MINDMIND facility

Contact details:

Jeroen Pasterkamp
Universiteitsweg 100, 3584 CG

The MIND (Multidisciplinary Investigation of Neural Disorders) facility in Utrecht aims at analyzing and manipulating human brain cultures. It has unique expertise in human iPS cells and cerebral 3D organoid culturing technology, which it combines with state-of-the-art imaging and gene manipulation techniques. The MIND facility is unique world-wide and serves as a research hub in Utrecht, as it links different research facilities and initiatives

A wealth of information on brain disorders (e.g. ALS, stroke, schizophrenia) is accumulating from different disciplines (epidemiology, clinical genetics, neurobiology, social sciences and imaging) that needs to be translated into biological models for dissecting disease mechanisms and for setting up tractable therapy. Classically such translation is performed using animal cells and models but as a consequence translation towards therapies is not straightforward. However, recent technological developments allow us to generate human neurons from patients and healthy controls –which replaces the use of animal for this purpose. These neurons can be grown in two-dimensional but also in three-dimensional (3D) cultures (cerebral organoids; Figure 1), which more closely mimics the developing brain. Furthermore, new technologies have recently become available to manipulate and study 3D neuronal cultures with advanced microscopic techniques. The development of 3D cerebral organoid cultures is crucial as 3D interactions between developing neurons form the basis of the development of our complex brain and are disrupted in disease. The use of 3D culture models combined with advanced microscopy analyses will be the standard for future studies. It is anticipated that within the very near future data based on animal models alone will no longer meet the requirements for publication in international reviewed top journals. There is a great need and urgency to provide these highly specialized techniques and make them accessible to the broad community of (neuro)scientists present in Utrecht and the Netherlands.
Figure 1. Generating 3D human cultures. Recently developed induced pluripotent stem cell (iPSC) and cerebral organoid (human 3D culture) technologies allow the generation of human neurons in three-dimensional (3D) cultures. These new tools enable dissection of disease mechanisms and development of therapeutic strategies.
The MIND Facility brings together two existing facilities in Utrecht: the Brain Center Rudolf Magnus (BCRM) iPSC and Biology Imaging Center (BIC) Facilities to 1) develop iPSC and cerebral organoid technologies towards application for studying NDDs, and 2) implement novel microscopic approaches for visualizing and optogenetically manipulating 3D brain cultures.
The BCRM iPSC Facility
(http://research.umcutrechthersencentrum.nl/the-center-and-its-partners/g...)
BCRM iPSC is an iPS Facility in the UMCU. It provides researchers with the opportunity to develop and execute the core skills and competences required to successfully reprogram patient cells into pluripotent, well-characterized iPSC stem cells. In addition to the reprogramming platform, the possibility to differentiate iPSC cell lines into neural lineages is being offered in the facility. The BCRM iPSC is located in the Department of Translational Neuroscience and led by Prof. dr. Jeroen Pasterkamp. It has expertise in reprogramming, clone maintenance and characterization, and clone differentiation, genetic manipulation (CRISPR/CAS). BCRM iPSC also has unique technology for the development, analysis and manipulation of iPSC-based cerebral organoid cultures. Analysis tools include two Ultramicroscope lighsheet setups with corresponding data analysis and storage infrastructure. Ultrastructural analysis by specialized 2D and 3D-electron microscopy (EM) techniques occurs in the linked Cell Microscopy Center (CMC) of the UMCU (led by Prof. J. Klumperman). The BCRM iPSC and its staff is funded by the BCRM and further supported by several externally acquired funds (e.g. FP7, Marie-Curie ITN, TI Pharma, CTMM by Pasterkamp). The CMC facility is funded by the Center for Molecular Medicine (CMM) of the UMCU and supported by external grants to Klumperman (e.g. STW perspective, ESFRI project EuroBioImaging (H2020) and Utrecht Life Sicences grant on BioImaging).
The Biology Imaging Center
(http://cellbiology.science.uu.nl/biology-imaging-center-bic)
BIC is an important partner within Bioimaging Utrecht. BIC provides access, support and training in advanced light microscopy techniques for research groups within the Faculty of Science, as well as for groups from other institutes within and outside Utrecht University, and for industry. Over the past years, the BIC has developed and optimized high-resolution imaging of dynamic intracellular processes, high resolution live cell imaging, such as super-resolution PALM / STORM imaging and two-photon microscopy of live brain slices.

Connection to strategic developments
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Life Sciences & Health
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