Physiology

Immunomodulatory therapy for preterm brain injury

Supervisor

Associate Professor Mhoyra Fraser

Discipline

Physiology

Project code: MHS030

Brain injury as a consequence of oxygen deprivation while in utero or at birth is very common in premature infants. In addition to its contribution to mortality, it can lead to devastating lifelong effects on neurodevelopment, with increased risks of cerebral palsy, mental retardation, and cognitive deficits. Currently, no effective therapeutic strategies are available to prevent or improve the outcome of preterm infants with brain injury.

Our studies using a well-established animal model of preterm brain injury suggest for the first time that delivery to the brain of a therapy that manipulates a critical endogenous neuroprotective anti-inflammatory mechanism can reduce damage to specialised cells, called oligodendrocytes, which produce a fatty substance called myelin that electrically insulates neurons enabling efficient transmission of electrical brain waves.

These findings suggest that it is possible to preserve these myelin-producing cells by supporting natural pathways in the brain. This summer studentship project will seek to establish whether this therapy will have a sustainable long-term effect on survival of these myelin-producing oligodendrocyte cells following injury and improve recovery of brain waves. The project ideally suits students with a strong background in neuroscience and physiology who are considering undertaking an Honours or a MSc project.

Skills:
• Analysis of physiological data
• Immunocytochemistry and immunofluorescence analysis
• Data collection and statistical analysis
• Literature review
• Report writing
• Presentation of results

Preventing the sensitization of the cardiac sensory afferent in heart failure

Supervisor

Carolyn Barrett

Discipline

Physiology

Project code: MHS066

We propose a novel approach for the treatment of heart failure, targeting receptors found on the sensory nerves in the heart. We hypothesize that preventing the sensitization of the cardiac sensory nerves in response to cardiac ischemia will prevent the reflex activation of sympathetic activity and thus ameliorate the progression of heart failure. The aim of this project will be to establish a protocol for blocking the activation of the cardiac sensory afferents.

Skills taught will include small animal surgery, data acquisition and analysis, as well as report writing.

This project will best suit a student with a strong cardiovascular background, ideally having completed MEDSCI 311.

Beyond the diffraction limit: super-resolution imaging of the transverse tubules in heart failure

Supervisor

Dr David Crossman

Discipline

Physiology

Project code: MHS038

The transverse tubules are cylinder-shaped extensions of the plasma membrane, approximately ~300 nm in diameter, that penetrate deep into the cardiac myocyte allowing rapid cell wide propagation of the electrical signal that synchronises contraction. The disorganisation of the transverse tubule network is thought to be a major contributor to the loss of contractility in heart failure. Previous analysis of transverse tubule structure has predominately utilised diffraction-limited confocal microscopy with a resolution limit of ~300 nm. Diffraction limit is the theoretical limit to light microscopy that is proportional to the wavelength of light. However, recent advances in optics have led to the development of super-resolution light microscopes that break this limit. In this project super-resolution microscopy, with 10 fold improvement or 30 nm resolution, will be used to characterise changes in transverse tubule structure in order to provide an understanding of the remodelling process at nano-scale that contributes to the pathology of heart failure.

Finding new drug treatment targets in hypertension

Supervisor

Dr. Rohit Ramchandra

Discipline

Physiology

Project code: MHS008

Hypertension is associated with considerable morbidity and mortality. It is the leading risk factor for death and disability-adjusted life-years lost and accounts for 9.4 million of the 17 million cardiovascular-related deaths worldwide each year. Despite the astounding statistics, hypertension remains poorly treated. Globally, less than 60% of those with hypertension achieve adequate BP control which equates to one billion people with uncontrolled hypertension. Thus new treatment targets are urgently needed for this disease.

The aim of this summer studentship is to further establish the role of the carotid body chemoreceptors in mediating hypertension in a large animal model of hypertension. Recent studies have indicated that the carotid body chemoreceptors may be a viable target in hypertension but most studies to date have been carried out in rodent models. Using a large animal model will enable preclinical translational studies to be carried out which have more relevance to the clinical condition.

This project will introduce the student to a number of experimental techniques in conscious animals. Preference will be given to students who WANT to continue on with an Honours or a Masters project.

