Gene Myers, Janelia Farm Research Campus; Howard Hughes Medical Institute

Building Atlases Using Genetics and Light Microscopy
Arguably the most significant contribution of the human genome project is that we can now manipulate every gene and every regulatory region that controls the expression of a gene in the model organisms that have been sequenced, e.g. C. elegans (worm), D. melanogaster (fly), and M. musculus (mouse).  These manipulations include being able to attach fluorescent molecules that glow wherever a protein is in the cell or whenever it is being made in the cell, and this fluorescence can further be modulated via a change in temperature, light, or the introduction of a small drug or virus.  Combined with tremendous advances in light and electron microscopy in recent years, I believe we are now poised to directly visualize the meso-scale of the cell, and the development and detailed anatomy of small organs (e.g. a fly’s brain) and organisms (e.g. the worm) at the resolution of individual cells.  These advances require new imaging and data-mining methods for what I call “imaging bioinformatics”.

My lectures will focus on a number of our efforts to build “atlases” – complete models of some aspect of the cellular and developmental architecture of an organism.  We have already demonstrated a prototype system for single-cell analysis in the worm C. elegans, and believe we are on our way to building a complete atlas of every neuron in the fruit fly brain to 1micron resolution.  Finally, we believe that it will eventually be possible to follow the fate of every cell in an organism from a single zygote to some tens of thousands of cells after the first 24 hours of development in the fly and zebra fish.

References

  1. F. Long, H. Peng, X. Liu, S.K. Kim, and E. Myers,  ``A 3D Digital Atlas of C. elegans and Its Application to Single-Cell Analysis,''  Nature Methods 6, 9 (2009), 667-672.

  2. W. Pereanu, A. Kumar, A. Jennett, H. Reichert, and V. Hartenstein, ``Development-Based Compartmentalization of the Drosophila Central Brain,” J. of Comparative Neurology 518, 15 (2010), 2996-3023.

  3. P.J. Keller, A.D. Schmidt, J. Wittbrodgt, E.H.K. Stelzer, ``Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy,” Science 322, 5904 (2008), 1065-1069.