Biomedical Science

Why is diabetes associated with high rates of heart disease?

Supervisors

Kim Mellor
Parisa Koutsifeli

Discipline

Biomedical Science

Project code: MHS004

Heart disease is the leading cause of morbidity and mortality in diabetic patients. In diabetes, cardiac complications are evident even in the absence of vascular abnormalities and represent a primary manifestation of the disease. Understanding the mechanisms of cardiac pathology in diabetes is important for the development of new targeted treatment therapies. We have recently reported that a particular type of programmed cell death, autophagy, is upregulated in diabetic hearts but an understanding of how autophagy contributes to cardiac pathology in diabetes is lacking. Preliminary evidence suggests that the disturbed balance of systemic glucose, fructose and insulin levels in diabetes modifies key signaling pathways involved in autophagy induction. This project aims to investigate the molecular mechanisms underlying heart dysfunction in diabetes.

Extracellular vesicle therapy for ocular diseases

Supervisors

Assoc Professor Ilva Rupenthal
Dr Lola Mugisho

Discipline

Biomedical Science

Project code: MHS010

Extracellular vesicles (EVs) are cell-derived nanoparticles that have recently gained the attention of the scientific community due to their role in cell-to-cell communication as well as other physiological processes. More recently, studies have investigated the use of EVs as novel biomarkers in disease progression while others have harnessed their therapeutic potential in delivering cargo to the target tissue.

Our research group is interested in characterising the use of EVs in different ocular disease models. We have projects relating to the use of EVs as novel biomarkers in the progression of eye diseases as well as their potential as retinal drug delivery systems.

Skills developed include:

  • Isolation and purification of EVs
  • Tissue culturing
  • Immunohistochemistry
  • Confocal microscopy
  • Statistical analysis
  • Report writing

Imaging biomarkers in Parkinson’s disease

Supervisor

Assoc Professor Miriam Scadeng (ext 89659)

Discipline

Biomedical Science

Project code: MHS013

Currently there are no early biomarkers for Parkinson’s disease and most patients only present when the disease presents clinically, by which time much cell death has already occurred and preventative measures are not effective.

Abnormal metal distribution in the brain has been associated with Parkinson’s disease and other neurodegenerative diseases. There may also be a relationship between metals such as iron, copper and zinc, the presence or loss of neuromelanin, a neuroprotective protein that scavenges metals in the brain. Neuromelanin is visible on MRI, and we hypothesise that we can determine metal load in the brain of patients with Parkinson’s disease by melanin imaging.

The students will join the team at the Centre for Brain Research, and skills acquired during the project include an in-depth knowledge of the neurobiology of Parkinson’s disease, magnetic resonance imaging, histology and metal analysis, and potentially AI if interested.

Project suitable for neuroscientist interested in future graduate study, or medical student. Envisioned outcome: publication of paper.

3D MRI Atlas of Dolphin and whale Neuroanatomy

Supervisor

Assoc Professor Miriam Scadeng (ext 89659)

Discipline

Biomedical Science

Project code: MHS014

The brains of dolphins have striking resemblance to humans, in both size and structure, and it would appear that much of their function parallels human function, including language processing. The dolphin being a long-lived, large brained mammal, is proving to be an unexpectedly useful model for the study of human ageing and dementia. The development of a high resolution atlas based on 3D MRI imaging to act as a road map for future studies such as additional DTI and functional MRI studies, is a vital next step to moving the field forward. The MR imaging data for this project has been acquired.
Skills acquired during the project: in depth knowledge of neuroanatomy (human and dolphin), data segmentation. Suitable project for neuroscientist or medical student. Envisioned outcome: publication of atlas as a paper.

References:
Wright A, Theilmann R , Ridgway S, Scadeng M. Diffusion tractography reveals pervasive asymmetry of cerebral white matter tracts in the bottlenose dolphin (Tursiops truncatus) Brain Struct Funct. 2017 DOI : 10.1007/s00429-017-1474-3

Wright A, Scadeng M, Stec D, Dubowitz R, Ridgway S, Leger JS. Neuroanatomy of the killer whale (Orcinus orca): a magnetic resonance imaging investigation of structure with insights on function and evolution. Brain Struct Funct. 2017 Jan;222(1):417-436. doi: 10.1007/s00429-016-1225-x.

3D structural mapping of the sensory apparatus of balance

Supervisors

Haruna Suzuki-Kerr
Rachael Taylor
Peter Thorne

Discipline

Biomedical Science

Project code: MHS018

The peripheral vestibular system is the apparatus in the inner ear involved in balance. The vestibular system consists of three semi-circular canals and two otolithic organs, all embedded in the inner ear bony labyrinth.

This summer project aims to compare structures of the sheep vestibular system with that of human. The participating student will be trained to process sheep inner ear samples, scan them using micro-computerized tomography (microCT) and perform 3D data processing ultimately to construct a high-resolution 3D model of sheep vestibular system. These will be compared to existing databases on the human inner ear. Sheep are emerging as a popular large animal model for human diseases, and our research cluster plans to use sheep as a preclinical model for inner ear diseases including hearing loss and balance disorders. The outcome from this project will fill the knowledge gap between sheep and human vestibular systems for our future research.

The successful applicant should have a basic background in biology and physiology.
Interest in postgraduate research programmes will be preferable, but not essential. Interested candidates should contact Dr Suzuki-Kerr for further details on the project.

