Prince of Wales Medical Research Institute (POWMRI) Honours Projects
Dr J Brown
Project: Variations in lumbosacral, pelvic and abdominal geometry with aging. The lap portion of a motor vehicle seat belt is designed to work by anchoring the belt to the anterior superior iliac spines (ASIS) of the pelvis. Variations in lumbosacral and pelvic geometry will influence how well a seat belt achieves its purpose in a crash, and will also influence mechanisms of crash induced lumbar and abdominal injury. The performance of seat belts and other safety systems in protecting occupants are assessed using human surrogates, like crash test dummies. The objective of this work would be to retrospectively assess lumbosacral, pelvic and abdominal geometry using medical images across a range of ages and compare this to the construction of existing families of crash test dummies. This project is the first stage of a planned longer term prospective study of seated anthropometry. The results will have real world implications for both the assessment of vehicle safety technologies and broader ergonomic applications.
Dr C Dobson-Stone
Project 1: Analysis of a frontotemporal dementia – motor neuron disease (FTD-MND) protein. This project will identify proteins that bind to a protein that is involved in FTD-MND and other neurodegenerative disorders. This will help to shed light on the role(s) that this molecule plays in normal biological processes and disease pathogenesis. The project would be suited for people who are interested in gaining experience in molecular biology techniques such as Western blotting and fluorescent microscopy
A/Prof K Double
Project 1: Copper changes in Parkinson’s disease This project examines copper transport proteins in Parkinson’s disease and healthy brains to investigate how recently identified decreases in brain copper levels result. Skills learnt: immunohistochemistry, immunofluorescence, microscopy, Western blotting and statistical analysis.
Project 2: Stem cell changes in Parkinson’s disease This project investigates new cell birth in an animal model to determine if decreased neurogenesis results from Parkinson’s per se or from PD medications. Skills learnt: animal surgery, behavioural analyses, immunofluorescence, microscopy and statistical analysis.
Project 3: Is L-DOPA treatment toxic to the brain? This project utilizes an animal model to investigate the effects of L-dopa treatment on protein structure and brain cell survival. Skills learnt: animal surgery, animal behavioural analyses, immunofluorescence, microscopy and statistical analysis.
Dr R Fitzpatrick / Dr S Lord
Studies of human balance and voluntary and reactive stepping responses. This is sensorimotor physiology, psychophysics and behavioural research involving young and old people. This project would suit a student who is very interested in functional anatomy and neurophysiology.
Dr J Fullerton
Bipolar disorder is a relatively common and severe psychiatric disorder, which has a genetic basis. The project will involve investigating and identifying the genetic cause of bipolar disorder, using molecular genetic techniques including genotyping by PCR, gene association and gene expression. The project would suit students interested in human genetics.
Prof G Halliday
Projects on Lewy body diseases
Project 1: This study will screen DNA samples of autopsy-confirmed Lewy body dementia cases for gene mutations in a-synuclein (the non-amyloidogenic homolog of a-synuclein) and glucocerebrosidase (a lysosomal enzyme), as well as assess whether genetic variation in apolipoprotein E, a-synuclein and tau affect the degree of dementia-related pathologies. Families with sufficient members for linkage analysis will also be identified. Skills learnt: DNA extraction from blood and brain tissue, polymerase chain reaction and other methods for detecting genetic variation, assessment of familial inheritance patterns, statistical associations.
Project 2: This study will examine lysosomal pathology in Lewy body disease. For this the distribution of a number of lysosomal proteins, including cathepsin B, LAMP-2, GM2 ganglioside, glucocerebrosidase, ATP13A2 (which has recently been linked to PARK9) and a-synuclein and phosphorylated epitopes of a- and a-synuclein will be assessed in cases of Lewy body disease. Skills learnt: brain tissue processing, in situ immunohistochemistry, Western immunoblotting and quantitation, statistical associations.
Project 3: Our previous studies have shown that inflammatory molecules are necessary for cell death in Parkinson’s disease. This study will determine whether serum IgG identifies vulnerable cells and inflammatory mediators associated with IgG deposition in Parkinson’s disease. Skills learnt: blood and brain tissue processing for protein extraction and histological assessment, in situ immunohistochemistry, ELISA Mulitplex assay and quantitation, statistical associations.
Projects on frontotemporal dementia
Project 4: Degeneration of the posterior cingulate gyrus has been shown to be critical for the clinical expression of Alzheimer’s disease. This study will quantify using stereological methods the extent of neuronal degeneration in the posterior cingulate gyrus of frontotemporal dementia cases. The results will be compared with those already collected in Alzheimer’s disease and Lewy body dementia.
Project 5: There are no previous large studies of the neuropathology characterising Pick body disease, a form of frontotemporal dementia. We have identified a large sample for characterisation and comparison with the most common form of frontotemporal dementia with TDP-43 deposition.
Project 6 – Changes indicative of disturbed hypothalamic function occur early in frontotemporal dementia, including changes in eating habits, disruption of circadian rhythm and sleep changes. This project will determine whether there is substantial hypothalamic pathology in frontotemporal dementia using stereological methods.
Skills learnt for Projects 4-6: brain tissue processing, in situ immunohistochemistry, neuropathological assessment, stereological quantitation, statistical associations.
Dr P McNulty
Project 1: Little is known about the physiological mechanisms of motor recovery after stroke. This project will study motor control after stroke during low-level voluntary muscle contractions either during a constant force output, or during a dynamic task. Most daily activities like holding a telephone, fork or shopping critically depend on these types of contractions. Skills Learnt: recordings of muscle activity (using both global and single motor unit electromyography), joint range of motion, sensory thresholds, level of spasticity.
Project 2: Virtual reality is increasingly being used in many areas of rehabilitation including stroke. The aim of this project is to develop a cheap virtual reality game system for stroke rehabilition. For this system handsets will have extra weight and require a predetermined level of force before they are activated. You will be responsible for teaching stroke patients how to use the virtual reality system in the laboratory, assessing their motor function before they begin therapy and afterwards, and monitoring their training achievements and progress. Skills Learnt: physiological recording, analysis and interpretation.
Prof C Rae
Studies investigating the relationship between brain biochemistry and brain function using a range of approaches but most commonly neuroimaging (MRI). Example projects include:
Project 1: Alcohol and brain systems neurochemistry. Alcohol acts at the GABA-A receptor in the brain and may have numerous, other sites of non-specific activity. This project will use neurochemistry, NMR spectroscopy and metabolomics to classify the different effects of alcohol on brain metabolism and identify the mechanisms of its action.
Project 2: Binge drinking and brain development in adolescence. Adolescence is a critical period for development of the brain, particularly the frontal lobe. Alcohol consumption, particularly when consumed in a “binge” has been shown to alter behaviour and cognition but there are few studies extant on the effect of teenage binge drinking on brain morphology, connectivity and function. This project will examine the effect of binge drinking in 16-17 yo subjects using a combination of magnetic resonance imaging (MRI) approaches, questionnaires and cognitive tests. It aims to give us hard evidence one way or the other for the effect of alcohol on brain development in both males and females.
Dr C Shepherd
Project 1: Alzheimer’s disease (AD) is characterised at post-mortem by abnormal protein deposition along with significant neuronal loss and inflammation. Previous studies have shown that the neuronal loss correlates most closely with the clinical symptoms and is closely associated with inflammation. The precise role of inflammation in the disease process is not understood. Under normal circumstances the inflammatory response is transient and reparative, however, under conditions of chronic activation, such as that which occurs in AD, the inflammatory response may itself be damaging. Understanding the stimulators, mediators and downstream neurotoxic effects of inflammation will be the focus of this research project.