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					                                               Honours Program
                            ANATOMY & HISTOLOGY
                                             University of Sydney
                                                     www.anatomy.usyd.edu.au


                        PROJECTS AVAILABLE FOR 2008
For an Honours year in Anatomy & Histology, you need to:
• Have a Sci-WAM of at least 68*; pre-enrol with the Faculty of Science; organise a project with a lab head; confirm your intention to
do Honours with the Anatomy Honours Coordinator (A/Prof Frank Lovicu); be aware of our Summer Scholarship program.
Scholarships are primarily awarded according to SciWAM. To be eligible, you must be committed to Honours in Anatomy &
Histology. Application forms for Scholarships are at the end of this flyer or are available from A/Prof. Lovicu (Room S252).
*(If you are still interested in Honours but do not meet all the criteria, see A/Prof. Lovicu to discuss further options).

Our Honours Program in Brief
• Thesis (~25,000 words; November submission)
• Seminar (~20 minutes; November). You will present your year's work.
• Honours Meetings (attend meetings, 1 hour/week during semester). At these meetings, each student will present 2 seminars during
the year, outlining for example, project aims and their early results. These presentations will be to the other Honours students and the
Honours Coordinators.
W hen choosing a lab to do Honours, make sure that: you get on with Supervisor; the lab is well funded; the lab is filled with happy
and likeable people and has many recent publications; and most importantly you are interested in the project.



NEUROCHEMISTRY LAB
A/Prof Vladimir BALCAR Rm: S317 ext: 12837 vibar@anatomy.usyd.edu.au
*ATP receptors in brain - alternative exitations?
We now have a good picture of the effects of the most important excitatory neurotransmitter L-glutamate on the brain metabolism. Flux
through metabolic pathways increases and pools of metabolites undergo characteristic changes. But what will happen when the excitatory
receptors activated by extracellular ATP (P2X receptors) are switched on? Nothing is known of their role in the regulation of brain
metabolism. The project will aim at establishing the effects of P2X agonists and antagonists on metabolism in brain tissue in vitro, using
analyses by 13C-NMR spectroscopy.



CATARACT PREVENTION UNIT
Dr. Coral CHAMBERLAIN, Rm E214, ext. 1-5169 coralcha@anatomy.usyd.edu.au
By far the most serious clinical problem associated with the lens of the eye is cataract, a loss of lens transparency that leads to visual
impairment. In Australia, 25% of people aged 60-69 years have cataract; this rises to 100% at 90+ years. The Cataract Prevention Unit was
set up in 2000 by Dr Chamberlain, a former co-leader of the Lens Research Laboratory, who contributed for many years to its pioneering
work on the role of FGF and other growth factors in normal lens biology and the role of TGFβ in the development of certain forms of
cataract. Significantly, TGFβ is also implicated in the aetiology of PCO (aftercataract), a common sight-threatening condition that arises
from lens cells left behind at the time of cataract surgery. A very useful range of rat models for studying TGFβ-induced cataract and PCO is
now available in this Unit. The focus of the Cataract Prevention Unit is primarily on the development of new strategies for preventing or
treating TGFβ-related forms of cataract, including PCO. However, we also carry out interesting, clinically relevant studies of the effects on
lens cell behaviour of various anti-inflammatory drugs used routinely at the time of cataract surgery, under conditions that mimic events in
PCO formation. Commonly used techniques include: lens explant and whole lens culture, light microscopy, immunolocalisation, scanning
electron microscopy, ELISA and DNA assays. A position for an Honours student may be available in 2008 to carry out a project in one of
the above areas.



THE RETINA IN DEVELOPMENTAL NEUROBIOLOGY AND NEUROPATHOLOGY
A/Prof. Tailoi CHAN-LING Rm: S466 ext: 12596 tailoi@anatomy.usyd.edu.au
Our lab is currently supported by the National Health and Medical Research Council, International Science Linkages, The Financial Markets
Foundation for Children, The Baxter Charitable Foundation, The Macular Vision Support Society and the Rebecca Cooper Medical Research
Foundation. Our experimental approach is to use the retina, as a model of the brain, to further our understanding of the developmental
biology of CNS blood vessels and glial cells (in particular, the astrocytes and oligodendrocytes which are critical to the functioning of
neurones). While some of the projects are predominantly of a basic nature, others have clinical relevance to sight threatening retinopathies
such as Retinopathy of Prematurity and Age-Related Macular Degeneration, the leading causes of blindenss in infants and aging
respectively. The accessibility of the eye for experimental manipulation allow studies that lead to insights into various disease processes that
affect the CNS, in particular Retinopathy of Prematurity, Age-related macular degeneration (ARMD) and Spinal cord injury. We have a
number of existing collaborations with the Departments of Pathology at Sydney University and The Australian National University; The
John Curtin School of Medical Research - Division of Neuroscience as well as collaborations with a number of leading laboratories overseas.
Recent studies have contributed insights into the cellular and molecular processes in the formation and remodelling of CNS blood vessels.
Other studies have contributed to the understanding of the differentiation of cells of the astrocyte lineage in vivo.
Our lab currently has 5 Postgraduate students, one post-doctoral fellow, two part-time research associates and myself. Current projects on
offer: 1)Application of heamatopoietic stem cells in the treatment of ARMD 2) Developmental neurobiology of cells of the oligodendrocytic
and astrocytic lineages 3) Application of neural stem cells in regenerative medicine 4) Cellular and molecular processes in the formation of
the human retina and choroid. Our lab is keen to attract talented students interested to pursue a career in biomedical research, particularly
students interested to undertake a PhD candidature and opportunities exists for exchanges with collaborating national and international
laboratories in USA/Germany/Italy/New Zealand/Ireland. Please feel free to email or phone to have a chat about the possibilities. Two
current projects include: Stemming vision loss with stem cells.2. Characterisation and application of human neural precursor cells in cell-
based therapy.More lab details can be found at: About Associate Professor Tailoi Chan-Ling and a selected list of publications.
 http://www.usyd.edu.au/health/phds2008/opportunity_search.php?action=supervisor_detail&supervisor=133.




