Higher Degree Research

Dr Morven Cameron

m.cameron@westernsydney.edu.au

• Influence of melanopsin-containing ganglion cell photoreceptors on the physiology of the mammalian retina.

  The neural network of the mammalian retina is one of the most studied within the central nervous system. However, surprises are still common, with a third type of photoreceptor discovered in recent years. Melanopsin containing ganglion cells (mRGCs) are located on the opposite side of the retina from the classical rod and cone photoreceptors, and play a role in a number of sub-conscious functions like pupil light contraction, entrainment of biological clocks to the light-dark cycle and as well as contributing to aspects of conscious visual perception.

  Additionally, mRGCs are thought to be involved with many aspects of local retinal physiology, but this research area is in its infancy. This project will use cutting-edge chemogenetic tools to assess the impact of mRGC activation on retinal function. This will be assessed using a variety of methods in transgenic mice, ranging from in vivo electroretinographic recordings, to light-induced dopamine release.

  Techniques involved will be in-vitro electrophysiology, in vivo electroretinogram, immunohistochemistry and UHPLC-MS/MS quantification of dopamine. No technical experience is necessary as full training will be given, however candidates must have an interest in neuroscience/retinal biology and a life sciences/medical background.

• Rod and cone interactions in the mouse electroretinogram

  The mammalian retina functions over a very wide range of light intensities, from dim starlight to bright Australian sunlight. It does this by using two main photoreceptive systems: rods for dim light intensities, and cones for bright light intensities. However, these two systems are intrinsically linked within the circuitry of the retina and can influence the function of one another.

  This project will investigate the interaction between rod and cone neural pathways by measuring the mouse electroretinogram in a variety of transgenic mouse models. Fundamental insights into the function of rod and cone systems will be analysed including temporal properties, spectral sensitivities and light adaptation.

  The main technique involved will be electroretinogram but immunohistochemistry and single-cell electrophysiology will complement this technique. No technical experience is necessary as full training will be given, however candidates must have an interest in neuroscience/retinal biology and a life sciences/medical background.

Dr Yossi Buskila

Y.Buskila@westernsydney.edu.au

Project(s) offered:

• Astrocytic modulation of neuronal excitability and cell death in ALS

  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which patient’s loose motor functions due to progressive loss of motor neurons in the brainstem and spinal cord. Evidence from patients in the clinic suggests that prior to the presentation of clinical symptoms, familial and sporadic ALS patients display an increase in neuronal hyperexcitability, however the factors that instigate the changes in neural conductivity over the course of disease onset and progression are not well understood.

  In this project, we aim to investigate the ionic mechanisms governing changes in neuronal excitability in motor neurons of mice model for ALS. Specifically, we will assess the connectivity and function of astrocytes in the vicinity of these motor neurons and identify their effect on neuronal excitability in ALS.

  Interested candidates with a background in Neuroscience, biology, physiology, medical physics or related industry are encouraged to apply. Expertise using electrophysiological methods will be beneficial.

• The adaptation of spike propagation delays

  Neurons in the brain use action potentials (spikes) to communicate with each other. In the postsynaptic cell, these spikes are propagated through the dendrites as post-synaptic potentials and summed at the site of spike initiation.

  In recent years, several studies have reported large variability of spike propagation delays in networks of neurons processing these signals, and it is thought that these delays are modulated to enhance signal integration and thus optimize synaptic inputs. In this proposal we aim to study the impact of spike propagation delays on synaptic activity and the mechanisms that modulate signal propagation in cortical neurons. Interested candidates with a background in biology, physiology, medical physics or related industry are encouraged to apply.

Dr David A. Mahns

D.Mahns@westernsydney.edu.au

Project(s) offered:

• Characterising the molecular targets that underpin the transition from acute to chronic pain.

  Normally pain serves a protective role by triggering a reflex response and warning of impending damage. However when the pain outlasts the initial injury pain can become maladaptive leading to exaggerated and persistent responses. Over the past 5 years we have developed a range of models that have allowed us to explore these changes in normal and clinical patients. In this project will test whether experimentally induced (and the discomfort experienced by chronic pain patients) can be reversed by a range of putative neuroprotective agents. These experiments will be complemented by in vivo and in vitro studies that quantify the mode of action of neuroprotective agents.

• Can trigeminal and extra- ocular expression of photoreceptors explain the photophobia experienced during migraine.

  The skin contains a myriad of different nerve however the contribution of many of these fibres to perception is poorly understood. The expression of photoreceptors in a subset of nerves innervating the skin and cornea raises the possibility that during altered states of pain processing, such as those observed during migraine, incident light may be perceived as painful. This possibility will be tested in human models of pain processing. The contribution of different photoreceptors will be tested by systematically varying the wavelength of light used to illuminate the cornea and the skin.

Dr Rose Chesworth

R.Chesworth@westernsydney.edu.au

Project(s) offered:

• Genetic mouse models for schizophrenia: the candidate gene neuregulin 1

  Schizophrenia is a chronic and disabling mental disorder that is triggered by a combination of environmental and genetic risk factors. Laboratory mouse models can assist in understanding the complex relationship of genes and environment (e.g. chronic cannabis abuse, unhealthy diet, early life stress) in the development of behavioural symptoms and brain changes.

  My team uses multi-factorial animal models to pinpoint mechanisms involved the development of schizophrenia, thereby using behavioural, pharmacological and molecular tools.