Skills that will be taught and mentored through this studentship include;
• Literature review writing skills
• Surgical skills (assisting)
• Collection of physiological data in conscious animals
• Analysis of data
• Oral presentation skills

Every breath you take; does your sinus node quake?

Supervisor

Dr. Rohit Ramchandra

Discipline

Physiology

Project code: MHS009

Heart rate fluctuates with breathing. This variability is prominent at birth and exaggerated in elite athletes. As we age, this variability is reduced and is lost with the development of heart disease. Recent studies suggest that the changes in intra-thoracic pressures during the act of respiration have differential effects on the left and right sides of the heart. We will utilise a large animal model to explore changes in left and right heart dynamics during the act of breathing. The consequences of this for perfusion of different organs will be explored.

This project will introduce the student to a number of experimental techniques in conscious animals. Preference will be given to students who WANT to continue on with an Honours or a Masters project.

Skills taught and mentored during this studentship include;
• Literature review writing skills
• Surgical skills (assisting)
• Collection of physiological data in conscious animals
• Analysis of data
• Oral presentation skills

Optimizing Anaesthesia for Reperfusion Therapy in Ischemic Stroke - a Preclinical Study

Supervisor

Fiona McBryde
Julian Paton

Discipline

Physiology

Project code: MHS051

Stroke occurs because of a catastrophic failure of blood flow to part of the brain. Clinicians at Auckland City Hospital are world leaders in the revolutionary technique of endovascular clot retrieval, where a blood clot is physically removed from the brain to allow reperfusion of damaged tissues, with vast benefits to patient recovery. A pressing question remains about which anaesthesia is best during this reperfusion procedure. This project will examine the impact of anaesthesia choice on the recovery from ischemic stroke, using an animal model. This project is part of a research stream funded by the Health Research Council, and will be conducted in direct collaboration with clinical colleagues in the Departments of Neurosurgery and Anaesthesia at Auckland City Hospital.

Techniques and Skills:
• Long-term recording of blood pressure and brain blood flow
• Work with a model of experimental stroke
• Behavioural testing to assess the recovery after stroke
• Histology
• Data analysis
• Scientific writing

The CerebroVascular Research Lab is part of the Cardiovascular Autonomic Research Cluster in the Department of Physiology. We are a friendly and supportive team with a diverse range of research skills and interests into various cardiovascular diseases.

Interested students should email us directly with a copy of their academic transcript. Preference will be given to students with a genuine interest in further postgraduate study.

Protecting blood flow to the brain in health and disease

Supervisor

Fiona McBryde
Julian Paton

Discipline

Physiology

Project code: MHS052

The brain is completely reliant on a constant supply of blood and oxygen to maintain normal function. We believe that when brain blood flow is low, the ‘selfish’ brain demands high blood pressure to the rest of the body to protect its own blood supply. We have developed a novel approach that allows us to directly measure the pressure-flow relationship in conscious subjects, and assess whether the hypertensive brain is less able to protect itself from low blood flow.

Skills Taught
• Long-term recording of blood pressure and brain blood flow
• Infusions of various drugs to assess the autonomic nervous system control of brain blood flow
• Histology
• Data analysis
• Scientific writing

The CerebroVascular Research Lab is part of the Cardiovascular Autonomic Research Cluster in the Department of Physiology. We are a friendly and supportive team with a diverse range of research skills and interests into various cardiovascular diseases.

Interested students should email us directly with a copy of their academic transcript. Preference will be given to students with a genuine interest in further postgraduate study.

The 'Forgotten' Circulation - targeting the venous system to treat hypertension.

Supervisor

Fiona McBryde
Julian Paton

Discipline

Physiology

Project code: MHS053

Treatments for cardiovascular disease have overwhelmingly focused on the heart and arterial circulation. The venous circulation is a thin-walled, low pressure system which contains the majority of our blood volume. Venous blood can be actively mobilized into the arterial circulation by constriction of the veins, which encourages venous return to the heart and drive increases in cardiac output and arterial blood pressure. Little is known about the neural regulation of the venous system in health OR disease, and we propose to assess whether targeting the venous circulation could be therapeutic in hypertension.

