- NEUROCHEMISTRY LAB
| A/Prof. Vladimir BALCAR
- ANIMAL DEVELOPMENT
| Prof. Maria BYRNE
- THE RETINA IN DEVELOPMENTAL NEUROBIOLOGY AND NEUROPATHOLOGY
| Prof. Tailoi CHAN-LING
- PHYSICAL ANTHROPOLOGY & COMPARATIVE ANATOMY
| Dr. Denise DONLON
- MUSCLE RESEARCH UNIT
| Prof. Cris DOS REMEDIOS
- FUNCTIONAL ORGANISATION OF THE MAMMALIAN VISUAL SYSTEM
| Prof. Bogdan DREHER
- LABORATORY OF NEUROGLYCOBIOLOGY AND SENSATION
| Dr. Michelle GERKE
- ALZHEIMER'S DISEASE CELL BIOLOGY LABORATORY
| Dr Claire GOLDSBURY
- NEURAL IMAGING LABORATORY: PAIN RESEARCH
| Dr. Luke HENDERSON
- LABORATORY of NEURAL STRUCTURE & FUNCTION (Injury, Disability and Chronic Pain Research)
| A/Prof. Kevin KEAY
- LENS RESEARCH LABORATORY
| A/Prof. Frank LOVICU and Prof. John McAVOY
- PARKINSON DISEASE
| Prof. John MITROFANIS
- FEMALE REPRODUCTION and STRUCTURAL CELL BIOLOGY
| Prof. Chris MURPHY and Dr. Laura LINDSAY
- DEVELOPMENTAL NEUROBIOLOGY & GENOMICS LABORATORY
| Dr. Silke RINKWITZ and Prof. Thomas BECKER
- LABORATORY OF VISION & COGNITION
| Dr. Sam SOLOMON
firstname.lastname@example.org Metabolomics of mental disease: effects of neuroleptics on brain metabolome.
Neuroleptics of the second generation (NSG's, e.g. clozapine, introduced c. 1980) promised more refined and subtler therapy for mental disorders. However, despite many successful applications, wider use of NSG's has been limited because of uncertainty about their mechanisms of action (Kuroki et al. 2008) and side effects (Simpson et al. 2001).
We plan to use 13C-NMR spectroscopy combined with state of the art data analysis to generate a novel view of how some of these compounds exert their effects on brain. We have been using such approach to study how specific glutamatergic and GABAergic agonists and antagonists influence the brain metabolome (Rae et al. 2009). The "metabolome" in our experiments is defined as a set of metabolic parameters (total levels and metabolic rates of key biochemicals) in brain tissue kept under controlled conditions in vitro. We have been finding that each agonist and antagonist produces a typical pattern of changes - usually related to increased/decreased excitatory or inhibitory activities or energy metabolism. We intend to exploit this approach to determine how NSG's and related drugs alter the metabolome. Do they produce patterns of changes analogous to those observed with GABAergic and glutamatergic drugs? Will such metabolic "fingerprints" correlate with desirable or adverse actions? Mechanisms of NSG's are commonly explained in terms of actions on serotoninergic and dopaminergic systems (Kuroki et al. 2008). However, the most consistently reported neurochemical changes and the most "hopeful" candidate genes in schizophrenia relate to glutamatergic and GABAergic neurotransmission. Can our results help to resolve this apparent discrepancy?
Kuroki T, Nagano N & Nakahara T (2008) Neuropharmacology of second-generation antipsychotic drugs: a validity of the serotonin-dopamine hypothesis. Prog Brain Res 172 199-212
Rae C, Nasrallah FA, Griffin JL, Balcar VJ & (2009) Now I know my ABC. A system neurochemistry and functional metabolomic approach to understanding the GABAergic system. J Neurochem 109 (S1) 109-116
Simpson MM, Goetz RR, Devlin NJ, Goetz SA & Walsh BT (2001) Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods. J Clin Psych 62 694-700
Prof. Maria BYRNE. Rm S600. 9351 5166. email@example.com
Research in the Animal Development lab involves comparison of gametogenesis and development between closely related species that have contrasting patterns of embryogenesis. For this work we use several starfish and sea urchin species from which mature gametes are available at different times of the year. The main aim of our research is to determine the modifications in development exhibited by these animals and to elucidate the cellular mechanisms underlying these modifications. Documenting these phenomenon is key to understanding the role that development change has played in evolutionary events such as the formation of new species. We also use these animals as a model to investigate the affects of environmental changes associated with climate change will have on marine invertebrates. Several honours projects are available. To provide a few examples, these projects would involve research on the biology of fertilisation and early development of embryos cultured in the lab.
