Contractile Proteins
and the Cytoskeleton
in Morphogenesis
and Wound Healing
Our intellectual focus
is on identifying determinants
of cell shape that
function during development.
Utilizing molecular
genetic and reverse
genetic approaches
in Drosophila, we have
shown that conventional
nonmuscle myosin is
necessary for driving
both cell division
and post-mitotic cell
shape changes for morphogenesis,
and cellular locomotions.
Currently, we are investigating
how myosin elicits
cell shape change and
how its function is
regulated through filament
formation, phosphorylation,
sub-cellular targeting
and small GTP-binding
protein function.
We are characterizing
myosin light chain
kinase; a novel myosin
VII heavy chain; and
additional elements
that participate in
localizing myosin and
transmitting the forces
that it produces. We
used screens for aberrant
cell shape induced
in the yeast S. pombe
by expression of transfected
Drosophila cDNAs. These
experiments show that
elements that define
cell shape are conserved
throughout phylogeny
and that a screen in
yeast is a valuable
tool for recovering
heterologous cDNAs
that encode cytoskeletal
elements and the proteins
that regulate them.
In the fly, we are
identifying gene products
that are necessary
for myosin function
by genetically recovering
second site non-complementing
loci and biochemically
recovering proteins
that bind to myosin.
To date, our experiments
identify ~30 loci that
genetically interact
with myosin and a kinase
activity that phosphorylates
myosin heavy chain
and establish genetically
that the Rho signalling
pathway is required
in concert with nonmuscle
myosin II for morphogenesis.
We are also using
manipulation studies
to understand the forces
that drive cellularization
and morphogenesis.
We show that both the
amnioserosa and the
leading edge of the
lateral epidermis contribute
to the movements of
dorsal closure.
Finally, we are examining
the role these proteins
play in movements that
occur during wound
healing. Together,
our experiments promise
to reveal the nature
of cytoskeletal function
in cell shape determination
for cell division and
morphogenesis throughout
development.
Rotation students
and students who formally
accept the lab for
their Ph.D. work are
treated like much like
colleagues that are
intellectually responsible
for driving a project
related to the PI's
overall interests.
Technical and intellectual
training is provided
by the PI and other
lab members. Students
are required to participate
in and present at lab
meetings and national
scientific meetings.
Regular meetings between
the PI and the students
are planned for every
2-3 weeks.