Professor Tim Karl

T.Karl@westernsydney.edu.au 

Project(s) offered:

• Gene-environment interactions in schizophrenia
  
  Schizophrenia is a chronic and disabling mental disorder that affects 1% of the world’s population. A complex interaction of environmental and genetic risk factors appears to be causal for the development of the disease. Preclinical research has been instrumental in advancing our understanding the impact of those risk factors, both in isolation or in combination, on behaviour and brain development.
  
  Our team models schizophrenia by developing multi-factorial mouse models combining genetic and environmental disease risk factors. Genetically predisposed mouse mutants are exposed to disease-relevant environmental factors (e.g. chronic cannabis abuse, poor diet, deprived housing conditions) at critical stages of their development. Our team focuses on the neuro-behavioural characterisation of these models, applying a multitude of different neuro-behavioural phenotyping paradigms. This highly standardised research is necessary to determine disease-relevant interactions and to identify preventative and therapeutic measures for future clinical applications.
• The role of the endocannabinoid system in Alzheimer's disease
  
  Alzheimer’s disease is neurodegenerative cognitive disorder with an inflammatory component. More classically, Alzheimer's disease is described by extracellular amyloid deposition (building senile plaques) and tau hyper-phosphorylation (forming intracellular neurofibrillary tangles). These processes also impact on a variety of neurotransmitter systems and increased lipid peroxidation is found in affected brains supporting a role for oxidative damage in this disorder as well. Interestingly, the endocannabinoid system (eCB) plays a role in immunity, neuroprotection (i.e. anti-inflammatory and anti-oxidative effects) and can affect cognitive domains. Recent animal research suggests that manipulations to the eCB might have beneficial effects on the pathophysiology of Alzheimer's disease and disease-related cognitive impairments. Thus, my team evaluates the neuro-behavioural response of genetic mouse models for Alzheimer's disease to cannabinoid challenge with a particular focus on the effects of the non-psychoactive phytocannabinoid cannabidiol (CBD).

Prof Stewart Head

S.Head@westernsydney.edu.au

• Why is the “gene for speed” ACTN3 R577X polymorphism so common in humans

  One of the most striking aspects of the “gene for speed” ACTN3 R577X polymorphism in humans is its geographical distribution, low in equatorial Africa where modern humans evolved and high in the Northern hemisphere, where early humans migrated. If you are one of the 20% of people with this variant you will be better at endurance sports but worst at power sports.

  In Olympic finals, no sprinter has the polymorphism while most of the marathon runners do. There is strong genetic evidence that the asymmetric geographical distribution of ACTN3 577XX genotype in human populations is due to positive selection during recent human evolution. Long range linkage disequilibrium data show that the ACTN3 R577X polymorphism has undergone strong positive selection with the 577XX genotype increasing from less than 1% to around 20% to in some cases as high as 40% during the migration of early humans from Africa to the colder climates of the Northern hemisphere, leading to the cold adaption hypotheses which proposes the polymorphism improves adaption to cold environments.

  This cold adaptation hypothesis has been assessed through the analysis of global ACTN3 genotype and biodiversity data compared to geographical location.  In a recent study from my laboratory (Head et al. (2015). Altered Ca2+ Kinetics Associated with α-Actinin-3 Deficiency May Explain Positive Selection for ACTN3 Null Allele in Human Evolution. PLoS Genet 11(1): e1004862. doi:10.1371/journal.pgen.1004862) we proposed the positive selection pressure is due to the survival benefits the polymorphism confers on skeletal muscle metabolic functioning in cold climates. In this paper we used a humanised mouse model to demonstrate a variation in intracellular Ca2+ handling consistent with cold acclimatisation and thermogenesis.

  I am offering a project to a suitable student to further test this hypothesis to see if animals with the ACTN3 577XX genotype actually do perform better when exposed both acutely and chronically to cold conditions. Experimentally this will be carried out at several levels from whole animals to isolated muscle fibres, providing a rigorous and robust test of the cold adaption hypothesis. The student will be required to undertake several annual visits to my partner laboratory at the Murdock Children’s Institute in Melbourne (accommodation and airfares will be provided).

Dr Ritesh Raju

r.raju@westernsydney.edu.au

Project(s) offered:

• Isolation and identification of novel anti-inflammatory compounds from Australian Native plants

  Natural products have historically proven their value as a source of molecules with therapeutic potential, the most famous and well known example to date would be the synthesis of the anti-inflammatory agent, acetylsalicyclic acid (aspirin) derived from the natural product, salicin isolated from the bark of the willow tree Salix alba. This project is based on the systematic isolation and structural identification of phytoconstituents from selected rainforest Australian plants with potential anti- inflammatory properties.

  This will be achieved by bioactivity guided fractionation of crude extracts to isolate new/novel potent anti-inflammatory compounds. The anti-inflammatory activity will be assessed based on inhibition of LPS and IFN-γ induced inflammatory response in different cell lines. Bioactive compounds will be structurally identified using modern spectroscopic techniques like NMR (400 MHz) (1H, 13C, COSY, HSQC, HMBC, ROESY) and mass spectroscopy (HRMS).

  Techniques involved will be performing cell based assays, chemical analysis using HPLC/MS and the ability to interpret NMR data. No technical experience is necessary as full training will be given, however candidates must have a strong background knowledge in Organic/Analytical Chemistry and an interest in Pharmacology.