PATHOGENESIS OF ALZHEIMER'S DISEASE
*MICROVASCULATURE BREAKDOWN AND INFLAMMATION
Dr. Karen CULLEN Rm S464 ext 1-2696 kcullen@anatomy.usyd.edu.au
The major focus of the laboratory is on the pathogenesis of Alzheimer' disease (AD). AD is the most common form of dementia, and its
prevalence is increasing as the population ages. The key lesions in the disease result from breakdown of the cerebral microvasculature. Our
work studies normal and diseased microvasculature and the relationship of damaged vessels to neurodegeneration. We also examine the
processes of inflammation around damaged vessels. An example of the types of projects available: Immunohistochemical study of the
microvasculature and inflammation in AD brain tissue. This project involves the mapping of capillary damage and the sequence of
inflammatory events from fresh microhaemorrhage to scar formation. A second group of studies examines the role of quinolinic acid, a
neurotoxin produced by microglia and circulating macrophages, in the neurodegeneration of AD and related dementias. These studies are
done in collaboration with the Centre for Immunology, St Vincent’s Hospital.
*Pathogenesis of motor neuron disease.
Supervised jointly in the Disciplines of Anatomy and Histology and Pathology.
  Dr Roger Stankovic. Rm 520. Blackburn Bld. ext: 14159 rogers@med.usyd.edu.au
  Dr Karen Cullen Rm S464 Anderson Stuart Bld. ext 12696 kcullen@anatomy.usyd.edu.au
Motor neuron disease is a fatal neuromuscular disease for which there is no cure. The studies will examine inflammation and cytoskeletal
abnormalities in transgenic mouse models and human brain and spinal cord histopathology. Research Techniques involved include
immunohistochemistry, image analysis and electron microscopy.




PHYSICAL ANTHROPOLOGY & COMPARATIVE ANATOMY
Dr. Denise DONLON Rm W601 ext: 14529 ddonlon@anatomy.usyd.edu.au
Research in the Shellshear Museum focuses on human osteology with a focus on the identification of skeletal remains. There are a lack of
standards for the forensic identification of skeletal remains in Australia. We are interested in finding methods to identify ways of determining
ancestry, sex, age and stature of those remains found in NSW and particularly in the Sydney region. Present research focuses on
discriminating between human and non-human bone fragments and determination of sex of juveniles from dentition. Other areas of research
include the clinical implications of human cranial variations and the investigation of cranial and body proportions of Homo floresiensis.
Collections in the Shellshear Museum which are available for research include a large collection of Melanesian skulls, a collection of skeletal
remains from Pella, Jordan and a large varied range of mammal skulls and dentitions. There is one honours project for 2008 which involves
the description and analysis of the skeleton of a man with Marfan Syndrome (MfS). The skeleton is that of a donor to the Department of
Forensic Medicine who expressed the wish that his skeleton be used for medical research. Marfan Syndrome is a rare genetic disorder
affecting the connective tissue. It is caused by the mutation of the gene which produces the protein fibrillin, which binds the cells together.
The defective gene therefore, either produces an insufficient amount and/or an inferior strength of the protein, which weakens the connective
tissues, rendering them unable to withstand normal stresses. Skeletal features are abnormally long limbs and digits with joint laxity leading
to a higher risk of dislocation under normal physical stress and early onset of osteoarthritis. There can be vertebral (spinal) deformity such as
scoliosis, thoracic lordosis and/or lumbar/sacral complications. A dental abnormality identified with MfS is a high arched palate leading to
overcrowding of teeth with a pronounced overbite.



