Mouse BIRN (mBIRN) is a research and development effort funded by the National Center for Research Resources (NCRR) to produce an integrated framework for the collection, analysis, management, and visualization of diverse neuroscience data sets. It provides a test bed for the formulation of hardware, software, and protocols to produce a distributed adaptive database and multiscale, multimodality digital atlases of the mouse brain. These resrouces are used to share and mine multi-scale structural and functional data and integrate these with genomic and gene expression data. The goal is to create an infrastructure that can greatly enhance previously disparate data collections into a single system capable of quantitative visualization and linkage with previously disconnected knowledge bases.
mBIRN is acquiring complete volumetric coverage with MR, cryosections, conventional histology, and gene expression from the same specimen along with confocal light microscopy, and electron tomography from closely related specimens. This allows the neuroscientists studying the mouse models the ability to view the complex anatomy of the mouse brain in 3 dimensions at multiple scales for tissue and structure differentiation, along any arbitrary plane, and all from a single computer screen.
Combing these techniques with well characterized mouse models, gives us a powerful tool for investigating the disease mechanism and potential therapies. The development of MR microscopy in mouse models makes transition of imaging studies possible from mouse to human. mBIRN will complete the link making correlation possible between fundamental structural units (e.g., the dendritic spine), gene expression, traditional histology, magnetic resonance histology, and in vivo MR imaging. The products of mBIRN, including the initial data sets for these models, the tools for comparison, the infrastructure for sharing the data and the knowledge base, will all clearly be extensible to a much broader community as scientists seek to connect an exponentially increasing number of mouse models to human disease.
mBIRN integrates the activities of five existing laboratories:
- The MRI Center in the Biological Imaging Center (BIC) at the California Institute of Technology (CIT)
- The Center for In Vivo Microscopy (CIVM) at Duke University
- The Laboratory of Neuro Imaging (LONI)
- The National Center for Microscopy and Imaging Research (NCMIR) at the University of California at San Diego (UCSD)
- The Informatics Center for Mouse Neurogenetics at UTHSC, Drexel, and BIDMC ( Mouse Brain Library and The GeneNetwork )
These laboratories are connected by the networking and software infrastructure that is being co-developed with the BIRN Central Coordinating site (BIRN-CC).
We have chosen mouse models for three devastating and common human neurological diseases-multiple sclerosis, Alzheimer's disease, and Parkinson's disease. These models provide a well-delimited workspace for our collaboration and maintain firm linkage to the two active Human BIRN test-beds and the BIRN-CC. All three diseases have mixed genetic and environmental etiologies and are sufficiently complex to be challenging from a bioinformatics perspective.
These models came into the mouse BIRN project as part of collaborative mechanisms and act to drive development of an open data sharing infrastructure. Our collaborators include:
Dr. Joanna Jankowsky at Caltech for the Alzheimer's disease model (APP)
Dr. Rhonda Voskuhl at UCLA for the multiple sclerosis model (EAE) http://www.neurology.ucla.edu/
Dr. Eliezer Masliah at UCSD for the Parkinson's disease model (alpha synuclein-SNCA) http://medicine.ucsd.edu/
These individuals are leaders in the field of neurodegenerative diseases, and all have substantial practical experience managing, exploiting, and interpreting results generated using these three models.