Biomedical Science

Managing severe and chronic pain in the hospital has become an increasingly challenging task. Opioids have been the traditional mainstay for treatment of severe pain, however decades of over prescription and abuse especially in the Western World has led to increasing number of opioid dependent patients who are resistant to opioid treatment.

The financial burden of the opioid epidemic has been estimated to be $72 billion in the USA alone. Opioid overuse can lead to hyperalgesia and analgesic tolerance, which result in ineffective pain control. Ketamine is a widely used non-opioid anaesthetic with profound analgesic properties and is known to reduce opioid hyperalgesia. Ketamine however produces psychotomimetic side-effects which limit its clinical potential.

The aim of this project is to synthesise novel analogues of ketamine, which retain its desired analgesic properties while eliminating its undesired side-effects. The project will expose the student to synthetic organic chemistry techniques. No prior experience necessary.

Evolution has produced a myriad of adaptations for animals that thrive in extreme hypoxic conditions. These changes range from the generation of endogenous carbon monoxide to down regulate mitochondrial oxygen requirements during breath-holding when diving, to haemoglobin mutations, novel tissue oxygen storage methods and cooling. Some of these mechanisms are already being applied to human health interventions. An example is the use of carbon monoxide in the preservation of organs transplantation during transportation and after transplantation, and also as treatment for pulmonary hypertension.

The summer project will involve a literature review, and processing of imaging data from some of one of these hypoxia-tolerant species (e.g. emperor penguin, bar headed geese, marine mammal or egg development).

Skills required: Inquisitive mind and "out of the box” thinking. Attention to detail.

Skills to be learnt: Literature review methods, 3D image data processing (MRI or CT) using Amira software. If progress is good manuscript preparation for publication.

The autonomic nervous system plays a major role in atrial fibrillation (AF), the most common abnormal heart rhythm. Located on the heart surface are clusters of neurons known as ganglionated plexi (GP) which provide the final neural input to the heart to control rate and rhythm. In this summer project the goal is to identify structural changes in GP neurons occurring with AF using confocal imaging to gain information on changes in the relative frequency of GP neuronal phenotypes and synaptic connectivity that occur with AF. This data will assist in determining how GP neurons differ in AF patients that could increase AF susceptibility. This information is pivotal for developing neural therapies to stall AF, and identify how GP neuron properties regulate heart function.

Autism Spectrum Disorder (ASD) is a highly prevalent neurological disorder with a strong genetic cause. Multiple changes are known to occur in synaptic proteins in people affected by ASD, with the SHANK family of proteins being a major group affected in ASD. Other potentially important proteins include those regulated by zinc, both at presynaptic and postsynaptic sites. We have recently shown that dietary zinc can prevent or reverse ASD-associated behaviours providing a strong zinc link in ASD. In this project we will use cellular imaging via confocal microscopy to examine the extent of synaptic protein changes with dietary zinc to identify molecular mechanisms of ASD and zinc treatment pathways.

The discovery of new drug candidates for the investigation of validated drug targets is a cornerstone for advancing human health. This is typically achieved by the high throughput screening (HTS) of compound libraries against a disease-relevant target for the desired activity, however these methods are often either too slow, laborious, or costly, or present a very low hit rate. DNA-encoded libraries (DELs) are a smart technology that have recently emerged to address this challenge. DELs are pooled binding assays that can be used to screen ultra-large collections of compounds (>10^8) for their affinity to an isolated protein or protein complex of interest (POI). DELs utilise recent advances such as next-generation sequencing to enable simultaneous and incredibly deep sampling of chemical space, at a fraction of the cost of standard HTS.

This project will leverage the existing ACSRC novel building block and intermediates collection to start building a DEL and establish this exciting new technology at UoA for the first time. The student will gain exposure to the design, logistical aspects, chemoinformatic analysis and synthesis of DNA encoded compound libraries for drug screening.

Find out more information. 

Preterm brain injury can result in lifelong disabilities that impact the individual, their families, and the wider health care system. At present, we lack an accurate biomarker of preterm brain injury that would allow time critical treatments to be delivered to babies at risk to minimise brain damage. Fetal brain cells secrete extracellular vesicles (small lipid bi-layered particles) that carry cargo with a distinct protein profile representative of either a healthy or injured fetal brain. These extracellular vesicles are present within the cerebrospinal fluid.

This project will aim to investigate the biomarker potential of cerebrospinal fluid extracellular vesicle protein cargo collected from a fetal sheep model of hypoxia-ischemia mediated preterm brain injury. Techniques involved in this project include size exclusion chromatography, nanoparticle tracking analysis, bicinchoninic acid (BCA) assay, and western blotting.

This is an opportunity to work on the second clinical trial arising from the Tuhauora project, funded through the High Value Nutrition National Science Challenge in collaboration with Wakatu Incorporation, which aims to develop a functional beverage containing the taonga species kawakawa (Piper excelsum) for South Asian markets. Kawakawa (Piper excelsum), a relative of black pepper (Piper nigrum), is rich in pharmacologically active compounds such as the phenylpropanoids myristicin and elemicin, the lignans yangambin and excelsin, and amides such as piperine and pellitorin.

Kawakawa is a taonga and has an extensive history of use in Maori rongoa, or traditional medicine, for its analgesic, anti-inflammatory, and metabolic effects. Aqueous extracts of kawakawa have been shown to have anti-inflammatory potential through the reduction of IL-6 and TNF-a in human cell lines, and to influence the uptake of glucose and fatty acids within intestinal cell models. We have recently demonstrated effects upon glycaemic regulation in the first-in-human study of kawakawa tea consumption (1). We are conducting a clinical trial, Tuhauora ka rua, to study the effects of kawakawa consumption on biomarkers of chronic inflammation, metabolic and immune health.

Research question or hypothesis and rationale:

Objective: Undertake a two-arm six-week cross-over study with to compare daily consumption of water and the kawakawa ingredient to quantify effects on biomarkers of chronic inflammation, metabolic health and immune health.

Hypothesis: a six-week diet including a kawakawa-containing beverage will reduce plasma hs-CRP as a biomarker of chronic inflammation.

Trial design: A randomised, single blind, 6 week, 2-way cross-over study

Study setting: Liggins Institute Clinical Research Unit (CRU), University of Auckland

There is an opportunity for a Summer Student to participate in analysis of the plasma and urine samples collected from this study, to take responsibility for data processing and interpretation, and to be involved in communication of the results in the form of manuscripts submitted to a peer-reviewed journal.

1) Ramzan et al (2022). Acute Effects of Kawakawa (Piper excelsum) Intake on Postprandial Glycemic and Insulinaemic Response in a Healthy Population. Nutrients 14, 1638. https://doi.org/10.3390/nu14081638

Evidence suggests that the mechanisms of myopia progression and correction involve the retina. Outdoor light exposure can reduce the incidence of myopia development in children and in animal models. Among all wavelengths, blue/violet light has a suppressive effect on myopia. However, how is that light modulates the retina to prevent myopia progression is not known. In this project, we aim to investigate the cellular structure of the retina and neurotransmitter levels in a chick model of myopia exposed to blue light. The eyes will be assessed using techniques that can determine the molecular differences in retinal response between normal and myopic eyes exposed to light. The student for this project needs to have basic laboratory training but tissue processing, image analysis and data analysis will be some of the skills related to this project.

Head-mounted miniaturised microscopes (miniscopes) enable brain activity to be recorded in freely moving rodents. By using miniscopes we can directly decipher how brain cell activity underlies behaviour as it happens in the awake behaving animal. We are examining the cellular mechanisms that underlie behavioural deficits in Autism Spectrum Disorder (ASD). We utilise miniscopes to examine cellular activity in the hippocampus during spatial and social memory tasks in a mouse model of ASD.