BREAST CANCER: HOW THE CELLULAR IMMUNE SYSTEM RESPONDS TO
METASTASIS
Prof. Cris dos REMEDIOS Rm: W105 ext: 13209; mobile 0413482738; crisdos@anatomy.usyd.edu.au
*Breast cancer: how the cellular immune system responds to metastasis.
Supervisors: Prof. Cris dos Remedios, Dr Andrew Spillane
Project Description: This project will is a collaborative one with Dr Andrew Spillane, Breast Cancer Unit, Royal Prince Alfred Hospital. We
will isolate mononuclear cells isolated from 5 mL of whole blood from breast cancer patients. These cells will be examined by applying them
to a microarray of antibodies directed against leukocyte antigens. The pattern of leukocyte capture tells the story. We will ask: (1) Is there a
characteristic pattern of leukocyte immobilization from breast cancer patients that differs distinct from that of healthy blood donors? (2) Does
breast cancer induce a specific response in the surface CD antigens (for example cluster of differentiation antigens) patient's leukocytes that
differs from other malignant conditions (melanoma, bowel and prostate cancers)? (3) Can we detect a difference in leukocyte CD antigens
that tell us whether a patient with breast cancer is likely to develop or has developed a metastasis (secondary cancer) either local (axillary
nodes) or some distance from primary lesion in the breast. The project will involve collection of blood samples from the clinic, isolating
mononuclear cells from whole blood and applying them to the arrays in the Anatomy Department.
FUNCTIONAL ORGANISATION OF THE VISUAL SYSTEM
Prof. Bogdan DREHER Rm: S461 ext: 14194 bogdand@anatomy.usyd.edu.au
Work in our lab focuses on: 1) the role of the so-called ‘feedback’ projections from the ‘higher-order’ visual cortical areas to the ‘lower-
order’ visual areas (including the primary visual cortices) and subcortical visual nuclei and 2) the spatial extent and mechanisms underlying
the reorganization of visual cortices following circumscribed lesions of the retina in adult or adolescent mammals. We approach these
problems using physiological techniques, in particular study the receptive field ( both ‘classical’ and ‘extra-classical’) properties of single
neurones in a given area; selective, reversible inactivation of different visual cortical areas; cross-correlation analysis of discharges of
individual cells located in a given area or in the neighbouring areas.



LAB OF NEUROGLYCOBIOLOGY AND SENSATION
Dr. Michelle GERKE, Rm E411 ext: 14703, mbgerke@anatomy.usyd.edu.au
Work in this laboratory is currently focusing on a population of primary sensory neurons which are responsible for the initial detection of
painful stimuli (nociceptors), and their contribution to the onset and maintenance of chronic pain after nerve injury. Peripheral nerve injury
induces a number of changes in the phenotype of primary sensory neurons which may underlie the development of chronic pain states. A
discrete group of nociceptors which express binding sites for the plant lectin Bandeiraea simplicifolia I isolectin B4 (BS-IB4) are affected by
nerve injury such that they can no longer be visualised using lectin binding histochemistry. Whether this lack of lectin binding is due to
actual death of this group of nociceptors or whether they undergo phenotypic change such that they stop manufacturing the glycoconjugate
responsible for BS-IB4 binding has not been clearly defined. An understanding of how these nociceptors are affected by peripheral nerve
injury is an important step in understanding chronic pain states and necessary for the development of future pain therapies targeted towards
primary sensory neuron populations. In collaboration with Dr. Kevin Keay’s laboratory the Honours project offered through this laboratory
will involve the combination of neural tracing, behavioural and histochemical techniques, fluorescent and confocal microscopy to assess
what is actually happening to this population of nociceptors under the conditions of peripheral nerve injury leading to chronic pain.



ALZHEIMER’S AND PARKINSON’S DISEASE LABORATORY at the BRAIN & MIND
RESEARCH INSTITUTE: NEURONAL CELL BIOLOGY.
Dr Claire GOLDSBURY. BMRI Bldg, Level 4, 9351 0878, cgoldsbury@usyd.edu.au
*Roles of oxidative-stress and energy deprivation in regulation of Alzheimer’s disease related proteins
Oxidative stress and reduced glucose metabolism occur in the Alzheimer’s disease brain and are associated with neurodegeneration.
Evidence of oxidative stress has been found to precede the major development of senile plaques (comprised of beta-amyloid peptide
deposits) and neurofibrillary tangles (comprised of hyperphosphorylated tau protein). The aim of this project is to determine effects of
oxidative stress and energy deprivation on the generation of beta-amyloid peptides and tau phosphorylation in neurons. A combination of
techniques will be used including primary neuronal cell culture, cell viability assays, immunoprecipitation, Western blotting and
immunofluorescence.
*Signalling to the cytoskeleton during axon retraction
The response of neurons to spatial and temporal guidance cues is essential for establishing functional networks of connecting cells and for
the regeneration of connections after injury or disease. This is mediated by directional motility of growth cones at the tips of axons.
Reorganisation of the actin and microtubule cytoskeleton in growth cones causes assembly/disassembly cycles that lead to protrusion
(growth) or contractility (repulsion). Depending on their relative prominence the axon extends, forms branches or retracts. Using a
combination of primary neuronal cell culture, live cell imaging and biochemical techniques, this project investigates mechanisms that
generate the motility causing growth cone collapse and axon retraction.