Skills and Techniques:
• Long-term recording of arterial and venous pressures
• Working with an animal model of hypertension
• Histology
• Data analysis
• Scientific writing

The CerebroVascular Research Lab is part of the Cardiovascular Autonomic Research Cluster in the Department of Physiology. We are a friendly and supportive team with a diverse range of research skills and interests into various cardiovascular diseases.

Interested students should email us directly with a copy of their academic transcript. Preference will be given to students with a genuine interest in further postgraduate study.

Can we improve therapeutic hypothermia for babies with perinatal brain damage?

Supervisor

Guido Wassink

Discipline

Physiology

Project code: MHS094

Perinatal brain damage from hypoxia-ischaemia (i.e. oxygen deprivation) around birth is a significant contributor to death and neurodevelopmental disabilities in term babies. Therapeutic hypothermia is now standard-care treatment for these injured newborns, but its neuroprotection is partial. Thus, numerous babies still die or survive with debilitating handicaps. Recombinant human erythropoietin (rEpo) can protect neurons and white matter after hypoxia-ischaemia, but it is unclear whether rEpo can further improve hypothermic protection. This project will investigate whether combo-treatment with rEpo and hypothermia provides better protection for white matter than hypothermia alone.

For this summer studentship, immunohistochemistry, microscopy and cell quantification will be used to determine immature and mature oligodendrocyte cell survival and the degree of inflammation in white matter tracts of the near-term brain after prolonged hypoxia-ischemia, following combination treatment with rEpo and hypothermia, either intervention alone, or no treatment. This research will advance knowledge on rEpo as a potential neurotherapeutic for hypoxia-ischaemic brain damage.

Please send a CV and academic transcript if interested.

Skills Taught
• Immunohistochemistry
• Bright-Field Microscopy
• Cellular quantification
• Computerized data analysis
• Graphing and statistical analysis

Plasticity in the little brains of the heart

Supervisor

Johanna Montgomery

Discipline

Physiology

Project code: MHS071

Plasticity in the brain is well characterised, and is known to underpin cognitive, motor and sensory functions. However, many neurons and synapses exist outside of the brain, including on the surface of the heart, however little is known about the role of plasticity in these neurons. We hypothesise that plasticity in these neurons can contributes to the neural control of heart rhythm and also to the triggering of abnormal heart rhythms. In this project we will examine plasticity in the neurons of the heart, using both imaging and physiology techniques.

Investigating the double edged sword effect of reactive oxygen species in the lens

Supervisor

Julie Lim

Discipline

Physiology

Project code: MHS061

The number of people afflicted by cataracts is estimated to reach 30 million as the world’s population ages. Faced with a looming cataract epidemic, research has focused on developing anti-cataract therapies to prevent cataract and reduce the need for surgery. Since cataract is associated with oxidative damage, the use of antioxidant supplements has been advocated as a therapeutic approach to slow cataract progression. However, studies into their efficacy are mixed and in some cases, antioxidant supplementation has been shown to have pathological effects. The reason for this may be explained by accumulating evidence that suggests that rather than being harmful, physiological levels of reactive oxygen species (ROS) may in fact be beneficial, acting as signalling molecules important in maintaining normal cellular processes. With this new view in mind, we will study the role of physiological ROS in the lens and examine the interplay between “good” ROS and redox signalling pathways in the lens.

Research skills include: Dissection of ocular tissues, Immunolabelling, Confocal microscopy

Shedding new light on the lens: the role of circadian clocks in glutathione regulation of the lens

Supervisor

Julie Lim
Raewyn Poulsen

Discipline

Physiology

Project code: MHS063

Work by our laboratory has shown for the first time that the rat lens is able to export the antioxidant glutathione (GSH) into its surrounding environment. This suggests that nearby tissues may utilise this GSH to protect from oxidative stress. We propose that GSH release by the lens is regulated in a circadian manner and works in concert with the ciliary body to ensure GSH levels are maintained for normal tissue function. Since GSH levels become depleted in the eye as we age, understanding these mechanisms are essential for identifying interventions to restore GSH and protect from age related eye diseases.

