Honours and Postgraduate Projects
Projects Available for 2006
- Neurochemistry Lab (Vladimir Balcar)
- Laboratory of Neural Structure and Function: (Shock, Injury and Pain Research) (Richard Bandler & Kevin Keay)
- Animal Development (Maria Byrne)
- Cataract Prevention Unit (Coral Chamberlain)
- The Retina in Developmental Neurobiology and Neuropathology (Tailoi Chan-Ling)
- Human Retinal Biology Lab - Save Sight Institute (Karen Cullen)
- Pathogenesis of Alzheimer's Disease - Inflammation and Microvasculature (Karen Cullen)
- Physical Anthropology & Comparative Anatomy (Denise Donlon)
- Muscle Research (Cris dos Remedios)
- Functional Organisation of the Visual System (Bogdan Dreher)
- Neuroglycobiology & Sensation (Michelle Gerke)
- Dementia Lab at the Brain & Mind Research Institute (Jüergen Göetz)
- Neural Imaging Laboratory: Pain Research (Luke Henderson)
- Sudden Infant Death Syndrome (Rita Machaalani)
- Lens Research Laboratory (Lovicu, McAvoy)
- Female Reproduction & Structural Cell Biology (Chris Murphy)
- Human Molecular Genetics (Juergen Reichardt)
- Vision and Cognition (Samuel Solomon)
- Cell Biology and Diabetes (Anne Swan)
- Reproductive Toxicology Lab & CHALUS (Bill Webster)
Neurochemistry Lab
Laboratory of Neural Structure and Function
(Shock, Injury and Pain Research)
Dr. Kevin Keay - Room
S502 - Ext. 14132 - Email: <keay@anatomy.usyd.edu.au>
Prof. Richard Bandler - Room S233 - Ext. 12500 - Email: <periaq@anatomy.usyd.edu.au>
The central nervous system circuits and mechanisms which underlie an individuals response to traumatic injuries has been the major focus of research in our laboratory for a number of years. In particular, we are interested in two important questions:
(1) Why do some people develop conditions of chronic pain and disability following traumatic injury whereas others recover quickly and without complication ?
(2) What is the organization, connectivity and neurochemistry of the brain circuits which mediate shock following blood loss which is often associated with traumatic injury?
Our laboratory has developed animal models of pain, injury and disability which reflect closely human clinical conditions. Our experimental work is characterised by a strong multidisciplinary approach. We perform behavioural experiments identifying specific disabilities in complex behaviour including social interactions, reproductive behaviours, appetite and sleep-wake cycle function. Such studies are complemented with investigations of altered cardiovascular and endocrine function in behaving animals which display chronic pain and disability. We use also a variety of neuroanatomical techniques to identify the precise neural circuits involved in the development of chronic pain, disability and shock which include neuronal tract tracing, immunohistochemistry, in-situ hybridisation and immediate-early gene expression, data from which are analysed using conventional and confocal microscopic techniques. We use a range of state of the art molecular biological techniques to identify the acute and chronic changes in neural tissues following injury and blood loss, these include GeneChip technology, real-time RT-PCR as well as protein analyses (ELISA and Western blotting). We have collaborators both in Australia (i.e., University of Newcastle, POWMRI) as well as in France (INSERM), the USA (Salk Institute, Scripps Institute) and the UK (University College London) and have enjoyed a very successful collaboration with the Neural Imaging Laboratory in the Discipline of Anatomy and Histology in which brain imaging studies using fMRI have been performed. [back to top]
Animal Development
Cataract Prevention Unit
Dr. Coral Chamberlain - Room E214 - Ext. 15169 - Email: <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 TGF_ in the development of certain forms of cataract. Significantly, TGF_ 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 TGF_-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 TGF_-related forms of cataract, including PCO. However, also in progress are interesting, clinically relevant studies of the effects on lens cell behaviour of various anti-inflammatory drugs used routinely at the time of cataract surgery, carried out 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 2006 to carry out a project in one of the above areas.
