Introduction
This page is now out of date, please look at the Cell Biology Laboratory webpage.
The main aim of the Lab is to investigate
the role of the cell cytoskeleton and messenger RNA localization in
cell morphogenesis.
A sound bite from the Lab.
The shape of all cells is regulated by their internal cytoskeleton.
Cell shape is integral to cell function. The CBL investigates how
shape regulation is carried out through specific biological
mechanisms involving the cytoskeleton. The key cell to our studies is
the neuron.
Neurons are an excellent example of a highly differentiated
cell type in structure and function. Neurons are embryonically
derived from the ectoderm, as is the skin, and are initially not very
complex in shape or function. Their first function is to migrate into
their correct anatomical position, and resemble other cells which
migrate, such as fibroblasts with wound healing. When in place the
shape of neurons radically alters and extensive processes are
elaborated. These processes, neurites, are functionally immature and
differentiate through interaction with extracellular matrix and
target cells into dendrites and axons. The neuron now has a distinct
"polarity". An input side, dendrites and an output side, an axon.
Dendrites have targeted neurotransmitter receptors and axons have
transmitter vesicles. This differentiation is generated and
maintained by different cytoskeletal structure in axons, dendrites
and the cell body. At the simplest level it becomes a problem of
sorting. Sorting of the different components into different
cytoplasmic compartments. How is this achieved?
A research image from the Lab.
We suggest that the cell cytoskeleton is far
from a homogenous set of bones but is in itself both functionally and
structurally highly heterogeneous. This heterogeneity within the cell
may be supported by biological mechanisms that establish polarity in
the embryo itself, sorting at the level of the messengers that encode
the proteins themselves.
Our lab has described how the positioning
within the cell of protein translation, that is, intracellular
messenger RNA localization, may regulate the cell
cytoskeleton.
It has been shown that localization of
messenger RNA within the egg is critical in determining embryo
polarity. We are suggesting that such a fundamental mechanism in the
embryo is also utilized in somatic cells to regulate the cell
cytoskeleton and will possibly be involved in cell
plasticity/polarity. To this end the Lab is currently focused upon
the development of neurons. In particular the lab is investigating
actin mRNA localization.
The Lab is always looking for researchers at
doctoral and post-doc level with backgrounds in molecular biology,
neurobiology, tissue culture, and embryology.
If you find this subject interesting
email
for more detail.
Research Facilities
The laboratory has Tissue Culture (separate
cell line & primary culture), and Molecular Biology (gene
transfection facilities and in situ hybridization, ISH) for
intracellular localization of mRNAs.
Honours Projects
1. The Effect of Pressure in the development of Retinal
disease.
Glaucoma is a serious disease of the eye which leads to blindness.
The cause of this disease is still unknown. What is know is that
increased pressure inside the eye is associated with the death
(apoptosis) of the neurons projecting back to the brain (retinal
ganglion cells). This project involves subjecting cells to increased
pressures equivilant to those seen in glaucoma and comparing cell
death in these cells compared to controls.
2. Characterization of a new Retinal Ganglion Cell
Line.
One problem in studying neurons is that they are post-mitotic,
that is, they do not divide. This means that studies involving
neurons are restricted to cells originally isolated from animals. A
way around this has been to develop neuronal lines, cells which will
divide, but which can be made to behave as neurons. A collaborating
Lab in the US has just generated a retinal ganglion cell line which
would be very useful in studying retina development and disease. This
project involves generating a full characterization of these new
cells: proteins they express, growth factor resonse, cytoskeleton
changes.
3. Development of the Cell Cytoskeleton.
Cell shape and motility are controlled through the cell
cytoskeleton. In development, differentiation and disease, cells must
assume quite elaborate shapes and some cells are quite motile. Actin
microfilaments of the cell cytoskeleton are the key controllers of
shape and motility and have been totally conserved as a protein
through all mammals. We have developed cells which express a "fusion
protein" (a joint protein) of beta actin and green fluorescent
protein (GFP). This protein is used by the cell as its own actin, the
difference is that GFP can be observed through the microscope. The
project will involve following the localization of this fusion
protein in cells undergoing cell signalling (transduction)
processes.
4. Fragile X and neural development.
The disease Fragile X syndrome is the most common form of
inherited mental retardation in humans. Gene and mutation causing
this disease has recently been identified. The disease results from a
CAG expansion in the FMR1 gene located on the X chromosome (Xq27.3).
The protein (FMR1) encoded by this gene functions as an RNA-binding
protein in neurons, though the function of FMR1 has yet to be fully
shown. This project looks at the localization of this protein in
neurons and neuronal cell lines in relation to other cell structures.
Experiments will be carried out to alter FMR1 levels and to identify
messenger RNAs which it binds.
5. Targeting of mRNAs within the cell.
In embryonic development the establishment of cell polarity has
been shown to involve specific localization of messenger RNAs (mRNA).
We have shown in adult cells, signalling which establishes cell
polarity (directions) also is associated with targeted mRNAs. This
project looks at blocking localization of these targeted mRNAs in
cells and the subsequent effects upon the cells.
Other topics are also available within the Lab. Possible
projects and more details about the above projects should be
discussed with Dr Mark Hill (email: m.hill@unsw.edu.au or ph 9385
2477)
Vacation Scholarships
The laboratory has a number of Anatomy
Vacation Scholarship positions available for study over the
Summer vacation break. These positions can be applied for by either
Medical or Science students.
Author's Contact Details
Dr Mark Hill
Cell Biology Laboratory
School of Medical Sciences
The University of New South Wales
Sydney NSW 2052
AUSTRALIA
phone: +612 9385 2477
email: m.hill@unsw.edu.au
Web: http://cellbiology.med.unsw.edu.au/
For more information see About the Author