Skills developed include:

  • MicroCT
  • Tissue dissection
  • Image analysis
  • 3D image data processing
  • scientific report writing

Targeting connexin43 hemichannels for the treatment of chronic eye diseases

Supervisors

Dr Lola Mugisho
Assoc Prof Ilva Rupenthal

Discipline

Biomedical Science

Project code: MHS021

Connexin43 hemichannels are pathological pores that open in disease leading to inflammation-induced cell death. Opening of connexin43 hemichannels has been linked to numerous diseases affecting multiple organ systems. Our group focusses on understanding the role of connexin43 hemichannels in the development and progression of chronic diseases affecting the eye. We have projects relating to elucidating the mechanism by which connexin43 hemichannels contribute to disease pathogenesis, and evaluating the efficacy of connexin43 hemichannel blockers in models of several chronic ocular diseases.

Using human donor eye tissues to understand the pathophysiology of chronic eye diseases

Supervisors

Dr Lola Mugisho
Assoc Prof Ilva Rupenthal

Discipline

Biomedical Science

Project code: MHS022

Access to human donor eye tissues through the New Zealand National Eye Bank has provided a unique opportunity to study the pathophysiology of chronic eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). AMD and DR are the leading causes of vision loss in our aged and working age populations, respectively. The proposed project will characterize inflammatory markers within human donor tissues to inform drug development.
 
Skills developed include:
  • Human donor eye processing
  • Immunohistochemistry
  • Confocal microscopy
  • Statistical analysis

Regulation of lymphatic vessel growth

Supervisor

Jonathan Astin (ext 84480)

Discipline

Biomedical Science

Project code: MHS023

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.

Experiments could involve:

  • Imaging lymphatic vessel growth in mutant fish
  • Isolating genomic DNA for use in mutation mapping
  • Experiments focused on the validation of candidate mutations

Skills developed include:

  • Modelling organism genetics
  • Live cell imaging
  • Zebrafish husbandry

Drugging the lens – imaging uptake and distribution of ocular therapeutics in the ocular lens

Supervisor

Gus Grey

Discipline

Biomedical Science

Project code: MHS026

The ocular lens focusses light onto the retina at the back of the eye to form a sharp image. It remains transparent over several decades of life, and in the absence of a blood supply operates a microcirculation of water and nutrients to support tissue transparency. The lens suffers from off-target effects from some ocular drugs, while is itself a target for anti-cataract therapies, which are designed to delay or prevent the onset of lens opacities. However, it remains unclear where drugs are taken up into the lens, how they are transported within the tissue, and where they are metabolised. Using MALDI imaging mass spectrometry, this project will compare over time the uptake, transport and metabolism of different ocular drugs with different properties to inform the behaviour of drugs in different regions of the lens. This will inform the design of future therapeutic molecules designed to fight the cataract epidemic.

Skills developed incude:

  • Culturing tissue
  • Cryosectioning
  • Imaging mass spectrometry
  • Data anlaysis
  • Report writing

Non-aqueous eye drops for better drug penetration

Supervisors

Assoc Professor Ilva Rupenthal (ext 86386)
Dr Priyanka Agarwal

Discipline

Biomedical Science

Project code: MHS029

Local drug administration using topical eye drops is generally preferred when treating ocular surface conditions. However, poor drug penetration from water-based eyedrop is often an issue, especially when treating conditions beyond the surface of the eye. Non-aqueous eye drops may result in higher drug penetration into the ocular tissues, especially when delivering poorly water-soluble drugs.

This project will investigate drug penetration from non-aqueous eye drops using an ex vivo whole eye penetration model. Tissue drug concentrations after topical eye drop administration will be determined via analytical and imaging methods.

Skills developed include:

  • Eye drop formulation and characterisation
  • Investigating tissue penetration
  • Drug quantification
  • Microscopy
  • Image analysis

Characterisation of perivascular and vascular cellular involvement in the pathogenesis of Huntington’s disease using human brain tissue microarrays

Supervisors

Dr Malvindar Singh-Bains (85793)
Adelie Tan
Prof Mike Dragunow
Dist Prof Richard Faull

Discipline

Biomedical Science

Project code: MHS030

Huntington’s disease (HD) is a genetic progressive neurodegenerative disorder characterized by motor disturbances, cognitive loss, and psychiatric manifestations. HD is caused by an expansion of polyglutamine trinucleotide repeats in the IT15 [Interesting Transcript 15] gene on chromosome 4, which encodes a mutant protein called huntington. Recent studies indicate that disruption of the blood-brain barrier (BBB) and neurovasculature plays an important role in HD pathogenesis. This is hypothesised to increase the potential development of neuroinflammation, compromising the health of neurons already susceptible through aberrant functioning induced by the mutant Huntington gene (Waldvogel, Dragunow, & Faull, 2015). The BBB is an extremely important factor to consider when determining treatment strategies for HD, because crossing the BBB is an essential consideration in the development of brain-acting therapeutics. Therefore, one of the main aims of this study is to investigate the role of key cells within the BBB, perivascular and vascular cells, in the HD human brain. We will examine markers for basement-membrane associated molecules, endothelial cells, and mural cells using human brain tissue microarrays (TMA) comprised of clinically well-characterised HD and control post-mortem cases with variable pathological and clinical phenotypes.

