Wolfhard Almers, Ph.D.
After undergraduate studies at the Freie Universtät in Berlin, Wolfhard Almers attended graduate school at Duke University and the University of Rochester, where he received his Ph.D. in Physiology in 1971. He then spent three years as a postdoctoral fellow at the Physiological Laboratory at Cambridge University. He joined the Department of Physiology and Biophysics at the University of Washington as an assistant professor in 1974 and rose to professor in 1984. In 1992, he became the director of the Department of Molecular and Cellular Research, Max-Planck Institute, and from 1995 to 1999 was a professor in the Faculty of Biology, University of Heidelberg. In 1999, he joined the Vollum Institute as a senior scientist. In April of 2006, he was elected to the National Academy of Sciences.
Summary of Current Research
Eukaryotic cells pack enzymes, hormones, and transmitters into secretory vesicles and release them when the vesicles fuse with the plasma membrane during exocytosis. Cells must next retrieve the vesicle membrane by endocytosis to keep the plasma membrane from getting too large or contaminated. In the Almers lab, exo- and endocytosis are studied in live neurons and endocrine cells at the level of single vesicles and single molecules. Capacitance measurements are used to track the cell surface with millisecond time resolution as it changes during exo- and endocytosis. Even at their best, however, such electrophysiological recordings can only report how many vesicles undergo exo- and endocytosis and when these events occur. To detect signals from vesicles even before exocytosis and from the remnants of vesicles afterwards, the lab uses total internal reflection fluorescence microscopy, a method that lets them selectively image the surfaces of living cells to a depth of 100 nanometers. Vesicles can be imaged as they dock at the plasma membrane and then undergo exocytosis or as they withdraw from the plasma membrane during endocytosis. By labeling individual proteins with different colors, the group can observe the time-resolved recruitment and release of proteins during single exocytic and endocytic events. Questions of interest include: How do cells determine where on their surface vesicles dock for exocytosis? Once docked, in what sequence do vesicles recruit the proteins required for exocytosis? What are the mechanisms of membrane fusion and fission? How do cells select membrane for endocytosis? How is endocytosis regulated? Although the primary focus is on secretion and synaptic transmission, these questions relate broadly also to how cells crawl and determine their shape.
Barg S, Knowles MK, Chen X, Midorikawa M, and Almers W. (2010) Syntaxin clusters assemble reversibly at sites of secretory granules in live cells. Proc. Natl. Acad. Sci. USA. 107:20804-20809.
Knowles MK, Barg S, Wan L, Midorikawa M, Chen X, and Almers W. (2010) Single secretory granules of live cells recruit syntaxin-1 and synaptosomal associated protein 25 (SNAP-25) in large copy numbers. Proc. Natl. Acad. Sci. USA. 107:20810-20815.
Chen X, Barg S, and Almers W. (2008) Release of the styryl dyes from single synaptic vesicles in hippocampal neurons. J. Neurosci. 28:1894-1903.
Merrifield CJ, Feldman ME, Wan L, and Almers W. (2002) Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nature Cell Biol. 4:691-698.
Zenisek D, Steyer JA, Feldman ME, and Almers W. (2002) A membrane marker leaves synaptic vesicles in milliseconds after exocytosis in retinal bipolar cells. Neuron 35:1085-1097.
Steyer JA and Almers W. (2001) A real-time view of life within 100 nm of the plasma membrane. Nature Reviews Mol. Cell Biol. 2:268-275.
Zenisek D, Steyer JA, and Almers W. (2000) Transport, capture and exocytosis of single synaptic vesicles at active zones. Nature 406:849-854.
Steyer JA, Horstmann H, and Almers W. (1997) Transport, docking and exocytosis of single secretory granules in live chromaffin cells. Nature 388:474-478.