Erika Gyengesi

e.gyengesi@westernsydney.edu.au

Project(s) offered:

• Investigation of the anti-inflammatory effect of curcumin in a mouse model of chronic neuroinflammation – a route for a cure for Alzheimer’s disease?

  Impact:

  This project will investigate the effect of chronic glial activation on brain structure and function, and test the efficacy of two cytokine-suppressive anti-inflammatory drugs (CSAIDs) against chronic glial activation and the resulting neuronal damage. Significance: Activation of microglia and astroglia is a pathological process evident in many neurodegenerative diseases, including Alzheimer’s disease.  The currently used anti-inflammatory drugs such as NSIADs and corticosteroids have shown limited effects in many neuroinflammatory diseases. Consequently, it has been suggested that drugs targeting neuroinflammation such as CSAIDs might yield disease-modifying treatments for these neurodegenerative disorders.

  Our study:

  We will explore the GFAP-IL6 mouse, in which chronic neuroinflammation is induced by astroglia-specific production of interleukin 6 (IL6).  We will use a variety of behavioural tests to monitor motor skills and cognitive functions in these mice up to 24 months of age. Furthermore, the anti-inflammatory effects of two CSAIDs (curcumin and apigenin) will be tested in this model, first in a dose-response study, and then in prevention and a treatment studies. In the diagnostic/imaging arm of our study, we will investigate whether chronic neuroinflammation can be detected in our mouse model using a PET tracer for the 18 kDa translocator protein (TSPO), a marker of activated microglia. This will allow us to follow the success of treatment of neuroinflammation by CSAID in the live mouse.

  Pilot data:

  The GFAP-IL6 mouse shows increased microglial and astroglial activation, and a much faster decline in motor and cognitive skills compared to the WT. Apigenin and curcumin decreased the number of activated (Iba1+) microglia in the GFAP-IL6 mouse by > 40%. Apigenin improves spatial reference memory in the GFAP-IL mouse. TSPO+ microglia are also upregulated in the GFAP-IL6 mouse, allowing to image neuroinflammation (and potentially the treatment success with apigenin and curcumin) in the live mouse by positron emission tomography (PET).

  Potential for translation:

  a) If the utility of apigenin and curcumin as effective anti-inflammatory therapeutics can be demonstrated, future clinical trials with these, or similar CSAIDs, may be initiated for the treatment of a variety of neuroinflammatory neurodegenerative diseases. b) PET imaging of activated microglia and follow-up scans to monitor treatment success with CSAIDs with TSPO ligands could become standard procedure in preclinical research, clinical trials and, subsequently in clinical practice.

  Student qualifications:

  Techniques involved will be immunohistochemistry and/or behavioral analysis. No technical experience is necessary as full training will be given, however candidates must have an interest in neuroscience and pharmacology, and a life sciences/medical background.

Professor Tim Karl

T.Karl@westernsydney.edu.au 

Project(s) offered:

• The role of the endocannabinoid system in Alzheimer's disease
  
  Alzheimer’s disease is neurodegenerative cognitive disorder with an inflammatory component. More classically, Alzheimer's disease is described by extracellular amyloid deposition (building senile plaques) and tau hyper-phosphorylation (forming intracellular neurofibrillary tangles). These processes also impact on a variety of neurotransmitter systems and increased lipid peroxidation is found in affected brains supporting a role for oxidative damage in this disorder as well. Interestingly, the endocannabinoid system (eCB) plays a role in immunity, neuroprotection (i.e. anti-inflammatory and anti-oxidative effects) and can affect cognitive domains. Recent animal research suggests that manipulations to the eCB might have beneficial effects on the pathophysiology of Alzheimer's disease and disease-related cognitive impairments. Thus, my team evaluates the neuro-behavioural response of genetic mouse models for Alzheimer's disease to cannabinoid challenge with a particular focus on the effects of the non-psychoactive phytocannabinoid cannabidiol (CBD).

A/Prof Mourad Tayebi

m.tayebi@westernsydney.edu.au

Project(s) offered:

• Project description:

  Aging dogs spontaneously deposit human-type amyloid peptide (Aβ) and thus are a natural higher mammalian model of aging. The canine Aβ precursor protein (APP) is virtually identical to human APP (~98% homology). In parallel with progressive Aβ pathology, aged dogs show decline in measures of learning and memory that are correlated with the extent and location of Aβ. This project will focus on analysing brain tissues, blood and cerebrospinal fluids derived from aged dogs affected with declining learned behavior and memory to determine whether Aβ plaques as well as the neurotoxic Aβ and tau soluble oligomers are associated with this disorder in dogs.

  Project aim(s):

  The major aim of this study is to investigate whether the neuropathological and molecular features associated with aging dogs mirror the pathological and molecular hallmarks associated with human Alzheimer’s disease.

Dr Michael O'Connor

m.oconnor@westernsydney.edu.au

1. Clockwork organs: bioinformatic systems biology of human tissues.
2. Manipulating molecular circuits to identify and test novel drug targets.
3. Defining the molecular disease mechanisms induced by environmental risk factors.

Improving clinical therapies:

We use human pluripotent stem cells to make lens, retinal and gut cells/tissues in order to define the molecular events that cause diseases of ageing. We then use this information to identify and test improved drug and cell-based therapies.