Skills that will be learned through the project

• Behavioural testing on mice
• Analysis of mouse behaviour (automated)
• Analysis of brain activity recorded with miniscopes (semi-automated)

Interest/experience in neuroscience, animal behaviour, data analysis, Matlab or Python programming.

The neonatal immune system rapidly needs to adapt to the extrauterine environment in the first few weeks of life. Regulatory T cells (Tregs) play an important role in fine-tuning the appropriate level of immune reactivity and tolerance in this period. Maternal Tregs may be transferred into the neonatal gastrointestinal system during breastfeeding, however, it is currently unknown how the maternal Treg profile in breastmilk compares to peripheral blood.

In this project, we aim to characterise the immune phenotype of Tregs in breastmilk versus peripheral blood samples of lactating mothers, with particular emphasis on adhesion molecules that enable Treg translocation into the neonatal intestines.

Tregs will be isolated from peripheral blood samples and breastmilk. The isolation of immune cells from breastmilk is a methodological challenge due to the high fat content of breastmilk. Therefore, we will initially optimise isolation methods to ensure the highest possible retrieval of immune cells. Tregs will then be characterised using flow cytometry by a combination of cell surface and intracellular markers.

The above experiments will help us better understand the differences in Treg phenotype between maternal blood and breastmilk. They will help us elucidate factors that may potentiate the translocation of maternal Tregs into the neonatal intestine during breastfeeding, possibly contributing to maternal microchimerism in the neonate.

Skills and techniques taught: Experimental design, Immune cell separation, Flow cytometry, Statistics, Data interpretation

Scientists have recently developed an exciting new technology to study cancer known as tumour organoids. Organoids, or ‘mini tumours in a dish’, are tiny three-dimensional structures grown in the lab from tumours donated by cancer patients undergoing surgery. Organoids behave like donor patient’s tumour, in terms of their histological features, genetic mutations and drug response. This makes them a powerful tool to study cancer biology as well as test new drug treatments.

Our laboratory is currently generating a collection of organoids from New Zealand women recently diagnosed with breast cancer. The aim of this project is to explore the use of these organoids as a new platform for personalized medicine in our country. Organoids will first be characterised and compared to the original donor tumours to confirm they accurately model the patient’s disease. We will then determine the response of organoids to anti-cancer therapies, and explore the utility of novel drug-delivery systems.

This project will help to showcase the potential of organoid technology for translational cancer research. Skills and techniques that will be taught include cell culture, drug assays, microscopy, immunostaining and data interpretation/analysis.

Age-related eye disease such as cataract, macular degeneration, and glaucoma is known to result in debilitating vision loss. Oxidative stress and damage are known to play an important role in the pathogenesis of these diseases however antioxidant therapies aimed at minimizing oxidative stress have not been entirely successful. This is because the exact underlying mechanisms are still poorly understood. One such gap in our knowledge is the role of the cystine/glutamate antiporter or CGAP in the eye. In other tissues, CGAP is known to play two important antioxidant roles. The first is to import the amino acid cystine for the synthesis of the vital antioxidant, glutathione. The second is to maintain a reduction-oxidation balance in the extracellular space. In the eye, removal of GCAP using a knockout mouse model results in age-related changes such as cataracts and retinal spots. Hence the aim of this project is to investigate the role of CGAP in minimising oxidative stress in the eye. This project will allow the candidate to learn techniques such as ocular microdissections, western blotting, and immunohistochemistry.

While the role of the inflammatory cascade in exacerbation and propagation of the vicious circle of dry eye disease is well established, the exact mechanism by which inflammation is potentiated is poorly understood. Recently, upregulation of the NLRP3 multiprotein complex, the most widely investigated inflammasome was demonstrated in DED with the generation of reactive oxygen species (ROS) in hyperosmolar tears being one of the major causative factors.

Therefore, this study aims to develop an ex vivo organ culture model to evaluate the extent of inflammasome activation and ROS generation in corneal and conjunctival cells in response to hyperosmolar stress. Furthermore, the mechanism which by anti-inflammatory agents inhibit the inflammatory cascade will also be studied.

Huntington’s disease (HD) is the most common monogenic neurological disorder in the developed world, characterised by involuntary movements (chorea), cognitive and behaviour changes which manifest in midlife. A child born to an HD parent has a 50% chance of inheriting HD. In addition to neuronal loss, a key feature of HD is the formation of mutant huntingtin (mhtt) protein, which accumulates and misfolds to form aggregates in the brain, yet the precise cellular localization and distribution of mhtt aggregates is not well understood. Non-mhtt aggregates have also been reported in HD brains, including isoforms of Tau, aSYN, ubiquitin, polyubiquitin, and TDP-43. Therefore, the aim of this study is to investigate the role of pathogenic proteins in the HD human brain in relation to clinical symptomatology. We will examine markers of various pathogenic proteins using human brain tissue microarrays (TMA) and human tissue sections from well-characterised HD and control post-mortem cases with variable pathological and clinical phenotypes.

Skills

• Immunohistochemistry on paraffin embedded human brain sections and tissue microarrays
  
• The principles of tissue microarray
  
• Bright field microscopy
  
• Digital image acquisition
  
• Scientific report writing and figure making
  

Immunotherapy is the future of cancer care. By stimulating the innate ability of the patient’s immune cells to fight cancer cells, immunotherapy can cure cancer. Yet, this does not happen in most patients because the cancer sabotages their immunity. Most cancers sabotage anti-tumour immunity by producing a tryptophan metabolite called kynurenine that paralyses cancer-killing immune cells and undermines immunotherapies.

To make more patients benefit from immunotherapies, kynurenine production needs to be stopped. This research programme investigates the immunosuppressive tryptophan metabolism in cancer and develops innovative technologies for arresting kynurenine production in cancer patients.

A research question for the summer student project will be formulated based on the stage of the research programme at the given time and the student’s interests.

Skills required: None, but an ideal candidate will have a high dose of curiosity, proactivity, analytical mindset, investigative and problem-solving nature.

Skills taught: Critical reading & technical writing, experimental design, data analysis & presentation. Laboratory methods used will depend on the project selected.

During active labour, uterine contractions cause brief periods of oxygen deprivation which are normally well tolerated by healthy fetuses. Unfortunately when severe or prolonged, this repeated oxygen deprivation can lead to brain injury. There is good understanding of the pattern of severe brain injury that causes profound life-long disability, but there is far less knowledge surrounding the pattern of injury resulting from a more mild but prolonged period of oxygen deprivation. Increasingly it is understood that these milder injuries are considerably more common but often go undiagnosed.

During this summer studentship project, the student will examine grey and white matter brain injury from an animal model of labour-like oxygen deprivation. In the process, the student will master highly transferable skills including immunohistochemistry, microscopy, image analysis, cell quantification and statistical analysis. This research will help us better understand this pattern of brain injury and provide foundational knowledge for future studies examining treatments for brain injury.

Most eye drops are water-based; however, delivery of poorly water-soluble drugs using such eye drops is challenging. Our previous studies have demonstrated that non-aqueous eye drops may result in higher drug penetration into the ocular tissues, especially when formulated as a suspension.

This project will evaluate the safety and efficacy of non-aqueous eye drops using in vitro and ex vivo models. Ocular irritation potential and drug penetration into ocular tissues will be determined via analytical and imaging methods.

Skills gained: Eye drop formulation and characterisation, in vitro toxicity, drug penetration, drug quantification, microscopy, image analysis.

The targetted outgrowth of neuronal axons and dendrites (neurites) is a key stage of early brain development, and is fundamental for establishing the healthy brain functions needed throughout the rest of our lives. Many developmental neurological disorders show a pattern of dysregulated neural circuitry, although the underlying molecular mechanisms remain to be resolved.

