CURRENT HONOURS PROJECTS IN PHYSIOLOGY
|Honours Projects 2016 (PDF with all the projects below)|
OFFERED PROJECTS IN 2016
A/Prof Stephen AssinderPotential supervisors within the discipline should be contacted directly to discuss specific opportunities. The following research labs are associated with the discipline.
Nervous System, Senses and Movement:
RETINAL AND CEREBRAL NEUROBIOLOGY LABORATORYAnderson Stuart Building, Room N551, Tel. 9351 4740
Professor J Stone Dr Dan Johnstone.Our work concerns the stability of the central nervous system (retina and brain); how that stability breaks down in age-related diseases like dementia, parkinsonism and macular degeneration; and how these tissues can be conditioned – by a range of interventions – to resist the degenerations of age. We have recently identified the cause of age-related dementia (in the action of the pulse on the small vessels of the ageing brain) and are working on approaches to delay dementia by vascular repair
Project Title: Stability of the ageing brain and retina: neuroprotective interventions
Several projects are available under this general title. All concern the mechanisms of neuroprotection, analysed in animal or in vitro models of human disease.
MOLECULAR NEUROSCIENCE LAB
A/Prof Bill PhillipsThe Phillips lab studies the molecular mechanisms of synapse development and adaptation, focusing on the mammalian neuromuscular synapse. Developmental signalling pathways such as the muscle specific kinase (MuSK) system are thought to help the neuromuscular synapse adapt and survive. We use mouse and cell culture models to study how the MuSK system can help protect the synapse in mouse and cell culture models of several neuromuscular disease.
Project 1: Cell culture model of MuSK myasthenia gravisMuscle specific kinase (MuSK) is a receptor tyrosine kinase that coordinates the development of the neuromuscular synapse during embryo development. Myasthenia gravis is a muscle weakness disease caused by autoimmune antibodies that interfere with neuromuscular synaptic transmission. Some myasthenia gravis patients have antibodies that inhibit the activation of MuSK by its natural ligand, neural agrin. However MuSK is also capable of organising itself and other proteins into a specialized postsynaptic membrane patch in the absence of neural agrin. This project will use a muscle cell line to study these postsynaptic-like membrane domains in culture. We will use confocal microscopy to track MuSK (fused to green fluorescent protein) and study how it targets to membrane patches. We will also study the way in which the MuSK patches are disrupted by autoimmune antibodies from MuSK myasthenia gravis patients. These experiments should provide new insights into the influence of MuSK kinase in forming and maintaining postsynaptic membrane domains. This culture model may also provide a new assay for testing the pathogenic effects of MuSK autoantibodies from patients.
Project 2Neural basis of spasticity in the L25 transgenic miceMotor neuron disease often involves degeneration of descending inhibitory inputs to spinal motor neurons, reflected in spastic paralysis. We have been investigating a line of mice in which random insertion of a transgene appears to have disrupted a gene important for maintaining control of the lumbar spinal motor neurons (L25 mice). Affected L25 mice developed tremor and hind limb spasticity in the first three months of life, requiring euthanasia. These motor signs are reminiscent of some forms of motor neuron disease. The project will use histology and quantitative image analysis to compare the brains and spinal cords of affected L25 mice with wild-type littermate mice. The project will test the hypothesis that the spasticity was caused by degeneration of motor centres in the brains of L25 mice. If the histological evidence supports this hypothesis then L25 mice might offer a (much needed) new model for studying motor neuron disease pathogenesis and for testing potential therapies.
Project 3Can the MuSK system protect muscle fibres from degeneration in the mdx mouse model of Duchenne muscular dystrophy?In Duchenne muscular dystrophy, deficiency of the muscle membrane protein, dystrophin, leads to repeated rounds of degeneration and regeneration of muscle fibres, resulting in muscle atrophy. The absence of dystrophin certainly makes the muscle fibre membrane vulnerable to damage but the precise molecular pathways that lead to fibre degeneration/regeneration are only partially understood. Muscle specific kinase (MuSK) and rapsyn are part of a signalling pathway at the neuromuscular junction. They help to stabilize the postsynaptic portion of the muscle fibre membrane. This project will investigate whether MuSK and rapsyn can also protect the muscle fibre against degeneration in a mouse model of Duchenne muscular dystrophy (mdx mice). Adeno- associated viral vector will be used to drive MuSK or rapsyn expression in muscles of mdx mice. Fluorescence microscopy will be used to test whether MuSK and rapsyn can reduce the number of damaged and regenerating muscle fibres that occur spontaneously over several weeks in mdx mice. The project will test the idea that the MuSK-rapsyn system serves to protect muscle fibres from degeneration.
VISUAL NEUROSCIENCE RESEARCH GROUPSave Sight Institute, Sydney Eye Hospital, and Discipline of Physiology.
Prof Paul R. Martin: email@example.comWe study the connections of neurones in the retina and processing of visual signals in the brain. Our special interests are colour vision and interaction of visual signals with brain pathways controlling attention. Our laboratories are part of the ARC Centre of Excellence for Integrative Brain Function (CIBF, cibf.edu.au). In 2016 qualifying students will be offered CIBF scholarships and join this strong research network involving collaborative projects with Australian and International laboratories.
Project 1: Physiology of an ancient part of the visual systemYou will join our team of electrophysiologists to measure single and multi-cell activity in primate brains. We have discovered that one evolutionary old part of the visual thalamus is involved in brain pathways controlling slow- wave oscillations in sleep, anaesthesia and epilepsy. You will learn modern electrophysiological methods to record and understand how networks of nerve cells work to control brain rhythms.
Project 2: Parallel pathways in human and non-human primate retinasYou will help to expand and develop our new methods for identifying nerve cell connections in the fovea of human donor retinas and retinas of non-human primates. You will learn single-cell injection and immunochemical methods to help us identify new types of nerve cells and their connections in the retina.
LABORATORY OF DEVELOPMENTAL NEUROBIOLOGY
Dr Catherine A. LeameyPhone: 9351 4352
Anderson Stuart Bldg, Room N663
Neural connections underlie every aspect of our perception, behaviour and cognition and are a product of both genetic factors and environment/experience. The visual pathway is particularly useful for investigating the relative roles of specific proteins and experience in the assembly and function of neural circuits. We have recently discovered that a family of molecules, known as the Ten-ms or Teneurins, play important roles in wiring up binocular visual pathways. The miswiring present in the knockout strains leads to behaviorally measureable visual deficits.
Potential projects include:1) The capacity for Environmental Enrichment to restore function in Ten-m3 KOs: The
misalignment of projections present in Ten-m3 KOs leads to a form of functional blindness. Recent data suggests that enhancing the animals experience via environmental enrichment can lead to a recovery of vision. A number of projects exploring this important research avenue, including assessment of the degree of recovery following enrichment at different ages, investigation of underlying mechansims and mimicking enrichment by addition of pharmacological agents are available. 2) Impact of increased ipsilateral projections on binocular vision: Our preliminary data demonstrates that Ten-m4 KO mice have additional ipsilateral projections from dorsal retina. The chief aim of this study is to determine how these extra projections affect the visual ability of the mice using a new behavioural paradigm developed in the lab. 3) Cellular substrates of binocular vision: How does an environmental stimulus lead to a behavioural response? Recent work has demonstrated that ethologically-relevant visual stimuli trigger robust behavioural responses in mice. The circuits underlying theseresponses are not known, but provide enormous potential for understanding how visual input is processed and transformed to trigger an appropriate behaviour. The visual deficits present in Ten-m KO mice present additional windows into the function of specific cell types. Projects addressing these issues using multi-photon imaging, neural tracing and electrophysiological recording are available.