ALZHEIMER’S AND PARKINSON’S DISEASE LABORATORY at the BRAIN & MIND
RESEARCH INSTITUTE
Prof. Jürgen GÖTZ. BMRI Bldg, level 3, ext. 10799 or 10789, jgoetz@med.usyd.edu.au
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. There are
estimates that by 2040, approximately 500’000 Australians will suffer from AD, with associated health costs of about 3% of the GDP.
One of our main interests is the development of cellular and animal models for AD and related disorders, using tissue-culture,
transplantation, transgenic and knockout techniques. Currently, our research focuses mainly on two AD-related proteins, the microtubule-
associated protein tau and the serine/threonine-specific protein phosphatase PP2A. We are interested in their role under both physiologic and
pathologic conditions. We are further interested in the interaction of tau and β-amyloid, the principal proteinaceous component of the
amyloid plaques in AD brains. For that we have established a whole range of transgenic and tissue culture models which model key aspects
of the disease. With the help of both proteomic and transcriptomic approaches, we aim to identify the components of the patho-cascades and
to dissect pathogenic mechanisms in AD. Eventually we hope that our efforts will assist in the development of a safe treatment of AD.
Students that undertake Honours projects in our laboratory can expect to be exposed to a wide array of techniques, and conduct one of the
projects outlined below:
*Histological and functional validation of candidate proteins identified in models of Alzheimer’s by Functional Genomics
*Use of stereotaxic injections to address the transport of Aβ in the mouse brain
*Assessing the specificity of the Aβ-mediated induction of tau tangles (NFTs) in vivo by injecting amylin (which is found aggregated in
diabetes) into mouse brain.
*Exposing transgenic mice with an Alzheimer-like tau pathology to oxidative stress, determine functional impairment and correlate these
with the tau pathology in distinct brain areas using Western blotting and immuno-histochemistry
*Dissection of the functional domains of tau by a transgenic approach. The project involves the design of novel transgenic animal models
where individual interactions are disturbed.
*Transgenic mouse model with a brain pathology in the skin. This project involves a histopathological and Western blot analysis of a
novel mouse strain, combined with depilation to determine the hair cycle-dependent pathology.
NEURAL IMAGING LABORATORY:PAIN RESEARCH
Dr. Luke HENDERSON: Rm S420, ext: 17063, lukeh@anatomy.usyd.edu.au
*Brain changes associated with chronic pain in humans
The major aim of the laboratory is to define the brain circuitry underlying acute and chronic pain in humans. We are particularly interested in
defining the anatomical and functional brain changes associated with chronic pain following spinal cord injury and peripheral nerve injury in
humans. In collaboration with Professor Philip Siddall at the Pain Management Research Institute at RNSH we are using state-of-the-art
human magnetic resonance imaging techniques to explore anatomical and functional changes that occur in patients with pain following
spinal cord injury. In collaboration with Professors Greg Murray and Chris Peck at the Orofacial Pain clinic at Westmead hospital we are
exploring long-term brain changes in patients with various forms of orofacial chronic pain. Finally, in collaboration with Professor Vaughan
Macefield at UWS we are defining the brain circuitry responsible for acute skin and muscle pain in healthy individuals.



LABORATORY of NEURAL STRUCTURE & FUNCTION
(Injury, Disability and Chronic Pain Research)
A/Prof. Kevin KEAY: Rm: S502 ext: 14132 keay@anatomy.usyd.edu.au
Despite advances in the clinical management of acute pain, injury of the nervous system leads still, in a clinically significant number of
cases, to chronic neuropathic pain and striking disabilities characterised by alterations in complex behaviours and physiological dysfunction.
The combination of chronic neuropathic pain and disability is notoriously refractory to treatment.
Traumatic injuries lead to an "acute phase" response characterised by inflammation, pain and the disruption of ongoing behaviours. This
acute phase response is followed usually by a period of diminishing inflammation, reduced pain, healing of the injury and a return to normal
function. For a number of individuals however, pain and behavioural disruption persists beyond this acute phase and despite injury healing,
results in a state of chronic pain and disability. Injury triggers neuroplastic changes provoking altered activity in both peripheral nerves and
their spinal cord and brainstem projection targets. However, the specific neural adaptations leading to the development of a state of chronic
or persistent pain and disability on the one hand, or to a complete recovery on the other, are not understood. Recent work from our laboratory
has demonstrated that nerve injury evokes both pain and disabilities (i.e., disrupted social behaviours, disrupted sleep-wake cycle, changed
in appetite, metabolic and endocrine function, loss of the ability to cope effectively with stress/stressors) in a select subgroup of nerve-
injured rats. We have therefore suggested that this model of nerve injury is closer to the human clinical presentation than previously
appreciated. Our data suggest also that disabilities evoked by nerve damage reflect a specific and select neurobiological response to the
injury. We have characterised using molecular biological (i.e., gene-chips, RT-PCR, Western blotting) and functional-anatomical (i.e.,
immunohistochemistry) techniques unique sets of neural adaptations in sciatic nerve recipient areas of the spinal cord, and the supraspinal
areas which receive inputs from them in the subset of rats with pain and disability following injury. The broad aims of our research is to
identify the specific neural networks which undergo (mal)adaptation following injury and lead to both behavioural and physiological
changes which characterise individuals with chronic pain and disability. Our research will contribute to a better understanding of the
transition from acute injury to chronic pain and disability.




