

                    Abstract

                    In this project animal models were used to study the interaction between neuronal components of the GI tract and elements of the immune system, more particularly mast cells and dendritic cells, during inflammation. This interaction appears to play an important role in the inflammatory response and might offer a better insight for the observed hyperexcitability of afferent components of the enteric nervous system during gastrointestinal inflammation. This project will primarily focus on the possible role of cortistatin and urocortines in this interaction.

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                    Role of somatostatin and somatostatin receptors in the interaction between mucosal mast cells and enteric neurons during intestinal inflammation. 01/01/2008 - 24/08/2009

                    Abstract

                    1.Identification and topographical localisation of somatostatin receptors in the enteric nervous system of the non-inflamed mouse ileum using immunohistochemistry and reverse transcriptase-PCR. The somatostatin receptor-containing neurons are neurochemically characterised by means of multiple immunofluerescence stainings. 2.Comparison of the identity and expression pattern of somatostatin receptors in enteric neurons in 8-week Schistosoma mansoni-infected mice with non-inflamed ileum, using Real Time RT-PCR. 3.Optimisation of the protocol for isolation of mucosal mast cells from the lamina propria of 8-week Schistosoma mansoni-infected mice. 4.Identification and quantification of somatostatin receptors on in vitro mucosal mast cells and on mucosal mast cells isolated from the lamina propria of 8-week infected mice by means of immunohistochemistry, reverse transcriptase-PCR and Real Time RT-PCR. These results are substantiated in vivo by immunofluorescent detection of somatostatin receptors on mucosal mast cells in the gastrointestinal tract of Schistosoma mansoni-infected mice. 5.Study of a possible compensatory effect of somatostatin receptor type 2 deficiency on the identity and expression level of the somatostatin receptors in enteric neurons and musocal mast cells using immunohistochemistry, reverse transcriptase PCR and Real Time RT-PCR. 6.Study of the effect of administration of SOM and SOM analogues on the synthesis and secretion of inflammatory mediators by mucosal mast cells using cDNA microarray and ELISA. 7.Functional study of the effect of somatostatin on the neuroimmune interaction between mast cells and enteric neurons using mucosal mast cells and enteric neurons isolated from the gastrointestinal tract of Schistosoma mansoni-infected mice. Life cell imaging and multi-photon microscopy are applied to investigate the activity of both cell types after SOM stimulation.

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                    Expression of vascular adhesion molecules on endothelial progenitor cells and their relation to the homing capacity of these cells towards sites of tissue ischemia. 01/10/2007 - 30/09/2009

                    Abstract

                    This project proposal aims at verifying in which way the different homing signals originating from ischemic tissue lead endothelial progenitor cells - via induction of the PI3K-Akt-eNOS pathway - to express cellular adhesion molecules, which results in efficient homing, adhesion and diapedesis.

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                      Project website

                      Role of modulation subunits of K-channels in the heart. 01/01/2006 - 31/12/2009

                      Abstract

                      Specific aims of the project : 1) Detection of silent Kv subunits in the heart and their role in the slowly inactivating delayed rectifier current. 2) Transgenic analysis of the physiological role of silent subunits. 3) Do KChIP and KVI.5 interact stably and what are the functional consequences ? 4) What are the molecular determinants of the KChIP interaction with Kv1.5 subunits?

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                      Role of dystrophin-associated protein complex in contraction of hepatic stellate cells. 01/01/2006 - 31/12/2009

                      Abstract

                      In normal liver, intrahepatic resistance changes with variations in portal blood flow, thereby keeping porta )ressure within normal limits. In cirrhosis however, both intrahepatic resistance and splanchnic blood flow are ncreased, resulting in portal hypertension. Although structural changes contribute most to the increasec ntrahepatic vascular resistance, it has become clear that not only fixed, but also dynamic factors add significantly the increased resistance. This dynamic part is caused by active contraction of septal and/or portal nyofibroblasts, activated hepatic stellate cells (HSC) and portal venules. Activated HSC contract in response tc rarious vasoactive substances and the cells are currently regarded as target cells for treating porta lypertension. Recent years have seen considerable progress towards understanding the signaling mechanism egulating non-muscle cell contractility. Whereas contraction of smooth muscle cells is governed primarily by Ca2+ signaling contractility of non-muscle cells is principally mediated by Rho signaling. It is not known as yet which of both mechanisms plays a greater role in HSC contractility. However, it has been speculated that, as HSC arE Ictivated and exhibit smooth muscle-like features, Ca2+ signaling becomes more important.