Some of these are offered as collaborative projects in association with Dr Atomu Sawatari and Dr
Dario Protti’s laboratories. Other projects may also be available on request.
Dr Dario Protti,2 9351 3928
Our research work focuses on the function of the retina. Specific neuronal circuits provide ganglion cells, the output neurons of the retina, with excitatory and inhibitory inputs whose relative magnitude and timing determine the spatial and temporal properties of the electrical signals sent to higher visual centres in the brain. The relative impact of excitation and inhibition on ganglion cells output, however, is not well understood.
We are currently investigating the effect of cannabinoids, derivative compounds of marijuana, on the physiological properties of different types of ganglion cells in the eye.
Project 1: Pharmacological modulation of ganglion cell responses by cannabinoids:We have recently shown that exogenous cannabinoids modulate the transmission of visual
information in the retina. In addition, we showed that the endocannabinoid system is active in normal conditions. This project will investigate how and where cannabinoids act on the retina by studying the effects of drugs that target different components of the cannabinoid system.
Project 2: Impact of the balance between excitation and inhibition on the properties of ganglion cells of the eye:of ganglion cells. This project investigates how the balance of excitatory and inhibitory inputs
impact on ganglion cell responses. To gain insight into this, we inject to various combinations of excitatory and inhibitory currents into ganglion cells and record their responses. This link to our video article can give you a good idea of the experimental approach: http://www.jove.com/video/50400/implementing-dynamic-clamp-with-synaptic-
This is a joint project between Dr Dario Protti and Dr Jin Huang (N659. 9351 9065,
The techniques used in these projects are patch-clamp recordings, dynamic-clamp recordings, confocal microscopy and computer modelling. For more information please contact Dr. Dario Protti: firstname.lastname@example.org
Other projects are offered in collaboration with Dr. Cathy Leamey and Dr. Atomu Sawatari.
SYSTEMS NEUROSCIENCE LABORATORY
Dr Atomu SawatariAnderson Stuart Building. N104 Anderson Stuart Building
Ph: 9036 7127
We use a variety of anatomical, physiological, and behavioural methods to reveal the influence of environmental and genetic factors on the development and function of sensory and cognitive circuits.
Project 1: Revealing the Identity of Retinal Ganglion Cell Types that Contribute to BinocularCircuitry (A collaborative project with Dr. Dario Protti and Dr. Catherine Leamey).A combination of anatomical (retrograde tracing) and physiological techniques (single cell recording and labelling as well as possibly multiphoton imaging) will be used to identify and characterize retinal ganglion cells (RGCs) that contribute to the binocular visual processing in the mouse. During the course of the project, the student will acquire skills in surgery, in vitro patch- clamp recording, anatomical tract tracing, tissue processing, and data analyses. If time permits, the same combination of methods will be used to examine the homologous population of RGCs in a transgenic animal (the Ten-m3 Knock Out mouse) that exhibits specific and consistent deficits in the binocular pathway.
Project 2: Can the Application of Trophic Factors Mimic the Effects of Environmental Enrichment on Developing Cognitive Neural Circuits? (A collaborative project with Dr. Catherine Leamey). Environmental factors can dramatically influence the wiring and function of neural networks. Recent evidence has revealed that trophic factors can potentially mimic the effects of exposing
animals to enriched environments. The extent to which systemic application of neurotrophins can influence the emerging functionality of cognitive brain regions is not well characterized. For this project, a combination of anatomical (retrograde tracing) and behavioural techniques will be used to reveal the manner in which a specific neurotrophin influences the development and function of one of a number of brain regions associated with perception, decision making, learning, and memory.
LABORATORY OF MOTOR AND SENSORY SYSTEMS
Dr Haydn AllbuttPh: 02 9351 2515
This lab is interested in examining the earliest stages of Parkinson’s disease in order to explore potential initiating triggers for the disease. Evidence suggests that some environmental stimulus or stimuli induces misfolding and aggregation of the neuronal protein, alpha-synuclein and it is this protein which then spreads through the brain and gives rise to subsequent pathologies. It is the aim if this lab to screen for and identify possible initiating stimuli and examine methods of modifying this initiating process.
Cancer, Cell Biology, Reproduction and Development
ANDROLOGY RESEARCH GROUPMedical Foundation Building Room G46 Telephone: +61 2 90363614 email@example.com
Prostate disease is very common in the ageing male. Prostate cancer is the most commonly diagnosed cancer in men and second most frequent cause of cancer-related deaths. It is estimated that there is at least 1 death every 4 minutes worldwide attributed to prostate cancer.
Our research is focused on:
1. Endocrine regulation of cancer cell proliferation. In particular we are interested in how various hormones and cytokines affect tumourigenesis.
2. Understanding how the loss of structural proteins involved in organization of the cell cytoskeleton contribute to the development of cancers.
Project TitleDysregulation of receptor tyrosine kinase signalling antagonists leads to prostate cancer.Our recent research (Assinder et al., 2015) indicates that a co-repression of Sprouty and Spred, antagonists of FGF signalling, is associated with the development of prostate cancer. It is likely, due to the need for tight regulation of receptor tyrosine kinase signalling, that a family of SPRY and SPRED negative regulators provides a degree of redundancy. Until now, this has not been considered in the context of prostate cancer. The aim of this project is to demonstrate in vitro that compound loss of SPRY2 and SPRED2 induces an aggressive cancer phenotype. This project will employ many techniques including cell culture of normal human prostate and prostate cancer cell lines, RT-PCR, real time PCR, siRNA knockdowns, western blots, flow cytometry, growth, proliferation and phenotypic assays.
This project is in collaboration with Prof Frank Lovicu, Discipline of Anatomy and Histology.
Assinder SJ, Beniamen D, Lovicu F (2015). Co-suppression of Sprouty and Sprouty-related negative regulators of FGF signaling in prostate cancer: a working hypothesis. Biomedecine research International 2015:827462. doi: 10.1155/2015/827462. Epub 2015 May 17.
VITAMIN D, BONE AND SKIN LABORATORYAnderson Stuart Bldg, Room N543, Telephone: +61 2 9351 2561 or +61 2 9351 4099
Professor Rebecca Mason.The group has a particular interest in vitamin D and calcium physiology and, in particular, the role
of vitamin D compounds in protection of skin cells from UV irradiation.Project: DNA damageOur group has shown that vitamin D compounds, which are well known to be made in skin, have an important physiological function in skin to protect skin cells from the damaging effects of UV radiation. We have also shown that several types of DNA damage is reduced in skin cells and animal and human skin after UV when active vitamin D-like compounds are given immediately after irradiation and that these compounds protect from UV induced skin cancers (eg Dixon et al. Cancer Prev Res 4: 1485-94, 2011). The project will examine some likely mechanisms of action of the vitamin D compounds and other agents which act like vitamin D. These agents could potentially be used in sunscreens and after-sun preparations to reduce UV damage.
