Opportunities exist in our internationally recognised research programmes in the areas of Cardiovascular & Respiratory Physiology, Cellular & Molecular Neuroscience, and Membrane & Ion Transport.
Applications to undertake a PhD in Physiology are welcome at any time. Candidates can be of any nationality and must have attained an excellent degree (minimum of four years' study) in biomedical science or a closely-related subject.
Applicants must apply to the Department of Physiology as follows:
- Refer to the available projects listed below and contact the supervisor(s) whose project(s) interest you the most. In your email, include the following:
- Your name and country of citizenship
- Your CV
- Certified academic transcript (and, if applicable, an explanation of the content)
- Certified evidence of English language proficiency (eg IELTS or TOEFL results)
- The names of two referees
- If your application is to be considered, the supervisor will contact you to discuss the next steps, and our Departmental Administrator will check that your documents are complete.
Opportunities for PhD study in the Department of Physiology for 2018-2019.
Novel approaches for treating cardiovascular disease
Cardiovascular disease is the primary cause of death throughout most of the world, and existing therapeutic options are unsuitable for a large percentage of patients. Our group is exploring new targets in the heart and vessels to develop the next generation of cardiovascular treatments. Recent work from our group shows has identified a potential target: calcium/calmodulin dependent kinase II (CaMKII), a key protein mediator of cardiac and vascular dyfunction. We are seeking motivated students with an interest in cardiovascular physiology to join our team and examine the connection between CaMKII and cardiovascular disease. Projects in our group utilize state-of-the-art techniques and reagents, as well as genetic mouse models not available elsewhere in the world. Candidates with a wide range of interests, including molecular and protein biochemistry, fluorescent imaging, and physiological techniques (ex. echocardiography, force development measurements in isolated fibers, etc.) are encouraged to apply.
ENaC role as shear sensor in endothelial cells
The diameter of blood vessels is regulated by the blood flow (shear force), passing through the lumen of the vessels. This mechanism is dysregulated in cardiovascular diseases (e.g. hypertension, diabetes). We hypothesise that impaired vascular ENaC expression and function leads to the functional changes in the vascular responses. Therefore, the objective of this project is to determine the role of ENaC in endothelial cells that were grown under different shear stress levels by performing expression analysis and electrophysiology.
For any inquiry and/or more detailed information please contact Martin by e-mail (firstname.lastname@example.org)
The role of the Exocyst complex in trafficking ion channels in polarised epithelia
Proper trafficking of ion channels in epithelia is key to epithelial cell function. The Exocyst is a series of proteins that act as a complex and aids in tethering post-Golgi secretory vesicles for delivery of ion channels to the plasma membrane. The role of the Exocyst complex in trafficking ion channels still emerging. In this project, we will investigate the role of the Exocyst complex in the targeting of two epithelial ion channels to the appropriate membarne. This will be approached using a range of protein biochemistry, molecular biology, electrophysiological and imaging techniques. The implication of these results is to define novel trafficking partners of K+ and Na+ channels that may be used therapeutically in diseases.
Rhythms in brain circuits; mechanisms and modulation.
Rhythmic activity in brain neurons generates waves of activity or oscillations in brain networks. Different ranges of frequencies are associated with local neural circuit processing, wider network connectivity and plasticity, and are altered in brain disorders. We use in vitro slices of the mouse brain to study how intrinsic neuron membrane properties (i.e. membrane currents and ion channels, distributed in specific functional compartments of brain neurons) regulate oscillation and plasticity in brain networks. We investigate in vitro how these are influenced by medicines used (or potentially used) to treat psychiatric disorders, bipolar disorder in particular, and we collaborate in translational research using EEG recording in human volunteers, and computational modeling. If you would like to discuss potential research projects in more detail, please contact Dr Phil Heyward.
Regulation of corticotropin-releasing hormone (CRH) neuron excitability
The Iremonger laboratory focuses on understanding how the brain responds to stress. Corticotropin-releasing hormone (CRH) neurons are activated in response to stress and are responsible for controlling the level of stress hormones in the body. We are particularly interested in determining how synaptic inputs and neuromodulators regulate CRH neuron activity both before and after stress. Our research uses electrical recordings and imaging techniques to interrogate CRH neuron structure and function. For more information on this and other projects, please contact Dr Karl Iremonger.
Understanding and controlling cardiac arrhythmias
Cardiac arrhythmias remain the leading cause of death in patients with heart disease. An important trigger for arrhythmias is the inappropriate control of calcium within the cells of the heart. We study a protein (RyR2) responsible for regulating the release of calcium within the heart. Our overall aim is to better understand RyR2 and use this knowledge to develop new strategies for treating arrhythmia. We use a host of techniques including molecular biology and biochemistry through to single cell and whole heart calcium imaging in animal models. We are also now moving more of our work into living cardiac tissue from heart disease patients (see heart.otago.ac.nz). Various projects are available utilising a variety of techniques to study the function, dysfunction and pharmacological control of RyR2. Candidates with interests in cardiac muscle physiology and protein biochemistry are encouraged to apply.