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                      Involvement of nitric oxide pathway in activating endothelial progenitor cells towards homing after myodardial ischaemia. 01/01/2006 - 31/12/2009

                      Abstract

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                        Role of somatostatin and somatostatin receptors in the interaction between mucosal mast cells and enteric neurons during intestinal inflammation. 01/01/2006 - 31/12/2007

                        Abstract

                        1.Identification and topographical localisation of somatostatin receptors in the enteric nervous system of the non-inflamed mouse ileum using immunohistochemistry and reverse transcriptase-PCR. The somatostatin receptor-containing neurons are neurochemically characterised by means of multiple immunofluerescence stainings. 2.Comparison of the identity and expression pattern of somatostatin receptors in enteric neurons in 8-week Schistosoma mansoni-infected mice with non-inflamed ileum, using Real Time RT-PCR. 3.Optimisation of the protocol for isolation of mucosal mast cells from the lamina propria of 8-week Schistosoma mansoni-infected mice. 4.Identification and quantification of somatostatin receptors on in vitro mucosal mast cells and on mucosal mast cells isolated from the lamina propria of 8-week infected mice by means of immunohistochemistry, reverse transcriptase-PCR and Real Time RT-PCR. These results are substantiated in vivo by immunofluorescent detection of somatostatin receptors on mucosal mast cells in the gastrointestinal tract of Schistosoma mansoni-infected mice. 5.Study of a possible compensatory effect of somatostatin receptor type 2 deficiency on the identity and expression level of the somatostatin receptors in enteric neurons and musocal mast cells using immunohistochemistry, reverse transcriptase PCR and Real Time RT-PCR. 6.Study of the effect of administration of SOM and SOM analogues on the synthesis and secretion of inflammatory mediators by mucosal mast cells using cDNA microarray and ELISA. 7.Functional study of the effect of somatostatin on the neuroimmune interaction between mast cells and enteric neurons using mucosal mast cells and enteric neurons isolated from the gastrointestinal tract of Schistosoma mansoni-infected mice. Life cell imaging and multi-photon microscopy are applied to investigate the activity of both cell types after SOM stimulation.

                        Researcher(s)

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                        Purchase of a spectrophotometer. 13/04/2005 - 31/12/2005

                        Abstract

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                        Morpho-functional and neuropharmacological study of neuro-immune interactions in the gastrointestinal tract of the mouse. 01/04/2005 - 31/03/2006

                        Abstract

                        The aim of this study is the morphological, electrophysiological and neuropharmacological identification of the role, the mechanisms and the effects of the bi-directional interactions between the enteric nervous system and the enteric immune system on the functioning of the gastrointestinal tract under normal and inflammatory conditions.

                        Researcher(s)

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                        Study of the mechanisms underlying the immune modulating effects of alcohol within the gastrointestinal tract: involvement of a bidirectional interaction of mast cells and (afferent) neural pathways. 01/01/2005 - 31/12/2006

                        Abstract

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                        Study of the mechanisms underlying the immune modulating effects of alcohol within the gastrointestinal tract : involvement of a bidirectional interaction of mast cells and (afferent) neural pathways. 01/01/2005 - 31/12/2006

                        Abstract

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                        Excitability and connectivity of neural circuits. 01/01/2004 - 31/12/2007

                        Abstract

                        This project combines the technical expertise of the 3 research groups to study 3 topics: the cerebellum, enteric nervous system and potassium channels. Specifically we will study: classification of neurons in the granular layer, potassium channels in Purkinje cells and their inhibition of the deep nuclei; expression of potassium channels in viscerosensitive neurons and changes due to inflammatory mediators released by mast cells; and expression and function in the brain of 5 new potassium channel subunits.

                        Researcher(s)

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                        Cerebellar function in relation to cortex : models and experiments. 01/01/2004 - 31/12/2007

                        Abstract

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                        Analysis of neuro-immunie interactions in the small intestine during intestinal schistosomiasis. 01/01/2004 - 31/12/2007

                        Abstract

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                        Matching fund for the "Research Foundation ¿ Flanders" project "Analysis of neuroimmunologic interactions in the small intestine during intestinal schistosomiasis". 01/10/2003 - 31/12/2007

                        Abstract

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                        Effects of proteases, released by mast cells, on afferent pathways in the schistosomiasis inflammation model in the mouse gastrointestinal tract. 01/05/2003 - 30/04/2005

                        Abstract

                        PARs are one of the possible sensory oeuron-specific molecular targets that can be useful for therapeutic treatment in inflammatory bowel disorders and gastrointestinal pain. This project aims at elucidating the role{s} of these receptors in the neuroimmune interactions between mast cells and the afferent component of the enteric nervous system in our schistosomiasis inflammation model.