Direct inquiries can be made by email to: firstname.lastname@example.org
SKELETAL ENDOCRINE LABORATORYDr Tara Speranza: email@example.com or 9351 4099
Dr Speranza’s laboratory investigates the role of the musculoskeletal system in macro nutrient metabolism, focusing on the proteins, receptors and pathways involved in this multi-system endocrine loop. Studies also include investigations into possible therapeutic agents on the skeleton, with a focus on the actions of bone forming cells (osteoblasts) and bone resorbing cells (osteoclasts).
Project 1: The structural and cellular basis of skeletal fragility in type II diabetes mellitusPatients with T2DM have hyperglycemia and normal to high bone mineral density (BMD). This is usually associated with reduced fracture risk, yet patients with T2DM have a higher incidence of fragility fractures and an increased overall fracture risk. The increase in fractures in patients with T2DM is independent of factors such as age, sex, BMI, tendency to fall and visual impairment. This implies the increased fracture risk is driven by compromised bone quality. The aim of the current study is to test this hypothesis in mice and elucidate the specific mechanisms of action. Few rodent studies have assessed the total effects of hyperglycemia on the skeleton. Mice will be allocated to a normal chow or a high fat (60%) diet. Insulin sensitivity and glucose tolerance will be monitored. The effects of hyperglycemia on the skeleton will be tested by analysing microarchitecture using uCT methods, histologically via fluorescent calcein staining for dynamic histomorphometry and for immunohistochemical analysis of the incorporation of AGE products: CML and pentosidine. Lastly, the molecular pathways for the basis of these findings will be analysed via qRT-PCR and western blotting to analyse the sclerostin content in bone and BMP7/Smad1/5/8 pathway.
Project 2: The effects of hyperglycemia on human osteoclastic bone resorption in vitroIncreased bone fragility and reduced skeletal muscle quality are under-recognised complications of long-term hyperglycemia in type 2 diabetes mellitus. As a result, patients have an increased risk of falls, fractures, and a reduced quality of life. Overall, human data thus far suggests a deterioration of tissue mineral quality and strength, likely brought about by adverse effects of long-term hyperglycemia on bone matrix and the bone cells. T2DM patients have reduced bone formation markers and some evidence that resorption makers are reduced: , indicating bone cells are adversely affected. This project is aimed at testing whether hyperglycemia directly reduces the activity of the bone resorbing cells, the osteoclasts. Human blood monocytes will be cultured and differentiated on coverslips and treated with increasing concentrations of glucose over several weeks to form mature, bone resorbing osteoclasts. Cells will be stained for numbers and resorption markers and properties. Secondly, cells will be cultured and differentiated on slices of whale dentine in increasing concentrations of glucose. The dentine slices will then be analysed by electron scanning microscopy (SEM) to determine the amount of resorption carried out by these cells.
Project 3: The role of osteocalcin in the modulation of whole body energy metabolism
LIPID METABOLISM LABORATORYLab 3 West, The Hub, Charles Perkins Centre
Telephone: +61 2 9351 2514
Dr Andrew HoyThe Lipid Metabolism Laboratory investigates the mechanisms linking perturbed lipid metabolism and a range of pathologies. Currently, our primary interests are in insulin resistance/type 2 diabetes/obesity and cancer including breast, pancreatic and prostate, in particular how these cancers behave differently in an obese patient vs a lean patient. The lab located in The Hub, Charles Perkins Centre where the following projects will be available.
Project 1: Validating novel proteins that may play a role in fatty liver and insulin resistance
and bioinformatic approaches. In this project these highly novel candidate targets will be characterised using techniques including cutting-edge microscopy, cell culture, biochemical and radiometric metabolic analysis, and genetic manipulation.
Project 2: Lipid metabolism and prostate cancerLipid accumulation in prostate cancer is a common observation, especially in aggressive cancers. The vast majority of lipid is stored as triacylglycerols in lipid droplets within these cells. These lipid droplets are closely located to mitochondria, to serve a readily available supply of energy for tumour progression. This project will target the lipase responsible for the breakdown of triacylglycerols, ATGL, and to elucidate its function and potential for therapeutic targeting in prostate cancer. The project is part of a Movember funded program and will employ techniques including cell culture, genetic manipulation, radiolabel metabolic analysis, cutting-edge microscopy and cancer cell progression including proliferation, migration and invasion.
Project 3: Lipid metabolism and breast cancerLipid accumulation in breast cancer is a common observation, especially in aggressive cancers. The vast majority of lipid is stored as triacylglycerols in lipid droplets within these cells. These lipid droplets are closely located to mitochondria, to serve a readily available supply of energy for tumour progression. Annexin A6 (AnxA6), a member of the annexin family, is a multifunctional scaffolding protein with tumour suppressor activity in breast cancer, reducing cell proliferation, migration and invasion. AnxA6 is known to inhibit oncogenic signalling events, but novel observations made in the laboratory of A/Prof Thomas Grewal in the Faculty of Pharmacy, now link the regulatory role of AnxA6 in cell signalling with its ability to control lipid uptake and content. In collaboration with A/Prof Grewal, this project will elucidate the role that AnxA6 plays in regulating lipid homeostasis in breast cancer and its function in cancer progression. The project will employ techniques including cell culture, genetic manipulation, radiometric metabolic analysis, cancer cell progression including proliferation, migration and invasion.
Direct enquiries can be made by email to: Dr Andrew Hoy – firstname.lastname@example.org
DEVELOPMENTAL PHYSIOLOGY LABORATORYMedical Foundation Building, Room 232, 92-94 Parramatta Rd Camperdown, Telephone: +61 2
Dr Margot DayRoughly 3% of babies born in Australia result from assisted reproduction involving fertilization and then culture of the embryo in vitro. It is known that the embryo culture environment causes significant alterations in gene expression, epigenetics, metabolism and cell proliferation during preimplantation development and that these alterations may have effects on later life.
Our studies aim to help us to understand the impact of the culture environment on pre-implantation embryonic development in order to improve reproductive outcomes. We study the physiological processes involved in fertilization of the oocyte and proliferation of the cells in the preimplantation embryo.
To do this we use a range of techniques including in vitro fertilization, isolation and culture of preimplantation mouse embryos, gene expression, cell signalling, electrophysiology and live cell imaging.
Honours projects are available on the following topics:Prof. Phil Poronnik.
Direct enquiries can be made by email to: Dr Margot Day - email@example.com
EMBRYONIC STEM CELL LABORATORYMedical Foundation Building
Dr Michael Morrisph: 9036 3276; firstname.lastname@example.org
Room 139 Medical Foundation Building
How do mammalian, including human, embryos grow? And how can stem cells grown in the laboratory shed light on the highly complex mechanisms that control development? My lab focuses on understanding the complex molecular pathways and circuits that control early stages of development – from pluripotency to gastrulation to cells of the developing nervous system.Project Title: Modelling early embryo development and neurogenesis using embryonic stem cells in vitro We also develop protocols to direct the differentiation of ES cells to specific cell types that can be
used in animal models of human disease and injury. In addition, we apply the knowledge we have gained from stem-cell behaviour in vitro to determine if the development of embryos themselves is controlled by the same or similar mechanisms. Thus, these projects examine the processes of development from pluripotency to germ layer formation to early neurogenesis and on to mature neural cells such as neurons, glia and neural crest cells that make up the central and peripheral nervous system. Our focus is on the many interacting signaling pathways and metabolic events that drive this directed differentiation.