DEVELOPMENT AND PLASTICITY OF PERIPHERAL AND SPINAL NEURONS
A/Prof Janet KEAST, Pain Management Research Institute, RNS Hospital Ph: 99267194; jkeast@med.usyd.edu.au
Our research team explores the structure and function of the nervous system, particularly how the nervous system is affected by injury or
inflammation and also how nerve circuits develop to make appropriate contacts in the pre- and neonatal periods. We are interested in basic
neurobiology as well as in processes that relate to specific disease processes or injury states (e.g., interstitial cystitis, pain, spinal cord injury,
peripheral nerve damage). Honours projects would be suited to enthusiastic students who have very good motor and analytical skills,
excellent visual and observational abilities, and a broad interest in the nervous system. In these projects we use microscopy, imaging and
microsurgical techniques, as well as knockout mice, in vitro pharmacological assays, behavioral testing, neuronal cultures and molecular
biology.
*Developing new methods for improving nerve growth and function after injury.
We are particularly interested in understanding the effects of injury on pelvic autonomic nerves (which are often damaged during surgical
procedures such as hysterectomy and prostatectomy). We are trying to develop ways of promoting regenerative processes in these nerves by
investigating the actions of neurotrophic factors, guidance factors and endogenous steroids. In this project you will learn how to culture
neurons, investigate the molecular mechanisms of neuronal growth and, for students interested in in vivo function, study nerve regeneration
in knockout mice.
*How do natural steroids affect pain?
We are interested in the mechanisms by which estrogens affect pain signalling neurons (nociceptors) and related spinal circuits, and also how
inflammation triggers chronic pelvic pain. We hope to develop new ways to prevent or reverse these chronic pain states by manipulating
signaling pathways specific to these neurons. Depending on the interests of the student, this project may involve molecular studies on
signaling pathways and receptor trafficking in cultured nociceptors, behavioural studies of spinal reflex pathways, or neuroanatomical studies
on structure and activity of nociceptors and central reflex pathways.
*How do neurons know where to grow?
We have a number of projects available on the developing nervous system, that can be tailored to the interests of the student. For example,
we have a project investigating how gender differences are established in the pelvic autonomic nervous system (especially the role of
estrogens and androgens). Another project focuses on how neurotrophic factors and guidance factors control the survival and connections of
pelvic autonomic neurons or nociceptors. These research topics involve detailed microdissections of neural tissues, neuroanatomical tract
tracing, immunofluorescence, image analysis and use of gene knockout mice.
FOCAL ADHESION BIOLOGY
Dr. Geraldine O'NEILL, Oncology Research Unit, Children's Hospital, Westmead. 98453116. GeraldiO@chw.edu.au
*Moving cancer cells: A molecular analysis of the pro-metastatic molecule HEF1.
Project Description: A major problem in cancer treatment today is when the cancer spreads around the body, in a process known as
metastasis. Once this occurs the cancer becomes very difficult to treat. Our research has contributed to the increasing realization that the Cas
family of proteins, including the Cas protein HEF1, are vital determinants of cell migration in cancer. To understand how these molecules
cause the development of metastatic cancer, we need to define how these molecules work in the cell. Therefore, we are investigating the
molecular regulation of HEF1 by creating recombinant DNA molecules in which key HEF1 sites are mutated. We then test these mutant
cDNAs for their effects on cancer cell migration. Techniques used in the project are a range of molecular biology and cell biology techniques
with a strong focus on fluorescence microscopy including live cell imaging.




LENS RESEARCH LABORATORY
A/Prof. Frank LOVICU, Rm S252, ext: 15170, lovicu@anatomy.usyd.edu.au
Prof. John McAVOY, Save Sight Institute, johnm@eye.usyd.edu.au
Research in our laboratory is directed at identifying the molecular mechanisms that regulate eye lens development, growth and pathology.
Our research group has two major laboratories, one situated in the Anderson Stuart Building on the main University campus and the other at
the Save Sight Institute at Sydney Eye Hospital on Macquarie Street. Using a range of techniques such as tissue culture,
immunohistochemistry, in situ hybridisation, PCR, chromatography, Western blotting, light and electron microscopy, in vitro biological
assays and transgenic mouse strategies, we investigate the expression, effects and function of different growth factors their receptors and
regulation of intracellular signalling, in normal lens development and pathology. In particular we have shown that members of the fibroblast
growth factor (FGF) and Wnt families are important regulators of lens epithelial cell proliferation, migration and differentiation and are
important for the normal development and maintenance of the lens. Our studies have also shown that other growth factors, for example,
transforming growth factor ß (TGF-ß), induce the formation of fibrotic plaques that lead to cataract (loss of lens transparency), analogous to
that found in humans.
Students that undertake Honours projects in our laboratory can expect to be exposed to a wide array of techniques, encompassing cellular,
developmental and molecular biology, and can carry out a project in one or a combination of the following areas:
Normal Lens Biology
*Investigate the role of growth factors (FGF, PDGF, IGF, EGF, BMPs) and their signalling pathways in regulating lens cell proliferation and
fibre differentiation using lens epithelial explants and/or transgenic mouse models.
*Identify factors (related to Wnt signalling) that maintain the normal lens epithelial phenotypic characteristics including cell-cell and cell-
matrix adhesion and communication.
*Use in vitro assays and transgenic mice to determine the role of novel genes (Crim1, Sef, Sprouty) thought to be involved in regulation of
growth factor bioavailability.
*Use electron microscopy and tissue culture to identify the molecules in the ocular fluid that are important for lens cell differentiation and
how this contributes to lens transparency.
Lens Pathology (Cataract)
*Use transgenic mouse models to understand how TGFß induces and regulates cataract formation.
*Use lens explant cultures to determine how TGFß disrupts normal lens signalling pathways and induces an epithelial-mesenchymal
transition, characteristic of cataract.