Skills developed include:
  • 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

Characterisation of astrocytic involvement in the pathogenesis of Alzheimer’s disease using human brain tissue microarrays

Supervisors

Dr Malvindar Singh-Bains (85793)
Micah Daniel Austria
Prof Mike Dragunow
Dist Prof Richard Faull

Discipline

Biomedical Science

Project code: MHS032

Dementia is an emerging global public health challenge for our generation: over 35 million people are affected by this condition worldwide (Alzheimer’s Disease International, 2010). In New Zealand, one-in-three of those over 65 will develop an ageing-related brain disorder (primarily Alzheimer’s disease/dementia) (Brain Research NZ, 2015). Current evidence heavily implicates the involvement of neuroinflammation, an immune response in the brain, as one of the key features of Alzheimer’s disease (AD) pathology. It has been observed that astrocytes, one the brain’s primary supporting cells, have been implicated in neuroinflammation through a process known as reactive astrogliosis, which involves several changes to astrocytic morphology and phenotype (Sofroniew & Vinters, 2010; Serrano-Pozo et al., 2013). However, the spectrum of astrocytic cell involvement in AD has not been fully dissected, and is still far from being well understood. The objective of this project is to screen for astrocytic changes in the AD human brain with a wide range of immunohistochemical markers for proteins involved in astrocytic function. We will examine markers for astrocytes using human brain tissue microarrays (TMA) comprised of clinically well-characterised AD and control post-mortem cases.

Skills developed include:
  • Immunohistochemistry on paraffin embedded human brain sections and tissue microarrays
  • Understanding the principles of tissue microarray
  • Bright field microscopy 
  • Digital image acquisition
  • Scientific report writing and figure making

Using super resolution microscopy to study the extracellular barrier to movement of fluids in the lens

Supervisors

Rosica Petrova (09 923 8728)
Paul Donaldson

Discipline

Biomedical Science

Project code: MHS036

Cataract or clouding of the lens is the leading cause of blindness in the world today. The only available treatment for cataract is a surgical replacement of the cataractous lens with an artificial plastic lens, a procedure that may cause post-surgical complications for the patient and places an enormous financial burden on the national health system.

Recent research from our lab have shown that cataract formation is associated with a failure of the lens internal microcirculation system, which in the absence of a blood supply delivers nutrients to and removes waste products from the deepest parts of the lens. Therefore, the aim of this summer project is to visualise the operation of the microcirculation system. This will be achieved by using super resolution imaging to resolve the penetration of fluorescent tracer molecules into the lens to observe how the changes in the extracellular space between cells directs the delivery of molecules to the central core of the lens.

Skills developed include:
 
  • Fixation of the lens
  • Cryosectioning of the lens tissue
  • Labeling with specific membrane marker wheat germ agglutinin (WGA)
  • Super resolution imaging that will involve using either a dSTORM or airy scan microscopy to allow visualisation of the change of extracellular space at the nm range

Investigating exercise intolerance in hypertension

Supervisor

Rohit Ramchandra

Discipline

Biomedical Science

Project code: MHS038

Exercise improves outcomes for people of all ages. However, tolerance to exercise appears to be significantly limited in patients with cardiovascular disease, in particular in patients with hypertension. What drives this intolerance is not clear and this project will investigate the role of blood flow to the heart in limiting exercise tolerance.

We will utilise a large animal model to explore changes in heart muscle blood flow and autonomic drive during exercise. The consequences of hypertension for perfusion of coronary blood vessels will be explored. This project will introduce the student to a number of experimental techniques in conscious animals. Preference will be given to students who WANT to continue on with a Masters project.

Differentiation of adult stem cells for corneal endothelial regeneration

Supervisors

Jie Zhang (ext 81630)
Amatul Mateen

Discipline

Biomedical Science

Project code: MHS039

The human corneal endothelium is a single layer of cells lining the back of the cornea, the clear window at the front of the eye. It regulates the hydration status of the cornea. A major road block to true corneal regeneration is the inability of these cells to proliferate or regenerate in humans and the resistance of these cells to expand in culture. Corneal endothelial dysfunction results in corneal oedema, opacity, and loss of vision, for which full thickness or partial thickness (endothelial) corneal transplantation is the definitive treatment. In New Zealand, the limited supply of donor corneal tissue is the rate limiting step for corneal transplantation. New treatments for corneal endothelial diseases are required to overcome the current limitations of donor tissue supply.

The recent discovery of adult stem cells in the ‘Transition Zone’ (TZ) marks the beginning of exciting forage into their application for endothelial regeneration. Our team has successfully established a TZ explant culture protocol. TZ culture is a mixed population of more differentiated (corneal endothelial like) and less differentiated (stem cell like) cells. However, in order to advance this into an applicable therapy, better control of cell differentiation is required in order to avoid the risk of cancer formation from uninhibited proliferation of stem cells and allow the use of cells at earlier passages.

We aim to determine the potential of transition zone cells to be developed into cell therapies and tissue grafts for corneal endothelial diseases. We propose to drive the differentiation of TZ cells or use cell sorting to separate differentiated cells from stem cells as the first step. The differentiated cells will be delivered in ex vivo or in vivo models to determine their regenerative potential.

Key words: ophthalmology, eye, cornea, diseases, therapy, stem cells, regeneration

Skills developed include:

  • Cell culture
  • Quantitative polymerase chain reaction (qPCR)
  • Western blotting
  • Immunohistochemistry
  • Confocal microscopy

Retinal microglia: Novel molecular markers to diagnose early stage diabetic retinopathy

Supervisors

Monica L Acosta (09 923 6069)
Gaganashree Shivashankar

Discipline

Biomedical Science

Project code: MHS044

New evidence from diabetic animal models and human post-mortem tissues studied in our laboratory suggest that non-proliferative diabetic retinopathy (DR) is a multifaceted inflammatory disease of the retina. Microaneurysms and oedema in the diabetic eye are associated with a local inflammatory response that we discovered gets worse by microglia activation. The study will identify what molecular signals are elicited in DR tissues once microglia is activated to propose new therapeutic targets of early stage DR.