Techniques to be used in these projects include tissue culture, cell signalling analysis, gene expression analysis, immunohistochemistry and fluorescence microscopy, flow cytometry, and measurements of aerobic and anaerobic metabolism.
ENVIRONMENTAL CONTROL OF PHYSIOLOGY LABORATORY email@example.com
Dr Bronwyn McAllanAnimal models are frequently used to understand physiological mechanisms. Comparative Physiologists use the diverse information discovered from a wide variety of non-laboratory animals to help formulate ideas about physiological processes. Our current research has focused on the environmental control of structure and function in mammals, especially marsupials. Research includes the seasonal physiological and endocrinological changes in mammals and their morphological implications. We use the small marsupials Antechinus stuartii (brown antechinus), Sminthopsis macroura (stripe-faced dunnart), and S. crassicaudata (fat-tailed dunnart) as animal models. Projects include collaborations with other research groups at USYD and the UNSW.
Project 1: The regulation of reproduction and metabolism by photoperiod and temperature.Seasonal changes in reproduction and torpor use (measured by open flow respirometry) are important for the survival of many small mammals. By exposing the marsupials Sminthopsis macroura and Sminthopsis crassicadata to different photoperiods and temperatures we can understand more about the survival responses of mammals to environmental change.
Project 2: Understanding the common molecules needed for live birth in vertebrates. (With Prof Chris Murphy (Anatomy) & Prof Michael Thompson (Biol Sci))The evolution of complex placentae is a fundamentally interesting but rare event, because it requires development of new structures and processes. With 100+ origins of viviparity, reptiles and
mammals provide outstanding models for studying the evolution of a common vertebrate characteristic, namely viviparity and complex placentation. The honours project will focus on
molecules which are important in the plasma membrane transformation of the uterus in preparation for implantation and later placental development in a marsupial mammal, Sminthopsiscrassicaudata
MOLECULAR PHYSIOLOGY OF MEMBRANE TRANSPORT
Professor Philip Poronnikphilip.firstname.lastname@example.orgRm 253 Medical Foundation Building (K25)
Our group has 2 main areas of research. The first is in understanding how the location of membrane proteins in discrete complexes confers functional specificity. Many of the proteins that we
identified in epithelial cells are also found in the brain so our research seeks to understand how the same proteins can function in different contexts to effect cell specific outcomes. In terms of disease
states, our major emphasis is on diabetic nephropathy and neurodegeneration. Further information information on our research see http://www.ncbi.nlm.nih.gov/pubmed/?term=poronnik+p
The other area of interest is in science education and communication using new digital media.
Bench Research:Project 1: The role of Kchannels in the genesis and progression of diabetic kidney disease. We have strong evidence that inhibition of certain types of Kchannels can reduce the key hallmarks
associated with the development of kidney disease. This project is in conjunction with the laboratory of Prof Carol Pollock at the Kolling Institute and A/Prof Margot Day. It will involve measurements of Casignalling, confocal microscopy, Western blotting and RT-PCR in tissue culture cells.
Project 2The renal ubiquitome in diabetic kidney diseaseOur preliminary findings reveal dramatic changes in the renal ubiquitome in the diabetic kidney. This project will involve ubiquitomics analysis as well as target validation using Western blotting and confocal microscopy to understand what changes are occurring in the individual cell types that make up the kidney. This project is in collaboration with Dr Darren Saunders at UNSW, Prof Darren Kelly, University of Melbourne and Prof Carol Pollock at the Kolling.
Project 3: The ubiquitome and the ageing brainNeurodegenerative disease can be regarded as a failure of the normal regulatory systems that ensure
protein homeostasis, something that is know to involve the ubiquitin pathways. In this project we are seeking to answer the question – is dysfunction of ubiquitin dependent proteostatic pathways an inevitable consequence of normal ageing and is there varying susceptibility between individuals? This is project in conjunction with Dr Darren Saunders at UNSW using our newly developed ubiquitomic techniques and Professor Gillian Kril in Pathology to identify and validate target proteins.
Project 4: Imaging the pancreatic beta cell synapseresolution microscopy to determine the essential structure-function arrangement of the synapse. The outcomes of the project will be significant for both understanding and treatment of diabetes.
Science Education – communication: Project 1Creative coding toolkit for big dataWe are currently generating more and more “big” data and it is becoming increasingly challenging
for researchers to visualize and analyse the data. We are developing a creative coding toolkit to enable researchers to easily manipulate and interrogate their data. This in collaboration with Dr Ollie Bown at in Design at UNSW together with Dr Darren Saunders at UNSW and Dr Martin Krzywinski at UBC. You will require some level of competence in coding with Java and Processing.
Project 2Cognitive remediation for schizophreniaCognitive remediation therapy relies on repeated activities to improve neurocognitive abilities.
People living with schizophrenia have well characterised cognitive difficulties and there is some evidence to suggest that it can help improve outcomes for mental patients. This project involves developing wearable EEG technologies (such as Mindwave) to allow the user to create soundscapes and visual patterns as a therapeutic intervention. The project will require some familiarity with
basic coding and ideally, the use of MIDI interfaces. This is in collaboration with Professor Tim Lambert (Professor of Psychiatry), Dr Ollie Bown (UNSW), Dr John Taylor (Conservatorium) and Jim Cook (ICT Tech lab).
Project 3Learning from the CPC learning spacesThe Science of Learning Science research node at the CPC has an ongoing interest in understanding how both staff and students experience the new learning spaces in the CPC and the opportunities to develop new ways of teaching in these spaces. Ultimately we are working towards operationalizing a conceptual framework for the analysis of complex learning environments. This project involves learning the skills associated with qualitative education research – designing and analysing interviews and surveys as well as ethics and recruitment. The project is in the CPC in collaboration with Dr Tina Hinton and Professor Peter Goodyear in Education.
DEVELOPMENTAL & CANCER BIOLOGY LABORATORYAnderson Stuart Bldg, Room N401 Email: ; Tel: +61 2 9351 4267
A/Prof Matt NaylorResearch in the Developmental & Cancer Biology Lab focuses on understanding how normal development and cell function is controlled, and then, how this regulation is perturbed to result in human disease such as cancer. Specifically, research in the lab has focused on transcriptional and cell-matrix 'master' regulators of cell fate (eg. whether or not a cell undergoes proliferation or differentiation) in breast and prostate development and cancer. Using whole genome transcript profiling and subsequent mouse and human cell based models, we have identified several novel regulators of normal breast and prostate development and shown that altering the function of these genes can either speed up or slow down cancer progression.
1) Investigate the role of Paxillin in breast cancer & metastasistumourigenesis and metastasis. Techniques employed will include a combination of in vitro based techniques such as cell culture, morphology, migration and proliferation assays, shRNA, and in vivo based approaches such as genetic mouse models and xenografts.
2) Exploring the role of Paxillin in prostate cancer.of men and kills as many men as breast cancer does women each year. Similar to the Paxillin Breast Cancer Project, we have also recently demonstrated a role for a number of integrin and integrin related molecules in the progression of prostate cancer. This project will continue to explore the role of integrin signaling in prostate development and prostate cancer progression by using newly generated Paxillin floxed genetic mouse models, transgenic prostate cancer mouse models and by determining the effects of paxillin in prostate cancer cell function using cell culture, morphology, migration and proliferation assays, shRNA viral approaches, and further in vivo based approaches such as xenografts.