                        Researcher(s)

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                        Funding for the replacement of basic laboratory equipment intended for the extension of the existing LSM 510 two-photon microscope with the META system. 01/04/2003 - 31/12/2003

                        Abstract

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                        "Calimity fund": replacement of a defective centrifuge by an Eppendorf 5810R device. 01/03/2003 - 31/12/2003

                        Abstract

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                        In vitro study of the neuro-immune interaction between mucosal mast cells and extrinsic sensory, primary afferent neurons in mice infected with Schistosoma mansoni. 01/01/2003 - 31/12/2004

                        Abstract

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                        01/01/2003 - 31/12/2004

                        Organisation 13th European Microscopy Congress. 01/12/2002 - 31/12/2002

                        Abstract

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                          "Calimity fund": removal of the transformator of a defective electron microscope. 01/10/2002 - 31/12/2002

                          Abstract

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                            RAFO equipment fund: funding of basic equipment; purchase of a CO2 incubator module. 01/03/2002 - 31/12/2002

                            Abstract

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                              Molecular en functional analysis of novel K+channal subunits identified in the human genome. 01/01/2002 - 31/12/2005

                              Abstract

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                              Coronary flow after acute myocardial infarction: role of cytokine induced endothelial dysfunction and alfa-adrenergic coronary vascoconstriction. 01/01/2002 - 31/12/2005

                              Abstract

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                              The role of ghrelin, the recently discovered motilin related peptide, in the regulation of gastric motility in rodents 17/12/2001 - 17/12/2004

                              Abstract

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                              Research team(s)

                              Morpho-functional study of primary afferent neurons within intrinsic enteric reflexes in the gastrointestinal tract of guinea pig and pig. 01/10/2001 - 30/09/2003

                              Abstract

                              The aim of this study is to morphologically and electrophysiologically characterize the intrinsic sensory neurons by means of multi-site optical recording after chemical or mechanostimulation.

                              Researcher(s)

                              Research team(s)

                                Identification and characterisation of genes responsible for hereditary deafness and vestibular dysfunction. 01/01/2001 - 31/12/2004

                                Abstract

                                Within the morphological part of this project, the cellular localization and expression pattern of the DFNA5 gene product will be investigated by means of immunocytochemical techniques.

                                Researcher(s)

                                Research team(s)

                                Functional morphological study of the interaction between neuronal and non-neuronal elements in relation to oesophageal motility. 01/01/2001 - 31/12/2004

                                Abstract

                                The main aims of this project are the study of 1. the correlation between morphological and physiological features of intrinsic esophageal neurons and 2. the role of interstitial cells of Cajal in this part of the gastrointestinal tract.

                                Researcher(s)

                                Research team(s)

                                Study of the interaction between mast cells and enteric neurons in the ileum of Schistosoma mansoni-infected mice. 01/01/2001 - 31/12/2002

                                Abstract

                                Researcher(s)

                                Research team(s)

                                  A study of Golgi cell morphology in relation to the cerebellar cortex. 01/01/2001 - 31/12/2002

                                  Abstract

                                  Corticocerebellar Golgi cells are characterized as granule cell layer interneurones with large rounded or polygonal cell bodies and radiating dendritic arborizations. The present study will focus on Golgi cells in order to provide a more detailled morphological description, including their different synaptic inputs. In addition, Golgi cell morphology will be related to the whole of the cerebellar cortex.

                                  Researcher(s)

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                                    01/11/2000 - 31/12/2000

                                    Abstract

                                    Researcher(s)

                                    Research team(s)

                                      Development and optimalization of multisite optical recordings of enteric neurons using two-photon microscopy. 01/05/2000 - 30/04/2002

                                      Abstract

                                      Complementary to the classical intracellular recording technique, two-photon microscopy and specific Ca++-indicators and/or membrane potential-sensitive fluorescente substances will be used in order to visualize neuronal activity within enteric neurocircuits following application of mechanical, electrical and chemical stimuli.

