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Platform of Advanced Animal Model Support

Outline

Principle Investigator Kohzoh Imai
Visiting Professor and the Chair of Office of Support for Platforms for Advanced Technologies and Research Resources, the Institute of Medical Science, the University of Tokyo
Keyword for Support Function Technical Training Course for animal model, fostering young scientists, international exchange, construction of animal model, genetically modification, genome editing, pathological analysis, behavioral analysis, chemical sensitivity, optogenetics, multi-functional electrode,
zebra fish, molecular targeting and profiling (phenotype, chemical library, functional genomics, bioinformatics)
Grant period FY 2016 – 2021
URL http://model.umin.jp/

Platform of Advanced Animal Model Support

Support Categories

General Management Group

Technical Training Course for young scientists We organize seminars and lectures about the cutting-edge research including the technical content, by researchers involved in the platform. We also call on all participants to make presentations (oral or poster) or discussions. Our main objectives are to facilitate the understanding of construction and analysis of the advanced animal model, to promote networking among young scientists, and to promote joint research.
Outcome Presentation Symposium We aim to promote networking among researchers and joint researches by organizing the symposium, special lectures and workshops on the relevant research fields where researchers present their outcome of the research supported by the platform.

Support for Animal Model Construction

Support for Mouse Model Construction We construct and provide genetically modified mice upon requests from researchers.
We conduct homologous recombination and genome editing using ES cells and mice’s embryo to introduce gene knockout (conditional/conventional) and genetic modifications (insert, replace, and introduce a point mutation.)
Support for Rat Model Construction We construct and provide genetically modified rats (knock-out, knock-in, BAC-Tg and others) with the genome editing technology. The advanced and valuable rat models are available, including animal model of disease having human genetic mutation, tissue-specific Cre driver and GFP reporter genes.

Group for Pathologic Analysis

Pathologic analyses on eukaryotic animals, mainly rodents We can cover all sorts of pathologic alternations of living models, not only neoplasia but also inflammatory conditions, neurodegenerative diseases, and aging.
We can also support to analyze the iPS cell-derived animals.
Analysis on morphological changes of organs upon drug administration. (determination of the phenotypes of genetically engineered animals that affect the corresponding human diseases. ) Because all members cover the whole area of pathology, we are flexible enough to find your person in charge, providing a high possibility of determining the phenotypes of genetically engineered animals.
Pathologic analyses on cause of fetal death and formation of tumors We are experienced with the analyses on embryological abnormality and tumor forming ability with the advanced regenerative medical technology and developmental engineering such as iPS cells.
We can analyze the teratoid tumor and determine the fetus’s congenital anomaly and the cause of death.
Support and training for pathologic stain We can stain the tissues with Hematoxylin and eosin, in addition to special staining, and immunostaining. We can deal with in situ hybridization and capture the image with electron microscopes.

Group for Physiological Analysis

Support for behavioral analysis We analyze a comprehensive behavior of genetically modified mice or drug-administered mice. If we determine some phenotypes, we will conduct the additional behavioral experiment and additional in vivo Calcium imaging experiment.
If you cannot prepare mice, we support maintaining the mice under SPF conditions, and breeding.
Support for pharmacological analysis We examine the link between the genes and the susceptibility of the controlled substances through extracting and analyzing the genetic data of your interest, using clinical data of the conventional susceptibility test of the controlled substances, genome specimen, and the related database.
Also we analyze the genetically modified animals, and provide the biological specimen.
Support for operation analysis using the optical technology We operate the multidimensional optical signal to collect data of the cell function.
We develop and provide reagents used for light signal detection methods (R-CaMP2 and GECI etc.) as well as used in optogenetical operating method (ChR2 etc.). We support anything other than above related to optical technology.
Support for analyzing the obtained data using multi-functional electrodes Our technical and analytical support activities in neurophysiology research are stated below.
1. Multiple electrodes for recording activities of several nerve cells.
2. Electrodes made of tungsten polyurea insulating films capable for placing the metallic electrode for a long time.
3. Multiple independent light stimulation devices to conduct light simulation carried out by channel rhodopsin under the microscope.
4. Facility for small animals to experience the virtual reality. (Device for a wide-visual display action target and its software)
5. Fiber for intracerebral imaging. (Imaging system using micro-fiber to record the data in the deep brain.)
6. Phorometer and pupil analyzer (For humans.

Group for Molecular Profiling

Support for molecular profiling Our researchers with highly skilled technique and knowledge will be in charge to support your research.
We aim to (1) elucidate a biological activity of a compound, and (2) confirm the physiological property of regulatory molecules (chemical compound or gene) of your interest.
Molecular profiling based on the growth analysis across the cell line panels We detect the concentration of the start inhibiting the growth on the each of 39 human cell lines, and we collect the difference on the effective concentration as a fingerprint. By examining the similarity of fingerprints of the reference compounds, we estimate the mechanism of the tested compounds.
Molecular profiling based on the cell phenotypic analysis We evaluate the activity of the tested compound in the various physiological events such as epithelial-mesenchymal transition, autophagy, cell activity, and neuroprotection. These criteria are effective to evaluate the compound which does not show growth inhibition in the cell panels because it is phenotyping analysis without cytotoxicity.
Molecular profiling based on the transcriptome analysis With the Comprehensive Gene Expression Analysis (transcriptome analysis), we obtain gene signatures as the cells are treated with chemical compound. Then we compare it with other gene signatures stored in various databases to estimate the intracellular signaling pathway; compound locus.
Molecular profiling based on the proteomic analysis We add the test compound to the cells, analyze the fluctuation of proteome, and estimate the test compound’s locus by comparing it with the compounds having the clear locus. Further, we estimate and evaluate the pathway of the effective compound based on the information regarding the protein spots which have been changed significantly after chemical treatment.
Construction and distribution of chemical libraries We systematically collect various small molecule inhibitors including signaling pathway inhibitors, put them together as “standard inhibitor kit”, and provide it to the researchers. We also collect novel compounds deposited by researchers nationwide for chemical library.
Construction and distribution of RNA interference kits We collect many microRNAs having clear major physiological functions for chemical library, and distribute them to the researchers. Further, we design and synthesize the best small molecular inhibitor RNA (siRNA) suitable for the researcher’s purpose.
Molecular screening with a barcode shRNA sequence technique We conduct analysis and technical support for screening the target gene pathway with the pooled barcode shRNA libraries using virus-based vectors.

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