3) Metabolism and breast cancer.within a variety of different cancer types, including breast cancer. In addition, a key component in the progression of cancer is said to be the ability of a cancer cell to rewire its metabolic pathways to cope with increased energetic and biosynthetic demands required during tumour progression. We have demonstrated a novel role for ACC1 in this process. Using novel inhibitors in cell culture studies along with proliferation assays and mouse based carcinogenesis models, this project will investigate the effects of inhibiting lipogenesis and determine the subsequent effects on breast cancer cell growth and tumourigenesis.
4) Transcriptional regulators of mammary gland development and breast cancer.cell fate and normal cell function is critical during development and is often perturbed during carcinogenesis and tumour progression. We have identified and developed a number of new mouse and cell based models to investigate or continue to define a completely novel function for a number of transcription factors not previously implicated in both the regulation of normal breast development or breast cancer. This project will utilise similar approaches and techniques to the projects previously described to determine the role of these transcription factors in the breast.
DIABETES AND INSULIN SECRETION LABORATORYCharles Perkins Centre (current contact, email@example.com)
Professor Peter ThornOur group uses cutting-edge microscopy, transgenic and molecular approaches to understand how insulin secretion is regulated in health and disease. Our latest work suggests that insulin secretion from pancreatic beta cells is controlled through synaptic-like connections with the blood vessels of the islet (Low et al Diabetologia 2014). Our lab will move from Queensland to the Charles Perkins Centre in December 2015 and brings post-docs and students who will train and support the Honours students in these projects.
Project 1. Understanding how the pancreatic beta cell synapse controls insulin secretion.Our discovery that beta cells secrete insulin via a synaptic-like connection with blood vessels in the islet challenges accepted models of insulin secretion. Ongoing work in the lab is showing the synapse changes in type 2 diabetes, suggesting it may be significant in disease. The next step in this work is to prove that functional interactions in the synapse have significance for the control of insulin secretion. To this end, in this project we will stain for the key proteins in the beta cell synapse and use super resolution microscopy to determine their relative position. This approach will be complemented by live-cell two-photon imaging of insulin secretion. The outcomes of the project will be significant for both understanding and treatment of diabetes.
Project 2. Are pancreatic beta cells damaged in prediabetes?Prediabetes is a recognised as a medical condition where blood sugar levels are higher than normal but not in the diabetic range. It affects around 1/6 of the Australian population and is known to be a significant risk factor in developing type 2 diabetes. However, whether it is a disease and whether it should be treated is controversial. A step towards resolving the issue would be to show that fundamental changes are occurring in the regulation of insulin secretion. To this end, this project will study insulin secretion from prediabetic and diabetic pancreatic islets. Our preliminary data indicates that prediabetes is associated with pathological increases in insulin secretion and in this project these will be defined. Furthermore, we plan experiments to test the efficacy of a range of treatments.
HIGH BLOOD PRESSURE RESEARCH GROUPHigh Blood Pressure Research Group (affiliate to the Dept of physiology; University of Sydney) The Heart Research Institute
7 Eliza Street
0455 050 063
8208 8938 firstname.lastname@example.org email@example.com www.Pilowsky.org
OUR RESEARCHIn the High Blood Pressure Group we investigate the way that different neurons, and neurotransmitters, in the brainstem and spinal cord control the heart, blood vessels and breathing. We also investigate the ways that these pathways learn and remember information (neuroplasticity). From a disease perspective, we study how abnormalities of these critical neural pathways can lead
to high blood pressure and other health problems.
Projects:Role of PACAP in the regulation of arterial blood pressure.PACAP is a polypeptide that is present throughout the brain and plays an important role in
controlling sympathetic nerve activity and BP. We have discovered that it is present in neurons in the brainstem spinal cord, sympathetic nerves and adrenal medulla that are critical in the regulation of arterial blood pressure. Two disease states that we have a major interest in investigating, in which PACAP plays an important role are epilepsy and sleep apnoea.
Studies that are currently underway include molecular studies, histological studies, physiological and pharmacological studies.Role of microglia and inflammation in the regulation of arterial blood pressure.Traditionally, microglia – the macrophages of the brainstem – are not considered to play a soothing role in the regulation of neuronal function. Recently, we discovered that during epilepsy, microglia interact with sympathetic neurons in order to manage their level of excitation. We consider this to be an extremely important mechanistic finding and there is a great deal more to be investigated. Opportunities exist to study this question using functional neuroanatomy with novel monoclonal antibodies that we have invented and with regulatory, physiological and pharmacological methods.Role of the brainstem in metabolic syndrome.In addition to its well-known function in monitoring oxygen and acidity in blood, the brain also monitors temperature, glucose levels, lipids and electrolytes. The ability of the brain to achieve these latter functions occurs because of its exposure in the hypothalamus to circulating concentrations of angiotensin II and insulin. Specific receptors within the hypothalamus respond to these concentrations of peptide and cause changes in the activity of cardiovascular neurons in the brainstem leading to changes in efferent sympathetic activity to different populations of neurons. Our understanding of these changes, and the way that these changes are regulated, is at its earliest stage. Certainly, it seems likely that errors in function in relation to brain monitoring of insulin could easily lead to a metabolic syndrome with weight gain, hypertension, dyslipidaemia and diabetes. It is our intention, to develop a number of projects related to the questions raised above that would be suitable for long or short term study. For example, in the past, we have studied the effects of intermittent hypoxia as a way of investigating experimental sleep apnoea. In this project, we propose intermittent hyperglycaemia and intermittent hyperlipidaemia as a method of simulating the metabolic syndrome. In order to assess the involvement of neurons in the brain that are considered to play an important role in the metabolic syndrome, we would increase or decrease the activity of the arcuate nucleus or the orexin neuronsWe would also examine known models of diabetes or obesity or hypertension and repeat the studies in these in order to see if there are any interaction effects within the brainstem or hypothalamus. Animal models to be used would include the spontaneously hypertensive rat, the obese rats, and diabetic rats.Human studies.Opportunities are also available for students with a background in biomedical engineering to undertake studies that involve sampling of data from people or patients. Studies in the past have included changing position from lying to standing and feeding in males and females, patients with glaucoma, and women that were normal and that were normal but pregnant this project is continuing. The advantage that we have in our studies is that we possess a device that can measure continuous arterial blood pressure noninvasively from the finger, so that we can then derive an approximate value of sympathetic nerve activity from the systolic BP waveform. This value and the many other values that can be derived allow the student to obtain a considerable amount of data from even a small number of cases.Aortic valve stenosis.The sympathetic branch of the autonomic nervous system maintains a stable but adjustable level of blood pressure. In the case of heart failure secondary to aortic valve stenosis, the sympathetic drive is extremely high, as the brain attempts to maintain a minimum level of blood pressure against a mechanical obstruction. The aim of this project is to assess and quantify the level of sympathetic activity in heart failure patients.
The method used to quantify sympathetic activity in this project involves non-invasive recording of continuous blood pressure. Recordings are analysed using a fast Fourier transform. Patients will be assessed before and after they undergo surgery to correct a stenosed aortic valve. The project would is especially suitable for a student with an interest in biomedical engineering.
External Honours ProjectsThe Discipline of Physiology on occasion accepts into its Honours Course students who are performing their research in laboratories outside the Department. The project must be closely allied to physiology and an internal supervisor who is familiar with the area must be prepared to act as the associate supervisor. The student should normally have undertaken at least one 3rd year course in Physiology and must attend the teaching sessions for Honours students which occur weekly within the Discipline.