The project will be conducted in rodents. The study employs techniques similar to those used in an eye examination (fundus imaging, optical coherence tomography) followed by tissue dissection, protein extraction, immunolabelling and data analysis.

Experience in biomedical studies is preferred but is not essential.

Anti-inflammatory drugs for intervention in retinal dystrophies: Do they rescue vision loss?

Supervisors

Monica L Acosta (09 923 6069)
Assoc Professor Andrea Vincent

Discipline

Biomedical Science

Project code: MHS046

Inherited retinal dystrophies are a large group of diseases that result in death of photoreceptors, the light-sensing cells of the retina. Still largely incurable and progressive with age, protection of surviving photoreceptor cells is imperative. Multiple mechanisms of action have been proposed in the intervention of retinal dystrophies but there are no conclusive studies of the effect of the drugs on vision. We want to conduct a preclinical efficacy study to determine if it is safe to use anti-inflammatory drugs in damaged retinas. We will assess retinal function and cell survival as a function of drug dose and duration of treatment using rodent models. The study will assess the risk/ benefit of using an anti-inflammatory drugs in the treatment of retinal dystrophies.

The successful candidate should demonstrate knowledge of basic laboratory procedures and interest in learning about retinal pathology. The experiments will be conducted on rodent models of retinal degeneration where animal manipulation will be required. The study will assess retinal function using electroretinography and will employ immunolabelling techniques to demonstrate effect on biological pathways.

Developing an interprofessional learning software application

Supervisors

Nataly Martini (021 133 7367)
Craig Webster
Nasser Giacaman

Discipline

Biomedical Science

Project code: MHS047

To meet the learning needs of healthcare students, software simulations imitating real patients and clinical cases have become widespread in medical education. In interprofessional learning, simulations develop a wide range of non-technical skills in learners, including communication, teamwork and insight into others’ skills and roles.

Ready to Practice is a web-based software application (written in HTML5 and JavaScript, along with the Monkey cross-platform scripting language) enabling students to experience a critical and challenging emergency situation. This project aims to extend the existing application from a single-user application to a multi-user environment. This includes developing a messaging system, allowing an interprofessional team of students to care for the virtual patient, communicate through the application with each other, and send SMS messages via the application.

Skills required:

  • HTML5, CSS, JavaScript (essential)
  • Python (essential)
  • Django or other web-based frameworks (essential)
  • Monkey X or Cerberus X (valuable)
  • Various web-based APIs and protocols (valuable)
  • Server-side and front-end framework technologies (valuable)
  • SQL and/or JSON (useful)
  • Messaging services/APIs, SMS and/or email (useful)
  • Understand security and develop a secure solution (useful)

Skills developed inlcude:

  • Coding and problem solving in an existing clinical training environment
  • Integration of messaging in an existing user system
  • Experience of virtual patient design

Younger onset dementia clinical pathways in New Zealand: Identifying barriers to diagnosis

Supervisor

Brigid Ryan (027 699 7960)

Discipline

Biomedical Science

Project code: MHS050

As a direct result of patients’ relative youth, younger onset dementia takes longer to diagnose than late onset dementia. Diagnosis of younger onset dementia often takes five years or longer and delayed diagnosis is widely accepted to be a major burden on patients, families, and caregivers. Timely diagnosis is critical for access to dementia-specific services, successful clinical management, and patient and family well-being. It is therefore important to understand why diagnosis is delayed, and how it might be hastened.

In this study, we aim to identify factors determining the time to diagnosis for younger onset dementia (defined as symptom onset before 65) in a New Zealand cohort. Data will be collected via questionnaire and by reviewing medical records.

Skills developed include:

  • Knowledge of younger onset dementia
  • Data extraction from medical records
  • Quantitative data analysis.

A thermogelling system for the sustained, localised intratympanic delivery of ascorbic acid

Supervisors

Darren Svirskis (ext 81158)
Anusha Dravid

Discipline

Biomedical Science

Project code: MHS054

Ototoxicity is an irreversible adverse effect associated with a range of pharmacological agents, including aminoglycoside antibiotics, loop diuretics and platinum-based chemotherapeutics (1). The pathogenesis of drug-induced ototoxicity has been attributed to the production of free radicals within the inner ear, causing permanent damaging vital sensory cell populations (2,3). Localised delivery of antioxidant vitamins has shown to attenuate the ototoxic-effects of cisplatin, demonstrating potential as a protective adjunctive therapy (4). This project will aim to develop a thermogelling formulation for the sustained release of the antioxidant compound ascorbic acid for localised, intratympanic delivery to prevent drug induced ototoxicity.

Methods:

  • Quantification of Ascorbic Acid 
  • Develop poloxamer-based formulations
  • Assess formulation: sol-to-gel transition temperature, gelation time, gel hardness, ‘injectability’, in vitro drug release, FTIR, biocompatibility

References:
1. Yorgason JG, Fayad JN, Kalinec F. Expert Opinion on Drug Safety. 2006;5(3):383-.
2. Leis JA, Rutka JA, Gold WL. CMAJ. 2015;187(1):E52-E.
3. Sheth S, Mukherjea D, Rybak LP, Ramkumar V. Front Cell Neurosci. 2017;11:338-.
4. Rybak LP, Dhukhwa A, Mukherjea D, Ramkumar V. Front Cell Neuro2019;13:3

Please note that the student stipend for this project is being provided by the NZ Pharmacy Education and Research Foundation (NZPERF) therefore only current part II and III BPharm students are eligible to apply.