Intracellular transporter for microRNA in the cardiomyocytes
MicroRNAs play crucial role in pathophysiology of several diseases including cardiovascular diseases. MicroRNAs export out of the cells that synthesise them to produce effects on the neighbouring or remote cells. This project will use state-of-art technologies to identify the novel intracellular transporter of microRNAs in cardiomyocytes. Please contact A/P Rajesh Katare (email@example.com) to discuss the project in detail.
Therapeutic efficacy of microRNAs in treating diabetic wound
Diabetic patients have reduced blood flow to the periphery resulting in impaired recovery following the development of an ulcer. Our recent studies showed microRNAs are able to improve the vascular integrity in diabetic tissues. This project will aim to determine the therapeutic efficacy of microRNAs in diabetic wound using the animal model of type-2 diabetes. Please contact A/P Rajesh Katare (firstname.lastname@example.org) to discuss the project in detail.
Circadian rhythm of heart rate regulation in diabetes
Resting heart rate is the strongest predictor of mortality in patients with cardiac disease. Incompetence in heart rate regulation is an undervalued feature of the diabetic heart with major cardiovascular consequences. Heart rate fluctuates in a circadian manner, and people with diabetes tend to have disturbed circadian profiles of heart rate. However, the underlying mechanisms of the circadian rhythm in heart rate have been debated. The fluctuations can occur either because control of the heart by central nerves (autonomic) or the pacemaker cells within the heart varies their activity (intrinsic). Therefore, the aim of this PhD is to measure whether changes in autonomic control and/or intrinsic regulation is responsible for the disturbed circadian rhythm of heart rate in diabetes. We will address this question using recordings of autonomic nerve activity and isolated heart studies in a type 2 diabetic animal model.
Epithelial sodium channel as a target in breast cancer
Breast cancer is a major health problem comprising 28% of cancers that affect New Zealand women. Our new data shows that epithelial sodium channel, ENaC, expression in patients' tumours correlates with breast cancer prognosis. ENaC is located in the plasma membrane, and its large extracellular domain senses physical changes in the extracellular environment, while intracellular ENaC domains interact with the cytoskeleton. These connections allow ENaC to contribute to cell shape and rigidity, thus influencing cell migration and differentiation. Changes in mechano-sensing pathways and cell shape are tightly linked to the ability of cancer cells to undergo epithelial-mesenchymal transition (EMT), migrate and metastasise. This project will involve you assessing ENaC’s role in breast cancer cell EMT, migration, and proliferation, and determining physical characteristics of breast cancer cells with changes in ENaC expression by atomic force microscopy. Characterisation of the mechanisms by which ENaC promotes tumour generation will provide a previously unknown target for breast cancer therapy.
Characterising the role of endothelial ENaC for blood pressure regulation
The epithelial Na+ channel (ENaC) is crucial for maintaining electrolyte and water homeostasis and thereby a major molecule for blood pressure regulation. Beside its ubiquitous expression in epithelia, there is growing evidence that the channel is expressed in non-epithelial tissues such as endothelial cells of blood vessels. Knowledge about the role and function of ENaC in blood vessels is incomplete. This project aims to characterise the expression and function of ENaC in different types of blood vessels. In particular the association of the channel with the endothelial glycocalyx is a major aspect of the project. The results from this study will provide evidence for a new role of ENaC in endothelial cells that relies on the endothelial glycocalyx and that represents a new mechanism for blood pressure regulation.
The project involves expression analysis (quantitative/digital PCR) using different types of arteries from different species. Further, vessel structures will be assessed by histotology and immunohistochemistry. Cyrofix-cyrosubstitution transmission electron microscopy will be performed to determine the structure of the endothelial glycocalyx. ELISA will be performed to determine and quantify the components that constitute the endothelial glycocalyx. Candidates that are interested in the topic, have experimental research experience (Honours or Masters degree) and are looking for new challenges are encouraged to apply
Does retromer control epithelial polarity and ion channel delivery to the cell surface?
To achieve the optimal balance of intracellular and extracellular ion concentrations the numbers of ion channels situated at the cell surface are tightly regulated. Retromer is a recently described intracellular complex that controls whether cell surface proteins are recycled to the cell surface or degraded. In this project we will determine if two epithelial ion channels are regulated by retromer, and whether the polar distribution of these ion channels in epithelia are altered when retromer is disabled. The results will have implications for further understanding of electrolyte balance and blood pressure control.
Central modulation of cardiac Sympathetic Nerve Activity following acute MI.
