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RESEARCH
OPPORTUNITIES
My research program examines two fundamental areas of developmental
biology, patterning and cell fate specification, using the techniques of
molecular biology and the simple animal Hydra vulgaris as a model
system. "Patterning" refers to the processes by which the overall body
plan of an organism is established, while "cell fate specification" refers
to the processes that restrict or commit a cell to being only one specific
cell type, and prevent it from developing the characteristics of other
types of cells that are also found in the organism.
To study these processes, I use Hydra vulgaris , a member of the
evolutionarily ancient phylum Cnidaria, which also includes such
animals as sea anemones and jellyfish. There are several advantages to
using this animal as a model system for studying developmental processes.
First, the animal has a very simple body plan, with radial symmetry about
a single axis, so patterning essentially involves only one dimension.
Second, hydra has only 6 basic somatic cell types, which are organized
into two epithelial layers separated by an extracellular matrix. All the
non-epithelial cell types are located in the interstices between the
epithelial cells and are referred to as interstitial cells. Third, all
the epithelial cells of the body column are continuously mitotic, so
tissue is constantly being displaced either up or down the column. This
means that patterning processes must be continuously active in the adult
animal to maintain the normal body plan, unlike other animals in which the
pattern is established early in embryogenesis and remains static after
that. Fourth, all the interstitial cell types are continuously produced
from a population of multipotent stem cells, so cell fate specification
processes are also continuously active. Finally, because of the early
divergence of the cnidarians from the main line of metazoan evolution,
identification of the genes, molecules and mechanisms utilized by both
Hydra and other, more complex animals (such as nematodes, insects
and vertebrates) can provide insight into which developmental processes
arose early in the evolution of the metazoa and are likely to be
fundamental to multicellularity.
To explore the developmental processes described above, my laboratory uses
the techniques of molecular biology to isolate and characterize two
classes of genes: those encoding transcription factors, especially ones
which have been shown to play key roles in development in other systems,
and those encoding signaling molecules used for cell-cell communication
during development. Once identified and cloned, genes are both
characterized at the molecular level and analyzed for function in the
animal. Molecular characterization includes such techniques as DNA
sequencing, determination of gene copy number by Southern analysis, and
the use of gel shift assays and DNA footprinting to analyze the DNA
binding sites and cofactor or co-regulator requirements of transcription
factors. Functional analysis includes establishing the normal expression
pattern of the gene in question by in situ hybridization,
examining the effects of cellular and tissue manipulations on its
transcription in different cell types and body regions, and deliberate
alteration of the normal expression pattern to examine the effects of such
mis-expression on the animal.
Like virtually all work in the biological sciences, my research program is
a collaborative effort, not only between the members of my lab but also
with research groups at other institutions. Currently my major
collaborations involve the labs of Dr. H. Shimizu and Dr. T. Fujisawa at
the National Institute of Genetics in Mishima, Japan, Dr. S. A.
Hoffemeister-Ullerich at the University of Hamburg, Germany, and Dr. J. A.
Cassill's group at the University of Texas, San Antonio. Students who are
interested in joining my lab are encouraged to read my recent papers to
see the types of work currently underway, and to contact me to discuss
possible projects. All prospective student researchers must have
completed L211, Molecular Biology, or have previous laboratory experience
in molecular biology. Completion of L312, Cell Biology, and/or L317,
Developmental Biology, would also be helpful but is not required.
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