High resolution visualization of protein trafficking machinery in the lens fibre cells

Supervisors

Haruna Suzuki-Kerr (021 118 9953)
Julie Lim

Discipline

Biomedical Science

Project code: MHS056

The ocular lens of the eye is one of two tissues in our body with complete transparency. The lens consists of specialized cell called fibre cells that have elongated shape cell bodies arranged in highly ordered manner. Previous studies in the Molecular vision laboratory have shown that lens fibre cells actively respond to environmental stimuli by altering protein localizations (including purinergic and other receptor proteins), however the mechanisms is unknown. This project aims to shed light on the protein trafficking machinery in the lens fibre cells. The participating student will prepare rodent lens sample and use immunohistochemistry and super-resolution confocal microscopy to visualize small protein-containing vesicles at subcellular resolution.

The successful applicant should have a basic background in biology and physiology. Interest in postgraduate research programmes will be preferable, but not essential. Interested candidates should contact Dr Suzuki-Kerr for further details on the project.

Skills developed include:

  • Tissue dissection
  • Immunohistochemistry
  • Super resolution confocal microscopy
  • Image analysis
  • Scientific report writing

Purinergic signalling in the retina: Deciphering glia contribution

Supervisors

Haruna Suzuki-Kerr (021 118 9953)
Monica Acosta

Discipline

Biomedical Science

Project code: MHS058

The retina is the light sensing tissue of our visual system, where several types of neurons communicate with each other to decode visual image information before it is sent to the brain. Studies have identified that a group of purinergic receptors (P2X) expressed in neurons are involved in shaping visual information. However P2X are also expressed in glia and much of their function remains unknown. This project aims to identify the distribution of P2X in glia and in neurons. The participating student will prepare rodent retinal samples and use immunohistochemistry and microscopy to visualize location of P2X at high resolution. This information will give us clues to the potential function of P2X receptors in mediating neuron-glia interactions.

The successful applicant should have an academic background in biology or vision science. Interest in postgraduate research programmes will be preferable, but not essential. Interested candidates should contact Dr Suzuki-Kerr for further details on the project.

Skills developed include:
 
  • Tissue dissection
  • Immunohistochemistry
  • Confocal microscopy
  • Image analysis
  • Data analysis
  • Scientific report writing

Memory of previous cell damage

Supervisors

Assoc Prof Qi Chen (ext 85645)
Prof Larry Chamley

Discipline

Biomedical Science

Project code: MHS065

Preeclampsia, a human specific hypertensive disorder during pregnancy affects 5-8% of all pregnancies worldwide. There is rapidly growing evidence suggesting that women with a history of preeclampsia have an increased risk for recurrent preeclampsia and developing cardiovascular diseases later.This is despite the clinical symptoms and signs of hypertension resolving within a few weeks after delivery. However, the underlying mechanisms of this association have not been well understood. Dysfunction of endothelial cells is a fundamental feature of hypertension in pregnancy, and cardiovascular diseases. After the birth, dysfunction of endothelial cells in women who developed preeclampsia is still present and remains for many years. This slow recovery may indicate that endothelial cells memorise previous damage, a memory which persists for a long time. To date there is no intervention or prevention programmes for women with a history of preeclampsia, in order to reduce the risk of developing cardiovascular diseases later. In this project we will investigate whether calcium supplementation or aspirin treatment can prevent the transferring of previous damage onto the next generation, as both treatments have showed significant reduction of recurrent preeclampsia. In this project, general laboratory, and cell and tissue culture skills are required.

Residual beta cells in type 1 diabetic subjects may show defects in exocytosis of insulin

Supervisors

Dr Shiva Reddy (09 373 7599)
Dr Kevin Sun

Discipline

Biomedical Science

Project code: MHS067

Residual beta cells in type 1 diabetic subjects may show defects in exocytosis of insulin. This project involves direct assessment of the level of the key exocytosis protein in human pancreatic donors with diabetes for therapeutic rescue of insulin secretion.

Type 1 diabetes (T1D) remains a poorly understood serious chronic disorder, can manifest from early childhood and has no cure. Over the last decade, we have been witnessing a rapidly increasing incidence, particularly in younger children. Despite glucose control with daily insulin and strict nutrition and lifestyle regimens, the risk of sudden hyper- and hypoglycaemia, ketoacidosis and premature secondary complications remain stark.

Our studies of rare pancreatic samples from newly-diagnosed and long-term diabetic cases demonstrate persistence of a significant number of insulin-containing islets. However, such beta cells may be functionally impaired and unresponsive to glucose, after meal.

Physiological insulin release is a complex, multi-step process, culminating in exocytosis. During diabetes, beta cell failure may be partly due to defects in the docking and fusion of beta cell granules with the plasma membrane, immediately preceding exocytosis. This process hinges critically on the formation of a trimeric complex between the cytoplasmic insulin granule surface protein and two plasma membrane proteins, one of which is syntaxin-4 (Synt-4).

Here, we will test the novel hypothesis that the insulin secretory dormancy of persisting beta cells in T1D results from low expression of Synt-4.

