The membranes of
eukarytoic cells are in continual flux, trafficking receptors and other
proteins
to their appropriate intracellular destinations.
This process is important to signal transduction, cancer, and development.
The overall goal of my lab is to understand how membrane traffic is
regulated in normal cells and how this process goes awry in diseased
cells. Our research is designed to identify and understand the cellular
proteins that form, direct and regulate membrane traffic. One strategy
is to create "knock-out" cell lines with specific mutations
in gene products that mediate membrane traffic. We then test physiological
function in these mutant cells. A complementary strategy is to tag
normal and mutant proteins with the fluorescent tag, Green Fluorescent
Protein, and then examine the dynamic distribution of these proteins
in living cells.
Currently, we are focusing on the proteins that form the structural
coat of endocytic membranes, the clathrin coat, and on rabs, small
GTPases thought to regulate
the fusion or budding of endocytic membrane. To approach this problem we use
a combination of molecular biology, genetics and time-lapse fluorescence microscopy
to image living cells. As model systems, we use the single-celled organism, Dictyostelium
discoideum, and mammalian cells grown in tissue culture. |
Selected Publications
Damer, C.K., and O'Halloran, T.J. (2000) Spatially regulated recruitment
of clathrin to the plasma membrane during capping and cell translocation.
Submitted, Molecular Biology of the Cell.
Wessels, D., Reynolds, J., Johnson, O.,Voss, E.,Burns, R., Daniels, K.,Garrard,
E., O'Halloran, T., Soll,D.R. (2000) Clathrin plays a novel role in the regulation
of cell polarity, pseudopod formation, uropod stability and motility in Dictyostelium.
Journal of Cell Science. 113,
Dragoi IA, and O'Halloran TJ. (1997) Cloning and Characterization of a Dictyostelium
Gene encoding a Small GTPase of the Rab11 Family. J. of Cellular Biochemistry.
70: 29-37
Niswonger ML, and O'Halloran TJ. (1998) A novel role for clathrin in
cytokinesis. Proc. Natl. Acad. Sci. USA. 94, 8575-8578.
Niswonger ML, and O'Halloran TJ. (1997) Clathrin is essential for spore-cell
differentiation but is not required for stalk-cell differentiation. Development.
124, 443-451.
Riddelle-Spencer K, and O'Halloran TJ. (1997) Purification of clathrin from Dictyostelium
discoideum and characterization of the clathrin light chain. Protein Expression
and Purification 11, 250-256.
Ruscetti T, Cardelli JA, Niswonger ML, and O'Halloran TJ. (1994) The clathrin
heavy chain functions in sorting and secretion of lysosomal enzymes in Dictyostelium
discoideum. J. Cell Biol. 126, 343-352
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