The majority of people that suffer a heart attack (acute myocardial infarction; MI) die within the first few hours following the MI. This high early morbidity has been strongly linked with a sustained over-stimulation of the nerves that control heart function; specifically sympathetic nerve activity (SNA). Unfortunately, even if you survive the initial heart attack, this over-stimulated SNA to the heart facilitates progressive damage of the heart tissue, such that the long-term survival prognosis is bleak. Currently, the mechanisms that govern the increase in SNA following acute MI remains to be fully elucidated, although both peripheral and central modulation have been implicated via the cardio-cardiac reflex.
Research Question and Objectives
Advanced electrophysiological techniques will be used, in vivo, to address the fundamental objectives of this line of research, which are i) to broaden our knowledge concerning the central neural mechanisms that modulate cardiac SNA, with specific emphasis on the role of the paraventricular nucleus, ii) identify the relative role of the cardio-cardiac reflex (e.g. vagal and sympathetic) for modulating the central integration of SNA following acute MI and iii) identify potential therapeutic targets (within the CNS) to prevent the adverse increase in SNA following acute MI.
Modulation of the pulmonary vasculature in health and disease.
The pulmonary microcirculation is tightly modulated by the autonomic nervous system, the pulmonary vessel endothelium and the vascular smooth muscle. All components act synergistically to selectively perfuse well-ventilated alveoli and, thus, optimize ventilation-perfusion matching. During hostile challenges to the pulmonary microcirculation, such as chronic hypoxia, each of these components can potentially undergo adverse functional changes, which ultimately culminates in the onset and development of pulmonary arterial hypertension. This research essentially aims to investigate the various mechanisms that modulate pulmonary vascular tone, with the ultimate goal of further understanding the pathomechanisms that contribute to the development of pulmonary hypertension. Experiments will be designed to assess the relative role of the autonomic nervous system, endothelium and smooth muscle in modulating pulmonary vascular tone in specific animal models susceptible to pulmonary hypertension, such as obesity, age-related and hypoxia sensitive subjects.
Changes in cerebral blood flow trigger an increase in sympathetic nerve activity – implications following acute myocardial infarction
Heart function is controlled by the sympathetic nervous system. Following a heart attack (myocardial infarction: MI), cardiac sympathetic nerve activity (cSNA) becomes dangerously elevated, triggering irregular heartbeats (arrhythmias) that often prove fatal. In those who survive the initial MI, the sympathetic hyper-excitation is irreversible and facilitates permanent structural and functional damage of the heart. cSNA is ultimately driven by the brain and we have recently shown that the hypothalamic paraventricular nucleus (PVN) appears to facilitate this increase in SNA following MI. However, the trigger that activates these oxytocin neurons following MI remains to be determined. Neuronal activity is modulated by cerebral blood flow (CBF). CBF is impaired in chronic heart failure, which is thought to cause the sustained increase in cSNA. Hence, a sudden decrease in CBF following an MI may trigger PVN activation providing the drive for the increase in cSNA.
Research Question and Objectives
The overall aim of this study is to test the hypothesis that decreased CBF activates PVN neurons to increase cSNA following acute MI. Specifically, i) advanced Synchrotron Radiation microangiography (Hyogo, Japan) will be utilized to image the changes in cerebral blood flow associated with acute MI, ii) changes in CBF will be correlated with PVN activation (immunohistochemistry) and cSNA (electrophysiology).
Micro RNA-126 as a novel therapeutic target underpinning exercise-mediated cardioprotection in diabetic heart disease.
Diabetes, which has reach epidemic proportions world wide, is associated with numerous long-term health complications, in particular cardiovascular disease. Recent research from our lab has shown that exercise is an effective strategy for preventing the onset of diabetic heart disease. However the unpinning mechanisms governing this cardio-protection remain unclear. microRNAs (miRs) have recently evolved as key players in modulating the cardiovascular system through the regulation of cardiac gene expression. This study aims to identify whether the cardiac protective properties of exercise in diabetes is mediated through modulation of the cardiac specific miR-126, since this particular miR is adversely down-regulated in diabetic heart disease. Experiments will utilize a range of advanced experimental techniques, using knock-down or knock-in animal models of miR-126, to determine whether the beneficial effects of exercise are directly dependent on miR-126.
Investigation of the structural and functional consequences of advancing age on skeletal muscles, motor nerves, and neuromuscular junctions. The main emphasis on the work is the investigation of the cellular mechanisms by which advancing age results in loss of skeletal muscle mass.
Investigation of the impact of age and exercise on the neuromuscular consequences of anticancer drug treatment. The main emphasis of the work is to investigate the cellular mechanisms by which anticancer drug treatment results in loss of muscle mass, and the effects that age and exercise status might have on those mechanisms.