Department of Pharmacology Honours Projects

Dr Trudie Binder
Project: Peripheral opioids in chronic and acute inflammatory pain. Peripheral inflammation leads to an increase in the synthesis of opioid receptors and hence receptor up regulation as well as increased opioid analgesic efficacy during inflammatory pain. This project utilizes a rat model of inflammation to assess peripherally mediated opioid analgesia and potential mechanisms that can enhance opioid efficacy.
Skills Learnt: Animal handling and behavior monitoring, paw pressure thresholds (analgesymeter), clinical scoring [radiography and histopathology], immunohistochemistry.

Prof Elizabeth Burcher
Work in collaboration with Dr Lu Liu and Dr Kylie Mansfield studies the involvement of the nervous system in the intestine and the bladder. Current research is targeted towards the involvement of the bladder lining (the urothelium) in normal and abnormal function of human and pig bladder. Techniques to study neurochemical and receptor changes in healthy and diseased human tissues include quantitative RT-PCR, isolated organ pharmacology, radioligand binding, autoradiography and confocal immunohistochemistry.
Project 1: Role of neurochemicals including ATP,  in the bladder urothelium
Skills Learnt: Quantitative RT-PCR, isolated organ pharmacology, radioligand binding, autoradiography and confocal immunohistochemistry.

Dr Angela Finch
Project 1: Design and development for selective modulators of the alpha1D adrenergic receptor. Newly designed and synthesised compounds will be tested to determine their affinities, efficacy and selectivity for the alpha1D adrenergic receptor.
Project 2: The role of key structural regions in the expression and function of adrenergic receptors . This study is examining mechanisms that control the activation and expression of adrenergic receptors.
Project 3: The regulation of prostate cancer proliferation by biogenic amines. This study is examining the ability of agonist and antagonsits of a1-adrenergic and 5-HT receptors to effects the proliferation of prostate cancer cells
Skills Learnt: Cell culture, Western blotting, receptor binding assays, receptor signalling assays, mutagenesis, PCR.

Dr Ross Grant
Characterisation and Modulation of NAD Metabolism in Health and Disease: NAD is well known as an important cofactor for a range of metabolic activities vital for energy (ATP) production. However it has recently become known that NAD is also a requisite substrate for essential DNA repair processes and gene signalling; essential elements of a cells resistance to, and recovery from, oxidative stress and DNA damage.
Project 1: Assess the relative production of all KP metabolites produced form C13 labelled tryptophan using LC-MS/MS in unstimulated and IFN-g stimulated brain cells (astrocytes, neurons, microglia, oligodendroctyes).
Project 2:Changes in NAD(H) levels in exercise: implications for aerobic fitness and tissue repair. Co supervised with Dr David Bentley (Exercise and Exercise Science)
Project 3: Investigation of the effect of altered NAD levels on DNA repair and survival in fibroblasts & keratinocyts (skin) cells following oxidative and U.V. damage. Co-supervised with Dr Gilles Guillemin (CFI, St Vincent’s Hospital), Dr Christian Khalil (Risk & Safety Science).
Project 4: Characterisation of the kynurenine pathway & NAD metabolism in adipose (fat) tissue. Co supervised with Dr Gilles Guillemin (CFI, St Vincent’s Hospital)
Project 5: Does drinking red grape juice (or red wine) fortified with a natural stimulant affect serum oxidative stress markers and NAD metabolism: A prospective study. Co-supervised with Dr Gilles Guillemin (CFI, St Vincent’s Hospital)

A/Prof Renate Griffith
Design and synthesis of subtype selective modulators of a₁-adrenergic and of 5HT₁ serotonergic receptors.
Projects 1 and 2 in collaboration with Dr A Finch and Dr N Kumar (School of Chemistry) :
Project 1: is a computer-aided drug design project and will introduce the student to a variety of contemporary techniques: homology modelling, docking, pharmacophore development and database mining.
Project 2: is a synthetic chemistry project and would suit a student with an interest in both medicinal chemistry and pharmacology.
Depending on the interests and background of the student(s), collaborative projects under the joint supervision of all three academics are also available, combining computer-aided design with some synthesis and some pharmacological characterisation.
Project 3: Design of HIV-1 reverse transcriptase inhibitors with a novel mode of action. This computer-aided drug design project will introduce the student to a variety of contemporary techniques: docking, molecular dynamics simulations, pharmacophore development and database mining.