HUMAN RETINAL BIOLOGY & EYE TUMOUR LAB - SAVE SIGHT INSTITUTE
Dr Michele MADIGAN Save Sight Institute, Sydney Eye Hospital. 9382 7283. michele@eye.usyd.edu.au
Dr. Karen CULLEN - Room S464 Ext. 12696. kcullen@anatomy.usyd.edu.au
Project Title: Growth Factors, Proteinases and Human Foveal Development
Supervisors: Dr Michele Madigan, Dr. Karen Cullen
The fovea centralis ('fovea') is the part of the retina we use to resolve fine details, including reading and seeing people's faces. The foveal
region is less than 1mm in diameter, but responsible for almost all of our useful vision. The retina is highly specialized at the fovea,
including deflection of the inner cells 'outwards'/peripherally to make a depression, a peak concentration of cone photoreceptors, and the
absence of retinal vessels. The retinal photoreceptors are the most metabolically active cells in the body. The absence of vessels is
paradoxical, because usually parts of the brain with a higher metabolic rate demand a more dense blood supply. So what controls the growth
of the retinal vessels? This project aims to look at regulation of human retinal endothelial cell migration and proliferation in relation to the
developing fovea, including the role of growth factors such as TGF-ß, FGF-2 and proteinases.
This project is based at the Save Sight Institute, Sydney Eye Hospital, in collaboration with the Research School for Biological Sciences,
ANU (A/Prof Jan Provis).
*Complement Pathway Proteins in Normal, Normal Aged & AMD Retinae
Supervisors: Dr Michele Madigan, Dr. Karen Cullen
Age-related Macular Degeneration (AMD) - involving loss of central macular photoreceptors with (wet) or without (dry) retinal
neovascularization - is a major cause of irreversible visual loss. In Australia, AMD affects 1 in 4 people over the age of 60 (~1 million
people), and accounts for almost half of all cases of blindness.
Epidemiological and family studies clearly indicate that AMD develops from the interplay of environmental and genetic factors.
Environmental factors that influence the onset and progression of AMD include light exposure, levels of physical activity and smoking.
More recently, polymorphisms in several genes with strong associations to the onset of AMD have been identified, including polymorphisms
in the complement factor H (CFH) gene, and other complement pathway-associated genes, consistent with a major role for inflammation in
the pathogenesis of AMD. Another biomarker of chronic inflammation, C-reactive protein (CRP), assists in complement binding to the
surface of foreign and damaged cells, and may be involved in humoural responses to disease and infection. This project will investigate
immunoreactivity to complement pathway proteins and CRP in Normal Aged and AMD human retina and choroid. Expression of these
proteins will be compared with immunolabelling for GFAP (an established marker of retinal stress) and L/M opsin (cone photoreceptor
marker). The project is based at the Sydney Eye Hospital, in collaboration with the Research School for Biological Sciences, ANU (A/Prof
Jan Provis).
*Expression of the ADAM/ADAMTS Family in Primary Eye Tumours
Supervisor: Dr Michele Madigan
Retinoblastoma (Rb) and uveal melanoma are the most common primary eye tumours in children and adults respectively, and display distinct
clinical features, growth patterns and histopathology. Rb is derived from retinal neuroblasts and generally has an undifferentiated
morphology, similar to neuroblasts in developing retina. The most common route of local invasion in Rb is along the optic nerve. Uveal
melanomas are derived from uveal (choroid, ciliary body or iris) melanocytes.
The ADAM and ADAMTS family of zinc-dependent metalloproteinases can mediate both adhesive and proteolytic interactions, and interact
with integrins. These molecules are also implicated in the proteolytic cleavage of cytokines such as TNF-a, and may be involved in the
shedding of cell adhesion molecules, important for cell migration and axonal guidance in the CNS, or perhaps invasion of CNS by tumour
cells (as seen for example, when Rb cells spread along the optic nerve).
In this project the expression of ADAM/ADAMTS family members will be studied in normal retina and choroid, uveal melanomas and Rb.
We will also use cell lines (uveal melanoma, Rb and conjunctival melanoma) to investigate the relationship between tumour cell
invasiveness and ADAM/ADAMTS expression. Finally, there will be potential to develop an in vitro model to investigate the role of
proteinases (including ADAMs) in the spread of Rb cells along the optic nerve using tissue culture and in situ zymography approaches. This
project is based at the Save Sight Institute, Sydney Eye Hospital.