Research skills: Dissection of ocular tissues, Immunolabelling, Confocal microscopy

Can anti-inflammatory drugs be used for the treatment of inflammation-related neonatal brain injury

Supervisor

Justin Dean
Jaya Prasad

Discipline

Physiology

Project code: MHS043

Very preterm infants exhibit high rates of injury and impaired growth of white and grey matter regions of the brain, which are highly associated with subsequent neurodevelopmental impairment. There is strong evidence for a link between brain injury and exposure to low-level infection or inflammation around the time of birth. However, the mechanisms and exact timing of brain injury following infection are not fully understood.

The aim of this project is to investigate how blockade of the systemic inflammatory response will attenuate neurological and behavioural deficits associated with inflammation/infection.

This project will involve a range of methodologies including immunohistochemistry, fluorescent light microscopy, and confocal microscopy.

Targeting IGF-1 signaling for the treatment of inflammation-related neonatal brain injury

Supervisor

Justin Dean
Jaya Prasad

Discipline

Physiology

Project code: MHS044

Subclinical inflammation plays an important role in the development of brain injury in preterm born infants, and is characterised by subtle white matter abnormalities that manifest as fine motor deficits, cognitive and learning impairments, behavioural disturbances, and sensory deficits that persist into adulthood. Interestingly, preterm born infants show long-term reductions in circulating insulin-like growth factor-1 (IGF-1), which is further reduced in infants with perinatal inflammation. Importantly, these deficits in IGF-1 are strongly associated with impaired brain development in these infants.

The aim of this project is to investigate whether restoring IGF-1 levels will improve cortical development following inflammation-related brain injury.
This project will involve a range of methodologies including immunohistochemistry, fluorescent light microscopy, and confocal microscopy.

A novel role for the extracellular matrix sugar hyaluronan in induction of neonatal seizures following hypoxia-ischemia

Supervisor

Justin Dean
Jaya Prasad

Discipline

Physiology

Project code: MHS170

Newborn babies are at high risk of injury to the brain after exposure to adverse events around the time of birth, such as reduced brain blood flow and oxygen supply. Seizures often occur after this brain injury, which can further increase the risk of injury and life-long neurological problems. Although the proper management of neonatal seizures is important for improving the developmental outcomes for these children, there is currently no effective treatment for seizure inhibition. The overall goal of our research is to develop practical drug treatments to reduce seizures and brain injury after reduced brain blood flow and oxygen supply in these infants. Recent studies, including our own pilot work, indicate that loss of the extracellular matrix molecule hyaluronan can cause seizure-like activity. Further, preliminary evidence shows that hypoxia-ischemia to the developing brain causes a marked reduction in brain hyaluronan levels.

The aim of this project is to determine whether hypoxia-ischemia reduces hyaluronan levels in the developing brain in vivo, and its association to the extent of injury.

Discovering how the obesity gene, melanocortin-4 receptor, signals to moblilise intracellular calcium.

Supervisor

Kathy Mountjoy

Discipline

Physiology/Centre for Brain Research

Project code: MHS174

The melanocortin system plays a important, sometimes critical, role in many physiological functions including appetite regulation, body weight regulation, glucose homeostasis, the stress response, immune function , pigmentation, nerve regeneration, brain development and temperature. Melanocortin receptors are 7 transmembrane receptors and they function by coupling to G proteins and also independent of G proteins. Impaired melanocortin -4 receptor (MC4R) function is strongly associated with causing human obesity. It is unknown which of the numerous MC4R signal transduction pathways contributes to the obese phenotype. Our laboratory has evidence that the agonist activation of the MC4Rr expressed HEK293 cell cultures functionally couple to a signalling pathway that mobilises intracellular calcium. The importance of MC4R signallling to mobilise intracellular calcium causing obesity is unknown but our studies to date indicate that this is going to be important for body weight regulation. The signalling pathway used by the MC4R to moblilise intracellular calcium stores is unknown. This project will use specific cell signalling protein inhibitors to block selective signalling pathways including protein kinase A, EPAC and pERK1/2 with the aim of delineating the MC4R signalling pathway used for mobilisation of intracellular calcium. Overall we want to understand how the MC4R signals to cause human obesity.