Prof. Tailoi CHAN-LING NHMRC Principal Research Fellow; Professor of Neurobiology & Visual Science
Room S466. 9351 2596. firstname.lastname@example.org
Our lab is currently supported by the National Health and Medical Research Council, International Science Linkages Program, 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, including Multiple Sclerosis 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 international laboratories. Recent studies have contributed insights into the cellular and molecular processes in the formation and the role of circulating stem cells in repair of damaged 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 Professor Tailoi Chan-Ling and a selected list of publications.
Dr. Karen CULLEN. Rm S464. 9351 2696. email@example.com
Inflammation and Microvasculature
The major focus of the laboratory is on the pathogenesis of Alzheimer's disease (AD). AD is the most common form of dementia, and its prevalence is increasing as the population ages. The key lesion in the disease is 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.
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 firstname.lastname@example.org
Dr Karen Cullen Rm S464 Anderson Stuart Bld. ext 12696 email@example.com
Motor neuron disease is a fatal neuromuscular disease for which there is no cure. Our laboratory is currently looking at the mechanisms involved in motor neuron degeneration. Some aspects of this research involve the use of human tissue and various mouse models of the disease. We are specifically interested in inflammation, cytoskeletal abnormalities and certain stress-induced proteins (such as metallothionein) that are involved in the pathogenesis of the disease. Research techniques involved include immunohistochemistry, immunofluorescence, morphometric analysis, confocal imaging, laser capture microdissection and transmission electron microscopy.
Research in the Shellshear Museum focuses on human osteology with a focus on the identification of skeletal remains. Present research focuses on discriminating between human and non-human bones as well as finding methods to identify ways of determining ancestry, sex, age and stature of those remains found in NSW and particularly in the Sydney region. Other areas of research include the clinical implications of human cranial variations, the anthropometry of early British settlers in Australia. 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 casts of human dentition.
Prof. Cris DOS REMEDIOS. Rm W105. 9351 3209; m: 0413482738. firstname.lastname@example.org
The dos Remedios laboratory engages in research in the following fields:
Molecular defects in human heart failure;
Effects of age on the molecular changes in non-failing human hearts;
Analyzing leukocytes surface protein markers in Acute Coronary Syndrome;
Detecting toxic chemicals in water; and
The role of cytoskeleton in cardiomyocyte function.
The tools we use include: transcriptomics, proteomics, tissue Microarrays, protein microarrays, vibrational spectroscopy, mass spectrometry, NMR spectroscopy, and scanning electron microscopy.
Prof. Bogdan Dreher. Rm S461. 9351 4194. email@example.com
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 in determining the functional properties of neurons in these areas and 2) the role of commissural (callosal) connections from homologous areas in the visual cortices of opposite hemisphere, in determining the functional properties of single cortical neurons whose receptive fields are located in the vicinity of representation of the vertical meridian. We approach these problems using physiological techniques such as study the receptive field (both 'classical' and 'extra-classical') properties of single neurones in a given area and selective, reversible inactivation (by cooling) of different visual cortical areas.
Dr. Michelle GERKE. Rm E411-414. 9351 4703. firstname.lastname@example.org
Research in this lab is currently focussing on the contribution of both ‘peripheral’ nociceptors and ‘central’ glial cells to the development of chronic neuropathic pain states in an attempt to elucidate a link between these cells types and the perpetuation of sensory abnormalities. Neuropathic pain is a persistent pain state that arises from damage to the nervous system and is usually accompanied by sensory abnormalities including hyperalgesia and allodynia. The animal model used in these projects has been shown to closely reflect the neuropathic pain state experienced by humans.