Techniques: Pathology of diabetes, multiplex immunohistochemistry, microscopy, immunology, image acquisition and processing.

Glutamate transporter expression in the human Alzheimer's disease brain

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Biomedical Science

Project code: MHS070

Glutamate is the main excitatory brain neurotransmitter and it plays an essential role in the function and health of neurons and neuronal excitability. Altered glutamatergic signalling plays a key role in a number of pathological conditions affecting the nervous system, including Alzheimer`s disease (AD). AD is characterized by progressive loss of neurons, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD. Understanding the remodelling of the glutamatergic system in brains of people stricken by AD will help decide what type of drugs to use or design. The gradual neuronal degeneration and decreases of synaptic density in AD affected brain areas precedes increment in aberrant electrical activity. Modulation of the balance between excitatory and inhibitory neurotransmission early in AD is one of the targets of the glutamatergic drugs in the AD brain.

The aim of this project is to characterize the expression of glutamate transporters in the Alzheimer's disease hippocampus.

We offer a stimulating and collaborative research environment. The successful candidate will join a lively community of students at the Centre for Brain Research. The ideal candidate is ambitious and highly motivated for pursuing a career in neuroscience.

Skills developed include:

  • Neural tissue collection and fixation 
  • Combination of molecular, anatomical and imaging techniques
  • Data collection, analysis and presentation

Understanding GABA signalling in the vasculature of healthy and Alzheimer’s disease brains

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Biomedical Science

Project code: MHS073

Alzheimer`s disease (AD) is characterized by progressive loss of neurons in the hippocampus and cerebral cortex, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD. Cerebrovascular dysfunction is strongly associated with the pathogenesis of AD, often significantly preceding the onset of clinical symptoms. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) can regulate vascular function in the brain, controlling vasoconstriction and blood flow – however the mechanisms underlying this are poorly understood.

The aim of this project is to understand how the GABA signaling system regulates vascular function in the human brain and how this function is altered in AD.

We offer a stimulating and collaborative research environment. The successful candidate will join a lively community of students at the Centre for Brain Research. The ideal candidate is ambitious and highly motivated for pursuing a career in neuroscience.

Skills developed include:

  • Neural tissue fixation, processing 
  • Fluorescence immunohistochemistry 
  • Imaging techniques (light and confocal microscopy)
  • Data collection, analysis and presentation

Neuroinflammation in the human Cingulate Cortex in Huntington’s disease

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Biomedical Science

Project code: MHS076

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease. Previous studies have reported significant neuroinflammatory changes in HD. Whether these changes are neuroprotective or are further destructive is still unclear. Similarly, the impact of neuroinflammation in controlling cellular and molecular pathways leading to cell death is not well understood. The cingulate cortex plays a vital role in learning, memory and emotion processing. Previous research in our laboratory suggests that the cingulate cortex is affected in HD.
The aim of this project is to investigate whether there is significant neuroinflammation in the cingulate cortex of human HD cases using immunohistochemistry on tissue sections of HD cases and controls.

We offer a stimulating and collaborative research environment. The successful candidate will join a lively community of students at the Centre for Brain Research. The ideal candidate is ambitious and highly motivated for pursuing a career in neuroscience.

Skills developed include:
  • Human post-mortem tissue processing
  • Immunohistochemistry
  • Light and confocal microscopy
  • Data collection, analysis and presentation

Optogenetic modulation of neuronal network changes in an in vivo Alzheimer's disease mouse model

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Biomedical Science

Project code: MHS079

Alzheimer's disease (AD) is characterized by progressive loss of neurons, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD. A feature of the pathogenesis of AD is the increased concentration of neurotoxic soluble oligomers of beta amyloid peptides. Optogenetics is the combination of genetic and optical methods. It uses light-activated ion channels (opsins) for temporal control of neuronal excitability limited to specific selected cell-types mediated by viral vectors and light stimulation that is delivered at a specific brain region; and predicted to be the next generation of deep brain stimulation technology.
 
The aim of this project is to design an optogenetic stimulation approach to ameliorate neuronal function and behavior in an in vivo Alzheimer`s disease mouse model.

We offer a stimulating and collaborative research environment. The successful candidate will join a lively community of students at the Centre for Brain Research. The ideal candidate is ambitious and highly motivated for pursuing a career in neuroscience.

Skills developed include:
  • Animal handling
  • Stereotactic brain surgery
  • Mouse behavioural testing
  • Neural tissue collection and fixation 
  • Combination of molecular, anatomical and imaging techniques
  • Data collection, analysis and presentation

Biased agonist signalling through melanocortin receptors

Supervisors

Kathy Mountjoy (ext  86447)
Shree Kumar

Discipline

Biomedical Science

Project code: MHS083

Melanocortin peptides play pivotal roles in numerous physiological responses, including pigmentation, adrenal gland development, the stress response, immune response, appetite, body weight and metabolism. Melanocortin peptides (adrenocorticotropin, alpha, beta or gamma-melanocyte stimulating hormone, desacetyl-alpha-melanocyte stimulating hormone, diacetyl-alpha-melanocyte stimulating hormone) are produced from the large precursor protein, pro-opiomelanocortin, through a co-ordinated, tissue-specific series of proteolytic cleavages and post-translational modifications, which influence the activity of the peptides. These peptides can similarly bind one or more of 5 melanocortin receptor subtypes, resulting in different physiological effects. This project will investigate biased agonist signalling for these peptides on melanocortin receptors expressed exogenously in HEK293 cells. Ultimately, we will identify specific signalling mechanisms associated with specific melanocortin physiological responses.