Dr Gilles Guillemin
The catabolism of the essential amino acid tryptophan (via the kynurenine pathway) is involved in the neuropathogenesis of several major neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, motor neuron diseases and brain tumour. We are trying to characterize and understand tryptophan catabolism in these diseases and develop new therapeutic strategies.
Project 1: Characterization of the kynurenine pathway in choroid plexus cells.
Project 2: Characterization of the kynurenine pathway in human platelets.
Project 3: Production of Heat shock protein by human brain cells treated with the neurotoxin quinolinic acid.
Project 4: Characterisation of quinaldic acid production by human brain cells.
Project 5: Effects of different interferons on IDO1, IDO2 and TDO expression in human brain cells and macrophages.
Project 6: Effects of quinolinic acid on p53 gene expression in human brain cells. Relevance for the development of brain tumor.
Project 7: Screening of natural inhibitor for IDO-1 and KMO in human macrophages
Project 8: Effects of quinolinic acid on the production of inflammatory mediators by human macrophages and microglia.
Project 9: Characterization of the C Type lectin receptors in human brain cells. Relevance for HIV infection.
Project 10: Characterisation of the kynurenine pathway in human adipocyte.
Project 11: Effects of quinolinic acid on ubiquitination in human brain cells
Skills Learnt (≠ between projects): Primary cultures of human brain and/or blood cells, immunocytochemistry, microscopy, quantitative PCR, Western blot, HPLC, Mass spectrometry, enzymology.

Prof Peter Gunning / Dr Justine Stehn / Dr Galina Schevzov
Project 1: Development of anti-cancer drugs which target the cytoskeleton of melanoma cells. The project will test the ability of these drugs to induce cell death in melanoma tumour cell lines and identify the underlying mechanism of action.
Skills Learnt: FACS analysis, cell culture, Western blotting, immunohistochemistry, microscopy, live cell imaging, luciferase assays.
Project 2: Characterisation of a new class of anti-actin chemotherapeutic compounds for the treatment of colon cancer. The project will characterise the actin cytoskeleton of a panel of colon cancer tumour cell lines and test the efficacy of the compounds in inducing tumour cell death.
Skills Learnt: FACS analysis, cell culture, Western blotting, immunohistochemistry, live cell imaging, microscopy, siRNA directed gene silencing, High Content Imaging, Image software analysis.
Project 3: Identification of cytoskeleton drug targets for anti-cancer therapy. The project will use genetic manipulation of components of the cytoskeleton to evaluate their role in cancer cell growth.
Skills Learnt: FACS analysis, cell culture, Western blotting, immunohistochemistry, live cell imaging, microscopy, siRNA directed gene silencing, gene transfection.
Project 4: Drug optimisation of compounds which target the cytoskeleton of tumour cells. The project will test the correlation between the effectiveness of anti actin compounds and their impact on the cytoskeleton of neuroblastoma tumour cells.
Skills Learnt: FACS analysis, cell culture, Western blotting, immunohistochemistry, live cell imaging, microscopy, High Content Imaging, Image software analysis.
Project 5: Examining the function of the cytoskeleton in tumour cell death. The project will investigate the role the cytoskeleton of tumour cells plays in chemotherapeutic induced cell death or apoptosis.
Skills Learnt: FACS analysis, cell culture, Western blotting, immunohistochemistry, microscopy, live cell imaging, luciferase assays.

Dr Nicole Jones
Project 1: Can preconditioning with hypoxia stimulate cell proliferation after a brain injury? This study will look at whether hypoxic preconditioning can induce changes cell proliferation (neurogenesis, gliogenesis and angiogenesis) after an ischemic brain insult.
Skills Learnt: Small animal surgery, histology, immunohistochemistry, microscopy, data analysis.
Project 2: Neuroprotective roles for HIF-1 in primary cultures of neurons and astrocytes. This study will examine the potential protective roles for HIF-1, its regulatory enzymes and target genes in primary astrocyte and neuronal cultures.
Skills Learnt: Primary tissue cultures, immunocytochemistry, microscopy, cell viability assays, data analysis.
Project 3: Does maternal obesity affect ischemic brain injury in offspring? (co-supervised with Professor Margaret Morris). This study aims to determine whether maternal obesity can exacerbate brain injury in offspring and will examine molecular processes involved.
Skills Learnt: Small animal surgery, histology, immunohistochemistry, PCR, western blotting, data analysis.

Dr Lu Liu
Chronic constipation is a functional disorder of the gastrointestinal tract, affecting up to 34% of the population. Slow transit constipation (STC) is a severe motility disorder with unknown aetiology. STC occurs predominately in reproductive-age women and effective therapies for STC have been hindered by a lack of understanding of its aetiology. Our recent exciting research results have suggested that colonic mucosal abnormality may contribute to intestinal dysmotility. The overall aim of our study is to reveal the role of the mucosa in the pathophysiology of STC and other motility disorders of the colon.
Project 1: Effects of progesterone and oestrogen on the expression of connexin proteins in the colonic muscle and mucosa.
Project 2: Role of endocannabinoids in the pathogenesis of colonic dysmotility.
Skills Learnt: Real time PCR, cell culture, immunohistochemistry, organ bath pharmacology, bioluminescence detection of cellular ATP release.