Whilst the main project on offer is made up of a number of ‘puzzle pieces’, our primary focus to date has been assessing the effect of nerve damage on the expression of the sugar code of nociceptors and the time course of microglial infiltration into the area of the superficial dorsal horn innervated by the injured nerve. Recent work from our laboratory has shown that alterations in nociceptors and microglia occur at the same anatomical location within the spinal cord of animals showing sensory dysfunction after nerve injury. The next step is to resolve whether or not glial infiltration is actually triggered by the altered nociceptors and to investigate whether the prevention of ‘glial triggering’ effectively stops pain perpetuation or sensory dysfunction.
Our current approach to unravelling the neuron glial-link is to exploit the neuronal sugar code and use targeted cell death as a means to remove specific cell types from the neuropathic pain equation. The rationale here is that removal of particular cell types from the equation will allow us to assess the role that particular cell types play in neuropathic pain development and perpetuation. These projects are also pointed towards assessing the efficacy of such targeted cell death as a selective and long lasting pain therapy.
Results from these projects will help build on our current knowledge of the mechanisms underlying chronic pain perpetuation whilst giving students an opportunity to gain research skills and a more through understanding of some of the cellular players in pain transmission and perpetuation. Students will gain skills and experience in animal handling, sensory and behavioural testing, surgery, tissue collection, histological and immunostaining techniques along with fluorescence microscopy and image analysis.
Oxidative-stress and mitochondrial dysfunction in the initiation of Alzheimer-like cytoskeletal abnormalities
Oxidative stress and mitochondrial dysfunction are associated with neurodegenerative diseases including Alzheimer’s disease (AD). Evidence of oxidative stress has been demonstrated during mild cognitive impairment and early on in AD along with the development of neuropathological lesions that include characteristic intracellular inclusions of hyperphosphorylated tau protein and extracellular amyloid deposits. The aim of this project is to determine whether there is a relationship between mitochondrial function, oxidative stress and tau hyperphosphorylation in neurons. A combination of techniques will be used including primary neuronal cell culture, cell viability assays, immunoprecipitation, Western blotting, and fluorescence microscopy.
Dr. Luke HENDERSON. Rm S420. 9351 7063. email@example.com
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.
(Injury, Disability and Chronic Pain Research)
A/Prof. Kevin KEAY. Rm S502. 9351 4132. firstname.lastname@example.org
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.
A/Prof. Frank LOVICU. Rm S252. 9351 5170. email@example.com
Prof. John McAVOY. Save Sight Institute. 9382 7369. firstname.lastname@example.org
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, Sydney Eye Hospital on Macquarie Street. Using a range of techniques (including 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 and their receptors as well as the regulation of their intracellular signalling, both in normal lens development and pathology. To date, 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 other studies have also shown that growth factors such as transforming growth factor ß (TGF-ß), induce the formation of fibrotic plaques that lead to cataract (loss of lens transparency), similar 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 promote fibre cell alignment and orientation so that lens develops its highly ordered three-dimensional cellular architecture.
*Identify factors that maintain the normal lens epithelial phenotypic characteristics including cell-cell and cell-matrix adhesion and communication.
*Use transgenic mice and in vitro assays to determine the role of novel genes (Crim1, Sef, Sprouty1/2, Spreds1/2/3) thought to be involved in regulation of growth factor bioavailability and signalling.
*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.
* Use lens explant cultures to identify putative inhibitors of TGFß signalling as a means of preventing cataract.
Prof. John MITROFANIS. Rm S463. 9351 2500. email@example.com
The inability to control ones movement and/or posture is a terrifying and striking affliction. Perhaps the best known movement disorder is Parkinson disease where individuals suffer a variety of symptoms including tremor (shaking), slowness of movement and stiffness (statues). Parkinson disease manifests after a loss or degeneration - by causes unknown - of several cell groups or centres in the brain, particularly in the basal ganglia, thalamus and brainstem. These losses contribute substantially to creating the shaking (tremors) and statues (stiffness) seen in individuals with the disease. In this lab, we explore the circuits and pathways involved in normal movement and examine the suspected abnormal mechanisms that may manifest in the shaking and/or the statues. We are also looking at mechanisms that generate the loss of cells in the disease, together with ways in which to save the cells from death. For instance, we are currently exploring the exciting possibility that near infra-red light treatment neuroprotects or saves cells from parkinsonian insult in a mouse model of the disease. We use modern anatomical methods, such as tract-tracing and immunocytochemistry to examine these issues.