Our laboratory explores the role of the extracellular matrix in brain development, using in vitro and in vivo models. Hyaluronan is a unique sugar, synthesised directly on the neuronal membranes, and present particularly on growing neurite tips. This summer studentship will utilise molecular biology and microscopy methods to characterise changes in neuronal hyaluronan in models of hypoxic and inflammation-induced developmental neural injury.

Skills:

• Neuronal cell culture
• Light microscopy
• Molecular biology: Hyaluronan Quantification Enzyme linked immunosorbent assays (ELISA) and immunocytochemistry.

Like other types of extracellular vesicles (EVs), placental EVs carry many functional proteins, regulatory RNAs, DNA, and lipids, and phagocytosis of placental EVs by the target cells can impact the functions of target cells. Placental EVs have shown their functions in the regulation of maternal adaptation, including vascular adaptation in pregnancy. We have previously reported that pre-phagocytosis of placental EVs prevented endothelial cell activation induced by stimuli. In addition, our recent study shows that injection of placental EVs derived from normotensive placentae can reduce the blood pressure or slow the increase of blood pressure in spontaneously hypertensive rats (SHR).

Although the underlying mechanism of this change is unclear, this observation could be due to the changes in the function of endothelial cells, as the dysfunction of endothelial cells is a fundamental feature of hypertension and cardiovascular diseases. Therefore, in this project, we will investigate whether phagocytosis of placental EVs derived from normotensive placentae could reverse the activation of endothelial cells induced by stimuli, such as IL-6 or PMA. In this project, general laboratory, and cell and tissue culture skills are required.

Head-mounted miniaturised microscopes (miniscopes) enable brain activity to be recorded in freely moving rodents. By using miniscopes we can directly decipher how brain cell activity underlies behaviour as it happens in the awake behaving animal. We are examining the cellular mechanisms that underlie behavioural deficits in Alzheimer's Disease (AD). We utilise miniscopes to examine cellular activity in the hippocampus during spatial and object memory tasks in a mouse model of AD.

Skills that will be learned through the project:

• Behavioural testing on mice
• Analysis of mouse behaviour (semi-automated)
• Analysis of brain activity recorded with miniscopes
  

Interest/experience in neuroscience, data analysis, Matlab, Python, machine learning preferred.

X-linked Dystonia Parkinsonism (XDP) is an X-linked recessive, genetically inherited neurodegenerative disease endemic to the island of Panay in the Philippines. Clinically, XDP is characterized by the initial appearance of dystonia. Over time, parkinsonian traits such as bradykinesia, rigidity and tremor also appear. There are limited reports of XDP neuropathology, however the studies consistently agree on the presence of atrophy in basal ganglia structures, particularly in the striatum. The genetic basis of XDP is thought to be a hexameric repeat insertion within the TAF-1 gene. Our neuroanatomy research group is now studying this disease as part of an exciting international collaborative effort, together with research centres in Boston, U.S.A, and the Philippines.

The aim of this project is to investigate pathological changes in the XDP human brain with a wide range of markers to target various pathological features using diseased and control post-mortem human brain tissue.

Skills

• Immunohistochemistry using human brain sections
  
• Brightfield microscopy
  
• High throughput image acquisition
  
• Image analysis
  
• Statistical analysis
• Scientific report writing
  

Cerebral palsy is one of the most devastating consequences of brain injury caused by reduced oxygen and blood flow (hypoxia-ischemia), and is very common in preterm babies. Our group has recently found evidence of damage to the brain regions that surround cells (i.e., the extracellular matrix or ECM) following preterm brain injury. Further, this ECM damage seems important for controlling the survival of brain cells and the development of seizures. Thus, reducing injury to the ECM may be a novel treatment strategy to promote or restore brain function after preterm brain injury.

The aim of this preclinical study is to determine whether pharmacological blockade of abnormal ECM degradation is an effective therapeutic strategy to reduce brain injury.

During this summer studentship, the student will be involved in the assessment of cell survival, neural connectivity, data analysis and basic statistics.

This research will provide new knowledge on the mechanism of preterm brain injury, and practical information on optimizing new interventions to improve outcomes for preterm babies at risk of brain injury.

Post-pancreatitis diabetes mellitus (PPDM) is an exemplar secondary diabetes. It develops following an attack of pancreatitis – the most common disease of the exocrine pancreas. There has been a fundamental shift in our understanding of the pathogenesis of PDDM over the past quinquennium. The overall aim of this project is to provide deeper insights in regards to the metabolic pathways underlying PPDM. The project is part of a larger research theme of the COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatitic diseaseS) group. The group offers a vibrant research environment, comprehensive research training, and clinical research experience. For more information, please visit cosmos.auckland.ac.nz

Skills Taught

• Working in a clinical research team environment
• Extraction of clinical, diabetes-related data from a database
• Laboratory bench work
• Preparation of a manuscript for publication in an international peer-reviewed journal
  

Diabetic retinopathy (DR) is a sight-threatening complication of diabetes that is caused by a combination of elevated blood glucose levels (hyperglycaemia) and chronic inflammation. Over 250,000 New Zealanders have been diagnosed with diabetes, of which 20 to 25% are affected by DR. The other 75 – 80%, however, are at high risk of developing DR. The proposed project aims to investigate serum-based inflammatory markers that could enable prediction of DR onset and progression allowing early intervention.

The project will involve correlating laboratory test results (blood counts, liver and kidney function test results, C-reactive protein (CRP) and blood glucose levels) and diabetic retinopathy grades obtained over a five-year period to determine the best predictors of DR progression. Therefore, this project will suit a student with a background in biostatistics and/or bioinformatics.

Our sense of hearing originates in the inner ear organ called the cochlea. Cochlea is a pea-sized organ taking shape similar to snail shell, containing complex networks of vasculatures, innervations, sensory cells and neurons. To better understand the complex tissue physiology and fluid dynamics within the cochlea, this summer studentship project aims build anatomical models of sheep and human cochlea. In collaboration with the Virtual Brain Group (ABI), the student will take series of high resolution microCT datasets of human and sheep cochlea through image processing to build 3D model of cochleae with features including bones, nerve fibres, sensory epithelium and vasculatures.

The successful applicant will have strong interests in biology/physiology, have keen eyes for anatomy and in learning new skills. Please enquire to find out more details on the project.
Over the course of summer, the student will learn skills: Image analysis & processing by filtering and segmentation, 3D modelling and visualization, literature review and report writing.

The inner ear, the structure responsible for our balance (vestibular system) and hearing (cochlea), is deeply embedded in the temporal bone of our skull. Blood vessels and nerve fibres move through the bone surrounding the cochlea to reach sensory and neuronal components of the cochlea. We speculate that a network of vasculature within the bone play a vital role in the inner ear physiology.

This summer studentship project will investigate the interface between the bone and the blood vessels of the cochlea. The student will microdissect cochlea of human/animal to expose the internal surface of the cochlear bone, and use microscopy (fluorescent, scanning electron microscopy) to visualize the bony canals that contains the vasculature.

The successful applicant will have strong interests in biology/physiology, have keen eyes for anatomy and in learning new skills. Feel free to email Haruna to find out more about the project before you apply.

The student will learn over the course of summer: Tissue dissection, tissue preparation for microscopy, image analysis, literature review and report writing.

Glaucoma is the leading cause of preventable blindness in New Zealand and impacts 1 in every 10 people over the age of 70, and 3-5% of the population. Glaucoma is a chronic disease which is silent in the early stages of the disease.

One of the important aspects of glaucoma care is regular engagement with patients to provide education and support. With the Covid pandemic, the importance of communication and engagement through mediums other then in-person contact has emerged.