Skills that will be taught are: Sterile technique for cell culture, transfection of recombinant DNA in cultured cells, fluorescent reporter assay to quantitate mobilisation of intracellular calcium, data analysis, statistics and interpretation of data, accurate laboratory record keeping.

Preference will be given to students wanting to continue with postgraduate research working in the area of melanocortin research.

Making recombinant protein for development of antibodies that will specifically detect melanocortin receptor accessory protein.

Supervisor

Kathy Mountjoy

Discipline

Physiology/Centre for Brain Research

Project code: MHS178

The melanocortin system plays an important, sometimes critical, role in many physiological functions including appetite regulation, body weight regulation, glucose homeostasis, the stress response, immune function , pigmentation, nerve regeneration, brain development and temperature. There are 5 subtypes of melanocortin receptors and each one of these interacts with a melanocortin accessory protein (MRAP) in vitro. These interactions alter each melanocortin receptor differently. If these interactions occur in vivo there is potential for MRAP to be an important modulator of the melanocortin receptor-driven physiological responses e.g. appetite and body weight regulation. There are commercial antibodies available that would recognise all splice variants and homologous proteins but there are no antibodies available that will specifically measure each one of MRAPalpha, MRAPbeta and MRAP2. This project will develop a MRAPalpha recombinant protein to be used for developing a specific antibody that recognises only human MRAPalpha. The antibody will be a valuable future resource for detecting, quantitating and studying the in vivo function/s for MRAPalpha.

Skills that will be taught are: Handling recombinant DNA, E. Coli transformation, bacterial protein expression and purification, 2D gel electrophoresis and accurate laboratory record keeping.
Preference will be given to students wanting to continue with postgraduate research working in the area of melanocortin research.

Structural changes in the auditory nuclei in the brainstem in a model of premature birth

Supervisor

Meagan Barclay

Discipline

Physiology

Project code: MHS198

Hearing impairment arises not only from loss of sensitivity to sound, but also from a reduced ability to distinguish features of sound that are necessary for the detection of important signals, like speech, in noise. Some of these deficits seem to arise from abnormal development or loss of part of the auditory nerve that carries sound signals from the cochlea to the brain. This project will examine the how lack of oxygen at birth or premature birth affects the structural development of auditory nuclei in order to gain some insight to where pathology arises and how this affects our perception of sound information.

This project will use techniques including histology, immunohistochemistry and microscopy to examine the changes in volume of the auditory nuclei as well as changes in the neural populations in these nuclei.

The improper processing of auditory information that can occur in children that were born premature affects their language aquisition and learning, thus better understanding the deficits that arise here will allow for more targeted treatment.

Optimizing optogenetic ChR2-Assitted Circuit Mapping (CRACM) to reveal the neuronal microcircuitry within the subthalamic nucleus

Supervisor

Peter Freestone
Janusz Lipski

Discipline

Physiology

Project code: MHS209

Recent advances in optogenetic techniques will allow us to study the subthalamic nucleus microcircuitry with unparalleled temporal and spatial resolution. In particular, the optogenetic technique of ChR2-Assisted Circuit Mapping (CRACM) can be applied to study neuronal networks with single neuron resolution. This approach uses targeted light-stimulation to selectively activate (excite) neurons leading to depolarization and action potential generation in that neuron. Electrophysiological recording from a central neuron will allow the detection of post-synaptic currents evoked by light-activation of the upstream (pre-synaptic) neurons. CRACM experiments are conducted in brain slices (ex vivo) prepared from mice made to express the light-sensitive protein channelrhodopsin (ChR2) in subthalamic neurons. Combined with pharmacology to isolate the involvement of specific neurotransmitters, this approach enables high-throughput assessment of functional neuronal networks.

Optimization of the experimental and analytical aspects of this novel technique needs to be carried out to maximize information gained from each experiment. Specifically, whether a newly developed ChR2-variant (SoCoChR2) that is somatically targeted, can be used to improve resolution of CRACM-generate circuits.

Gaining a deeper understanding of the organization within the subthalamic nucleus is vital to improving existing treatments of Parkinson’s disease, as this nucleus becomes overactive in the disease state.