Supervisors and laboratories which have indicated their interest in taking such students are listed below. You should contact the supervisor of the project directly to express your interest.
Heart Research Institute,Immunobiology GroupDr. Christina Bursill, Dr. Joanne Tan firstname.lastname@example.org
The Immunobiology Group focusses on exploring the molecular mechanisms involved in vascular complications associated with heart disease, with the goal of revealing potential therapeutic targets. Our group has recently published 3 articles describing the ability of high density lipoproteins (HDL, “the good cholesterol”) to regulate angiogenesis (new blood vessel formation) in a multifunctional manner, depending on the pathophysiological context. We find HDL suppresses unwanted inflammatory-driven angiogenesis (i.e. cancer and atherosclerosis) but augments ischaemia-driven angiogenesis (i.e. myocardial infarction and wound healing), which is essential for tissue repair. We now seek to further elucidate the mechanisms of HDL in the regulation of angiogenesis.
Project Title: The role of high-density lipoproteins in the regulation of VEGFR2 and angiogenesis. Angiogenesis is the process by which new blood vessels are formed. It is critical for tissue repair following injury or in ischaemia, which occurs, for example, following a heart attack. Vascular endothelial growth factor (VEGF) receptor-2, is a key receptor that regulates angiogenesis. We have recently found that high-density lipoproteins (HDL), also known as the ‘good cholesterol’, increase the expression of VEGFR2 in endothelial cells. In this project we will determine the mechanism by which HDL regulates VEGFR2 in vitro. This project will employ a broad range of techniques including: tissue culture, RT-PCR, Western blotting, flow cytometry, siRNA knock-down
techniques and functional in vitro angiogenic assays. All methods/techniques are well established in our laboratory. All training will be provided in a modern facility in the heart of Newtown.
Project Title: Investigating the role of microRNAs in mediating the action of HDL-induced rescue of diabetes.
Type 2 diabetic patients have an increased risk of developing a heart attack as they suffer from increased vascular complications which is associated with impaired angiogenesis (formation of new blood vessels). High density lipoproteins (HDL), the “good cholesterol”, has been shown to have cardio-protective and anti-diabetic effects. Our preliminary findings show that HDL can also rescue diabetes-impaired angiogenesis, however the exact mechanism is unknown. Increasing evidence suggests that microRNAs, small non-coding RNAs that regulate gene expression, play a key role in angiogenesis. In this project we will determine the role of microRNAs in mediating HDL-induced rescue of diabetes in vitro and in an in vivo model of ischaemia-induced angiogenesis. This project will provide the opportunity to learn a broad range of techniques including tissue culture, RT-PCR, Western blotting, flow cytometry and miRNA knock-down/overexpression in vitro as well as provide experience with an animal surgical model of angiogenesis. All methods/techniques are well established in our laboratory. All training will be provided in a modern facility in the heart of Newtown.
INFLAMMATION GROUP, HEART RESEARCH INSTITUTE.Inflammation Group, The Heart Research Institute, 7 Eliza Street, Newtown NSW 2042. www.hri.org.au
Supervisors: Dr. Ben Rayner and Assoc. Prof. Clare Hawkins
The Inflammation Group is interested in the vascular cell dysfunction, damage and death associated with the inflammatory response evident during atherosclerotic lesion development. In particular, research undertaken within the group is focused on the specific role oxidants generated through the actions of the haem enzyme myeloperoxidase have within the disease.
Project Title: Investigating the molecular mechanisms involved in endothelial cell damage and death, within the setting of atherosclerosis.
There is epidemiological, clinical, and experimental evidence that cellular stress and excessive inflammation are causally linked to various pathological conditions including atherosclerosis (hardening of the arteries). Leukocyte infiltration and the resultant oxidant formation within atherosclerotic lesions in the vascular wall leads to oxidative stress, damage and ultimately death to cells of the vasculature. This accelerates lesion formation and can also result in the destabilisation of lesions, which ultimately triggers thrombosis and heart attacks. This project will focus on understanding how inflammatory oxidants modulate apoptosis, the oxidative stress response, and transcriptional regulation within endothelial cells. Techniques that will be employed to achieve this goal include gene analysis by quantitative real-time PCR, protein expression analysis by Western blotting and ELISA, and flow cytometry to analyse cellular dysfunction and death. Delineation of oxidant-induced molecular pathway activation will be targeted using a combination of pharmacological and siRNA transfection-mediated inhibition. The detailed knowledge relating to the biochemical mechanisms of endothelial cell damage during lesion development is important for the design of new therapeutic agents to modulate inflammation and slow the progression of atherosclerosis.
Dr Bronwyn Brown and Assoc Prof Clare Hawkins
Email contact: email@example.com
The Inflammation Group is also focussed on understanding how the damaging oxidants produced by peroxidases affect cells and low-density lipoproteins (LDL) in the wall of human arteries and how this contributes to the development of heart disease. This is very important for the development of protective strategies to minimise cardiovascular disease.
Project Title: Role of LDL modification in macrophage dysfunction and inflammation and atherosclerosis
Atherosclerosis is characterised by lipid accumulation within the intima of the artery wall and chronic inflammation, eventually leading to blockage of blood flow and clinical symptoms such as angina, heart attack or stroke. A key event in the initiation of atherosclerosis is the oxidative modification of low-density lipoprotein (LDL), which causes the uncontrolled cellular uptake of lipid and triggers a cascade of inflammatory events. Myeloperoxidase (MPO) is released by activated white blood cells at sites of inflammation, including atherosclerotic lesions. It forms reactive chemical oxidants including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN), which kill bacteria, but also damage host tissue and accelerate lesion development in atherosclerosis. HOCl and HOSCN both modify LDL, which results in its uptake and accumulation in macrophages. However there is a lack of data relating to the mechanisms involved in the cellular processing of these modified LDLs, and the resulting detrimental effects on cellular function. The aims of this study are to examine the pathways and receptors responsible for the propagation of inflammation by HOCl- and HOSCN-modified LDL, and to establish the efficacy of novel therapeutic agents to modulate these reactions.
This project will provide training in various biochemical assays, LDL isolation and modification, primary cell culture, flow cytometry, HPLC, quantitative real-time PCR, Western blotting and ELISA techniques.References1) Ismael F.O. et al., Comparative reactivity of the myeloperoxidase-‐derived oxidants HOCl and HOSCN with low-‐density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis. Arch Biochem Biophys, 573, 40-‐51, 2015. 2) Rayner, B.S, et al., Comparative reactivity of myeloperoxidase-‐derived oxidants with mammalian cells. Free Radic Biol Med, 71, 240-‐55, 2014.
Translational Research Group, Heart Research InstituteSupervisors: Dr. Yuen Ting (Monica) Lam and Assoc. Prof. Martin Ng. Contact Email: firstname.lastname@example.org
The Translational Research Group, led by A/Prof Martin Ng, a physician-scientist and cardiologist, investigates the mechanisms of endothelial cell dysfunctions and cardiovascular complications in diabetes. The focus is on understanding key molecular mechanisms for cardiovascular repair and regeneration in response to ischaemic injury (the lack of oxygen supply). Understanding the mechanisms involved in promoting angiogenesis, the process of which new blood vessels are formed, is critical for developing potential treatment strategies for patients with cardiovascular disease. Our group has developed in vivo ischaemia models and in vitro angiogenic functional assays for the investigation.
