Department of Pharmacology Honours Projects
Dr T 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 E 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.
Prof R Day / A/Prof K Williams (Clinical Pharmacology St. Vincent’s Hospital)
Optimising drug therapy for patients suffering with diabetes, pain and disability in musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, gout and chronic pain states. Areas of investigation include individualising therapy based on a patient’s characteristics e.g. pharmacokinetic and pharmacogenomic variables; pharmacodynamic mechanisms; new chemical entity testing; combination drug therapy investigation.
Project 1: Pharmacotherapy of gout: epidemiology, drug usage, therapeutic drug monitoring, optimization of dosing with hypouricaemic therapies.
Project 2: Pharmacotherapy of type II diabetes with focus upon metformin: epidemiology, drug usage, therapeutic drug monitoring, optimization of dosing to avoid toxicity especially in renal impairment.
Project 3: Effectiveness of decision support to improve prescribing quality and safety
Project 4: Studies on the mechanisms of action of paracetamol.
Project 5: Opioids in chronic non-malignant pain: therapeutic drug monitoring, dose optimisation
Project 6: Optimisation of drug therapy with clozapine in mental illness for effectiveness and safety
Dr A 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.
Prof G Graham
Project 1: The mechanism of action of paracetamol and related phenolic compounds. Research techniques include the measurement of the effects of the drugs on the synthesis of prostaglandins and hypochlorous acid by intact cells and isolated enzymes.
Project 2: Clinical pharmacokinetics of anti-HIV drugs, allopurinol and peptide inhibitors of secreted phospholipase A2. Research techniques include the analysis of the drugs and their metabolites in plasma and urine and the computerised fitting of the data by pharmacokinetic models and functions.
Dr R 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 R 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 G Guillemin
Project 1: Characterisation of the kynurenine pathway & NAD metabolism in adipocyte. Co supervised with Dr Ross Grant (UNSW, Pharmacology) Project 2: Does drinking red wine fortified with a natural stimulant affect serum oxidative stress markers and NAD metabolism: A prospective study. Co supervised with Dr Ross Grant (UNSW, Pharmacology) Project 3: Effects of kynurenine pathway metabolites on amyloid beta production by human neurons. Relevance for Alzheimer’s disease. Project 4: Effects of quinolinic acid on inflammatory mediator production by human macrophages and microglia. Project 5: Effects of different interferons on IDO1, IDO2 and TDO expression in human brain cells and macrophages Project 6: Effects of kynurenine pathway metabolites on blood brain barrier cohesion. (in Collaboration with Sydney University) Project 7: Characterization of the C Type lectin receptors in human brain cells. Relevance for HIV infection. Project 8: Characterization of the kynurenine pathway in human platelets and red blood cells. Project 9: Characterization of the kynurenine pathway in choroid plexus cells. Project 10: Effects of quinolinic acid on p53 gene expression in human brain cells. Relevance for the development of brain tumor.
Prof P Gunning
Project 1: Development of anti-cancer drugs which target the cytoskeleton.The project will test the ability of these drugs to induce cell death in tumour cell lines and identify the underlying mechanism of action.
Project 2: 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: will include FACS analysis, cell culture, Western blotting, immunohistochemistry, live cell imaging, siRNA directed gene silencing, gene transfection.
Dr N 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 L Liu
Project 1: Novel tachykinins in human intestinal function and inflammation. Tachykinins released from enteric nerve system regulate gastrointestinal (GI) motility, secretion, and immune function. The newly discovered tachykinins, hemokinin and endokinins from non-neuronal sources provide a new mechanism in the regulation of intestinal inflammation. In this project, we will characterize and localize novel tachykinin in human colon and investigate their impact on intestinal inflammation.
Project 2: Interactions between prostaglandins and human enteric nervous system. The aims of the project are to characterise prostaglandin receptors in human colonic neuromuscular tissue; to establish expression profiles of receptors and prostaglandin synthases, and to determine whether changes in expression occur with intestinal diseases.
Skills learnt: Real time PCR, immunohistochemistry, confocal microscopy, isolated organ pharmacology, radioligand binding, and radioimmunoassay.
Prof M 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 L 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.
Dr S 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.