Skills
Experience in electrophysiology (MedSci309) and/or optogenetics preferred (MedSci317). Keen interest in technology-driven science. Experience with computer programming and/or signal analysis would be beneficial.

Drug delivery through the round window membrane of the inner ear

Supervisor

Peter Thorne
Srdjan Vlajkovic

Discipline

Physiology

Project code: MHS129

Background: The inner ear in humans is deeply embedded in the temporal bone which makes access to the inner ear for diagnostic or treatment purposes quite challenging. In the past few years our research group has developed novel and effective pharmacological agents for the treatment of acute cochlear injury caused by exposure to traumatic noise, ototoxic anti-cancer drugs and aminoglycoside antibiotics. However, treatments for inner ear disorders are limited by the systems available to accurately and safely deliver therapeutic compounds to the inner ear. We are developing a new drug delivery system involving procedures to increase the permeability of the round window membrane, which separates the middle and inner ears. This will be a novel drug delivery method for safe, accurate and reliable treatment of acute and chronic hearing disorders.

Aims: The overall project will use sheep temporal bones as a model system. The summer studentship project aims to investigate the structure of the round window membrane (RWM) of the sheep cochlea for comparison with human and to provide detailed anatomical data for modelling its mechanical characteristics. It will use standard histological techniques, immunohistochemistry and microCT (high resolution CT scanning) to look at the tissue properties and to reconstruct the structure of the round window and measure its physical parameters.

Skills to be taught: Tissue dissection, histology and microCT (microtomography or CT scanning) as well as morphometric techniques and light microscopy data analysis, scientific writing.

Pre-requisites: A student with background and interest in auditory neuroscience (eg. MEDSCI 316, 739) is preferred, but this would also be suitable for students with general interest in neuroscience or medicine

Improving electrochemical detection of the neurotransmitter dopamine with conductive polymers – Implications for a better understanding of the role of this neurotransmitter in the brain.

Supervisor

Prof. J. Lipski
Dr P. Freestone

Discipline

Physiology

Project code: MHS057

Our laboratory investigates the mechanisms of neuronal damage in models of Parkinson's disease (PD) and the properties of dopaminergic neurons in the Substantia Nigra which are affected by this disease. PD is a movement disorder caused by degeneration of dopaminergic neurons in the Substantia Nigra, leading to a loss of the neurotransmitter dopamine. The disease is most frequently treated with L-DOPA (Levodopa), the precursor to dopamine, which ameliorates motor symptoms by increasing dopamine production. Given the major role dopamine plays in PD and in control of movement in general, it is important to use sensitive and accurate detection techniques for measuring this neurotransmitter in the brain.

Through a collaboration with a group of scientists at the University of Arizona, we have recently developed a novel electrochemical technique (‘Fast-scan controlled-adsorption voltammetry’; FSCAV) for measuring dopamine levels in brain tissue based on detection of this neurotransmitter with carbon fibre microsensors (Burrell et al, ACS Chemical Neuroscience, 2015, 6: 1802). The goal of the summer project is: (1) to further improve this technique by modifying the surface of the sensors with synthetic polymers, which should increase their sensitivity and selectivity to dopamine; and (2) to measure dopamine levels in isolated brain tissue before and after L-DOPA application with standard and modified sensors to validate the effectiveness of the coating with conductive polymers.

This project will be offered to an enthusiastic student with a cumulative GPA =6.5 who has interest both in chemistry and neuroscience. Preference will be given to a student intending to continue with studies in these areas.

Skills taught:
- Construction and polymer coating of carbon fibre microelectrodes (microsensors)
- Detection of dopamine using electrochemistry in control solutions
- Learning how to prepare brain slices from rodents
- Detection of dopamine using electrochemistry in brain slices
- Computer data analysis and data interpretation
- Literature search and scientific writing/ oral presenting skills

Do fetal seizures cause cerebral hypoxia?

