CURRENT HONOURS PROJECTS IN PHYSIOLOGY
|Honours Projects 2017 (PDF with all the projects below)|
OFFERED PROJECTS IN 2017
The projects listed below are available to "Honours" candidates in 2017. These one-year research programs are available in a number of themes that can accommodate a wide range of students. The Honours home page gives information on the current program and expectations.
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 LABORATORY
Anderson Stuart Building, Room N551
Professor J Stone and 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.
In recent developments:
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.
We have developed the concept that conditioning to resist age-related stress – also known as neuroprotection – is part of a body-wide pathay of acquired resilience. In this pathway, sub-lethal stress (ischaemia including exercise, plant toxins, sunlight, hunger and physical damage) upregulates an active response in all body tissues, increasing their resilience in the face of further damage. We are developing this concept as a way of enabling healthy ageing – including neuroprotections
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.
Mechanisms of resilience:
MOLECULAR NEUROSCIENCE LAB
Supervisor: A/Prof Bill Phillips email:email@example.com
The 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 help this synapse adapt and survive. We study these physiological systems and their protective effects in cell culture models of neuromuscular diseases.
Project 1: Can the MuSK system protect muscle fibres from degeneration in the mdx mouse model of Duchenne muscular dystrophy?
In Duchenne muscular dystrophy (DMD), deficiency of the muscle membrane protein, dystrophin, makes the muscle fibre vulnerable to damage and repeated rounds of fibre degeneration and regeneration leads to muscle atrophy. This project will investigate a previously unknown role of the muscle specific kinase (MuSK)/rapsyn system: protecting muscle from damage, in the mdx mouse model of DMD. Adeno-associated viral vector will be used to drive MuSK-GFP or rapsyn-GFP expression in muscles of mdx mice. Fluorescence microscopy will be used to test whether MuSK and rapsyn can prevent muscle fibre degeneration in these dystrophic mice. Immunofluorescence and RNA analysis will be used to assess the mechanism by which MuSK and rapsyn protect muscle fibres from damage.
Muscle specific kinase (MuSK) is a receptor tyrosine kinase that coordinates the embryonic development of the neuromuscular synapse. In some myasthenia gravis patients, autoimmune antibodies bind to MuSK and interrupt MuSK signalling in the postsynaptic membrane, resulting in loss of postsynaptic acetylcholine receptors. These same antibodies also prevent the adaptive response of the nerve terminal: to increase in acetylcholine release. We now find that overexpression of MuSK in healthy muscle fibres suppresses neuromuscular transmission. The mechanism behind these effects of interfering with MuSK is not yet understood. From cell culture studies we know that MuSK can mediate both transcriptional regulation and posttranslational signalling. This project will use confocal immunofluorescence microscopy and RNA analysis to assess which of these signalling systems might mediate feedback control of acetylcholine release from the nerve terminal.
VISUAL NEUROSCIENCE RESEARCH GROUP
Save Sight Institute, Sydney Eye Hospital, and Discipline of Physiology.
We 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 system
You 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 retinas
You 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. Leamey
Phone: 9351 4352
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:
The capacity for Environmental Enrichment to restore function in Ten-m3 KOs:
Impact of increased ipsilateral projections on binocular vision:
- Cellular substrates of binocular vision:
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.
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.
Cannabinoids effects on vision:
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. For these studies we use genetically modified animals that express the light-sensitive membrane protein channelrhodopsin and other animals in which membrane channels have been knocked out.
The yin and yang of excitation and inhibition in the retina:
of these inputs determine the output properties 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:
This is a joint project between Dr Dario Protti and Dr Jin Huang (N659. 9351 9065, firstname.lastname@example.org)
The techniques used in these projects are patch-clamp recordings, optogenetics, dynamic-clamp recordings, confocal microscopy and computer modelling. For more information please contact Dr. Dario Protti: email@example.com
Other projects are offered in collaboration with Dr. Cathy Leamey and Dr. Atomu Sawatari.
SYSTEMS NEUROSCIENCE LABORATORY
Dr Atomu Sawatari
Anderson 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 Binocular Circuitry (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.
Cancer, Cell Biology, Reproduction and Development, Endocrinology
ANDROLOGY RESEARCH GROUP
Medical Foundation Building Room G46 Telephone: +61 2 90363614 firstname.lastname@example.org
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:
Endocrine regulation of cancer cell proliferation. In particular we are interested in how various hormones and cytokines affect tumourigenesis.
