The microscope has been a ubiquitous tool of biological research for over two centuries; indeed it has almost become a symbolic icon for biomedical research. Interest and developments in microscopy have waxed and waned over the years. However at the present time, more than ever before, there is a demand for microscopy, to study the structure and dynamics of cellular machinery. Much of this demand is being fueled by the extraordinary advances in genomics of the past few years. The yeast genome has been completely sequenced, and recently, the first genomic sequence of a multicellular organism, Caenorhabditis elegans, was completed. The human genome sequence has been targeted for completion in the foreseeable future. These remarkable endeavors are providing the complete parts lists of the target organisms. The primary sequence of every component protein of an organism can be deduced from these genomic sequences. This means that probes (such as antibodies) can be made to any protein and used to identify the location and distribution of that protein within an organism. The new challenge is to see how all these parts fit together and function as a living ensemble. Four Dimensional (4D) Microscopy, which uses a combination of optical sectioning microscopy together with computational techniques to study the structural dynamics of developing organisms, has become a powerful way to meet this challenge. By using 4D microscopy it is now possible to study three-dimensional dynamics of living tissue. We propose to develop a software system that will become a powerful tool for the study of embryogenesis. The system will be platform independent and accessible over the World Wide Web. It will be used to establish a database of 4D developmental sequences of embryos that will be accessible to research workers and students worldwide.

We have set up a three-way collaboration between the Molecular Biology Laboratory, the Space Science and Engineering Center and the Computer Science Departments at the University of Wisconsin to develop an integrated software suite that will be used to capture, archive, visualize, analyze and distribute multifocal plane, time-lapse (4D) recordings of embryonic development. Advanced visualization aids including roaming in space and time, 3D rendering and arbitrary plane slicing will facilitate perception of complex structural dynamics. A comprehensive annotation system will enable extensively labeled canonical developmental sequences to be established in a database thereby providing a powerful educational resource for students of embryology.

The CAMBIO initiative (Computational Algorithms for Multidimensional Image Organization) will not only establish a means for 4D image manipulation, storage and dissemination of embryo data, but will also establish a framework for sharing and visualizing 4D data that are generated in other biological studies such as cytoskeletal dynamics and organogenesis.