FEMALE REPRODUCTION and STRUCTURAL CELL BIOLOGY
Prof. Chris MURPHY Rm: N364; Ext: 14128; e-mail: histology@anatomy.usyd.edu.au
Dr. Laura LINDSAY Rm: N364; Ext: 14128; e-mail: laural@anatomy.usyd.edu.au
The work in this lab is centred around reproductive biology and medicine and in particular the biology of the uterus, uterine receptivity for
blastocyst implantation and hormonal influences on the uterus. We are interested in how it is that the uterus manages to tightly regulate those
times during the reproductive cycle when it will allow the blastocyst to attach but to prevent attachment and the beginning of a pregnancy at
other times. We are particularly interested in uterine epithelial cells and the molecular interactions that occur between the surface of these
cells and the implanting blastocyst. A variety of methods are available including light & electron microscopy, immunohistochemistry,
Western blotting and PCR. The work uses both animal and human tissues and involves basic cell biological research as well as work on
human tissues of direct relevance to the human menopause and to In vitro fertilisation (IVF) programmes. The laboratory also has extensive
contacts with The School of Biological Sciences and the Electron Microscope Unit (EMU) which involves a major project on the evolution
of viviparity (live birth) and the development of the placenta. This work involves study on mammals and lizards in particular but also other
animals to understand the biology of different types of placentas. We also have an interest in one of the major diseases of the uterus which
affects over a million Australian women endometriosis - and have collaborations with Westmead hospital to study this disease. In 2008 we
would accept students interested in mammalian reproduction and/or students interested in working on an aspect of the evolution of live birth
and placentation. An honours place in conjunction with the EM Unit could also be arranged.



OPIOID RECEPTOR SIGNALLING
Dr Peregrine OSBORNE. Pain Management Research Institute. Royal North Shore Hospital 99265539, p.osborne@usyd.edu.au
*The role of receptor trafficking in opioid receptor signalling
We are offering a cell biology project that will study how the movement of opioid receptors through different cellular compartments determines
signalling in neurons. The kinetic movement of G protein-coupled receptors has been linked to a diversity of functions that were not recognised
until recently. In the case of opioid receptors, trafficking has been linked to uncoupling and internalisation of receptors which are processes
relevant to opioid tolerance; and also G protein-independent signalling and crosstalk with other signalling pathways that could function in other
long term effects of drug exposure, such as opioid dependence and sensitisation. This project will involve neuronal cell culture, fixed and live
cell imaging, and possibly electrophysiology.



HUMAN MOLECULAR GENETICS
Prof. Juergen REICHARDT Medical Foundation Bldg; 9036 3356; jreichardt@med.usyd.edu.au
As human molecular biologists and geneticists we wish to understand how the human genome in conjunction with the environment produces
the multitude of human phenotypes, especially complex diseases such as cancer. We are particularly interested in the contribution of human
genetics. We also have an interest in understanding the genetics of human metabolism and genetic variation thereof. This laboratory has a
longstanding tradition of characterizing human galactose-metabolic enzymes and associated diseases. We are currently also investigating two
complex disease phenotypes with significant public health impact: various cancers and heart disease. Our strategy is to dissect these diseases
through a step-wise, “candidate gene” approach. Our systematic choice of candidate genes for these diseases was dictated by the
hypothesized involvement of particular metabolic pathways in pathogenesis. In prostate cancer we are currently investigating various
androgen metabolic genes since androgens have been reported to regulate cell division in the prostate. We have focused on the steroid 5 -
reductase type II (SRD5A2) locus and are currently exploring also the AKR1C2, CYP3A4, HSD3B2, HSD17B3 and SRD5A1 genes.
Investigations into glioblastoma, melanoma and atherosclerosis are also under way.
  *Mehrian-Shai, R and Reichardt, JKV (2006) Genomics in Breast and Prostate Cancer: Assessment of the Current State and Future
Perspectives, Fut. Oncol. 2, 357-362
  *Mehrian Shai R, Chen CD, Shi T, Horvath S, Nelson SF, Reichardt JKV, Sawyers CL (2007) IGFBP2 is a Biomarker for PTEN Status
and PI3K/Akt Pathway Activation in Glioblastoma and Prostate Cancer, Proc. Natl. Acad. Sci. 104, 5563-5568
http://www.medfac.usyd.edu.au/people/academics/profiles/jreichardt.php