Our approach:

We are world-leaders in using stem cell technology to investigate diseases of ageing, such as cataract (e.g., Murphy et al. 2018 Development), macular degeneration and gut disorders.  Our approach is powerful and innovative, applying state-of-the-art techniques including stem cell culture, flow cytometry, genomics (RNA-seq, PCR, etc), proteomics (mass spectrometry, Western blotting, etc), bioinformatics, drug investigations and cell therapy development.

Projects:

We have developed and validated new bioinformatic approaches for analysing gene expression data that identify how growth factors control intracellular signalling pathways, transcription factors and gene expression networks. A number of bioinformatic projects are available to evolve these methods and/or apply them to analysis of lens, retinal and gut gene expression datasets. Stem cell culture projects are also available to investigate how signalling and transcriptional networks can be manipulated to identify and test novel drug targets, and to define how environmental risk factors lead to disease.

Research environment:

You will join a vibrant, interactive and world-leading team consisting of postdoctoral fellows, PhD students and Master students who work on clinically-relevant problems. You will become expert in the use of the Scientific Method as well as a range of cutting-edge technologies broadly applicable to biomedical research. Extensive hands-on training will be given in the techniques relevant to your project. The skills you develop during your project will provide strong opportunities to develop a career in regenerative medicine, with the previous graduates from my laboratory now working in academia or industry.

Prerequisites:

Prospective students need to have: a keen interest in regenerative medicine; undergraduate training in either bioinformatics or computer science, life sciences, or medicine; the ability to project manage within a collegial environment with weekly supervisory meetings; and a desire to improve patient treatments.

Dr David Harman

d.harman@westernsydney.edu.au

Project(s) offered:

• The mechanism of action of novel prostate cancer drug c2: Does it inhibit the enzyme hGIIA?

  Co-supervisor: Assoc Prof Kieran Scott (kieran.scott@westernsydney.edu.au)

  Over 3300 men die each year from prostate cancer in Australia, despite improvements in standard of care therapy in recent years. That is on average one man every three hours, 24/7. So there is a need for new therapies to treat advanced prostate cancer.

  We have discovered and developed novel cyclic peptide compounds that target a secreted phospholipase A2 enzyme (hGIIA, Fig. 2) A clinical trial of one of these compounds, c2 (Fig. 1), has been approved to commence shortly at Liverpool Hospital, however its mechanism of action is not fully understood. hGIIA is an epidriver of prostate cancer and inhibition of the enzyme slows cancer cell growth in culture and in xenograft tumour models of both androgen-dependent and castrate-resistant prostate cancer.

  hGIIA regulates the production of lipid mediators, however, the identity of the mediators affected by hGIIA inhibition are not well described. We have recently shown that c2 can block production of the eicosanoid lipid mediators PGE2 and 5-HETE, however, these lipids are not directly metabolised or produced by hGIIA. We know that hGIIA directly converts the lipid mediator phosphatidic acid (PA) to lysophosphatidic acid (LPA, Fig. 3), the only water soluble lipid mediator that is itself a potent growth factor for cancer cells, with high specific activity in vitro.

  Cultured prostate cancer cell lines such as PC-3, LNCaP and Du145 will be treated with either c2 or the known hGIIA inhibitor LY315920 and the concentrations of PA and LPA will subsequently be measured by LC-MS/MS. The results will be compared with that of vehicle only control and conclusions will subsequently be drawn about whether c2 directly affects hGIIA activity in prostate cancer cells.

  Prerequisites:

  This project would best suit researchers interested in cell culture work and instrumental analysis, particularly mass spectrometry.

• Unravelling the mechanism of action of novel prostate cancer drug c2: A native protein electrospray ionisation mass spectrometry study

  Co-supervisor: Assoc Prof Kieran Scott (kieran.scott@westernsydney.edu.au)

  A novel cyclic peptide drug to treat advanced prostate cancer has been recently developed, which is going into a clinical trial at Liverpool Hospital. However, the mechanism of its action is not well understood. The broad aim of this research project is to better understand how drug c2 actually kills cancer cells.

  Evidence exists that there is an interaction between drug c2, the secreted phospholipase A2 enzyme hGIIA, and the protein vimentin, but at present a detailed understanding is lacking. During this project, the researcher will study the interactions in solution of hGIIA, vimentin and c2, using the relatively new technique of native protein electrospray ionisation mass spectrometry. In this technique, an intact and functional protein is dissolved in an aqueous solution of a volatile pH buffer, then infused by syringe into the source of a high resolution mass spectrometer. The resulting positive ion mass spectrum is recorded and consists of a distribution of different charge states. Interactions between proteins, or between a protein and a drug, result in measurable changes to the observed mass spectrum and inform the researcher about the nature of bonding between the species.

  Prerequisites:

  This project would best suit researchers interested in protein interactions and/or instrumental analysis.

• Development of a mass spectrometry-based method for the early diagnosis of atherosclerosis.

  Co-supervisor: Dr Aiden O’Loughlin (A.OLoughlin@westernsydney.edu.au)

  Atherosclerosis, the obstruction of arteries caused by the accumulation of fatty plaque deposits, is the single largest cause of human death worldwide. Despite the serious disease burden presented by this condition, medicine still lacks a simple, cheap, non-invasive test permitting its detection well before symptoms are observed. At present, diagnosis often relies upon angiography, a technique which is expensive, time consuming and imparts a significant radioactivity load to the patient.