The Retina in Developmental Neurobiology and Neuropathology
Our lab is currently supported by the National Health and Medical Research Council, The Financial Markets Foundation for Children, The Baxter Charitable Foundation 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 direct clinical relevance. 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, Spinal cord injury, and Dementia in aging. We have a number of existing collaborations with the Departments of Pathology at Sydney University and Australian National University, as well as collaborations with a number of leading laboratories overseas. Recent studies have contributed key 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 2 Postgraduate students, one post-doctoral fellow, two part-time research associates and myself. Current projects on offer: 1) Novel therapies for prevention and treatment of AMD 2) Developmental study of glial-vascular biology in the mammalian retina. 3) In vitro studies of cells of the astrocytic lineage 4) Microvascular and inflammatory response in aging of the retina. Our lab is keen to attract talented students interested to pursue a career in biomedical research, particularly students interested to udertake a PhD candidature and opportunities exists for visits to other laboratories. Please feel free to email or phone to have a chat about the possibilities. [back to top]
Human Retinal Biology Lab - Save Sight Institute
Dr. Karen Cullen - Room S464 - Ext. 12696 - Email: <kcullen@anatomy.usyd.edu.au> and
Dr. Michele Madigan - Save Sight Institute - 9382 7283 - Email: <michele@eye.usyd.edu.au>
This project, based at the Sydney Eye Hospital, in collaboration with ANU (A/Prof Jan Provis) is concerned with differentiation and development of central retina, including the fovea centralis and its blood supply. 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. A person without good foveal function is legally blind. The retina is highly active and retinal photoreceptors are the most metabolically active cells in the body. At the fovea centralis the retina is highly specialized, including deflection of the inner cells 'outwards'/peripherally to make a depression (pit=L. fovea), a peak concentration of photoreceptors (only cones), and the absence of retinal vessels. The absence of vessels is paradoxical, because usually parts of the brain with a higher metabolic rate demand a more dense blood supply. We also know that if the small region where blood vessels are absent does not form, then the fovea itself does not form! So what controls the growth of these retinal vessels? This project aims to look at factors that might regulate (ie decrease) proliferation rates in, and migration of, human retinal endothelial cells. Techniques for growing these cells are established. But what is the effect of treating the growing cells with factors that are highly expressed at the fovea, but at low levels in the periphery.
Pathogenesis of Alzheimer's Disease - Inflammation and Microvasculature
Physical Anthropology & Comparative Anatomy
Muscle Research
The Muscle Research Unit examines the structure and function of contractile proteins (particularly actin, myosin) and cytoskeletal proteins; the molecular basis of human heart failure; use of protein microarrays in inflammation and autoimmunity; and a new bioassay for water pollution. Research is funded by grants from the ARC, the Heart Foundation, the Hermon Slade Foundation, the US Defence Advanced Research Projects Agency (DARPA), the Victorian Psoriasis Association, and industry collaboration. [back to top]
Functional Organisation of the Visual System
Work in my lab focuses on; (i) the functional organisation of mammalian striate and extra-striate cortices, especially the interaction between different information channels and 2)the role of the so-called "feedback" projections from the "higher-order" extra-striate visual areas to the "lower-order" visual areas (including the primary visual cortices) and subcortical visual nuclei. We approach these problems using physiological techniques, in particular study the receptive field properties of single neurones in a given area; selective inactivation of so-called Y-information channel; selective reversible inactivation of different cortical areas; cross-correlation analysis of discharges of individual cells located in a given area or in the neighbouring areas. The third problem on which we currently focus on is the extent, time-course and the mechanism(s) of topographic reorganisation in mammalian visual cortices following circumscribed lesions of retina in adult or adolescent mammals.
Neuroglycobiology & Sensation
Dr. Michelle B. Gerke - Room E411 - Ext. 14703 - Email: <mbg@anatomy.usyd.edu.au>
Research in this laboratory focuses on primary sensory neurons. These are the first neurons in sensory pathways, having receptors in peripheral tissues (skin, muscle, viscera), cell bodies in the dorsal root ganglia and axons which terminate in the spinal cord.
It has been shown that, along with their expression of specific channels and receptors, primary sensory neurons responsible for detecting different stimuli can be distinguished on the basis of the constellation of sugars expressed in their cell membrane (neuroglycobiology). Identification of sensory neurons on the basis of their unique ‘sugar code’ allows for the focused study of those populations which are responsible for mediating particular sensations under healthy conditions and also provides an avenue for assessing their specific involvement in sensory dysfunctions associated with particular disease states.