                                      Researcher(s)

                                      Research team(s)

                                        An integrated computer modelling and experimental study of the operations and function of the cerebellum. 01/01/2000 - 31/12/2003

                                        Abstract

                                        Notwithstanding the simple and regular anatomical organisation of the cerebellum, its function and activity remains unclear. This project aims at better understanding the function and activity of the cerebellum applying computer simulations and experiments in both men and animals. To that end morphological and electrophysiological techniques will be used on rats and functional magnetic resonance imaging will be performed on rat and men.

                                        Researcher(s)

                                        Research team(s)

                                        Electrophysiology and multisite optical recordings of enteric neurocircuits after electrical and chemical stimulation. 01/10/1999 - 30/11/2000

                                        Abstract

                                        By means of visualization and recordings of membrane potential and/or intracellular Ca2+-changes, it will be attempted to analyse the spread of excitability in enteric neurons and to assess the differential activity of functional enteric neuron types in response to specific stimuli

                                        Researcher(s)

                                        Research team(s)

                                          RAFO funding 'basic equipment' for the purchase of a knife maker. 01/07/1999 - 31/12/1999

                                          Abstract

                                          RAFO funding for the purchase of a knife maker to make glass knives to be used for making ultrathin sections with the ultramicrotome.

                                          Researcher(s)

                                          Research team(s)

                                            Comparative study of neurotransmitters present in distinct functional enteric neuron populations in whole mounts and after dissociation in organotypic culture. 01/05/1999 - 30/04/2000

                                            Abstract

                                            This study has a dual aim: 1. Identification and analysis of intrinsic pathways in the porcine and human enteric nervous system using carbocyanine tracing. 2. Development of a dissociation technique for enteric neurons in large domestic animals in order to study the electrophysiological properties of various functional DiI-identified neuron classes.

                                            Researcher(s)

                                            Research team(s)

                                              Gastro-intestinal regulatory mechanisms. 01/01/1999 - 31/12/2018

                                              Abstract

                                              Some aspects of the research themes of the participating groups are studied in collaboration, using a multi-disciplinary approach made possible by combining the know-how of the different groups. The central theme is regulation-mechanisms in the gastrointestinal tract. Specific goals are: a) NANC-neurotransmission, especially NO- and VIP-mediated; b) mechanism of action of motilin and motilides; and c) the interaction between the enteric nervous system and inflammatory mediators.

                                              Researcher(s)

                                              Research team(s)

                                              The correlation between neuronal morphology and physiological function. 01/01/1999 - 31/12/2002

                                              Abstract

                                              We will study the relation between neuronal morphology and physiological function at several levels of complexity and in two different neuronal systems (the cerebellum and the enteric system). We want to determine the importance of single cell morphology for the classification of different neurons and its effects on second messenger metabolism, on the firing behavior of a particular neuron type, and at the network level. The reconstruction of the neuronal morphologies will be carried out jointly by the two research groups, while the applied physiological research methods are dependent on the neural systems under investigation.

                                              Researcher(s)

                                              Research team(s)

                                                The mouse as a study object for the examination of the pathogenesis of intestinal suffering by schistosomiasis: a morphological analysis of the enteric nervous system. 01/01/1999 - 31/12/2000

                                                Abstract

                                                Using a recent tracer technique within organotypic cultures, combined with immunocytochemical and in situ hybridization methods, the effects of schistosomiasis on the intrinsic component of the enteric nervous system, i.e. on the course of intrinsic nerve tracts and on the neurochemical characteristics of neurons, and also on the expression of cyto- and chemokines in non-neuronal cells, will be morphologically analyzed.

                                                Researcher(s)

                                                Research team(s)

                                                  A study of Golgi cell morphology in relation to the cerebellar cortex. 01/01/1999 - 31/12/2000

                                                  Abstract

                                                  Corticocerebellar Golgi cells are characterized as granule cell layer interneurones with large rounded or polygonal cell bodies and radiating dendritic arborizations. The present study will focus on Golgi cells in order to provide a more detailled morphological description, including their different synaptic inputs. In addition, Golgi cell morphology will be related to the whole of the cerebellar cortex.

                                                  Researcher(s)

                                                  Research team(s)

                                                    Bridging credit for cofinancing the post doctoral fellowship of Luc Van Nassauw. 01/10/1998 - 30/09/1999

                                                    Abstract

                                                    Immunohistochemical and in situ hybridisation study of the enteric innervation of the mouse under normal and inflammatory conditions.