  Furthermore, existing technologies only enable detection of the disease in its more advanced stages. In contrast, the development of a new and more sensitive test would enable atherosclerosis to be detected in its early stages, thus providing an opportunity for prevention of acute coronary events, including heart attack. A class of biomarkers which potentially exhibit high specificity for only atherosclerosis have been identified. Micro ribonucleic acids (miRNAs) are short, non-coding RNA molecules containing approximately 20 nucleotides, their function thought to be mainly gene regulation.

  A liquid chromatography/mass spectrometry method to detect and quantify miRNAs has recently been developed, and this method will be applied to this project. The project will be extended by extracting synthetic miRNAs spiked into human blood and confirming their identity and relative quantities by LC-MS/MS.

  Prerequisites:

  This project would best suit researchers interested in medical diagnostics and/or instrumental analysis.

Tara Roberts

Tara.Roberts@westernsydney.edu.au

https://tararoberts.inghaminstitute.org.au/

Project(s) offered:

• Characterisation of drug resistance mutations in lung cancer

  Co-supervisors: A/Prof Therese Becker, Dr Victoria Bray, Dr Wei Chau, Dr Pei Ding.

  Lung cancer is the greatest cause of cancer related death. Approximately 30% of lung cancer occurs in non-smokers, especially the sub type identified by mutations in the epidermal growth factor receptor (EGFR). The mainstay of treatment for these patients is targeted therapies that inhibits EGFR signalling, however resistance to these drugs is almost universal.

  This project will establish cell lines which harbour mutations originally identified from drug resistant patients. These cell lines will then be characterised to determine the role of the individual mutations in drug resistance and whether these mutations could predict which new drug patients will respond to.

Professor Golo Ahlenstiel

(Primary Supervisor)

Dr Scott Read

s.read@westernsydney.edu.au

(Co-Supervisor)

Project(s) offered:

• Using organoid models to better understand liver immunology

  Applications are currently being accepted for a 3 year PhD project in the immunology of Non-alcoholic fatty liver disease (NAFLD) at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of excess fat in the liver, termed steatosis. NAFLD encompasses simple steatosis and its inflammatory state called non-alcoholic steatohepatitis (NASH) which is a core driver of liver cirrhosis, and hepatocellular carcinoma (HCC). This project will focus on the generation of colon and liver organoid culture systems to study the interaction between intestinal immunity and permeability with liver inflammation in NASH.

  Organoids are three dimensional structures grown in vitro from primary tissue that retain the characteristics of their primary source, including self-renewal, organisation, and differentiation. As such, they are an optimal model to study the influence of genetic and environmental factors on disease progression and treatment. Using in vitro co-culture systems, this project will examine the factors that contribute to “leaky gut” in NASH, and how translocating microbes influence liver inflammation.

  In addition to enteric bacterial, fungal and human viruses, this project will contain a unique focus on bacteriophages, and their contribution to chronic immune stimulation in both the gut and liver. This study utilises cutting edge primary cell culture, flow cytometry and molecular biology techniques to discover unknown connections between gut and liver immunity, and will enable a better understanding of inter-organ interactions that contribute to NASH pathogenesis. Applicants should submit their CV and a covering letter, including full contact details of two referees, to Dr Scott Read at s.read@westernsydney.edu.au.

• The role of interferon lambdas in liver inflammation and fibrosis

  Applications are currently being accepted for a 3 year PhD project in the immunology of Non-alcoholic fatty liver disease (NAFLD) at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of excess fat in the liver, termed steatosis. NAFLD encompasses simple steatosis and its inflammatory state called non-alcoholic steatohepatitis (NASH) which is a core driver of liver cirrhosis, and hepatocellular carcinoma (HCC). This project will focus on the role of interferon lambdas (IFN-λs) on the progression of liver inflammation and fibrosis.

  Interferon lambda (IFN-λ) is a central antiviral cytokine in the liver that is elevated in NASH, and that contributes to the progression of liver inflammation and fibrosis. The mechanism of IFN-λ induction, and cells involved however, remain unknown. We hypothesise that microbial ligands originating from the gut, enter the liver in the portal blood and stimulate IFN-λ expression. This project will aim to determine the contribution and identity of intestinal biota that stimulate IFN-λ, the responsive cells, and the mechanisms by which IFN-λ drives liver inflammation.

  We will utilise cutting edge genomics, primary cell culture, flow cytometry and molecular biology techniques to shed some light on the role of IFN-λ in NASH. This study will pave the way for future treatments aimed at halting the progression of inflammation in NASH.

  Applicants should submit their CV and a covering letter, including full contact details of two referees, to Dr Scott Read at s.read@westernsydney.edu.au.

• Understanding immune dysregulation in obesity

  Applications are currently being accepted for a 3 year PhD project in immune dysregulation in obesity at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Obesity is associated with alterations in metabolism, immune function, inflammation and microbiome, however the inter-relationship between these factors remains ill-defined. Blacktown Public Hospital has recently implemented a large healthy weight and bariatric surgical program, which provides the ideal environment to address the poorly understood, but essential aspect of obesity. Samples obtained pre- and post-bariatric surgery will be used to understand how obesity and metabolic syndrome cause immune dysregulation promoting subsequent development of obesity related complications in liver, gut and cardiovascular system.