Project Title: Modulations of angiogenesis in ageing endothelial cells by androgens under high glucose conditionsThis project aims to investigate the role of androgens in mediating angiogenesis (the sprouting of new blood vessels) in ageing cells under diabetic conditions. Endothelial cells play a key in maintaining cardiovascular homeostasis and experience replicative cellular ageing, known as senescence, which in part leads to a reduction of angiogenic functions. In this study, the effects of androgens on angiogenic functions will be examined in young endothelial cells and ageing cells that have undergone replicative senescence. In addition, young and aged endothelial cells will be exposure to normal and high glucose conditions. This study involves cell culture techniques, in vitro angiogenic functional assays and molecular techniques such as real-time qPCR, Western blotting.
Supervisor: Dr Jun Yuan and Assoc. Prof. Martin Ng.
Senior Research Officer, Translational Research Group, The Heart Research Institute
Senior Lecturer, Sydney Medical School, University of Sydney
Project Title: The protective effects of fenofibrate in diabetes-related vascular complicationsassociated with impaired tolerance to hypoxia, though the mechanisms for this are poorly understood. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) placebo- controlled randomised trial, led by our collaborator Professor Anthony Keech (NHMRC clinical trial centre) demonstrated for the first time that fenofibrate therapy in type 2 diabetes significantly and substantially reduced the risk of microvascular-related complications (Lancet, 2004, 2007,2009This project will be focus on investigating the effects of fenofibrate, a lipid lowering agent, on
impaired hypoxia tolerance in diabetes mellitus in vitro. This project will apply cell culture, RT- PCR, and western blot techniques to assess the effects of fenofibrate on functions and gene expression of endothelial cells under diabetic and hypoxic conditions.
Project TitleThe Role of Thioredoxin Interacting Protein (TXNIP) in the Pathogenesis of Diabetic Vascular
Short, simple description of project offered and the types of techniques employed (maximum 10 sentences).Endothelial damage, impaired endothelial regeneration and endothelial dysfunction play a critical role in the onset and progression of diabetic vascular complications. Chronic hyperglycemia is a major initiator of diabetic vascular complications. TXNIP, an exquisitely glucose-inducible gene, is a multi-functional protein that is emerging as a key regulator of endothelial biology.
This project seeks to investigate the role of TXNIP in the pathogenesis of diabetic vascular complications, with a particular focus on the mechanisms by which TXNIP modulates diabetes- related susceptibility to endothelial damage and dysfunction.
This project will apply cell culture, RT-PCR, and western blot techniques to assess the roles of
TXNIP on functions and gene expression of endothelial cells under diabetic and shear stress conditions.
Vascular Complications Group, Heart Research Institute.
Dr Mary Kavurma,Mary.email@example.comThe role of Wnt signaling in the regulation of vascular calcificationThis project seeks to investigate the potential of targeting the Wnt signalling pathway in vascular calcification in aging. In particular, we aim to test whether Wnt signalling contributes to vascular calcification by regulating the expression of osteoprotegerin (OPG, an inhibitor of vascular calcification), receptor activator of nuclear factor-κB ligand (RANKL, an activator of osteoclastogenesis and vascular calcification) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL, modulator of RANKL expression) in aging vascular smooth muscle cells (VSMCs). Importantly, these molecules are known for their link between bone metabolism and vascular calcification [1, 2].Overview of studies: 211 Di Bartolo BA, Cartland SP, Harith HH, Bobryshev YV, Schoppet M, Kavurma MM. TRAIL- Deficiency Accelerates Vascular Calcification in Atherosclerosis via Modulation of RANKL. PloS one.2013; 8: e74211.2 Di Bartolo BA, Kavurma MM. Regulation And Function Of Rankl In Arterial Calcification. Current pharmaceutical design. 2014; 20:5853-61.
Neuro-Otology LaboratoryBrain & Mind Research Institute, Room 507, Telephone +61 2 93510748
Dr Daniel Brown is the head of the Neuro-Otology laboratory, whose primary aim is to investigate the physiology underlying hearing and balance disorders such as Meniere’s Disease. Primarily, we are interested in fluid dynamics of the inner ear. Our research combines in vivo electrophysiological experiments in guinea pigs, novel techniques for post-mortem imaging and 3D reconstruction of the inner ear labyrinth, and measurements of physiological responses from humans.
Project 1: Functional Role of Valves in the Membranous Labyrinth in the Inner EarMeniere’s Disease is a hearing and balance disorder that afflicts approximately 50,000 Australians.
It is characterised by fluctuating hearing loss, tinnitus, fullness in the ear, and severe attacks of vertigo. The hallmark of Meniere’s is a bloating of the fluid-filled membranous labyrinth in the ear, which houses the mechanically sensitive cochlear and vestibular hair cells. Our resent research has focused on the function of a tissue duct in the membranous labyrinth that separates the vestibular system from the cochlea. This duct appears to function as a fluid valve (it’s called the ‘Valve of Bast’), temporarily opening when cochlear pressure increases, squirting fluid into the vestibular system and causing a transient loss of balance sensitivity. To investigate the symptoms of Meniere’s, and the function of the various inner ear valves, we perform a variety of physiological experiments such as injecting artificial endolymph with biomarkers into anaesthetised guinea pigs, whilst monitoring in vivo electrophysiological responses from the cochlea and vestibular system. We also image inner ears post-mortem and reconstruct in 3D using techniques such as Micro-CT or using our custom-built Light Sheet Fluorescent Microscope.
Project 2: Functional & Morphological changes resulting from Increased Blood-Labyrinth-BarrierPermeabilityLike the Blood-Brain Barrier that limits fluid and molecule communication between cerebrospinal
fluid and blood, the capillaries of the inner ear also have tight junctions that limit the communication between blood and inner ear fluid (perilymph) – the Blood-Labyrinth-Barrier (BLB). An immune response of the inner ear causes an increase in the BLB permeability, resulting in a moderate swelling of the membranous labyrinth and fluctuating hearing loss, and changes in
the extracellular matrix proteins in the ear. This typically resolves within a week or so, and the inner ear recovers. It’s thought that in some people, this transient immune flare-up in the ear can permanently alter the ears fluid dynamics, resulting in a chronic build-up of fluid in various compartments. Which parts of the ear become damaged resulting in this build-up of fluid is not yet clear, but is vital to our understanding of Meniere’s Disease. Our laboratory is developing the tools and techniques, including in vivo electrophysiology and whole-mount post-mortem imaging, to investigate the long-lasting effects of immune challenges in the inner ear.
NEURODEGENERATION RESEARCH LABORATORYAssociate Professor Kay Double
Brain and Mind Centre Mallett Street, Camperdown firstname.lastname@example.org
Our laboratory studies neurodegenerative disorders, particularly the common movement disorder Parkinson’s disease. We aim to understand how brain cells die in these disorders so we can develop treatments to slow or halt brain cell death. We primarily work with post-mortem human brain tissues.