Prof Margaret Morris
Project 1: How does maternal obesity influence offspring obesity risk? This study aims to determine the effects of maternal obesity on expression of key metabolic markers in offspring, and investigate strategies for intervention.
Skills Learnt: Animal handling, dissection, histology, PCR for mRNA , data analysis
Project 2: Stress and Obesity. Early trauma contributes to psychosocial disorders later in life, and palatable food dampens stress responses. This project will examine the effect of palatable cafeteria high-fat diet on behavioural responses following early life stress in the rat.
Skills Learnt: Animal handling, dissection, behavioral testing, PCR for mRNA, data analysis

Dr Shaun Sandow
Project: 'How cells in arteries communicate'. Arteries consist of two main cell types; endothelial cells and smooth muscle cells. These cells communicate with each other by chemical and electrical signalling, with sites for this signalling being altered in diseases such as diabetes and obesity. This project will identify signalling pathways that are altered in vascular disease.
Skills Learnt: Animal handling, fine dissection, immunohistochemistry, Western blotting, isolated artery pharmacology, calcium imaging.

A/Prof Larry Wakelin
The design and synthesis of novel intercalating and alkylating agents that bind to DNA and inhibit DNA replication, poison topoisomerases and antagonise transcription. The work involves chemical synthesis, evaluation of DNA-drug interactions by using NMR spectroscopy, X-ray crystallography, mass spectrometry, spectrophotometry, gel electrophoresis, and DNA sequencing methods, and the measurement of cytotoxicity towards cancer cells in culture, together with biochemical studies of the poisoning of topoisomerases and the inhibition of transcription.

Department of Clinical Pharmacology & Toxicology, St. Vincent’s Hospital

For a pdf list of projects and contact details, please click here.

Prof Ric Day / Dr Melissa Baysari
Project: Antibiotic Stewardship. Background: Improper antibiotic use -> drug-resistant bacteria and adverse drug reactions; Antibiotic stewardship programs (ASP) in hospitals aim to encourage judicious use; Guidelines, formulary restrictions, and audits may improve ASP. Objectives: to identify facilitators and barriers to compliance with antibiotic guidelines; to recommend remedies. Methods: Semi-structured interview of prescribers and pharmacists and microbiologists; Testing remedial interventions e.g. educational programs.

Prof Ric Day / Dr Wendy Lipworth
Project: A critical look at Drug Development. Background: Globalisation of drug development (DD) -> trend towards conducting trial in developing countries; Changing scientific paradigms-> emphasis on pharmacogenomics and ‘personalised medicine’; Commercialisation of DD -> commercial imperatives and close academic-commercial relationships. Outline of Project: How medicines are discovered, tested, regulated and/or translated to clinical practice. Focus: Globalisation; Changing scientific paradigms; Commercialisation; Subsidisation through the Pharmaceutical Benefits Scheme (PBS); Production and uptake of clinical practice guideline; Other critiques of drug development.

Prof Ric Day / A/Prof Ken Williams / Dr Melissa Baysari
Project: Electronic Decision Support in Hospital Prescribing. Background: Prescribed Drugs for Hospitalised Patients - Old system -> Paper charts; New system -> Electronic prescribing - Orders legible; Reduced medication errors; Electronic decision support available;.E.g. Drug information, interactions, directed advice. Objectives: Improve the utility of electronic prescribing. Methods: Interviewing doctors - Opinions and perceptions, Observation of doctors prescribing in clinics and hospital wards (shadow observation), Target use of selected drugs.

Prof Ric Day / A/Prof Ken Williams / Prof Garry Graham / Dr John Ray
Project: Clinical Pharmacokinetics. Background: Many drugs have highly variable pharmacokinetics; Response and toxicity also highly variable and dependent upon individual pharmacokinetics; Optimisation of dosage difficult. Drugs studied: Allopurinol (gout), Metformin (antidiabetic), Itraconazole (antifungal), Clozapine (antipsychotic). Methods: Clinical - patient recruitment, blood collections; Analytical - chromatography (HPLC), DNA extraction and genetic analysis (SNP); Data Analysis - computerised PK modelling, simulations and optimising dosing, correlations with patient response.

Prof Garry Graham
Project 1: Effect of Paracetamol on Myeloperoxidase. Background: Paracetamol - major analgesic drug; Myeloperoxidase - enzyme of neutrophils; Myeloperoxidase produces HOCl - tissue oxidant; Myeloperoxidase present in atherosclerotic lesions; Paracetamol is substrate and inhibitor of myeloperoxidase; Paracetamol may decrease atherosclerosis; Interactions of paracetamol analogues withmyeloperoxidase? Methods: Enzyme assay; Chromatography - HPLC, UV spectroscopy; Nuclear magnetic resonance spectroscopy; Statistical analysis.