The purpose of this summer studentship is to develop an App that will be useful to glaucoma patients and provide education. The necessary applicant should have some experience in App development and computing skills. The applicant will work closely with Glaucoma NZ, a nation-wide charity for the prevention of blindness from glaucoma.

Background

Various anaesthetic agents cause at a low dose cognitive impairment and eventually loss of consciousness. In anaesthesia this level of consciousness can be measured with EEG monitors. It is known that these monitors are not equally sensitive to the various anaesthetic monitors. This difference could be due to the different binding mechanisms of anaesthetic agents.

Previously, two novel quantitative EEG analysis algorithms have been developed that proved specifically sensitive to hyperbaric nitrogen and nitrous oxide. Their specificity has been explained as a difference in the receptor binding by these two agents.

Objective

This study aims to use the two analysis algorithms to test the hypothesis of receptor specific anaesthetic agents causing different EEG patterns by applying both algorithms to available EEG recordings of participants exposed to propofol, hyperbaric nitrogen, nitrous oxide and ketamine.

Methods

EEG recordings will be analysed in Matlab (computational software) with previous developed analysis algorithms.

Research impact

This research will help to increase the understanding of the binding mechanism different anaesthetic agents and the effect this has on the EEG recorded.

Skills learnt

• Teamwork and research coordination skills
• Join the supervisors in recording EEG
• Quantitative EEG analysis with Matlab (previous programming experience is desirable)
• Oral presentation and scientific writing skills

Output

Support the drafting of a journal article.

Microglia are the predominant immune cells in the brain. They respond to injury and recent evidence suggests that they also contribute to causing neurodegeneration. Microglia are highly flexible cells and can take on many different forms and functions. However, it is still unknown which microglial phenotypes are more helpful, or harmful, in disease. This project will involve staining for novel microglia markers in human brain post-mortem tissue that will allow us to distinguish helpful from harmful microglia. This will help to identify new ways in which we can target microglia to treat disease.

We work within the Centre for Brain Research, alongside Prof. Mike Dragunow’s neuro-pharmacology lab.

Techniques include:

• Immunohistochemistry for protein expression changes in human brain post-mortem tissue.
• High throughput tissue microarray and multiplex immunochemistry platforms.
• Brightfield and fluorescence microscopy.
• Automated image analysis.
• Experimental Design and Data interpretation.
• Scientific report writing and figure making.
  

Cardiovascular disease affects over 30% of people worldwide, and is a leading cause of death. Elevated sympathetic nerve activity is a common feature of cardiovascular disease, contributing to end-organ damage, morbidity and mortality. Recent findings indicate that short-circuiting sympathetic nerve overactivity by removal of the stellate ganglion can eradicate arrhythmias, emphasising the need for novel therapeutic targets to correct signalling non-invasively. Unexpectedly, we have found upregulation of a subtype of purinergic receptors (P2X3) in the stellate ganglion of animals and humans with cardiovascular disease. We hypothesise that P2X3 within stellate ganglion contribute to excessive sympathetic drive to the heart in cardiovascular disease and the development of hypertension and cardiac arrhythmias.

We aim to determine cardiac effects of P2X3 within the stellate ganglion, and its role in hypertension and cardiac arrhythmias. With this information, we aim to uncover the therapeutic potential of a novel receptor antagonist already approved for clinical trials and translate our findings to benefit patients with cardiovascular disease. There are opportunities to contribute to this aim through molecular characterisation of P2X3 purinergic receptors in the stellate ganglion using techniques such as immunoflouresence, ddPCR and RNAscope, or analysis of functional cardiac responses (haemodynamic, electrical and pro-arrhythmic).

Dopamine is a key neurotransmitter that underlies many behaviors in health such as learning and memory, and reward, and is central in the pathophysiology of many neurodegenerative diseases (e.g. Parkinson’s disease) and neurological disorders (e.g. ADHD).

Our recent work has functionally characterized a novel dopamine pathway from the substantia nigra pars lateralis (SNL), that neighbors the better studied SNc, to the tail of the striatum. We have shown this projection have some overlap with the classic pathway, but there are several features which require further anatomical investigation.

This project will use advanced whole-brain tissue clearing, light-sheet microscopy (Auckland Bioengineering Institute) and tractography to trace the intact projection from the SNL to the tail striatum. Knowledge about this novel pathway could be beneficial to understanding the non-motor symptoms of Parkinson’s disease given the key role the tail striatum plays in processing sensory information.

G Protein-Coupled Receptors are critical to mammalian physiological function and are established as therapeutic drug targets. However, the complexity of the mechanisms controlling receptor signalling and downstream effects leaves huge scope for further discovery.

We are interested in how the receptor ligand, subcellular location of receptor and signalling mediators, temporal integration of signals, and protein-protein interactions induce unique cellular signalling fingerprints to influence downstream functional outcomes.

This summer studentship will investigate an aspect of receptor signalling in these contexts, utilising new resonance energy transfer biosensors that enable measurement of signalling responses and/or protein-protein interactions in real time and in cellular sub-compartments. We have particular interest in the cannabinoid receptors, but also study other GPCRs of physiological and disease relevance.

Specific objectives for this summer project will be decided closer to the start of the studentship to align with priorities in the research programme and the student's interests.

Skills Taught/Utilised

• Mammalian cell culture and transfection
• GPCR signalling assays and use of DNA-encoded biosensors

A background in molecular pharmacology is preferred, but this project is suitable for students with general interests in mammalian cell biology and/or drug development.

There are opportunities for continued study at Honours, Masters, and PhD level.

https://profiles.auckland.ac.nz/n-grimsey

Are you interested in using computational methods to diagnose disease?

Every individual has an underlying genetic susceptibility for disease. We want to know which variables predispose individuals to glaucoma. The successful applicant will use machine learning to utilise data on nearly 500,000 individuals to predict, from thousands of environmental, physical, and biological parameters (including genetics), the clinically relevant features which best predict risk for glaucoma and predict disease progression. Predicting risk from such alterations is fundamentally and technically challenging (e.g. combinatorically enormous number of ways that a genome can be altered), but our successfully established computational/bioinformatic approaches provide functional interpretation of the impact of genetic variation to identify personalised risk factors.

This project will be supervised by Professor Helen Danesh-Meyer (Ophthalmology, University of Auckland, New Zealand) and Dr William Schierding (Liggins Institute, University of Auckland, New Zealand), as part of a very productive and supportive research team.

MASDIR sequences are a new MRI technique that use old-school inversion recovery sequences in a new way. By creatively adding, subtracting, multiplying, and dividing images obtained using different inversion time, one can create images both exquisitely sensitive to small changes in T1 and synergistically sensitive to changes in T1, T2, and diffusion coefficient.

While prostate cancer is typically diagnosed on MRI as areas of decreased T2 signal and decreased apparent diffusion coefficient, MRI fingerprinting has suggested that the most telling characteristic of prostate cancer (as opposed to normal prostate tissue) is decreased T1. Note that these tissue properties are opposite most other diseases, which increase T1, T2, and diffusion coefficient.

Matai, in conjunction with Hauora Tairawhiti, is implementing a new prostate cancer diagnostic pathway involving pre-biopsy MRI and image guided biopsies. We will be investigating the use of MASDIR sequences to see if they can increase the diagnostic performance of MRI. The student will help with MASDIR image creation, radiology-pathology correlation, and assessment of the new sequence’s performance.

Skills: MATLAB, image processing, data analysis.

Mild traumatic brain injury (mTBI, e.g. concussion) has recently received media attention, especially for athletes in contact sport. The significance of mTBI is well accepted, however the detailed pathophysiology of the impact and associated symptoms is still under investigation. Researching mTBI is further complicated by difficulties in both data collection and experimentation due to large variability in the sustained injury and subsequent symptomology. A virtual brain model can address this problem as a simulation based on MRI scanned geometry can establish a framework to predict areas of high stress concentration for a particular impact.