Oxytocin, the hormone of love. Our recent work has indicated that oxytocin acts at the prostate to increase de novo steroidogenesis. It has also shown that this hormone might also affect tissues important in regulating energy balance.
Project 1: Understanding the interaction between steroid hormones and the metastasis suppressor NDRG1 in prostate and breast cancer cells.
Prostate and breast cancers are the most prevalent neoplasms in men and women, respectively, and are responsible for 1000’s of deaths in Australia each year. These cancers are also influenced by steroid hormones including oestrogen, testosterone and progesterone, which can either drive or inhibit cancer progression, depending on the molecular context of the cancer cells. Importantly, these hormones can also influence the success of current chemotherapies.
The metastasis suppressor gene, NDRG1, plays an important role in the regulation of both prostate and breast cancers, with increased levels of this protein being correlated with less invasive cancer and better patient prognosis. Hence, NDRG1 is an ideal therapeutic target for the treatment of these cancers and a novel class of anti-cancer agents has recently been developed that can target this molecule. However, to date there has been no research into how NDRG1 is affected by steroid hormones in prostate and breast cancers, or how NDRG1 influences the response of cancer cells to these hormones. This is vital to assess, as our preliminary data demonstrates that NDRG1 can influence the expression of the oestrogen, androgen and progesterone receptors. This project will examine, for the first time, the effect of these vital hormones on NDRG1, and vice versa, in order to elucidate the complex mechanisms that determine how different cancers respond to hormones. This knowledge will be essential in terms of understanding breast and prostate cancer biology and will foster the development of more effective treatments for these deadly diseases.
Two projects will be available, with one focusing on prostate cancer, while the other focuses on breast cancer.
- Culture a range of different breast or prostate cancer cells as well as normal cells for comparison in the presence of different hormones.
- RT-PCR and Western blot analysis.
- Immunofluorescence and Confocal Microscopy
-siRNA studies to knock-down NDRG1
- MTT assays to examine cell proliferation
- 3D colony formation assays
This project is in collaboration with the Richardson Lab (Pathology) and will be co-supervised by Dr Dr. Zaklina Kovacevic and Prof. Des R. Richardson.
Project 2 How might the “hormone of love” mitigate obesity and type 2 diabetes?
Following birth oxytocin is important in stimulating the release of milk during breast-feeding. Since the description of these classical actions oxytocin has been shown to have key roles in modulating maternal behaviour as well as other social behaviours such as pair-bonding. Indeed, it is for these roles that oxytocin has been dubbed “the hormone of love” (reviewed in Tom and Assinder, 2010). More recent evidences suggest positive metabolic effects of oxytocin through improved glucose metabolism, circulating lipid profiles, and increased insulin sensitivity (reviewed in Elabd and Sabry, 2015; Altirriba et al., 2015). Hence, oxytocin is suggested to have pharmacological efficacy in treating obesity and type 2 diabetes.
In this project we will determine: 1) how oxytocin modulates adipose and adrenal secretion of hormones important to maintaining energy balance; 2) how oxytocin affects lipid metabolism in adipose tissue and the liver and; 3) whether it modulates liver glucose metabolism.
This project is in collaboration with Dr Andrew hoy.
VITAMIN D, BONE AND SKIN LABORATORY
Anderson 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.
Our 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.
SKELETAL ENDOCRINE LABORATORY
Dr Tara Speranza: email@example.com
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 mellitus
Patients 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 vitro
Increased 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
JCI, 122:4172-4189, 2012). The mechanism by which the body senses osteocalcin is still unclear although evidence points to a Class C G-protein coupled receptor (the GPRC6A) as the osteocalcin receptor. This project aims to uncover the controversies surrounding osteocalcin-sensing by the body as well as further understanding the pathways by which this little protein from the skeleton controls whole body energy metabolism using molecular and cell biology techniques and mouse models.
