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Lab PageGraduate Student, Cellular and Molecular Biology Program
B.S., University of Bonn, 1995
Address: Rm. 329 Zoology Research Bldg.; 1117 W. Johnson St., Madison, WI 53706
Phone: (608) 265-2520
Email: mkoeppen@students.wisc.edu
Research Interests:
Many events during animal development involve the ability of epithelial cell sheets to undergo dynamic changes in shape and the formation of three-dimensional structures. I am interested in understanding the molecular basis underlying these properties of epithelia.
In particular, I am interested in the role of epithelial cell junctions since they are important for the major characteristics of epithelia: mechanical strength, the ability to undergo morphogenetic changes, the polarity of epithelial cells and the role of epithelia in physically separating compartments in an organism.
I am using is the nematode C. elegans as an experimental organism since it is a genetic system that allows many aspects of epithelial morphogenesis to be studied at the cellular and molecular level. My main focus is the central morphological event during C. elegans embryogenesis: the elongation of the initially spherical embryo into a worm. This process is driven by the dynamic change in shape of an epithelium called the hypodermis. Several components of epithelial cell junctions of the hypodermis have already been shown to be required during elongation (Costa et al., 1998).
I have begun to study another component of epithelial junctions of C. elegans, the protein MH-27. It localizes to all adherens junctions of the nematode with the exception of the spermatheca, where it localizes to junctions resembling septate junctions of arthropods (D. Hall, personal communication). This expression pattern suggests several possible roles for MH-27: it could function in cell adhesion as a component of the known cadherin/catenin complex. Alternatively, the protein might have a function similar to that of a tight junction protein, or have different functions in different tissues. These possibilities make MH-27 a very interesting molecule.
Cloning and sequencing of mh-27 revealed the protein
to be novel, showing similarities to coiled coil domains of several
proteins involved in binding and cross-linking cytoskeletal components.
Northern analy Return
to Hardin Lab Pagesis and cDNA cloning suggest alternative
splicing of the transcript.
Knocking out MH-27 using RNA interference causes embryos to arrest at the 2-3 fold stage during elongation with large vacuoles forming inside the embryo, suggesting a possible leakiness of hypodermal junctions in the absence of MH-27.
One current set of experiments is a screen for an mh-27
mutant. A mutant would allow structure/function analysis of the
MH-27 as well as mosaic analysis to study the role of the protein
in other epithelia of C. elegans. In addition, I am performing
overexpression experiments of mh-27 together with Jeff
Simske in the lab. In order to get a better understanding
of the mh-27 knockout phenotype, I am planning to do TEM
analysis of mh-27 RNAi embryos and mutants in collaboration
with John White's laboratory on campus. To investigate a possible
requirement of MH-27 in sealing hypodermal junctions, I will test
whether the mh-27 RNAi phenotype can be rescued or enhanced by
a decrease or increase in osmolarity of the surrounding medium.
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