Prof. Chris MURPHY. Rm N364. 9351 4128. firstname.lastname@example.org
Dr. Laura LINDSAY. Rm N364. 9351 2508. email@example.com
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. 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.
firstname.lastname@example.org Prof. Thomas BECKER. BMRI. 9351 0977. email@example.com
Establish the food intake control system in zebrafish to analyze human obesity candidate genes
Lifestyle is thought to have a critical role in the increasing number of obese people. Recent genetic studies however have led to the conclusion that unlimited access to food is should be seen as a permissive factor for the genetically predisposed. Most prominently, obesity predisposition can be related to genes that regulate energy balance. Such genes code for molecules acting on centers in the brain that are involved in the control of food intake. Examples are the functions of leptin, a hormone made in adipose tissue, and its receptor, located in the hypothalamus. When the leptin receptor becomes activated it reduces hunger.
We use the zebrafish as a developmental vertebrate model organism to elucidate the role of hypothalamic obesity candidate genes. The zebrafish is a well-established model organism for forward and reverse genetic approaches. External development, large numbers of eggs, transparency of the embryos and larvae and rapid differentiation (eating behavior starts at 5 days post fertilization) make this laboratory organism especially suitable for studying the role of genes in physiological or behavioral processes. Our projects aim to characterize zebrafish versions of genes that control energy homeostasis in humans and that are active in the zebrafish hypothalamus and brainstem.A selection of genes marking the food intake control system in zebrafish as well as three obesity candidate genes need to be analyzed for their sites of activity in the adult zebrafish brain. Once the expression patterns are established the knowledge can be applied to characterize the distribution of fluorescent proteins that are activated by the regulatory control regions of these genes in transgenic zebrafish used as live markers. Such studies will establish zebrafish as a vertebrate model system of obesity and will further shed light on the roles of human obesity candidate genes and their disease causing mechanisms.
Analysis of genes involved in X-linked neurological diseases using the genetic model system zebrafish
As part of an international consortium, our lab focuses on the genetic basis underlying X-linked neurological diseases. Current estimates suggest close to 100 loci causing X-linked intellectual disability (XLID), as well as numerous loci involved in demyelinating diseases, epilepsy, autism and spastic paraplegia and some eye anomalies. Because of their relatively high prevalence and their social importance, the genetic defects underlying XLID are actively pursued at many levels. Severe XLID is often caused by chromosomal aberrations or defects in specific genes, while milder forms are thought to result from interaction of multiple genes and environmental factors.
Since the gross brain anatomy and the neurotransmitter systems as well as the genetic mechanisms in brain development are well conserved between human and zebrafish, we use the zebrafish as a model system to analyze the function and regulation of disease genes. An external, rapid development, transparent embryos and a sequenced genome established this model especially for the genetic study of developmental processes and diseases. We use transgenic approaches for analyzing X-linked neurological disease genes. We create zebrafish lines with genomic modifications that can be used to reveal the sites of activity of the gene of interest and also, for functional analyses, to modify the activity of the gene in living embryos/larvae. The project aims to characterize the fluorescent expression pattern of a transgenic zebrafish line expressing a reporter under regulatory control of a XLID gene to indicate its expression sites in the developing brain. The findings will be related to the human brain to get indications of disease causing mechanism in intellectually disabled patients. This work required breeding of fish, egg collection, staging/handling of larvae, immunohistochemial procedures (antibody stainings), tissue sectioning and microscopy. The student should have interest in brain anatomical studies, brain development and brain diseases.
Dr. Sam SOLOMON. Rm E501. 9036 9926. firstname.lastname@example.org
Processing of motion by visual cortex
The middle-temporal (MT) area of visual cortex is specialised for the processing of motion in the visual world, and uses those signals to drive eye movements. The interested student will determine the robustness of the code for motion that MT provides, by measuring responses of single neurons to textures whose properties approximate those of natural visual images, and determining from those responses the minimally discriminable motion difference. The observations will be related to complementary behavioural work on humans.
Large scale activity of neurons in visual cortex
We know a lot about the activity of single neurons in the visual system, but we know little about how they provide signals as populations. This work will utilise recordings from microelectrode arrays consisting 64 channels and implanted in ~ 1mm of visual cortex. The question will be how is the motion of an object decoded from a population of motion selective neurons. This project will require some competence in programming, preferably in the Matlab environment.