  National statistics from Australian sources predict that normal-weight adults will constitute less than a third of the population by 2025, and that the prevalence of obesity will have increased by 65%. Bariatric surgery targets individuals with a body mass index (BMI) above 35, and significantly reduces stomach size by resection, diversion or banding. Patients achieve significant weight loss, resolution of diabetic state, improvement in cardiovascular risk factors and reduction in mortality.

  This project will examine the effects of bariatric surgery and subsequent weight loss on systemic, as well as liver and intestinal immune activity and dysregulation. In particular, how rapid weight loss alleviates chronic inflammation and immune exhaustion associated with obesity. Changes in microbiome and intestinal permeability will also be examined with respect to liver inflammation and immunopathology.

  This project will possess a strong clinical and translational focus, relating immune parameters to clinical outcomes. In vitro analysis of immune cell phenotypes will be performed by flow cytometry, RNAseq and primary liver and intestinal cell culture will be used to elucidate pathological mechanisms.

  Applicants should submit their CV and a covering letter, including full contact details of two referees, to Dr Scott Read at s.read@westernsydney.edu.au.

• Achieving sustainable outcomes in obesity

  Applications are currently being accepted for a 3 year PhD project to study the role of interventions based around nutrition, lifestyle, mental health or metabolism to treat obesity and/or fatty liver disease. The project will be conducted under supervision by Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Obesity is a multifactorial condition associated with a high risk for hypertension, dyslipidaemia, Non-Alcoholic Fatty Liver Disease (NAFLD), diabetes mellitus, cardiovascular complications, stroke, obstructive sleep apnea, osteoarthritis, and even cancers. Despite a growing understanding of disease aetiology and advances in pharmacological therapy, obesity rates have quadrupled between 1986-2000. National statistics from Australian sources predict that normal-weight adults will constitute less than a third of the population by 2025, and that the prevalence of obesity will have increased by 65%.

  To cure obesity, long-term weight loss needs to be achieved. While lifestyle interventions can be successful, long-term efficacy results are disappointing. Hence, bariatric Surgery is now considered the most effective modality for sustainable weight loss and for curing co-morbidities. NSW Health has recently invested into the largest publicly funded obesity program in Australia based at Blacktown Hospital that A) provides a multidisciplinary approach to obesity and B) funding for 100 bariatric surgeries per year. Multi-centre ethics covering three large tertiary hospitals and two research centres is approved allowing for longitudinal data collection, biobanking and data linkage.

  This provides an opportunity examine the role of nutrition, lifestyle, mental health or metabolic interventions to achieve long-term sustainable outcomes in obese patient in the context of a multi- and interdisciplinary setting.

  We welcome applicants from a range of backgrounds, that possess research experience and a background in medical/health science/nursing/allied health and/or psychology.

  Contact Prof Golo Ahlenstiel (G.Ahlenstiel@westernsydney.edu.au) to discuss your eligibility, the project requirements and your intention to apply.

• Immune related memory in liver disease

  Applications are currently being accepted for a 3 year PhD project to study the role of immune related memory viral and autoimmune hepatitis at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Immunological memory defines the ability of the immune system to (1) rapidly and specifically recognize an antigen that the body has been previously exposed to and (2) initiate a highly specific immune response. Traditionally, immune related memory is attributed to the adaptive immune response, i.e. T cells and B cells through cytokine release, direct cellular toxicity via antibodies. Natural killer (NK) cells are usually considered part of the innate immune system and considered not to be antigen-specific. However, recent publications suggest that NK cells can, under certain conditions, express memory-like features.

  Using state-of-the-art techniques including flow cytometery and CyTOF in in vitro (organoid) and in vivo models (human and mouse), this projects will examine the role of memory-like NK cells in acute and chronic infection as well as autoimmune context with a focus on liver disease to assess their role in pathogenesis, disease progression in liver disease as well as their therapeutic potential in this context.

  We welcome applicants from a range of backgrounds, that possess laboratory experience and a background in medical/health science and/or molecular biology. In particular, the project is suitable for candidates with strong interests in immunology or liver disease.

  Contact Prof Golo Ahlenstiel (G.Ahlenstiel@westernsydney.edu.au) to discuss your eligibility, the project requirements and your intention to apply.

• Drivers in advanced liver disease

  Applications are currently being accepted for a 3 year PhD project examining the role of inflammation and altered protein metabolism in the context chronic liver disease at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Chronic inflammation and altered protein metabolism caused by infection, alcohol, fat or autoimmune disease not only drive progression to end-stage scarring, a state called liver cirrhosis, but also subsequent chronic liver failure and hepatic decompensation with high liver-related mortality. Various markers have been associated with hepatic decompensation, but it remains ill understood what actually initiates the event and how such markers relate to short and long-term survival.

  This project aims what to clarify how chronic inflammation and altered protein metabolism contribute to disease progression and activity and clinical severity in advanced liver disease using human samples and mouse models. We will utilise cutting edge genomics, primary cell culture, flow cytometry and/or CyTOF as well as molecular biology techniques. This study will identify new biomarkers predicting clinical outcomes and new targets for therapeutic intervention.

  We welcome applicants from a range of backgrounds, that possess laboratory experience and a background in medical/health science and/or molecular biology. In particular, the project is suitable for candidates with strong interests in the immunology of chronic hepatic and gastrointestinal disease.

  Contact Prof Golo Ahlenstiel (G.Ahlenstiel@westernsydney.edu.au) to discuss your eligibility, the project requirements and your intention to apply.