LIPID METABOLISM LABORATORY
Lab 3 West, The Hub, Charles Perkins Centre Telephone: +61 2 9351 2514
Dr Andrew HOY
The 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 Title: Novel proteins involved in fatty liver and insulin resistance
Insulin resistance is a unifying feature of the metabolic syndrome. The liver is an early site of perturbed insulin action and a critical regulator of whole body glucose and lipid homeostasis. The lipid droplet is the major site for storage of lipids and the movement of stored lipids out of this
reservoir is highly regulated. We have recently identified proteins that locate to the lipid droplet whose abundance is altered in fatty liver and insulin resistance using innovative mass spectrometry 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 Title: Lipid metabolism and prostate cancer #1
Lipid 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 enzymes that regulate lipid flux at the lipid droplet, and elucidate their 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 Title: Lipid metabolism and prostate cancer #2
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, yet nothing is known about its role in prostate cancer. 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.
DEVELOPMENTAL PHYSIOLOGY LABORATORY
Medical Foundation Building, Room 232, 92-94 Parramatta Rd Camperdown, Telephone: +61 2
Dr Margot Day
Roughly 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:
The mechanisms by which the amino acids improve blastocyst development in vitro.
The role of cell cycle regulated K channels in proliferation of embryonic cells.
The expression of scaffolding proteins during early embryo development (in collaboration with Prof. Phil Poronnik).
EMBRYONIC STEM CELL LABORATORY
Medical Foundation Building
Dr Michael Morris
ph: 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
Dr Bronwyn McAllan
Animal 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, Sminthopsis crassicaudata.
MOLECULAR PHYSIOLOGY OF MEMBRANE TRANSPORT
Professor Philip Poronnik:
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 digital multimedia.
Project 1The renal ubiquitome in diabetic kidney disease
Our 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 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 and Prof Darren Kelly, University of Melbourne (and CEO of Occurx).
Project 2: The ubiquitome and the ageing brain
Neurodegenerative 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 Jillian Kril in Pathology to identify and validate target proteins.
Project 3: Imaging the pancreatic beta cell synapse.In collaboration with Professor Peter Thorn at CPC. Recent work from Peter’s lab suggests that insulin secretion from pancreatic beta cells is controlled through a synaptic-like connection with blood vessels (Low et al Diabetologia
2014). This Honours project, based in his new lab in the Charles Perkins Centre, will use super resolution 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.
Project 1Creative coding toolkit for big data
We 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 and students to easily manipulate and interrogate their data. This is a project funded by the DVC-Education in collaboration with Dr Ollie Bown at in Art and Design at UNSW together with Dr Darren Saunders at UNSW and Dr Martin Krzywinski at UBC.
Project 2True Life – public display of scientific data through Vivid
In 2016 we had an extremely successful projection for Vivid in Pitt St Mall called True Life. This installation featured projections of microscopic data. In this project we seek to create complex visuals to explore new ways of communicating science to the general public en masse. It is expected that part of this project will feature in Vivid 2017. Part of the project will involve growing cells on 3D printed scaffolds and creating movies and other content using these cells and involves some of the leading light artists as collaborators.
Joe Crossley (Astral Projekt), Bruce Ramus (Ramus), Dr John Taylor (Sydney Conservatorium), Dr Caitilin de Berigny (Architecture and Design) and Jim Cook (ICT Techlab).
Project 3Learning from the CPC learning spaces
The 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.
DEVELOPMENTAL & CANCER BIOLOGY LABORATORY
Anderson Stuart Bldg, Room N401 Email: ; Tel: +61 2 9351 4267
A/Prof Matt Naylor
Research 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.
Investigate the role of Paxillin in breast cancer & metastasis.Breast cancer is the most common invasive cancer of women, with Australian women having a lifetime risk of 1 in 9 for developing the disease. Although prognosis for early or locally contained disease is good, patients diagnosed with metastasis have a long term survival rate of only 5-10%. We have previously shown that Integrins, which regulate the interaction between a cell an its local environment, control normal breast development and cancer progression. The role of paxillin, an integrin adaptor protein in this process remains unknown, but its expression is correlated with aggressive disease and cancer cell migration. This project will explore the role of paxillin in breast cancer cell function, tumourigenesis 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.
Exploring the role of Paxillin in prostate cancer.
Metabolism and breast cancer. There is a clear link between metabolic disorders and obesity 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.
Transcriptional regulators of mammary gland development and breast cancer.
DIABETES AND INSULIN SECRETION LABORATORY
Professor Peter Thorn
Our 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. Our lab is based in the Charles Perkins Centre and consists of 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.
