HONOURS PROGRAM - ANATOMY & HISTOLOGY
University of Sydney
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 todo 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 do not meet all the criteria but are still interested in Honours, 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.
When 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.
PROJECTS AVAILABLE FOR 2010
A/Prof Vladimir BALCAR Rm: S317. 9351 2837 vibar@anatomy.usyd.edu.au
NEUROCHEMISTRY LAB
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 mbyrne@anatomy.usyd.edu.au
ANIMAL DEVELOPMENT
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.
Tailoi CHAN-LING NHMRC Principal Research Fellow; Professor of Neurobiology & Visual Science
THE RETINA IN DEVELOPMENTAL NEUROBIOLOGY AND NEUROPATHOLOGY
Room S466, Anderson-Stuart Building, F13. 9351 2596 tailoi@anatomy.usyd.edu.auOur 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. Nick Cole. Rm W315. 9351 7629. njcole@anatomy.usyd.edu.au
MUSCLE AND LIMB/FIN DEVELOPMENT AND EVOLUTION
Initiation, specification and control of vertebrate limb and muscle development
The general aim of my research is togenerate a detailed understanding of the morphological and genetic control of precursor specification, migration and proliferation that is deployed to generate vertebrate limbs and muscle. The fundamental question of how different populations form within an embryo has until now, been extremely difficult to address in conventional systems purely due to logistical constraints; mammalian embryos develop in- utero, and direct visual observation of living muscle is all but impossible. In contrast, the zebrafish develops ex-utero and is optically clear during the embryonic and juvenile stages– yielding a unique possibility to examine development in vivo.The muscle structure of zebrafish represents a relatively simple paradigm where muscle precursors specification and subsequent myoblast elongation, fusion and attachment can be followed in real time using time-lapse photo microscopy. Just as in human embryos, the appendicular muscles of zebrafish are formed from populations of long-range migrating precursors that originate in the somites and express the gene lbx1. In addition, our limbs evolved from the paired fins of ancestral fish, such that initiation and outgrowth of fins is genetically similar to early limb formation. These characteristics make zebrafish a powerful and genetically tractable model system for the analysis of vertebrate limb initiation and muscle development.
The long-term outcome of this work will enhance our understanding of limb formation and how stem cell-driven muscle formation and repair occurs in vertebrate embryos. This knowledge will have profound implications for our understanding of the pathology and treatment of limb developmental defects and degenerative muscle disease.
Projects will involve developmental and molecular biology, incorporating modern research techniques (in-situ hybridisation, confocal and electron microscopy, PCR, bioinformatics, fish husbandry, transgenic fish technology, immuno-histochemistry, histology, in-vivo cell lineage tracking) and utilising the zebrafish model system.
Embryonic origins of vertebrate muscle
Limb muscles are formed by the long-range migration of precursor cells from the developing embryonic somites. Zebrafish fin muscle precursors possess molecular and morphogenetic identity with these limb muscle precursors. The mechanisms controlling precursor specification, initiation, migration and differentiation are yet to be determined. In addition the embryonic origin of many other muscle groups is still unknown. We now have a unique opportunity to utilise the resolving power of novel transgenic tools to permanently in vivo track the derivatives of muscle precursors in real time and therefore determine the spatial and temporal origins of migratory muscles. A deeper understanding of muscle lineage specification will provide insights into the normal, as well as pathological, aspects of skeletal muscle, heart and craniofacial development.Determining the position and timing of limb initiation.
The developmental origins and molecular processes that generate our legs and associated musculature have not been fully defined. To date, only two hind-limb specific genes have been discovered (Pitx1 & Tbx4). Tetrapod hind-limbs evolved from the pelvic fins of ancestoral fish and the signaling centres involved in limb formation are similarly involved in fin formation, for example, Pitx1 and Tbx5 are required for pelvic fin development. Therefore, examining the genetic control of pelvic fin development will shed light upon the developmental mechanisms of correct hind limb formation. We will utilize the power of the zebrafish vertebrate model to investigate the genes responsible for pelvic fin specification, initiation and outgrowth. In addition, we have pelvic fin and pectoral fin (evolutionary forerunner to tetrapod fore-limb) deficient zebrafish. Elucidating the gene or signaling centre responsible for these morphologies will highlight genes involved in limb development and disease.
Dr. Karen CULLEN Rm S464. 9351 2696 kcullen@anatomy.usyd.edu.au
PATHOGENESIS OF ALZHEIMER'S DISEASE
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 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. 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.
Dr. Denise DONLON Rm W601 ext: 14529 ddonlon@anatomy.usyd.edu.au
PHYSICAL ANTHROPOLOGY & COMPARATIVE ANATOMY
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 Britich 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; mob: 0413482738;
crisdos@anatomy.usyd.edu.au
MUSCLE RESEARCH UNIT
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 bogdand@anatomy.usyd.edu.au
FUNCTIONAL ORGANISATION OF THE MAMMALIAN VISUAL SYSTEM
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, mbg@anatomy.usyd.edu.au
LABORATORY OF NEUROGLYCOBIOLOGY AND SENSATION
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.