Dr Shameran Slewa-Younan

s.younan@westernsydney.edu.au

Project(s) offered:

• The mental health literacy of refugee populations and cross cultural populations
• Mental Health First Aid with a focus on Culturally and Linguistically Diverse populations
• Mental health promotion programs for refugee populations

Project focus:

Since 2008 Dr Slewa-Younan has undertaken work as a clinical academic on projects examining trauma related mental health disorders in refugees. These include the measurement of psychological and physiological measures of distress, the mental health literacy of refugee populations and more recently mental health promotion programs for those who assist in the resettlement of refugees and refugee communities.

Professor Tim Karl

T.Karl@westernsydney.edu.au 

Project(s) offered:

• Gene-environment interactions in schizophrenia
  
  Schizophrenia is a chronic and disabling mental disorder that affects 1% of the world’s population. A complex interaction of environmental and genetic risk factors appears to be causal for the development of the disease. Preclinical research has been instrumental in advancing our understanding the impact of those risk factors, both in isolation or in combination, on behaviour and brain development.
  
  Our team models schizophrenia by developing multi-factorial mouse models combining genetic and environmental disease risk factors. Genetically predisposed mouse mutants are exposed to disease-relevant environmental factors (e.g. chronic cannabis abuse, poor diet, deprived housing conditions) at critical stages of their development. Our team focuses on the neuro-behavioural characterisation of these models, applying a multitude of different neuro-behavioural phenotyping paradigms. This highly standardised research is necessary to determine disease-relevant interactions and to identify preventative and therapeutic measures for future clinical applications.

Dr Poonam Mudgil

p.mudgil@westernsydney.edu.au

Antimicrobial resistance (AMR) is a serious public health issue around the world. Australia’s recent National Antimicrobial Resistance Strategy emphasizes on reducing antibiotics usage and investigating alternatives to antibiotics in wake of rising drug resistance among bacterial pathogens. The projects given below signify research in this area.

Project(s) offered:

• Antimicrobial properties of tears

  Bacterial ocular infections are significant eye problems and have the potential to cause irreversible ocular damage, corneal ulcers and blindness. These infections are generally treated with topical antibiotics but they can cause systemic side effects which can be serious in paediatric patients.

  Increased usage of antibiotics is also causing drug resistance among bacterial pathogens which is a huge public health challenge. Human tears act as first line of defence for the eye and have complex composition containing various proteins, lipids, mucin and salts. There is a need to recognise the antimicrobial potential of various tear components so that antibiotic independent treatments for eye infections can be devised which can help in reducing antibiotic usage, side effects and drug resistance.

  This project will involve assessing antimicrobials in tears using in-vitro susceptibility assays and determining possible mechanism of action of the effective agent looking at alterations in membrane fluidity and cell wall using Ultra Performance Liquid Chromatography-Mass Spectroscopy, Scanning Electron Microscopy, Transmission Electron Microscopy, and STEM.

  Training for all advanced techniques will be provided, however candidates should have an interest in microbiology/ophthalmology and a background in biological sciences/biomedical sciences.

• Antimicrobial properties of emu oil

  Methicillin resistant Staphylococcus aureus (MRSA), the multidrug resistance bacteria, causes life-threatening infections in humans and is termed as a serious threat to global public health by World Health Organisation. Misuse and overuse of antibiotics is increasing resistance to commonly used antibiotics in these bacteria.

  This necessitates testing compounds that are natural, safe and can help in combating antibiotic resistance. Emu oil, extracted from the fat tissues of Emu birds, has traditionally been used by native Australian Aboriginals to treat wounds, sores, pain and arthritis. Although it is known for its anti-inflammatory properties, its antimicrobial properties are yet to be explored. Emu oil contains oleic acid as the major fatty acid and our previous research has shown oleic acid to be antibacterial against both Gram positive and Gram negative bacteria.

  We have also standardized techniques for studying membrane phospholipid composition and cell wall of MRSA after treatment with antibacterial agents. This project will investigate the antibacterial properties of emu oil against clinical MRSA isolates to explore its potential as an alternative to antibiotics and help in reducing drug resistance in bacteria. Antibacterial effects of emu oil will be tested using in-vitro bacterial susceptibility assays and the mechanism of its action will be determined by studying alterations in membrane integrity and cell wall using UPLC-MS, SEM, TEM, and STEM.

  Training for all advanced techniques will be provided, however candidates should have an interest in microbiology and a background in biological sciences/biomedical sciences.

Dr Iman Hegazi

i.hegazi@westernsydney.edu.au

Project(s) offered:

• Exploring the factors contributing to changes in moral development during medical training

  Medical practice requires the application of knowledge, skills and wisdom.  Wisdom, the best use of available knowledge, is underpinned by moral judgement and experience.

  Medical students need to graduate with the ability to make moral decisions related to patient care and their professional behaviour. During medical training, moral development is influenced by maturity, the formal curriculum and the ‘hidden curriculum’ embedded in experiences and role modelling within clinical settings.

  Understanding the factors that promote, impede or segment moral development in medical students is important for the design of medical curricula and systems of student support and faculty training. Appropriate student support would, in turn, reduce students’ distress and improve their well-being throughout their education and future career. Consequently, this will be reflected in patient care and health outcomes.