                                                    Researcher(s)

                                                    Research team(s)

                                                      RAFO co-funding 'large equipment' for the replacement purchase of an ultramicrotome Leica Ultracut UCT with cryo-chamber FCS. 01/05/1998 - 31/12/1998

                                                      Abstract

                                                      RAFO co-funding for the purchase of an ultramicrotome with freeze unit to trim tissues and to prepare ultrathin sections and ultrathin frozen sections for TEM study, and semithin sections and semithin frozen sections for light microscopic research.

                                                      Researcher(s)

                                                      Research team(s)

                                                        Detection and distribution pattern of neuropeptide-receptors in the enteric nervous system of mammals, using fluorescent-labeled ligands. 01/01/1998 - 31/12/1999

                                                        Abstract

                                                        Using so-called "fluopeptides" this study not only tries to determine the distribution pattern of several neuropeptides-receptors in the gastro-intestinal tract, but also to study the kinetics of these receptors under well-defined circumstances.

                                                        Researcher(s)

                                                        Research team(s)

                                                          Central and peripheral effects of the natural peptide motilin and of the new class of prokinetic drugs, the motilides, in the rat. 10/12/1997 - 10/03/2001

                                                          Abstract

                                                          After identifying the sequence of motilin antibodies will be prepared in the rabbit to map motilin-containing cells by immunocytochemistry. Apart from the topographical localisation, the neurochemical features of neuron populations expressing motilin binding sites in the central nervous system will be determined. In addition, central effects will be studied by means of functional MRI after intraventricular injections of motilin and motilides.

                                                          Researcher(s)

                                                          Research team(s)

                                                            Identification of primary afferent enteric neurons in the gastrointestinal tract of large mammals using Dil-tracing in organotypic culture 01/05/1997 - 30/04/1999

                                                            Abstract

                                                            Using a combined method of neuronal tracing and immunocytochemistry, it is attempted to analyse the topographical ditribution and neurochemical coding of distinct enteric neuron populations in the digestive tract of large mammals

                                                            Researcher(s)

                                                            Research team(s)

                                                              Neuroendocrine interactions in the gastrointestinal tract under normal and pathological conditions. 01/01/1997 - 31/12/2001

                                                              Abstract

                                                              This network aims at investigating the neuroendocrine interactions in various segments of the gastrointestinal tract from a functional-morphological and pharmacological point of view. In a first phase, the enteric nervous system and the relation to the specific targets (enterocytes, endocrine cells, neurons, muscle fibres) will be focused on. The task of this laboratory comprises the neurochemical and electrophysiological characterization of the different enteric neuron populations.

                                                              Researcher(s)

                                                              Research team(s)

                                                                Synthesis of bio-active substances in neuro-epithelial endocrine cells by means of in situ hybridization. 01/05/1995 - 30/04/1997

                                                                Abstract

                                                                Using non-radioactive labeled mRNA- or oligonucleotideprobes, in situ hybridization is applied to gain a better insight in the panel of bio-active substances that can be produced by the neuroepithelial endocrine cells in the respiratory system of vertebrates.

                                                                Researcher(s)

                                                                Research team(s)

                                                                  Confocal microscopy and 3D-reconstruction techniques as the means for solving a number of morphological problems related to the study of the enteric nervous system, the pulmonary acinus and the extracellular matrix. 01/01/1995 - 31/12/1998

                                                                  Abstract

                                                                  1) Enteric neurontypes are morphologically identified after intracellular marking; their synaptic input under normal circumstances is quantified; 2) They are morphologically characterized with inflammatory gut diseases and experimentally induced parasitory inflammation processes in the gut wall; 3) Study of the extracellular matrix and its role in cell migrations; 4) Postnatal development of the pulmonal acinus.

                                                                  Researcher(s)

                                                                  Research team(s)

                                                                    Gastro-intestinal regulatory mechanisms. 01/01/1994 - 31/12/1998

                                                                    Abstract

                                                                    This project comprised the study of the neuroendocrine regulation mechanisms of visceral function with special attention to: 1. the non-adrenergic, non-cholinergic (NANC) component of the enteric nervous system; 2. the working mechanism of motilin; and 3. the relation between motility and inflammation.

                                                                    Researcher(s)

                                                                    Research team(s)

                                                                      Study of afferent pathways to sympathetic ganglia in relation to brain-gut interactions. 01/10/1992 - 31/12/1995

                                                                      Abstract

                                                                      Using immunocytochemical and tracing techniques the topographical and immunocytochemical characterization of afferent nervepathways in relation to brain-gut interactions is attempted.

                                                                      Researcher(s)

                                                                      Research team(s)