To date, most of the research done by members of this lab has focused on identifying and studying a population of small diameter primary sensory neurons which express the sugar α-D-galactose in their cell membrane. We have provided evidence that these neurons, which can be distinguished from other primary sensory neurons on the basis that they selectively bind the plant lectin Bandeiraea simplicifolia I isolectin B4 (BS-IB4), are present in the dorsal root ganglia and spinal cord of a variety of mammalian species, primarily innervate the skin (as opposed to muscle and viscera) and generally display the anatomical, ultrastructural and electrophysiological features of neurons responsible for the initial detection and transmission of noxious / painful stimuli (also known as nociceptors). Thus, the identification and specific study of primary sensory neurons which express α-D-galactose (those that bind BS-IB4) can provide a thorough understanding of the morphology, molecular phenotype and physiology of nociceptors in general, and can be applied to enhance our knowledge regarding the transmission of painful stimuli from the periphery to the spinal cord in both healthy and diseased states.
Current research in this laboratory applies the ability to distinguish and label nociceptors to investigations aimed at enhancing our understanding of:
- The sensory innervation patterns of peripheral tissues involved in common pain conditions such as headache, muscle and joint pain.
- The anatomical basis of referred pain.
- The anatomical and phenotypic changes associated with chronic pain.
The Laboratory of Neuroglycobiology and Sensation collaborates closely with the Laboratory of Neural Structure and Function to investigate the role and contribution of nociceptors in the development and maintenance of chronic pain conditions which occur after nerve injury. The ultimate goal of this collaborative research is to unravel the contributions that nociceptors make to the development of sensory and behavioural dysfunctions associated with nerve injury pain with a view to identifying new therapeutic targets towards which neuron-specific pain treatments might be aimed.
Dementia Lab at the Brain & Mind Research Institute
Prof. Jüergen Göetz - BMRI Bldg, level 3 - Ext. 10799 or 10789 - Email: <jgoetz@med.usyd.edu.au>
Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. The social and economic burden of AD is enormous. 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:
(A) Histological and functional validation of candidate proteins identified in models of Alzheimer's disease by Functional Genomics
(B) Use of stereotaxic injections to address the transport of A& in the mouse brain
(C) 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.
(D) 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
(E) 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.
(F) 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
The laboratory is investigating pain processing in both human and animal models. In collaboration with Dr Macefield at POWMRI and Dr Keay and Dr Bandler in the Laboratory of Neural Structure and Function in the Discipline of Anatomy and Histology, we have been using fMRI and magnetic resonance spectroscopy to explore brain activation patterns during skin and muscle pain in human subjects. In addition, the cardiovascular consequences of these manipulations are being investigated using microneurography (measures sympathetic nerve activity in human subjects).
In collaboration with Dr Keay, we are investigating superficial and deep pain processing circuits in animals using both behavioural and immunohistochemical techniques. Future investigations will include the use of MicroPET imaging to further our understanding of the neurochemical basis of pain processing. [back to top]
Lens Research Laboratory
Dr. Frank Lovicu - Room S252 - Ext. 15170 - Email: <lovicu@anatomy.usyd.edu.au> andProf. John McAvoy - Save Sight Institute - Email: <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 techniques such as tissue culture, immunohistochemistry, in situ hybridisation, RT-PCR, Northern blotting, chromatography, Western blotting, light and electron microscopy, in vitro biological assays and transgenic mouse strategies, researchers in our laboratory have investigated the expression, effects and function of several growth factors and their receptors 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. Other studies have shown that other growth factors, for example, transforming growth factor ß (TGF-ß) induce the formation of cataract (loss of lens transparency) that resembles that seen in humans.
Students that undertake Honours projects in our laboratory can expect to be exposed to a wide array of techniques, including cellular and molecular biology, and conduct 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.
* Use lens epithelial explant cultures to identify factors (growth factors, Wnts and retinoic acid) that maintain the normal lens epithelial phenotypic characteristics including cell-cell and cell-matrix adhesion and communication.
* Using lens epithelial explants and the characterisation of transgenic mice to determine the role of novel lens-specific 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)
* Using transgenic mouse models to further understand how TGFß induces and regulates cataract formation.
* Using lens epithelial explant cultures to determine how TGFß disrupts the normal lens signalling pathways and induces an epithelial-mesenchymal transition characteristic of cataract.
* Using electron microscopy and immunolabelling techniques to characterise the initiation and progression of cataract formation in transgenic mouse models and mutant Small eye mouse models (Pax 6 haploinsufficient).