LABORATORY OF VISION & COGNITION
Dr. Sam SOLOMON, Rm E501 Ext 69926. samuels@medsci.usyd.edu.au
*Cortical mechanisms of motion detection
Supervisors: Dr Solomon, Dr Tailby
The detection and discrimination of moving surfaces is necessary for any interaction with the external environment, and is especially
important in controlling eye movements. Using extracellular recordings from visual cortex, and anatomical tracing techniques, your project
will be investigate the neural mechanisms that code visual motion.
*Constraints on information flow through the visual thalamus
Supervisor: Dr Solomon
The optic nerve consists hundred of thousands of axons that form several parallel pathways, the main ones coursing through the thalamus to
primary visual cortex; from this the brain must interpret the outside world. What information about the outside world is provided by the
signals of neurons that provide the input to visual cortex? How much of the signals provided by an individual neuron are redundant, present
in the signals of other neurons? Your project will use extracellular recordings from the lateral geniculate nucleus of the thalamus,
simultaneously recording from multiple electrodes, to determine this.
*Functional properties of visual brain areas in mice suffering abnormal cortical development
Supervisors: Dr Solomon, Dr Camp
Your project will use in vitro and in vivo methods to study the functional organisation of visual cortical pathways in a knockout mouse
model of abnormal cortical development. The visual pathway is the best understood of all cortical processes; by comparing its functional
properties in these knockout mice and their wildtype counterparts, we can begin to understand how abnormal cortical development has an
impact on neural processing.




CELL BIOLOGY & DIABETES LAB
Dr Anne SWAN. Rm W222-4 ext 13027 swan@anatomy.usyd.edu.au
*Study of the cell biology of artificial beta cells.
DIABETES: Type I diabetes is an autoimmune disease in which the beta cells of the pancreas are destroyed, causing severe insulin
deficiency. This affects children so it is also known as Juvenile Diabetes. As well as insulin injections which can lead to complications,
another treatment is to transplant beta cells. However, this requires a large number of donor islets as well as immunosuppressive drugs. If the
patient's own cells could be engineered to secrete insulin, these problems would be avoided. In collaboration with Professor Ann Simpson of
UTS, our group, funded by NHMRC is engineering various liver cells to produce insulin. So far, this has included cultured liver cell lines as
well as primary liver cells of mice and rats. The mice and rats were treated to destroy beta cells. After their hepatocytes were engineered to
secrete insulin they were able to survive with normal blood glucose levels for six months or more. The aim of the project is to determine
whether these various artificial beta cells store insulin in secretion granules. The only way to determine this is by immunoelectron
microscopy. The ultimate aim of the research is to genetically engineer the patient's own liver cells to secrete insulin to a glucose stimulus so
that immunosuppressive drugs would not be required. The project will involve studying engineered cells by conventional transmission
electron microscopy to determine whether they contain secretion granules, and if so, determining whether the secretion granules contain
insulin using immunoelectron microscopy. Another aspect of the project is to study whether the exo-endocytic cycle is the same as in normal
beta cells, using confocal microscopy of EGFP-insulin transfected cell lines and cell labelling techniques. You will apply your knowledge
from the EMHU 3002 course to this project and learn additional cell biological techniques. Animal handling will not be required.
Note: The project is only available to students who are currently enrolled in EMHU3002.




AGEING, PRESBYOPIA & CATARACT RESEARCH - SAVE SIGHT INSTITUTE,
Prof. Roger TRUSCOTT, Sydney Eye Hospital. 9382 7310. rjwt@eye.usyd.edu.au
The human lens is an ideal tissue for studying aging. This is because the lens that was present at birth is still there in the adult, with little or
no turnover of macromolecules. Structural proteins comprise the bulk of the lens and these proteins become truncated, deamidated, modified
by reactive small molecules and also progressively bind to membranes. The composition of the fibre cell membranes also changes.
Characterising these alterations at the molecular level may not only enable an understanding of the basis for presbyopia (where the lens
nucleus hardens so that focusing on near objects becomes impossible after age 45) but also of age-related nuclear cataract (most common
form of blindness). It is also possible that the biochemical processes that we uncover in the lens may apply more generally to other aging
tissues in the body.
To understand lens aging at the molecular level, several projects are available.
*MALDI Imaging Of Lenses.
Using a new MALDI (Matrix Assisted Laser Desorption Ionisation) mass spectrometer we aim to determine the distribution of various
phospholipid molecules across the human lens and to see where these change with age. Such changes may well impact on the fluidity of the
membranes and consequently the stiffness of the tissue (presbyopia). It is already known that the overall distribution of phospholipids alters
significantly over our lifespan.
*Age-Related Changes To The Water Channel Protein, Aquaporin 0.
Membrane proteins are also truncated during aging of the lens. One in particular that is cleaved is the water channel protein, aquaporin 0.
This major membrane protein loses a peptide from the C-terminus however it is not yet clear if this truncated aquaporin 0 is functional as a
water channel. This is important because a barrier to diffusion forms in normal lenses in middle age and this barrier appears to be responsible
for the later onset of nuclear cataract. In this project, the aim would be to investigate methods for characterising the truncated aquaporin. This
would involve methods such as peptide mass fingerprinting with MALDI mass spectrometry. Structural changes in various lens regions
would be correlated with immunohistochemistry. This project would provide experience in protein chemistry and immunohistochemistry.

				
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