Research Impact:
The results from this project may lead to identification of new therapeutics for human diseases and ultimately improve health for all New Zealanders.

Skills developed include:

  • Cell culture
  • DNA transfection
  • Cell signalling
  • Data analysis
  • Statistical analysis

Preference will be given to students wishing to continue with honours or masters degree.

Signalling in space and time: Exploring spatio-temporal factors in cannabinoid receptor 2 signalling bias

Supervisor

Natasha Grimsey (ext 81886)

Discipline

Biomedical Science

Project code: MHS087

Cannabinoid Receptor 2 (CB2) is a G Protein-Coupled Receptor (GPCR) expressed primarily in the immune system. CB2-targeted drugs are promising therapeutic leads in a wide range of disorders involving immune system dysregulation, including multiple sclerosis, autoimmune disorders, atherosclerosis, stroke and inflammatory bowel disease.

We are particularly interested in studying functional selectivity, wherein a single GPCR has the potential to mediate the activation or inactivation of diverse signalling pathways and each molecule that interacts with the receptor has the potential to induce a unique ‘fingerprint’ of signalling events within the cell and thereby induce different functional consequences. An emerging concept in functional selectivity is that of spatio-temporal modulation, wherein the location of the receptor and/or induced signal may give rise to unique downstream effects.

This project will investigate the spatio-temporal signalling profiles of a selection of CB2 ligands which have been suggested to give rise to distinct signalling and/or functional profiles. We will utilise cutting-edge signalling pathway biosensors that allow real time measurements of signalling in specific subcellular locations.

Skills developed include:

  • Mammalian cell culture and transfection
  • GPCR signalling assays and use of DNA-encoded biosensors
  • Data analysis, graphing, statistics
  • Scientific writing

A student with background and interest in molecular pharmacology (eg. MEDSCI204, 304) is preferred, but this would also be suitable for students with general interests in mammalian cell biology, medicinal chemistry / drug development and/or immune-related therapeutic application (eg. BIOSCI201, 203, 353, 349, CHEM390, 392, MEDSCI202, 314).

There are opportunities for continued study at Honours, Masters, and PhD level.
https://www.findathesis.auckland.ac.nz/research-entry/10385612
https://unidirectory.auckland.ac.nz/profile/n-grimsey

Understanding the Neurochemical Architecture of the X-linked Dystonia Parkinsonism Human Brain

Supervisors

Dr Christine Arasaratnam (ext 86053 )
Dr Malvindar Singh-Bains
Associate Professor Henry Waldvogel
Distinguished Professor Sir Richard Faull

Discipline

Biomedical Science

Project code: MHS088

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. Thus, XDP shares some clinical similarities to the symptomatology of Parkinson’s disease, and similarities to the genetic inheritance pattern and atrophy of the striatum of Huntington’s disease. 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. Past studies have shown a loss of medium spiny neurons in XDP but an extensive study of the GABAergic and cholinergic interneuronal changes in XDP has not been conducted. The aim of this project is to investigate interneuronal changes in the XDP human brain with a wide range of immunohistochemical markers using diseased and control post-mortem human brain tissue.

Skills developed include:

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

Charaterisation of hepatic neutrophil accumulation in the progression of non-alcoholic fatty liver disease

Supervisors

Dr Randall F D'Souza (021 060 1101)
Dr Troy L Merry

Discipline

Biomedical Science

Project code: MHS090

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide affecting upto ~25% of the general population. Initially fatty liver presents as benign steatosis (NAFL) (hepatic lipid accumulation), and can escalate to more severe steatohepatitis (NASH) (steatosis + inflammation with or without fibrosis) whereby liver function becomes impaired. In the USA, NAFLD is already the leading cause of liver transplants. Spontaneous escalation of NAFL to NASH may occur in a subset of patients but the underlying mechanisms are poorly defined. Neutrophils are the first responders to inflammatory stress, and preliminary data from our animal models suggests that hepatic neutrophil infiltration may be a likely contributor to this escalation in disease severity. The aim of this summer project therefore is to characterise from paraffin-embedded human and mouse liver samples the abundance of neutrophils in sections of liver from controls, NAFL and NASH. This will be undertaken in patient and animal samples to be assessed via histology to identify abundance of neutrophil infiltration. The relationship of neutrophil infiltration to disease progression at the histological and circulatory biomarker levels will be examined to determine whether a relationship exists between the degree of neutrophil infiltration and progression of non-alcoholic liver disease.
 
Skills developed include:
  • Immunohistochemistry on paraffin embedded human and murine liver sections
  • Bright field and fluorescent microscopy
  • Digital image acquisition 
  • ImageJ data generation and analysis
  • Scientific report writing
  • Figure making

The little brains on the heart: Pioneering 3D imaging of human cardiac neurons in health and disease

Supervisors

Jesse Ashton (09 373 7599 ext 83259)
Johanna Montgomery

Discipline

Biomedical Science

Project code: MHS095

Interconnecting clusters of neurons - termed ganglia - situated in fat on the surface of the heart constitute the final node in a sophisticated network that controls heart rhythm. Maladaptive changes in cardiac neuronal function are associated with development of abnormal heart rhythms in conditions of cardiovascular disease and with aging. Nerve stimulation which reverses this neuronal plasticity has emerged as a viable therapeutic strategy for treating abnormal heart rhythms. This project will help advance this treatment strategy by improving our understanding of human cardiac ganglia structure and function.