Dr Claire GOLDSBURY. BMRI. 9351 0878, cgoldsbury@usyd.edu.au
ALZHEIMER'S DISEASE CELL BIOLOGY LABORATORY
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, lukeh@anatomy.usyd.edu.au
NEURAL IMAGING LABORATORY: PAIN RESEARCH
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.
A/Prof. Kevin KEAY: Rm: S502. 9351 4132 keay@anatomy.usyd.edu.au
LABORATORY of NEURAL STRUCTURE & FUNCTION
Injury, Disability and Chronic Pain Research
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 Janet KEAST, Pain Management Research Institute, RNS Hospital. Ph: 9926 4995. jkeast@med.usyd.edu.au
DEVELOPMENT, REGENERATION AND PLASTICITY OF SPINAL & PERIPHERAL NEURONS
Our research team explores the structure and function of the nervous system, particularly how it develops after birth and how the adult nervous system is affected by injury or inflammation. We are interested in basic neurobiology as well as in processes that relate to specific disease processes or injury states (e.g, persistent pain, spinal cord injury, peripheral nerve damage, inflammation). 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 fluorescence and confocal microscopy, imaging and microsurgical techniques, as well as knockout mice, in vitro pharmacological assays, behavioral testing, neuronal cultures and molecular biology. The choice of technique will depend on the project and will also take into account the skills and interests of the student.Developing new methods for improving nerve growth and function after injury.
There is an urgent need to understand the effects of injury on pelvic autonomic nerves and the spinal cord that controls them. These nerves are often damaged during surgical procedures such as hysterectomy and prostatectomy and this leads to major problems with sexual function and control of voiding. 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 the impact of injury on neuronal circuits, study spinal circuits and nerve regeneration in vivo. Projects can be directed towards clinical problems associated with either reproductive or bladder function.How do natural steroids affect pain?
We are interested in the mechanisms by which estrogens affect nociceptors and their related spinal circuits, and how inflammation triggers pelvic pain. We hope to develop new ways to prevent or reverse these persistent 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 nociceptors and their connections with spinal cord.How do neurons know where to grow and what to connect with?
We have a number of projects available on the developing nervous system, which 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, nociceptors, and spinal control circuits. These research topics involve detailed microdissections of neural tissues, neuroanatomical tract tracing, immunofluorescence, image analysis and use of gene knockout mice.
A/Prof. Frank LOVICU, Rm S252. 9351 5170, lovicu@anatomy.usyd.edu.au
Prof. John McAVOY, Save Sight Institute, 9382 7369, johnm@eye.usyd.edu.au
LENS RESEARCH LABORATORY
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 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. Chris MURPHY Rm: N364; 9351 4128; histology@anatomy.usyd.edu.au
Dr. Laura LINDSAY Rm: N364; 9351 2508; laural@anatomy.usyd.edu.au
FEMALE REPRODUCTION and STRUCTURAL CELL BIOLOGY
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 2010 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.
Prof. Juergen REICHARDT Medical Foundation Bldg; 9036 3356; jreichardt@med.usyd.edu.au
HUMAN MOLECULAR GENETICS
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 5a-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.http://www.medfac.usyd.edu.au/people/academics/profiles/jreichardt.php
Dr. Silke RINKWITZ, BMRI; Ext: 9351 0866; e-mail: srinkwitz@med.usyd.edu.au
Prof. Thomas BECKER, BMRI. Ext: 9351 0977; e-mail: tsbecker@med.usyd.edu.au
DEVELOPMENTAL NEUROBIOLOGY & GENOMICS LABORATORY
Estrogens are steroid hormones that signal through its receptors, which are ligand-activated transcription factors. Linking the hormonal system with gene control creates flexible, powerful machineries that regulate many important neuronal and neurosecretory responses. We use the zebrafish as an experimental system. The zebrafish is a well-established vertebrate model organism for forward and reverse genetic approaches. External development, large numbers of eggs, transparency of the embryos and larvae and rapid differentiation make this laboratory organism especially suitable for studying the role of genes in physiological or behavioral processes.With this project the zebrafish gene coding for the estrogen receptor beta shall be cloned and the pattern of its expression shall be analyzed in the brain of developing larvae by in situ hybridization. Further, the regulatory control regions of the gene in the genome shall be identified using genome sequence databases and then isolated to be cloned into reporter gene constructs. The construct DNA shall be injected into fertilized zebrafish eggs with the goal to establish transgenic zebrafish lines that express GFP in the cells and neurons in which the estrogen receptor is active. The fluorescent larvae shall be used to analyze the function of estrogen and its receptor in the hypothalamus. The project involves DNA cloning, histology, in situ hybridization techniques, genome database analyses, microinjection and handling of embryonic, larval and adult zebrafish.
Dr. Sam SOLOMON, Rm E501. 9366 9926. samuels@medsci.usyd.edu.au
LABORATORY OF VISION & COGNITION
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.