This project will build on a pre-existing large human MRI database, collected over a season of rugby. There are two major parts: the first is to perform a manual segmentation of the brain, including the skull and different white matter tracts. The second part will use the segmented geometry from the first part, run a simulation of the impact, and run correlation tests with cognitive testing and instrumented mouthguard data.

Once the simulation has been validated to replicate the injury truthfully, this will serve as a significant foundation to the next phase of the project: the human mTBI simulation.

All software and simulation training will be provided.

The brain floats inside the cranium, supported by cerebrospinal fluid (CSF).

The blood pulsation, coupled with the CSF motion, induces time-varying pressure on the brain parenchyma. The pulsatile movement of the brain can provide important material property parameters that can distinguish between healthy and diseased states non-invasively. The brain is generally assumed to be incompressible, however due to interstitial fluid volume and structural organisation, different regions can move relative to each other by a small amount. These movements are concentrated around the brainstem and diencephalon area. Amplified MRI (aMRI) allows enhanced visualisation of these subtle movements which will have significant clinical relevance as a non-invasive tool to assess changes in brain material properties.

The goal of this project is to investigate the relationship between CSF flow, blood pulsation, and associated aMRI motion changes in a healthy subject. An expected outcome of the project is physiological explanation of changes in observed aMRI motion based on the CSF and blood volume changes.

We are looking for a student with an interest in brain imaging and post-processing, including 4D flow. The project will provide an exciting opportunity to work within a large multidisciplinary team, involving both medical imaging and bioengineering.

Do you have an interest in computational or statistical machine learning? No prior computational background necessary! You will learn important transferable research skills related to data handling, scientific writing, and advanced computational skills.

Every individual has an underlying genetic susceptibility for cancer development. Across all cancer types, the full complement of events driving tumour development still defies identification and, in many cases, no genetic drivers are found. Working within the internationally renowned Liggins Institute, the successful applicant will use machine learning to predict the genomic elements active in driving common cancer types. Detecting such alterations is fundamentally and technically challenging (combinatorially enormous number of ways that a genome can be altered), but our successfully established computational/bioinformatic approaches provide functional interpretation of the impact of genetic variation, genome structure, and gene expression to identify personalised risk factors.

This project will be supervised by Dr William Schierding (Liggins Institute, University of Auckland, New Zealand), and collaborate with Professor Justin M. O’Sullivan (Liggins Institute) and Professor Cristin Print (Molecular Medicine and Pathology) as part of a very productive and supportive international research team.

Amplified MRI (aMRI) is a new imaging method that magnifies very small motion of the brain as the heart beats. The aMRI method takes a standard dynamically resolved MRI sequence (available on all scanners to-date), and produces an amplified movie of brain motion.

This approach reveals deformations of the brain parenchyma and displacements of arteries due to cardiac pulsatility, especially in the brainstem, cerebellum, and spinal cord, which have not been observed before. The method has shown early promise for detecting pathological brain motion due to diseases or disorders that obstruct the brain or block the flow of cerebrospinal fluid, such as in Chiari Malformation I (CMI) patients. The project aims to enhance our knowledge about the link between obstructive brain disorders and brain motion.

Skills: MATLAB, image processing, biomechanical modelling, data analysis

Management of several conditions, characterized by high intracranial pressure (ICP), is hampered by the lack of a reliable, non-invasive technique to confidently determine if ICP is elevated. Raised ICP can severely compromise brain perfusion. Currently, the only way to definitively determine ICP is to measure it directly, requiring a highly invasive skull burr hole.

What if there was a way to determine the ICP with a non-invasive Magnetic Resonance Imaging (MRI) scan? We have developed a method called amplified MRI (aMRI), which can detect changes in brain motion with changes in ICP. We have acquired aMRI and physiological data on Intracranial Hypertension patients, to determine whether a link exists between brain motion based on aMRI and ICP. Such a link may pave the way to a diagnostic measure of brain pressure which may help to assess whether ICP is elevated to assist surgeons in their decision to perform surgery.

Skills: MATLAB, image processing, biomechanical modelling, data analysis

Parkinson’s disease (PD) is the fastest-growing chronic neurological disorder affecting 10 million people worldwide. Current therapies are symptomatic and do nothing to stop disease progression. We know that alpha-synuclein aggregate formation plays a crucial role in toxicity and progressive neurodegeneration. Still, it does not explain the variability in cell types affected and symptoms observed in patients with PD. The recent identification of fibrillar alpha-synuclein aggregates with noticeable differences in structural and phenotypic traits led to the hypothesis that different alpha-synuclein 3D conformations or ‘strains’ may be in part responsible for the heterogeneous nature of PD.

We hypothesize that the variability that occurs in PD can be stratified based on the alpha-synuclein strains and that effective treatment requires a strain-specific approach. Novel key genes and proteins linked to the specific strains have been identified through RNA sequencing. Modification of these targets could lead to the development of novel therapeutics to treat the underlying mechanisms in PD.

In this project, you will validate the expression of newly identified targets in human brain sections from PD cases and normal tissue. You will identify cell-type specificity, localisation of the protein relative to alpha-synuclein aggregates, cellular compartments and regional variability throughout the brain.

Heart failure is the inability of the heart to pump enough blood to supply the body’s energetic demands. A notable pathological feature of the failing heart is fibrosis, where excessive production of proteins, including collagen, fills the extra-cellular matrix (ECM). The ECM can be thought of as flexible scaffold that organises the cardiac myocytes into functional pump. At a macroscopic level fibrosis leads to both impaired relaxation and impaired contraction. However, limited data exists on the organisation of collagen at the nanoscale.Recent data from the Cardiac Nanobiology Group demonstrates excessive production of the rarely studied type VI collagen appears to disrupt nanoscale intra-cellular organisation of the calcium signally apparatus that controls contraction.

In this project you will use cutting edge super-resolution microscopy to characterise fibrosis and myocyte remodelling at the nanoscale. This will provide new insight on the structural changes that drive heart failure.

Stroke is the leading cause of adult disability worldwide. The Biomarkers And Recovery In Stroke (BARISTa) study was carried out to interrogate biomarkers in the initial days and weeks after stroke. The BARISTa platform collected biological samples (blood and urine), as well as clinical and demographic data.

This summer studentship will assess and validate the measurement of neurally derived biomarkers in biofluids for initial stroke-related damage and prediction of recovery in stroke. Technology platforms that will be used include cutting edge technology called Single Molecular Array (SIMOA), with the first platform in New Zealand being acquired by Dr Erin Cawston.

Specific objectives for this summer project will be decided closer to the start of the studentship to align with priorities in the research programme and the student's interests.

Skills Taught/Utilised

• Experimental Design and Data interpretation.
  
• Scientific report writing and figure making.
  
• Cultural, Ethical and Biological aspects of utilising human blood samples and clinical data.
  
• Utilisation of technologies for the detection on proteins in blood, including Single Molecule Array technology.
  

Havening is an innovative psychosensory intervention for the psychological trauma that utilises nurturing touch and is used by therapists worldwide. However, very little empirical evidence exists to understand the psychological and biological mechanisms through which Havening might work.

Our work investigates the role of nurturing touch during Havening therapy for psychological trauma on wellbeing. Participants (n=27) who had experienced mild psychological trauma underwent a Havening intervention that included either a touch component (H+, n=15) or a no-touch component (H-, n=12). H+ showed greater improvement in subjective wellbeing than H-. Brain function, as assessed using electroencephalography (EEG), has also been collected before and after the intervention. We propose to use machine learning methods to 1) Understand the brain response to H+ compared to H- conditions; 2) Predict response to H+ and H-. We have previously used Spiking Neural Networks (SNN) to investigate the effect of other interventions (e.g. Mindfulness) on brain function in which we predicted response to intervention with 93% accuracy, and demonstrated that improvement in mood paralleled improvement in functional connectivity. We will apply similar methods to our Havening data to understand neurocognitive mechanisms by which nurturing touch improves wellbeing and who might benefit most from such interventions.

