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Faculty
 William
A. Mohler
Assistant Professor of Genetics & Developmental Biology
Director, Graduate Program in Genetics & Developmental
Biology
2005 Osborn Biomedical Science Graduate Teaching Award Recipient
wmohler@neuron.uchc.edu
Areas of Interest:
We are pursuing three projects that extend from our interests in the
development of tissues and the innovative application of light
microscopy to biology: Developmental cell fusion, Second-harmonic
generation microscopy, and Genome-wide imaging of C. elegans
development.
Developmental cell fusion: Formation of multinucleate syncytia
(giant cells) is essential to the development and regeneration of human
skeletal muscle, and is key to fertilization and the formation of
various specialized cell types in many species. Yet the mechanism by
which fusing cells recognize each other and merge their membranes is
poorly understood. We use genetics and microscopy in the nematode worm
C. elegans to study the mechanisms by which cells fuse during this
animal's development. Our recent studies of the unique cell-fusion
protein EFF-1 indicate that the molecular machinery of cell fusion has
been re-invented during evolution of different cell types and divergent
organisms. We are also investigating the mechanism of mammalian myoblast
fusion, combining experimental tools developed specifically for that
system with our experience from the study of C. elegans syncytia.
Second-harmonic generation (SHG) imaging: We recently
discovered that thick myosin filaments in the actomyosin lattice of
striated muscle cells produce second-harmonic generation. This
non-linear optical effect produces bright contrast from the endogenous
unlabeled proteins themselves. The second harmonic light can be imaged
at high three-dimensional spatial resolution on a microscope, yielding a
digital profile of the arrangement and internal structure of muscle
fibers in live tissue. We are applying SHG microscopy to the study of
degenerative muscle diseases and aging, as well as the process of
myofibrillogenesis in the differentiation of muscle cells.
Genome-wide imaging of C. elegans development: We are working
to develop a database of genome and proteome activity in the developing
nematode C. elegans. This tiny yet complex animal is remarkable both for
its transparency and the cell-by-cell invariance its developmental
program. We plan to use two distinct fluorescence imaging technologies
to record the dynamics of expression and localization of GFP-tagged gene
products within live worms and embryos. The standardized digital data
produced by these instruments will then be correlated to find genes and
proteins that work coordinately in the formation of specific cell types
and tissues.
Lab Rotation Projects:
Cell-cell fusion in mammalian and invertebrate development. Muscle and
connective tissue structure imaging. Genomic-scale imaging of gene
expression in embryogenesis.
Mohler Lab Web Page
Selected Publications:
Mohler WA, Shemer G, del Campo JJ, Valansi C, Opoku-Serebuoh,
Scranton V, Assaf N, White JG, and Podbilewicz B. 2002. The type I
membrane protein EFF-1 is essential for developmental cell fusion. Dev.
Cell. 2: 355-362.
Campagnola PJ, Millard AC, Terasaki M, Hoppe PE, Malone CJ, and
Mohler WA . 2002. Three-dimensional high-resolution second-harmonic
imaging of endogenous protein structural proteins in biological tissues.
Biophys. J. 82: 493-508.
Campagnola PJ, Clark HA, Mohler WA , Lewis A, and Loew LM. 2001.
Second-harmonic imaging microscopy of living cells. J. Biomed. Opt. 6:
277-286.
Skop AR, Bergmann D, Mohler WA , and White JG. 2001. Completion of
cytokinesis in C. elegans requires a brefeldin A-sensitive membrane
accumulation at the cleavage furrow apex. Curr. Biol. 11: 735-746.
Heid PJ, Raich WB, Smith R, Mohler WA , Simokat K, Gendreau SB,
Rothman JH, and Hardin J. 2001. The zinc finger protein DIE-1 is
required for late events during epithelial cell rearrangement in C.
elegans. Dev. Biol. 236: 165-180.
Hoier EF, Mohler WA , Kim SK, Hajnal A. 2000. The Caenorhabditis
elegans APC-related gene apr-1 is required for epithelial cell migration
and Hox gene expression. Genes Dev, 14:874-886.
Mohler WA and Squirrell JM. 2000. Multiphoton imaging of embryonic
development. In: Imaging Neurons: A Laboratory Manual. Yuste R, Lanni F,
Konnerth A. eds. Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, NY.
Charlton CA, Mohler WA , Blau HM. 2000. Neural cell adhesion molecule
(NCAM) and myoblast fusion. Dev Biol, 221:112-119. |