Supervisor

Professor Laura Bennet
Dr Chris Lear

Discipline

Physiology

Project code: MHS134

Seizures are a common occurrence after exposure to an adverse event such as hypoxia before or during birth. There is a significant debate about whether seizures can exacerbate brain injury after hypoxia. Currently, we know very little about how the brain is oxygenated during seizures when they occur before birth. Using pre-clinical experimental data, students will evaluate changes in fetal cerebral oxygenation and perfusion derived from near infrared spectroscopy and Doppler ultrasound probes and blood pressure. Further, students will explore whether an index of cerebral autoregulation can be derived from these factors to create a cerebral oximetry index (COx) that may help us detect the at risk baby.

Skills: learning to use physiology data analysis programmes, excel, Graph making using Graphpad, statistics using SPSS, literature searches using PubMed, and literature referencing using Endnote. Students will be able to increase their knowledge about fetal physiology and pathology particularly on fetal hypoxia and how to assess seizures, and the clinical burden of both preterm birth in New Zealand. They will also be introduced to the use of clinical medical devices such as EEG and near-infra-red spectroscopy to monitor the wellbeing of newborn babies and for seizure monitoring. The project will allow them to learn about the impact preterm birth has on the long-term health of NZ babies, and how this disproportionately affects our Maori and Pacifica communities. Finally, the will learn about the important role of biomedical science in informing and changing clinical practice. We are looking for students interested in future studies in biomedical research

Identifying pathways for insertion of the water channel AQP5 in the fiber cell membranes of the rat ocular lens

Supervisor

Rosica Petrova
Paul Donaldson

Discipline

Physiology

Project code: MHS139

This project is designed to attract a young investigator willing to make a difference in the lens field by contributing to a line of research which looks into ways of keeping the lens of the eye healthy and transparent. The aim is to determine the physiological conditions that trigger insertion of the water channel AQP5 into the membranes of peripheral fiber cells of the rat lens. Previously, we showed a spontaneous insertion of AQP5 after 15 hours of incubation which we propose is initiated by removal of the lens from the eye. Following on this observation we will extend this study by screening for pharmacological reagents that increase the rate and extent of the spontaneous insertion of AQP5.To achieve this, lenses organ cultured in the presence, or absence of a pharmacological reagent will be fixed, cryosectioned, immunolabelled with AQP5 antibodies and the membrane marker WGA, imaged by confocal microscopy, and the relative change in the subcellular distribution of AQP5 quantified using image analysis software.

The outcome of this study will determine how members of the aquaporin family enable the lens to adapt in response to changes of the external and/or internal cellular pressure to stay transparent and fulfil its light focusing properties.

Mapping adenosine receptors in afferent synapses of the developing rat cochlea

Supervisor

Srdjan Vlajkovic
Shelly Lin
Peter Thorne

Discipline

Physiology

Project code: MHS142

We have previously identified adenosine A1 receptor (A1R) as one of the most promising targets for the treatment of acute noise-induced cochlear injury. Systemic or local administration of A1R agonists leads to the improvement of auditory thresholds, reduced expression of oxidative stress markers and increased survival of sensory hair cells in the noise-exposed cochlea. A1R also seems important in other forms of sensorineural hearing loss such as from cytotoxic drugs, e.g. cisplatin and aminoglycosides. This supports our view that A1R is an important regulator of cochlear survival in stress and injury.

In this study we are proposing to investigate the broader role of adenosine receptors in regeneration of afferent synapses in the cochlea after excitotoxic injury. Glutamate excitotoxicity is the underlying mechanism of cochlear synaptopathy and several forms of sensorineural hearing loss. We postulate that adenosine receptor targeting could be an effective therapeutic strategy to prevent the loss of afferent synapses and primary auditory neurons. Before we can test this hypothesis, we need to determine exact localisation of adenosine receptors at the afferent synapse (presynaptic or postsynaptic), which is the primary objective of this summer studentship.

The principal aim of this project is to explore immunolocalisation of A1 and A2A adenosine receptors in cochlear afferent synapses and changes in receptor distribution after excitotoxic injury.

Skills to be taught: Cochlear tissue dissection, organotypic cultures, immunofluorescence, high resolution imaging, data analysis, scientific writing.
A student with background and interest in auditory neuroscience (eg. MEDSCI 316, 739) is preferred, but this would also be suitable for students with general interest in neuroscience.

Honours, Masters and PhD projects are also available in related areas of study.