We are looking for a curious student with an interest in computational modelling of brain data who can learn and assist with the analysis and interpretation of our EEG data and provide a draft for publication. They will get to experience working in a cross-disciplinary team between psychology, neuroscience, and artificial intelligence.

Expression of growth hormone (GH) is detected in a variety of different human cancers and is associated with reduced overall survival for breast and endometrial cancer patients. Despite the growing body of evidence implicating GH in cancer, preclinical studies investigating the therapeutic potential of inhibiting the GH receptor for the purposes of treating cancer have been hindered by a lack of an effective GH inhibitor suitable for in vivo studies.

This summer student project is part of a wider drug discovery effort aimed at developing novel GH receptor antagonists. In this project you will purify a series of novel GH receptor antagonists and determine whether they can neutralise GH action in cell-based and molecular biology assays.

The lymphatic vasculature is essential for fluid homeostasis in the body. When lymphatic vessels are obstructed or damaged this results in lymphoedema, the painful and debilitating accumulation of lymph in tissues. Secondary lymphoedema is one of the most significant survivorship issues following surgical and/or radiological treatment for tumours and is caused by incomplete lymphatic growth following lymph node removal.

Almost nothing is known about how lymphatic growth is regulated. To help further our knowledge of this process, we have isolated mutant zebrafish which display either undergrowth or overgrowth of lymphatic vessels. This project will help characterise these lymphatic mutants to uncover the genetics that control lymphatic vessel growth and repair.

Experiments could involve: 1) imaging lymphatic vessel growth or repair in mutant fish. 2) Isolating genomic DNA for use in mutation mapping or 3) experiments focused on the validation of candidate mutations.

Skills: Confocal imaging, genetics, molecular biology

How can we produce enough food to feed the ever growing world population?
How can we provide more nutritious food at lower cost to fight the diabetes epidemic?
How can we reduce the environmental impact from conventional farming?

One answer is cellular agriculture - culturing meat in the laboratory.

Growing meat in the laboratory requires the right cells to produce the meat being grown on a suitable scaffold with the right nutrients to produce the overall texture and taste of a meat product.

In this project we are looking at a novel source of cells from which to produce meat.

The project will examine the ability of using umbilical stem cells isolated from sheep to produce skeletal muscle cells with the eventual aim of producing engineered lamb.

Skills taught will include cell and tissue culture, cell differentiation, microscopy and PCR.

Our lab is currently investigating whether stem cells isolated from human umbilical cords have the capability to restore sight. Conditions which cause damage to eye tissues often lead to visual loss and significant drop in the quality of life. This project will look at whether stem cells isolated from human umbilical cords have the ability to repopulate diseased eye tissue. The cells face many challenges on the way to regeneration being survival followed by incorporation, differentiation and functional integration.

Key skills learnt: human tissue culture, stem cell culture, microscopy and PCR.

The brain is greedy - weighing only 2 percent of body weight, it uses a whopping 25 percent of the cardiac output. However, the brain is also vulnerable - when the flow is too low, we risk a stroke, and when the flow is too high we risk raised pressure within the brain. Cerebral autoregulation describes an elegant self-preservation mechanism; the brain acts to maintain a stable blood flow in the face of fluctuating supplying blood pressure. The breakdown of this cerebral autoregulation has been proposed to be an important contributor to poor outcomes in acute neurologic diseases such as traumatic brain injury, subarachnoid haemorrhage and stroke. However, the application of cerebral autoregulation monitoring in the stroke population has been limited.

This project will develop and validate signal processing techniques in a preclinical model of ischaemic stroke with opportunities to extend into the clinical population. The student will be trained in advanced signal processing techniques to validate the autoregulation measurements from time-series physiological data. Relationships will then be explored between cerebral autoregulation and functional outcome measures after stroke. It is anticipated that this will result in a high impact publication in a clinical stroke journal. This project would particularly suit prospective students interested in the intersection of physiology and clinical medicine.

Dr Joseph Donnelly (Department of Neurology, ADHB) and Dr Fiona McBryde (Department of Physiology, UoA) will be co supervisors for this project.

The venous circulation is often “forgotten”, with the focus of cardiovascular research and therapeutic intervention predominantly on arteries. However, the systemic veins store two-thirds of blood volume at rest, with reservoir beds such as the mesenteric (gut) circulation able to mobilize blood between the venous and arterial circulations. This shift in blood volume is vital to maintain blood pressure in the face of challenges such as blood loss, or an increase in blood volume.

We have directly measured high-resolution (beat to beat) blood pressure and blood flow to “venous storage” organs such as the gastrointestinal tract. Our data reveals that the relationship between blood pressure and the blood flow to the mesenteric circulation is altered under disease states such as hypertension, and acutely altered by changes in sympathetic nervous system activity. We have used cutting edge technologies to investigate the pressure-flow relationship under conditions of health and cardiovascular disease (hypertension), and during interventions to challenge the pressure-flow relationship.

A full understanding of the dynamic relationship between pressure and flow requires us to go beyond simple temporal correlations. Rich information and insight can be extracted from the frequency characteristics of our simultaneous measures of pressure and flow, through frequency domain analyses such as fast Fourier transforms and coherence functions. We would like to examine “steady state” differences between (for example) data from subjects with high blood pressure, compared to those with normal blood pressure. A detailed understanding of the pressure-flow relationship is essential to help us understand how organ perfusion is maintained in health and may be impaired under conditions of cardiovascular disease.

Outcome: To use methodological and modelling approaches to interrogate the relationship between venous and arterial pressures and flows under physiological and pathological conditions.

Supervisors: Dr Tonja Emans (Research Fellow Physiology), Dr Fiona McBryde (Senior Lecturer Physiology), Dr Sarah-Jane Guild (Senior Lecturer Physiology and Bioengineering)

The fundamental purpose of blood pressure is to facilitate the delivery of adequate blood flow to every organ in our body. However, the relationship between blood pressure and blood flow is not linear. Instead, a range of intrinsic and extrinsic mechanisms continuously constrict and dilate the blood vessels, to ensure that blood flow is matched to the metabolic demands of the tissue or organ being supplied.

Recent data reveals that the relationship between the “supply” pressure and the blood flow to organs can be chronically altered under disease states such as hypertension, or acutely altered by changes in autonomic nervous system activity. We have used cutting edge technologies to investigate the pressure-flow relationship under conditions of health and cardiovascular disease (hypertension), and during interventions to challenge the pressure-flow relationship. We have directly measured high-resolution (beat to beat) blood pressure and blood flow to highly metabolically active “consumer” organs such as the brain, which at rest requires ~20% of total cardiac output despite only consisting 2% of body weight.

A full understanding of the dynamic relationship between pressure and flow requires us to go beyond simple temporal correlations. Rich information and insight can be extracted from the frequency characteristics of our simultaneous measures of pressure and flow, through frequency domain analyses such as fast Fourier transforms and coherence functions.

We would like to examine “steady state” differences between (for example) data from subjects with high blood pressure, compared to those with normal blood pressure. Bidirectional feedback models would permit us to examine the potential directionality of pressure-flow modulation; it is well-established that pressure is a key driver of flow (pressure?flow), but we also believe that the reverse may also be true (ie flow?pressure). A detailed understanding of the pressure-flow relationship is essential to help us understand how organ perfusion is maintained in health and may be impaired under conditions of cardiovascular disease.