Professor David James
Metabolic Cybernetics Laboratory
General description of the labs research
We are a lively and interactive team of ~20+ Postdocs, PhD & Honours students and RAs with a broad range of expertise spanning biochemistry, cell biology, animal physiology, systems biology and bioinformatics.
We study insulin action, exercise and metabolism in health and disease in a broad range of
systems, including fat and muscle cells, mice, flies and humans.
We use diverse methods ranging from single cell live microscopy, mass spectrometry, CrispR gene editing, screens in ~200 fly strains to bioinformatic analysis of complex Omics data.
Project 1: Identification of novel players in insulin action – Dr Jacky Stoeckli
Insulin regulates many cellular processes. In adipocytes insulin is known to control glucose metabolism, fatty acid metabolism, protein synthesis and transcription. We recently analysed the insulin-stimulated phosphoproteome in adipocytes and identified 37,000 phosphosites. Many of these changed in response to insulin. The aim of this project is to characterise novel insulin- regulated phosphoproteins with a view to uncovering novel actions of insulin. Methods: cell culture, Western blotting, production of recombinant proteins, protein-protein interaction analysis, cDNA cloning, transfection, fluorescence microscopy, retrovirus.
Project 2: Mechanism of insulin regulation of lipolysis in adipocytes – Dr Jacky Stoeckli
The release of fatty acids via lipolysis from adipocytes provides an energy source for organs such as the heart and muscle during fasting. This process is inhibited by insulin although the mechanism for this effect is not known. This project will investigate two phosphoproteins that may play a role in insulin’s regulation of lipolysis in adipocytes. Methods: cell culture, Western blotting, lipolysis assay, cDNA cloning, transfection, retrovirus.
Project 3:Interplay between metabolism and signalling in insulin resistance – Dr Daniel Fazakerley
Impaired metabolism is at the heart of many complex diseases, ranging from cancer to insulin resistance and Type II diabetes. Signalling cascades direct metabolic pathways such as glycolysis to respond to changes in nutritional status. Thus, metabolic defects in disease are often considered a result of signalling defects. However, we have exciting evidence that flips this relationship on its head: several metabolic pathways that are dysregulated in insulin resistance play a key role in regulating insulin signalling. This project aims to understand how these metabolic pathways regulate insulin signalling. Methods: Cell culture, induction of insulin resistance in cell models, Western blotting, protein-protein interaction analysis, cDNA cloning, retrovirus, glucose/amino acid transport assays, mitochondrial bioenergetics.
Project 4: Oxidative stress and insulin resistance – Dr Guang Yang
An important driver of insulin resistance and Type 2 diabetes is mitochondrial dysfunction and oxidative stress. Protein oxidation may contribute to the insulin resistant phenotype and we have
recently identified several proteins that undergo significant changes in oxidation in insulin resistant cells. The aim of this project is to determine whether these targeted oxidation reactions play a role in causing insulin resistance. Methods: Cell culture, induction of insulin resistance in cell models, Western blotting, cDNA cloning, retrovirus.
Project 5: Individuality at the single cell level – Dr James Burchfield
In biology it is often assumed that individual cells respond to perturbations in a predictable manner that depicts the overall response of the population. We have found this not to be the case - there is substantial heterogeneity in the response of individual adipocytes to insulin. The aim of this project is to employ unique approaches to interrogate insulin responses at the single cell level using live cell microscopy techniques to understand the basis for heterogeneous responses. Methods: Cell culture, live cell fluorescence microscopy, image analysis, transfection, cDNA cloning, Western blotting.
Project 6: Exercise signalling in muscle – with Dr Ben Parker
Exercise has many beneficial effects including improved insulin sensitivity and even improved memory and reduced anxiety. The mechanism by which exercise mediates these effects is not known. We recently determined the exercise-mediated phosphoproteome in human skeletal muscle. This aim of this project is to investigate the signalling pathways that are induced by exercise, of which most are not well studied with the ultimate goal to identify the mechanism by which exercise induces beneficial effects. Methods: Cell culture, Western blotting, phosphoproteomics, data analysis, bioinformatics.
Dr Melissa Cameron
Anderson Stuart Building (E216); ; (02) 93515228
The regulation of blood pressure is tightly regulated in the resistance blood vessels within the body; therefore understanding how these vessels vasodilate and vasoconstrict is of considerable importance. My research studies the evolution of signalling pathways in the vasculature of vertebrates. In particular, I focus on nitric oxide and endothelium-derived hyperpolarisation in non- mammalian vertebrates and how these systems have evolved comparatively to mammals.
