Core--Imaging and Histology

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Gene therapy as a discipline cuts across the entire spectrum of biomedical research, and a successful program requires access to all of the technical resources available to modern biology. As one of these technologies, biological imaging, including histology, has made major contributions to our biomedical knowledge in recent years as the instrumentation and techniques available have become not only more sensitive, more diverse, and more robust, but also easier to use. We have developed within the past year the wholly new Michael Hooker Microscopy Facility which will allow the Imaging & Histology Core to offer to the UNC gene therapy research community a suite of state-of-the-art technologies and technical assistance to aid their work. UNC's gene therapy research focuses on an expansion of knowledge of molecular mechanisms involved with the delivery and permanent expression of the therapeutic transgenes, with the long range objective of providing novel therapeutic modalities for treating monogenetic diseases such as cystic fibrosis and hemophilia. From the experience of two controlled clinical trials, the UNC Program has established the following objectives, 1) translational research with defined clinical endpoints, that provide a basic understanding of efficient gene delivery to airway epithelia for CF and liver cells for hemophilia; 2) the development of high titer viral vectors that offer safe, efficient long-term transgene expression; and 3), the development of novel animal models to help us better understand rate limiting steps in target cell transduction. The first and last of these requires heavy utilization of imaging and histology which the Imaging & Histology Core will serve with specific aims pertinent to the provision of [i] digital based widefield and confocal microscopy and cryo-cooled CCD-based luminometry, [ii] electron microscopy (including freeze fracture/freeze etch), [iii] tissue processing and sectioning for frozen specimens, or embedding in wax or plastic as appropriate, for light microscopy, and [iv] tissue processing and ultrathin sectioning services for embedding in plastic as appropriate to transmission electron microscopy. The Core will also assist investigators with the development of techniques for the expression and visualization of probes within living specimens or of novel or improved histological methodologies, and Core staff will consult with gene therapy investigators on methods of image quantitation.