Outcome: To use methodological and modelling approaches to interrogate the relationship between blood pressure and brain blood flow under different physiological and pathological conditions.

Blood testing is commonly performed for diagnosis and management of various diseases. Though the tests are simple, straightforward, the sampling requires trained professional, is invasive (painful) and is very challenging when dealing with young children and individuals with blood taboos and needle phobia. In this project we are interested in investigating the potential of hollow microneedle (HMN) arrays as minimally invasive way to extract blood samples for diagnostic application. HMNs consist of multiple micron size needles which can effectively penetrate the skin and by utilizing an appropriate actuator mechanism (capillary action or pressure driven), small volumes of blood can be withdrawn using these arrays, without causing much discomfort to the patients. We are particularly interested in the possibility of combining HMN with our highly controllable motor driven injection devices that could be reversed to ‘suck’ a blood sample back through the HMN array.

During this project the student will fabricate HMN arrays using the precision machining capabilities at the Auckland Bioengineering Institute. These arrays will then be designed to operate with a motor driven device to apply a controlled suction through the HMN. Testing would then be performed on models of tissue to evaluate how well this approach may work as a blood sampling technique.

This project involves surgical dissection and 3D reconstruction of the right lymphovenous junction.

The project includes:
1- Literature Review
2- Dissection

Tuberculosis (TB) remains one of the world's leading global health threats. The 2020 Global TB Report by WHO suggests that the COVID-19 pandemic could cause an additional 6.3 million TB cases globally between 2020 and 2025. Today's treatments cannot most effectively combat the pandemic because they are too long, complex, and unable to sufficiently address the full spectrum of drug resistance.

The TB group at Auckland Cancer Society Research Centre (ACSRC) has been working with TB Alliance in developing new Anti-TB agents for many years. This project aims to improve the activity, solubility and stability by modifying the structures of the current leads. The summer student will get well trained in medicinal chemistry and drug development, including skills in drug design, literature searching using databases (SciFinder, Reaxys etc.), organic synthesis, compound purification (chromatography, HPLC etc.), structure characterisation (NMR, MS etc.), drug assay and evaluation.

A fume hood in a standard chemistry laboratory, personal protective equipment, a desktop with necessary software and safety training will be provided. ACSRC has a multidisciplinary and collaborative environment.

Experience working in a chemistry lab would be an advantage.

Severely ill patients generally require mechanical ventilation (MV). While lifesaving, MV is not innocuous and may, in fact, produce damage even to healthy lungs. This is termed Ventilator Induced Lung Injury (VILI), and it is currently prevented by carefully balancing the ventilatory parameters. However, this balance is very challenging to achieve and thus there is a great need to develop other approaches to prevent or treat VILI. Our group is currently undertaking research on this subject, and we are looking for a student to join us for the summer.

During the project, the student will:

• Complete a systematic literature review on animal models for VILI.
• Work on the design of novel devices to mitigate VILI.
• Participate in active pre-clinical research surrounding VILI.
  

At the end of the project the student will:

• Have the knowledge to conduct a systematic review of the literature from conception all the way to publication.
• Understand the importance of VILI.
• Have a general understanding of how research is conducted at the university.
  
• Have a general understanding of academia.
  

The retinal synaptic network continues its maturational refinement after eye opening. This synaptic refinement is dependent upon the levels of visual stimulation over many years in humans, and over just a few days in other species. In spite of existing evidence for age-dependent changes in light-evoked responsiveness, little is known about the maturation of synaptic function at the cellular level in the retina after eye opening. We have been examining the eyes of chicks stimulated with different light levels and wavelengths. We have collected tissues where we can examine the development of the retinal synaptic layers.

The summer project will consist on processing the retinal tissue for transmission electron microscopy, imaging and data analysis. The project has implication for the understanding of myopia and eye growth that will be incorporated into the discussion. The student for this project needs to have basic laboratory training but tissue processing, image analysis and data analysis will be some of the skills you will acquire in this project.

Stroke is one of the leading causes of mortality and long-term disability in New Zealand which disproportionally affect Maori and Pacific populations. While effective hospital-level interventions improve stroke patient outcomes, only a fifth of all stroke patients are eligible due to narrow treatment windows. Nebulized sodium nitrite is a potential strategy for extending the stroke treatment windows by selectively increasing blood flow to ischaemic brain regions. Using an animal-stroke model, this project will examine the therapeutic potential of nebulized sodium nitrite in improving brain blood flow and functional outcomes following ischaemic stroke.

Nebulized sodium nitrite could be administered quickly after stroke onset by first-responders, which could improve access for patients in geographically remote areas within New Zealand. Improving hyper-acute stroke management with supportive therapies could significantly improve healthcare for all Maori, but especially for the rural Maori communities. For these reasons, nebulized sodium nitrite has a huge potential to be translated into clinical practice rapidly and help reduce health inequity in New Zealand.

The studentship will require the applicant to perform integrative physiological research. The ideal candidate will need to have a keen interest in translational research and be comfortable working in a laboratory environment.

In textbooks, it has long been stated that there is a complete withdrawal of the parasympathetic nervous system during exercise. Recent evidence suggests that this is not the case and that cardiac parasympathetic nerve activity increases during exercise. What causes this increase in parasympathetic nerve activity during exercise is unknown. This summer studentship aims to establish if the metabo- or mechano-exercise pressure reflex activates cardiac vagal nerve activity during exercise. Using a large animal model will enable preclinical translational studies that have more relevance to the clinical condition.

This project will introduce the student to a number of experimental techniques in conscious animals, including aseptic surgery techniques (assisting with surgery), conducting experimental protocols in conscious animals and analysis of data. Preference will be given to students who would like to continue with postgraduate study in the form of an Honors 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
  

To date, direct study of the cardiac vagal branch has not been possible and limited the investigation into how the cardiac vagal nerve modulates the heart beyond heart rate control. Our laboratory has recently developed a method to directly record cardiac vagal nerve activity. This summer studentship will investigate how cardiac vagal nerve activity modulates different aspects of heart function, including contractility, coronary artery blood flow, and cardiac output. Using a large animal model will enable preclinical translational studies that have more relevance to the clinical condition.

This project will introduce the student to a number of experimental techniques in conscious animals, including aseptic surgery techniques (assisting with surgery), conducting experimental protocols in conscious animals and analysis of data. Preference will be given to students who would like to continue with postgraduate study in the form of an Honors 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
  

In textbooks, it has long been stated that there is a complete withdrawal of the parasympathetic nervous system during exercise. Recent evidence suggests that this is not the case and that cardiac parasympathetic nerve activity increases during exercise. What causes this increase in parasympathetic nerve activity during exercise is unknown. This summer studentship aims to establish if the metabo- or mechano-exercise pressure reflex activates cardiac vagal nerve activity during exercise. Using a large animal model will enable preclinical translational studies that have more relevance to the clinical condition.

This project will introduce the student to a number of experimental techniques in conscious animals, including aseptic surgery techniques (assisting with surgery), conducting experimental protocols in conscious animals and analysis of data. Preference will be given to students who would like to continue with postgraduate study in the form of an Honors 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
  

To date, direct study of the cardiac vagal branch has not been possible and limited the investigation into how the cardiac vagal nerve modulates the heart beyond heart rate control. Our laboratory has recently developed a method to directly record cardiac vagal nerve activity. This summer studentship will investigate how cardiac vagal nerve activity modulates different aspects of heart function, including contractility, coronary artery blood flow, and cardiac output. Using a large animal model will enable preclinical translational studies that have more relevance to the clinical condition.