Project Title: The expression of nitric oxide synthase enzymes in the fat-tailed dunnart, Sminthopsis crassicadata
This project will be in collaboration with Dr. Bronwyn McAllan. The project will involve exploring the molecular, protein and physiological presence of the nitric oxide producing enzymes, nitric oxide synthases (NOS), of which there are three isoforms (NOS1, NOS2 and NOS3).
Currently, the presence of NOS within the vasculature in marsupials has not been determined; therefore this project will determine the mRNA expression using PCR and cloning, protein expression using western blotting, immunohistochemistry and histology, and physiology using myography to determine the vasodilatory pathways involved.
External Honours Projects
The 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.
WEIGHT LOSS PHYSIOLOGY GROUP
Associate Professor Amanda Salis NHMRC Senior Research Fellow
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders Charles Perkins Centre
General description of the labs research (maximum 3 short sentences).
The 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.php
Project Title: The Biggest Loser effect – do weight loss diets result in enduring decreases in metabolic rate and increase in appetite?
Recent and widely publicised research on contestants from the Biggest Loser competition suggested that weight loss results in significant reductions in metabolic rate that persist even 6 years after completion of the diet. This finding is in line with separate research showing that weight loss in people with obesity results in significant increases in appetite that persist even at 3 years after completion of the diet. These observations, if confirmed, would have an important impact on the treatment and management of obesity, as they would mean that keeping excess weight off requires long-term reductions in food intake (to match the long-term reductions in metabolic rate) despite a long-term increase in the drive to eat.
This Honours project aims to determine the effects of weight loss on metabolic rate and appetite in women with obesity. The project is a sub-study of an ongoing NHMRC-funded clinical weight loss trial, the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimum metabolic health & body composition in Obesity). During 2017, the Honours student selected for this project will undertake the following measurements in women at 6, 12, 24 and 36 months after marked weight loss, for comparison against previously collected baseline data:
Metabolic rate, measured by indirect calorimetry
Appetite, measured in the fasting state and in response to a standard meal
The project will then involve determining whether weight loss results in any significant changes
from baseline in metabolic rate or appetite, and – if so – whether any such changes persist at 3 years after completion of the intervention. The successful applicant will receive training in all clinical, analytical, literature and writing techniques involved.
Energy Metabolism and Insulin Action Laboratory
Professor Gregory Cooney
Level 5 West, Charles Perkins Centre D17, (email@example.com)
Obesity is associated with the development of a number of serious diseases including, type 2 diabetes and liver disease. The broad aim of our research is to understand how different tissues and different genes contribute to the way the body balances food intake and energy expenditure to maintain healthy body weight and what goes wrong when this balance breaks down and obesity develops.
Project Title: Dissecting the mechanisms of obesity-induced insulin resistance
When humans and animals become obese the build up of lipid in tissues like liver, muscle and adipose tissue is associated with a reduced effectiveness of insulin. This resistance to the action of insulin is a major risk factor for the development of type 2 diabetes and cardiovascular disease but the exact mechanisms for how excess lipid interferes with insulin action at the molecular level are still not completely understood. We have developed dietary models of obesity in mice that differ in the degree of impairment of insulin action. This project will comprehensively examine the differences in insulin action in tissues from obese insulin-sensitive mice and obese insulin-resistant mice using metabolic flux measurements, assessment of insulin signalling pathways and lipidomic and proteomic analysis to tease out what aspects of obesity predispose animals to insulin resistance.
CANCER CELL BIOLOGY GROUP
Prof. 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 mechanisms
Chemo- or radiation therapies are employed to treat cancer or mitigate its symptoms throughout the various stages of disease progression. In spite of the best efforts to eliminate cancer by calculated dosage, some cancer cells survive the therapy through DNA damage repairing mechanisms, resulting in the recurrence of the disease. Due to side effect, the efficacy of chemo- or radiation therapies cannot be improved simply by an escalation of the dosage.
Cell cycle re-entry by quiescent cancer cells is central for cancer progression and recurrence. This project will focus on 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. The types of techniques employed for this Honours project include cell culture, flow cytometry, immunoblot, and colony forming assay.