Current position
Fellow in the Molecular Genetics and Evolution Group, RSBS, ANU.
Head of the Drosophila-mammalian interface laboratory.
Research interests
The laboratory is interested
in cloning and investigating the function of novel mammalian genes
involved in developmental and neurobiological processes. One of
these is the human FLII gene, a highly conserved homologue of
the D. melanogaster flightless I gene. Mutations in flightless
I are either lethal during early development in the fly, or cause
serious muscle defects. We have cloned the corresponding mouse
gene Fliih and knocked it out (in collaboration with the Gene
Targeting Laboratory, John Curtin School of Medical Research)
by homologous recombination in embryonic stem cells. The mutation
causes early embryonic lethality in mice, and we have shown that
the human FLII gene can fully replace the missing mouse gene,
restoring normal development. We are conducting a range of studies
on the molecular and cellular biology of this gene in various
organisms involving collaborations with other scientists at the
ANU, elsewhere in Australia, and overseas. In this way, we are
investigating the fundamental role of the gene. The encoded protein
is the most evolutionarily conserved member of the gelsolin family
of actin binding proteins which are involved in regulating the
actin cytoskeleton. Recently, it has been found that the FLII
protein is involved in nuclear signalling via hormone receptors
including the estrogen and thyroid hormone receptors.
Another major focus is
the human SOLH gene, a homologue of the D. melanogaster small
optic lobes gene. In the fly, this gene is involved in development
of the optic lobes of the brain, part of the visual system. Recent
discoveries indicate that common genetic pathways underlie eye
and visual system development in flies and humans. This is contrary
to previous expectations, as it had been thought for many years
that the insect and mammalian eye had evolved separately. We have
cloned the human SOLH gene and shown it is a candidate gene for
a human genetic eye disorder. We are characterizing the mouse
Solh gene and are planning gene knockout studies to examine its
biological role in mammals.
Selected Publications
Archer, S.K., Behm, C.A.,
Claudianos, C. and Campbell, H.D. (2004). Evolution of the gelsolin
family of actin-binding proteins as novel transcriptional coactivators.
BioEssays, 27, 1-9. [No link available yet]
Archer, S.K., Behm, C.A.,
Claudianos, C. and Campbell, H.D. (2004). The
Flightless I protein and the gelsolin family in nuclear hormone
receptor-mediated signalling. Biochem. Soc. Trans. 32,
940-942. [Abstract]
Lee, Y.-H., Campbell ,
H.D. and Stallcup M.R. (2004). Developmentally essential protein
Flightless I is a nuclear receptor coactivator with actin binding
activity. Mol. Cell. Biol. 24, 2103-2117. [Abstract]
Campbell, H.D., Fountain,
S., McLennan, I.S., Berven, L.A., Crouch, M.F., Davy, D.A., Hooper,
J.A., Waterford, K., Chen, K.-S., Lupski, J.R., Ledermann, B.,
Young, I.G. and Matthaei, K.I. (2002). Fliih, a gelsolin-related
cytoskeletal regulator essential for early mammalian embryonic
development. Mol. Cell. Biol. 22, 3518-3826. (Abstract)
Davy, D.A., Campbell, H.D., Fountain, S., de Jong, D. and Crouch,
M.F. (2001). The flightless I protein colocalizes with actin-
and microtubule-based structures in motile Swiss 3T3 fibroblasts:
Evidence for the involvement of PI 3-kinase and Ras-related small
GTPases. J. Cell Sci. 114, 549-562. {Abstract}
Campbell, H.D., Kamei, M., Claudianos, C., Woollatt, E., Sutherland,
G.R., Suzuki, Y., Hida, M., Sugano, S. and Young, I.G. (2000).
Human and mouse homologues of the Drosophila melanogaster tweety
(tty) gene: A novel gene family encoding predicted transmembrane
proteins. Genomics 68, 89-92. [Abstract]
Kamei, M., Webb, G.C., Heydon, K., Hendry, I.A., Young, I.G.
and Campbell, H.D. (2000). Solh, the mouse homologue of the Drosophila
melanogaster small optic lobes gene: organization, chromosomal
mapping, and localization of gene product to the olfactory bulb.
Genomics 64, 82-89. [Abstract]
Kamei, M., Webb, G.C., Young, I.G. and Campbell, H.D. (1998).
SOLH, a human homologue of the Drosophila melanogaster small optic
lobes gene is a member of the calpain and zinc-finger gene families
and maps to human chromosome 16p13.3 near CATM (cataract with
microphthalmia). Genomics 51, 197-206. [Abstract]
Campbell, H.D., Schimansky, T., Claudianos, C., Ozsarac, N.,
Kasprzak, A.B., Cotsell, J.N., Young, I.G., de Couet, H.G. and
Miklos, G.L.G. (1993). The Drosophila melanogaster flightless-I
gene involved in gastrulation and muscle degeneration encodes
gelsolin-like and leucine-rich-repeat domains, and is conserved
in Caenorhabditis elegans and human. Proc. Natl. Acad. Sci. U.S.A.
90, 11386-11390. [Abstract]
Back to top
Return to Molecular
Genetics and Evolution Group
|