This project will introduce the student to a number of experimental techniques in conscious animals, including aseptic surgery techniques (assisting with surgery), conducting experimental protocols in conscious animals and analysis of data. Preference will be given to students who would like to continue with postgraduate study in the form of an Honors 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
  

We discovered xanthenone-based chemistry is a novel and highly effective way of developing new drugs that selectively block mutated disease-causing kinases found in cancer cells.

Currently we are focusing on highly selective drugs targeting mutated forms of the c-Kit receptor. c-Kit (also called CD117 and stem cell factor) is a receptor tyrosine kinase involved in intracellular signalling and mutated form of c-Kit plays a crucial role in some cancers eg: c-Kit has been reported to be mostly correlated with gastrointestinal stromal tumour (GIST).

We are interested in developing our understanding of how these compounds work against the enzyme by modifying the inhibitor’s structure.

In this medicinal chemistry project, you will obtain experience in:

1. stepwise synthesis of drug molecules from commercially available building blocks (starting material), purification (various chromatographic techniques),
structure identification [nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy].
2. the use of scientific software relevant to medicinal chemistry (Scifinder, ChemDraw).
3. literature searching.

Second year chemistry knowledge would be helpful but not essential.

Stroke is a devastating disease with limited acute therapeutic options to improve outcomes. Recent findings in animals have shown that increasing nitric oxide (NO) bioavailability can selectively improve blood flow to ischaemic brain regions, thereby improving functional recovery and reducing stroke infarct volume. Nebulized sodium nitrite is an effective mean of increasing NO bioavailability in humans and has been shown to improve cardiac function in heart failure patients. However, its effects on the cerebrovasculature has not been examined in humans. Using a multi-model research approach, this studentship will examine the effects of nebulized sodium nitrite on cerebral haemodynamics. Findings from this study may lead to novel therapeutic strategies for improving patient outcome following stroke.

During this studentship, the successful applicant will learn how to perform integrative physiological research and duplex Doppler imaging. The ideal candidate will need to demonstrate a keen interest in human physiology and an aptitude for translational research.

Placental extracellular vesicles act as long distance fetal-maternal communicators during pregnancy. These EVs derived from the syncytiotrophoblast, the largest single cell in the body, can carry cargo capable of modulating maternal physiological, metabolic and immunological processes. Current proteomics analysis are performed on digested proteins from the whole EV, and does not differentiate between proteins carried on the inside, the surface, or attached to surface proteins (collectively called the protein corona) of extracellular vesicles.

The aim of this project is to develop and validate a protocol to separately isolate proteins from the corona, surface and internal cargo of placental extracellular vesicles. The protein profiles of each compartment can then be used for comparison between healthy and diseased pregnancies to help unravel the secrets of the mechanism by which the placenta contributes to the promotion and maintenance of healthy pregnancies, as well as triggering pregnancy complications such as preeclampsia and intrauterine growth restriction.

Recent evidence suggests that in humans, the outcome of pregnancy is associated with mum’s long term cardiovascular health. Women who experience preeclampsia (a hypertensive disorder) during pregnancy are at a higher risk of developing cardiovascular disease later in life – a risk higher than that imposed than smoking! Conversely, women whom have had multiple healthy pregnancies appear to be protected against developing cardiovascular disease. We think that the link between the outcome of pregnancy and future cardiovascular disease lies in the nature of placental extracellular vesicles.

Placental extracellular vesicles (EV) act as long distance fetal-maternal communicators during pregnancy. We have shown that these EVs derived from the syncytiotrophoblast, the largest single cell in the body, can carry cargo capable of modulating maternal vascular function and can protect maternal blood vessels against vasoconstrictors, such as angiotensin II, for months after exposure. In this project, we will use a state-of-the-art ultrasound to assess the cardiac function paired with non-invasive blood pressure measurements to determine whether exposure to healthy human placental EVs can rescue the spontaneously hypertensive rat from hypertension and premature heart failure.

Placental extracellular vesicles (EV) act as long distance fetal-maternal communicators during pregnancy. We have shown that these EVs derived from the syncytiotrophoblast, the largest single cell in the body, can carry cargo capable of modulating maternal vascular function and can protect maternal blood vessels against activation by vasoconstrictors, such as angiotensin II and endothelin-1, months after initial exposure. Furthermore, clinical evidence also show that healthy pregnancies appear to be protective against the development of cardiovascular disease later in life. However, the mechanism by which this protective effect occurs is unclear.

Using blood vessels taken from rodents previously exposed to placental EVs, this project will use a range of histological and immunoassay techniques to identify the involvement of potential pathways which regulate vascular resistance and blood pressure. Findings from this project may potentially inform of the mechanism by which placental EVs induce long term functional changes in the maternal vasculature.

Broth grown bacteria of a well characterised laboratory strain of Staphylococcus aureus have a minimum inhibitory concentration (MIC) of 2 µg/ml for flucloxacillin, an antibiotic that is active against beta lactamase producing S. aureus, but not MRSA. That same strain grown as a biofilm is not killed by 2 mg/ml flucloxacillin; 1000x more antibiotic than the MIC! When this biofilm biology occurs in an infection (and 70% of all infections are biofilms), it means an MSSA (methicillin sensitive S. aureus) strain behaves like an MRSA and is much harder to treat. Lactoferrin, a multifunctional protein of the innate immune system, brings the biofilm eradication concentration for flucloxacillin back down to 20 µg/ml, although it does not kill biofilm alone. The antibiotic adjuvant activity lactoferrin provides offers a new strategy to treat biofilm infections, and especially those MSSA infections that are still common in New Zealand. In this project you will investigate the biofilm killing potential of lactoferrin plus flucloxacillin against a range of clinical isolates to demonstrate the breadth of activity against two groups of MSSA, those that responded to flucloxacillin treatment, and those that did not.

Techniques will include: Microbiology in a PC2 lab, growth of mature S. aureus biofilms in a bioreactor, biofilm eradication assays for each isolate comparing the effectiveness of flucloxacillin, lactoferrin and flucloxacillin plus lactoferrin combinations, microscopy of biofilms to visualise biofilm killing or survival. Depending on time and student interest/skills there may be an opportunity to expand the scope of the project to other species of bacteria and other antibiotic/lactoferrin combinations.

In a mouse model of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease, pathogenesis is modulated by the gut microbiome. One member of the gut microbiome in particular, Parabacteroides goldsteinii, and its functional LPS component ameliorate lung inflammation. P. goldsteinii does not colonise the lung, so how does it exert its effect on the lung from the colon? Our hypothesis is that extracellular vesicles (EVs) derived from the outer membrane of the bacterium enable transport of the anti-inflammatory LPS to the lung.

In this project we will isolate EVs from P. goldsteinii cultures and characterise them: size, numbers, protein and LPS content, anti-inflammatory activity.

Techniques will include: Microbiology in a PC2 lab, anaerobic growth of Parabacteroides goldsteinii, isolation and purification of EVs, assays to quantify and size EVs purified, electron microscopy to demonstrate the presence of EVs, and the absence of other contaminating material, assays for protein, lipid and LPS, assays for anti-inflammatory activity.

The ocular lens remains transparent over many decades of life and plays a crucial role in focussing light onto the retina to facilitate vision. Cataract, the opacification of the lens, is the leading cause of blindness worldwide, with the major risk factors diabetes and aging leading to specific cataract phenotypes. Although a surgical cure for cataract exists, this approach is costly, and there is no cost-effective pharmaceutical treatment to delay or prevent the onset of lens cataract. This project aims to use advanced tissue imaging approaches to assess the anti-cataract potential of a range of chemical compounds. The uptake and metabolism of both existing ocular drugs and compounds derived from plants with a range of chemical properties will be studied. This will not only determine their anti-cataract properties, but also help in the design of effective therapeutic delivery strategies.

Skills: Lens dissection, tissue sectioning, MALDI imaging mass spectrometry, optical microscopy, data analysis.