Project Title: Investigating a novel protein aggregate associated with brain cell death inParkinson’s disease.In many neurodegenerative diseases brain cell death is associated with the abnormal accumulation of proteins into insoluble aggregates. Brain cell death in Parkinson’s disease is thought to be associated with the aggregation of the protein alpha-synuclein, although aggregation of this protein is also seen in brain regions where cells do not degenerate. We have recently identified a new type of protein aggregate in the Parkinson’s disease brain which is found only in brain regions where brain cells degenerate. Interestingly, a similar type of aggregate is also found in the degenerating spinal cord in another neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Clinical trials are now underway in ALS which target these aggregates for removal in the hope of slowing the disease process. We are studying the new aggregates in the Parkinson’s disease brain to determine how they compare with the aggregates seen in ALS and if their presence might explain the regional cell death that occurs in the Parkinson’s disease brain. If so, they may represent a new treatment target. Methods involved in this project include human tissue preparation, immunohistochemistry, mass spectroscopy and metal analyses.
WEIGHT LOSS PHYSIOLOGY GROUPAssociate Professor Amanda SalisNHMRC Senior Research FellowThe Boden Institute of Obesity, Nutrition, Exercise & Eating DisordersCharles Perkins Centre The University of Sydney email@example.comThe aim of the Weight Loss Physiology group is to discover better ways for people to attain and maintain an optimum body weight and composition throughout life, thereby promoting long-term cardiometabolic health and independence. The group’s research spans basic research on brain pathways controlling metabolism and body composition in mice, to randomised controlled clinical weight loss trials in overweight and obese adults. For more information: http://sydney.edu.au/medicine/people/academics/profiles/amanda.salis.phpProject: .In the race to find better treatments for overweight and obesity, there is much focus on reducing body weight, body fat and the risk of cardiometabolic disease. However, with the expansion of obesity in all age groups, as well as increasing life expectancy, it is important to consider potential long-term adverse effects of diet-induced weight loss and energy restriction, notably on body composition.Recent work from our team suggests that a single 8- to 26-week dietary weight loss intervention significantly reduces bone mineral density and muscle strength in overweight and obese adults. This change could place some adults at higher risk of osteoporosis, frailty and their negative consequences.23The aim of this Honours project is to determine the durability of this effect of weight loss on bone and muscle, as well as exploring potential mechanisms. The project will entail:• • literature about the effect of intentional weight loss in overweight and obese adults on the IGF-1 system, as this is a major regulator of bone homeostasis and strength.• clinical trial, to determine concentrations of insulin-like growth factor-1 (IGF-1) and IGF-1 binding proteins, as well as markers of bone turnover (e.g. osteocalcin). The systematic review will identify exactly which analytes would be of most relevance to measure in the laboratory.The successful applicant will receive training in all clinical, literature and laboratory techniques involved.
NUTRITIONAL IMMUNOMETABOLISM GROUPDr Laurence Macia
Charles Perkins Centre The University of Sydney Laurence.firstname.lastname@example.org
Eating healthy food is critical to ensure an efficient immunity but the mechanisms behind remain poorly understood. Our aim is to understand how by manipulating diet composition, we can boost the immune response to reduce inflammatory diseases development. We have a particular emphasis on the effects of dietary fibre and the products subsequently released by gut microbiota on the immune response.
Project 1Role of dietary fibre in rheumatoid arthritisRheumatoid arthritis is a debilitating autoimmune disease characterized by joints inflammation. In
mice, it is known that gut microbes can play a role in development of arthritis but the mechanisms involved remain elusive. This project consists in studying the role of dietary fibre, known to shape beneficially the gut microbiota, on the development of rheumatoid arthritis in mice.1. Mice will be fed on diets deprived, low or enriched in fibre. Joints swelling will be monitored aswell as histological analysis of the joints will be assessed to determine disease severity. Immune cell populations will be studied by flow cytometry and inflammatory cytokines levels will be measured by ELISA as an accurate measure of the inflammatory response.2. Gut bacteria ferment fibre and release subsequently short chain fatty acids (SCFAs) in the circulation. To determine whether potential beneficial role of fibre is mediated by SCFA, mice will be treated with SCFA at doses known to be beneficial in other disease models and arthritis development will be monitored as mentioned in point 1.This new understanding on how healthy diet can protect or reduce development of arthritis might open new therapeutic avenues to alleviate this disease.
Project 2Role of dietary fibre in psoriasisPsoriasis is an autoimmune disease characterized by localized skin inflammation known as plaque,
which are itchy and painful. While there is no treatment for psoriasis, the current strategy is to administer anti-inflammatory drugs to the patients. Dietary fibre are known to be beneficial in other inflammatory diseases such as colitis, asthma but their effects in skin inflammation have never been investigated. The aim of the project is 1) to understand whether fibre could play a beneficial role in psoriasis and 2) to determine the mechanisms involved.1. Mice will be fed on diet with low, normal or high fibre levels. By using a well-established model of psoriasis, skin inflammation will be scored and histological analysis will help determine whether fibre could play a role. The severity of the disease will also be accurately measured by looking atimmune cell populations in the skin and lymph nodes by flow cytometry and inflammatory cytokines will be measured by ELISA and real-time PCR.2. Fibre is fermented by gut bacteria, which release subsequently short chain fatty acids able to bindspecific receptors on immune cells. To determine whether these receptors are important, we will study the development of psoriasis in mice lacking the expression of these receptors (knockout mice) and assess disease severity as described above.This project will give insight into the link between diet, gut microbiota and skin inflammation and might offer a new therapeutic avenue by targeting specific metabolite sensing receptors.
CANCER CELL BIOLOGY GROUPProf. Qihan Dong MD. Ph.D Head,
Sydney Medical School Charles Perkins Centre Ph: 86271714
The overarching goal of the lab is to investigate the mechanism of, and the way to prevent, cancer recurrence. The team has identified a list of proteins that are required for quiescent cancer cells to re-enter the cell cycle. Based on the principal of efficacy and no toxicity, the team has determined the potential of compounds isolated from edible plant and herbal medicine in blocking the transition from the quiescent to actively dividing state of cancer cells, or sensitising cancer cells to radiation therapy.
Project Title: Sensitising prostate cancer cells to radiation via suppression of DNA damage repair mechanismsRadiation therapy is employed to treat prostate cancer or mitigate its symptoms throughout the various stages of disease progression. In spite of the best efforts to eliminate cancer by calculated radiation dosage, some prostate cancer cells survive the therapy through DNA damage repairing mechanisms, resulting in the recurrence of the disease. Due to radiation-caused inflammation in the lining of bladder and bowel, the efficacy of radiation therapy cannot be improved simply by an escalation of the dosage. This project will focus on the sensitization of prostate cancer cells to the radiation therapy via inhibition of the DNA damage repairing mechanisms by herbal medicines.
The types of techniques employed for this Honours project include cell culture, flow cytometry, immunoblot, comet assay, and colony forming assay.
PAIN MANAGEMENT CELLULAR RESEARCH GROUP, KOLLING INSTITUTENorthern Clinical School, University of Sydney at Royal North Shore Hospital, St Leonards, 2065.
Supervisor: Dr Chris Vaughan. Email: email@example.com. Ph: 99264950.
Chronic neuropathic pain, is caused by damage to the peripheral, or central nervous system resulting from trauma, or disease. It is characterised by a debilitating and abnormal pain syndrome, plus a range of psychosocial problems. Compounding this, the current treatment options have limited efficacy and produce problematic side-effects. Our group uses in vivo and in vitro approaches to identifying the mechanisms underlying this condition, with the aim of developing potential treatment targets.