  A qualitative approach through individual interviews and focus group discussions (FGD) will allow exploration of the medical students’ insights into their moral development and the effects of their experiences during clinical placements.

Dr Elizabeth O'Connor

E.OConnor@westernsydney.edu.au

Project(s) offered:

• A mixed methods approach to identifying Threshold Concepts in the Pre-clinical years of Medical Education

  The adequate understanding of biomedical sciences is the foundation for scientific reasoning, clinical decision making and practicing medicine intelligently. It has been reported that the depth of knowledge in biomedical sciences has declined since the introduction of learning-in-context and integrated medical curricula.

  There is also evidence suggesting that retention of biomedical sciences tends to decline as students progress in a medical course. An important hindering factor is students' level of understanding of the basic science concepts and the different ways students conceptualise and apply the information. This project aims to identify concepts that are crucial and essential for medical students to learn in order to develop authentic mastery in biomedical sciences, otherwise known as “threshold concepts” (TC).

  A mixed method approach will be employed in this study where information will be extracted from three sources; past assessment results, academic focus group discussions (FGDs) and student FGDs and interviews. The findings will inform curriculum design and planning of the intellectual journey for medical students and will contribute to improving the understanding of fundamental biomedical sciences, the process of scientific inquiry, and the translation of basic science knowledge to clinical practice.

Dr Steven Trankle

s.trankle@westernsydney.edu.au

Project(s) offered:

• Advance care plans (ACPs) have been shown to reduce length of hospital admission; however, studies indicate that family members and health professionals may not know their patient or family’s preferences for end-of-life care.

  Also, cultural differences strongly impact uptake of ACPs. We aim to better understand views of people from culturally and linguistically diverse (CALD) backgrounds in relation to end-of-life care and ACP, and also the challenges and facilitators health professionals encounter in discussing end-of-life issues with them. This knowledge will help us to develop appropriate strategies to promote ACP in different cultures and implement across a range of medical provider contexts.

  An opportunity exists for research into this and associated topics such as organ donation using a multiple methods approach grounded within an appropriate theoretical and epistemological framework.

  Student qualifications: Techniques involved will be in qualitative analysis and inferential statistics. No technical experience is necessary as full training will be provided, however candidates must have an interest in end-of-life care, and a social sciences/medical background.

Professor Golo Ahlenstiel

(Primary Supervisor)

Dr Scott Read

s.read@westernsydney.edu.au

(Co-Supervisor)

Project(s) offered:

• Using organoid models to better understand liver immunology

  Applications are currently being accepted for a 3 year PhD project in the immunology of Non-alcoholic fatty liver disease (NAFLD) at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of excess fat in the liver, termed steatosis. NAFLD encompasses simple steatosis and its inflammatory state called non-alcoholic steatohepatitis (NASH) which is a core driver of liver cirrhosis, and hepatocellular carcinoma (HCC). This project will focus on the generation of colon and liver organoid culture systems to study the interaction between intestinal immunity and permeability with liver inflammation in NASH.

  Organoids are three dimensional structures grown in vitro from primary tissue that retain the characteristics of their primary source, including self-renewal, organisation, and differentiation. As such, they are an optimal model to study the influence of genetic and environmental factors on disease progression and treatment. Using in vitro co-culture systems, this project will examine the factors that contribute to “leaky gut” in NASH, and how translocating microbes influence liver inflammation.

  In addition to enteric bacterial, fungal and human viruses, this project will contain a unique focus on bacteriophages, and their contribution to chronic immune stimulation in both the gut and liver. This study utilises cutting edge primary cell culture, flow cytometry and molecular biology techniques to discover unknown connections between gut and liver immunity, and will enable a better understanding of inter-organ interactions that contribute to NASH pathogenesis. Applicants should submit their CV and a covering letter, including full contact details of two referees, to Dr Scott Read at s.read@westernsydney.edu.au.

• The role of interferon lambdas in liver inflammation and fibrosis

  Applications are currently being accepted for a 3 year PhD project in the immunology of Non-alcoholic fatty liver disease (NAFLD) at Western Sydney University Blacktown and the Westmead Institute for Medical Research. The project will be conducted in the research group of Professor Golo Ahlenstiel and will remain open until a suitable candidate is found.

  Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of excess fat in the liver, termed steatosis. NAFLD encompasses simple steatosis and its inflammatory state called non-alcoholic steatohepatitis (NASH) which is a core driver of liver cirrhosis, and hepatocellular carcinoma (HCC). This project will focus on the role of interferon lambdas (IFN-λs) on the progression of liver inflammation and fibrosis.

  Interferon lambda (IFN-λ) is a central antiviral cytokine in the liver that is elevated in NASH, and that contributes to the progression of liver inflammation and fibrosis. The mechanism of IFN-λ induction, and cells involved however, remain unknown. We hypothesise that microbial ligands originating from the gut, enter the liver in the portal blood and stimulate IFN-λ expression. This project will aim to determine the contribution and identity of intestinal biota that stimulate IFN-λ, the responsive cells, and the mechanisms by which IFN-λ drives liver inflammation.

  We will utilise cutting edge genomics, primary cell culture, flow cytometry and molecular biology techniques to shed some light on the role of IFN-λ in NASH. This study will pave the way for future treatments aimed at halting the progression of inflammation in NASH.

  Applicants should submit their CV and a covering letter, including full contact details of two referees, to Dr Scott Read at s.read@westernsydney.edu.au.