Sudden Infant Death Syndrome
Dr. Rita Machaalani - Room 206 - Blackburn Building (D06) - Ext 13851 - Email: <ritam@med.usyd.edu.au>
The major focus of the laboratory is on the neuropathology of the Sudden infant death syndrome (SIDS). SIDS is the leading cause of death among infants (1-12 months of age) in developed countries. SIDS victims die suddenly during a sleep period, and the cause is still unknown, although a strong hypothesis is that it is a brainstem disorder of the cardiorespiratory system. SIDS is also associated with risk factors, the two most common being the prone sleep position and exposure to cigarette smoke. This project focuses on neuropathological changes in a piglet model of nicotine exposure (model designed to mimic passive smoking). The project will involve immunohistochemical and non-radioactive in-situ hybridisation staining for the expression of neurotransmitter receptors and/or growth factors in nicotine exposed vs non-exposed piglet brainstem. Staining will then be quantified using image analysis systems at the Electron Microscope Unit. [back to top]
Female Reproduction & Structural Cell Biology
Human Molecular Genetics
Prof. Juergen Reichardt - Medical Foundation Bldg. - 9036 3354 - Email: <jreichardt@med.usyd.edu.au>
As human geneticists and biochemists we wish to understand how the human genome in conjunction with the environment produces the multitude of human phenotypes. We are particularly interested in the contribution of human genetic variation to common, complex significant public health problems. 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 three 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 HSD3B2 and HSD17B3 genes. Investigations into colon cancer and atherosclerosis are also under way.
<http://www.angelfire.com/ri2/reichardt/homereichardt.html>
<http://www.usc.edu/programs/pibbs/site/faculty/reichardt_j.htm>
Vision and Cognition
Dr. Samuel Solomon - Room E501 - Phone 9036 9926
At the very earliest neuronal stage of vertebrate vision, the magnitude of response of photoreceptors in the retina is determined by the 'brightness' of the light falling on the retina. The photoreceptors are the first and last cells in the chain of visual processing which act largely (but not entirely) independently from its fellow group of cells (that is, other photoreceptors). From the photoreceptors onwards other neurons involved in the visual processing, interact strongly with each other and hence they are sensitive to the contrast rather than the brightness of the visual stimuli. Yet we know comparatively little about the neural mechanisms that regulate contrast sensitivity. A long-term aim of Dr Solomon's laboratory is to provide an integrated account of sensitivity regulation in early visual pathways, sub-cortical and cortical, through experimental studies in the primate visual system. [back to top]
Cell Biology and Diabetes
Note: The following projects are only available to students who are currently enrolled or who have majored in ANAT3003.
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 way of treating these patients is by transplantation of beta cells. However, this requires a large number of islets as well as immunosuppressive drugs. Unfortunately, it has been found recently that these transplants are now failing. If the patient's own cells could be engineered to secrete insulin, this problem would be avoided. Professor Ann Simpson, UTS, has engineered primary liver cell lines as well as cultured liver cell lines to produce insulin. The aim of the project is to determine whether these 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 the 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.
MALARIA: (Jointly supervised with Prof. Nick Hunt: Medical Foundation Bldg, K25. 90363242. <nhunt@med.usyd.edu.au>).
The malaria parasite kills 2 million people, mainly young children, each year. In some parts of the world, these malaria parasites have become resistant to anti-malarial drugs. There is a drastic shortage of effective anti-malarial drugs in the development pipeline. Dr Jiri Neuzil (Griffith University) has shown that certain derivatives of vitamin E have the property of entering tumour cells, destabilising the lysosomes within those cells and thereby causing the death of the tumour cells through apoptosis. Since the malaria parasite contains a food vacuole with the right chemical properties to accumulate these drugs, Dr Neuzil suggested that they might have anti-malarial activity. In preliminary experiments, we have shown that two such compounds do indeed kill Plasmodium falciparum (a form of malaria that infects human beings) in vitro. We now propose to extend these studies further, using malaria parasites (Plasmodium falciparum) cultured in vitro (supervised by Professor Hunt). The aim will be to establish the mechanism(s) by which the agents kill malaria parasites by studying the effects of the drugs on the ultrastructure of the parasites using transmission electron microscopy (electron microscopy will be supervised by Dr Swan).
Reproductive Toxicology Lab and CHALUS (Chemical Hazard Assessment Lab)
A project is available in 2005 for an Honours student as part of our Toxicology research. The lab is currently involved in research that investigates the toxicity of a range of chemicals used by Australian Air Force Personnel. Our aim is to test the hypothesis that these chemical mixtures can damage DNA. A range of in vivo and in vitro techniques are being utilised in an effort to assess the mutagenic potential of these chemical mixtures. This project is being funded by the Australian Department of Veterans Affairs. [back to top]