Biopsies of cardiac fat are obtained with consent from patients undergoing open heart surgery at Auckland Hospital. We then make electrophysiological recordings from neurons in intact ganglia to describe how they function and communicate, and then use microscopy to image single neurons in 3D to determine expression of proteins involved in synaptic communication. This project will involve scaling up our methods to image interconnecting ganglia and testing specific antibodies to help delineate functional classes of neurons involved in heart rhythm control. The student will develop skills in immunolabelling and 3D confocal microscopy. Preference will be given to students wishing to continue on to an Honours degree project.

Kidney organoids as a human stem cell-based platform to study disease

Supervisor

Veronika Sander (81223)

Discipline

Biomedical Science

Project code: MHS101

The kidneys are crucial organs for waste excretion from the body and maintaining the fluid and electrolyte balance of the blood. Damage to the kidneys caused by diabetes and hypertension, acute kidney injury by toxins, sepsis or ischemia as well as congenital renal malformations and renal cancers can progress to chronic kidney disease, a major global health concern. In recent years, organoids generated from human pluripotent stem cells have revolutionised how organ development and disease are studied. To overcome the urgent need for effective therapies for kidney disease, our lab has established a method to grow kidney organoids from human induced pluripotent stem cells (Przepiorski et al., Stem Cell Reports, 2018). Organoid development resembles nephrogenesis as it occurs in the human fetus and results in multiple kidney tissue types with high degree of maturation. Approaches currently undertaken in our lab use these kidney organoids to recapitulate different types of kidney disease. Our aim is to improve our understanding of the molecular mechanisms underlying these diseases and to develop new therapies. The summer student will be focusing on one of these projects.

The following techniques will be used:
  • Histology (paraffin embedding, sectioning, H&E- and trichrome staining)
  • Immunohistochemistry and confocal microscopy
  • RNA isolation and qPCR
  • Data analysis and presentation

If interested, please email your CV and academic transcript, and meet me for a chat about the project.

Sensory deficit in Alzheimer’s disease: What shows up in the eye?

Supervisors

Dr Monica Acosta (09 923 6069 )
Dr Ravi Telang
Professor Peter Thorne

Discipline

Biomedical Science

Project code: MHS111

In Alzheimer's disease (AD), vision is compromised. Accumulation of Aß peptides have been detected in the retina of various animal model of AD. Our previous studies show that retinal deposits occur in a parallel time to the development of brain pathology. In the APP/PS1 mouse model of AD we have found no differences in the structure of the retina compared with normal mice, but we have found synaptic and molecular changes that may affect the light transduction pathway. To continue this study, we will investigate the extent of synaptic remodeling in the retina of APP/PS1 mice at several ages of AD development and provide support for the hypothesis that remodeling is associated with glia activation.

The successful candidate student should demonstrate an interest in neuroscience studies, sensory systems involvement in diseases and imaging techniques.

The study will involve imaging of the ex-vivo eye, tissue processing, immunolabeling, quantitative image analysis, report writing.

Dermal delivery of Centella asiatica (CA) using microneedle delivery system for the treatment of skin disorder

Supervisors

Jingyuan Wen (ext 82762)
Shuo Chen
Sanjukta Duarah

Discipline

Biomedical Science

Project code: MHS113

Dermal drug delivery encounters several challenges. The major challenge for dermal delivery is the stratum corneum, which prevents the transport of external substance into the skin and limits the reservoir of the drug candidate in the deep layers. There is considerable evidence to use CA for the treatment of the skin disorders such as eczema, acne, lupus, psoriasis induced by free radicals and oxidation. However, no microneedle technology has been used to deliver CA so far.

Aim: To fabricate dissolving microneedles for the maximum dermal delivery of CA; investigate drug release profile; determine axial needle fracture force and evaluate lipid peroxidation product.

Skills developed include:
 
  • Fabrication of microneedles
  • In-vitro drug release
  • Cell culture technique
  • Sata processing
  • Scientific report writing

The gut-inner ear axis: on the road to discovery

Supervisors

Assoc Prof Srdjan Vlajkovic
Dr Ravi Telang
Dr Haruna Suzuki-Kerr

Discipline

Biomedical Science

Project code: MHS118

This study aims to explore possible connections between the inner ear and gastrointestinal system. We have coined a term “gut-inner ear axis” to describe the putative link between these two organ systems. The principal aim of the study is to determine how the cochlea of the inner ear responds to alterations in gut microbiota. Our key hypothesis is that a healthy gut is important for the maintenance of cochlear health, whilst the inflammatory processes in the gastrointestinal system can contribute to chronic inflammation in the cochlea and hearing loss. This study represents a novel approach to understanding the mechanisms regulating cochlear function in health and disease.

Study description: We will collect blood samples from mice on high fat diet and transfer their serum to naïve recipient animals on a regular diet by systemic (intravenous) or local (intratympanic) injection. Expression levels of inflammatory markers and the appearance of Iba-1+ migratory macrophages in the cochlea will be assessed 3 and 7 days after transfer using quantitative RT-PCR and immunohistochemistry.

Skills developed include:

  • Tissue dissection
  • Immunohistochemistry
  • Confocal microscopy
  • Image analysis
  • Data analysis
  • Scientific report writing

Understanding Equine Cushing’s Disease to improve horse and human health

Supervisors

Assoc Prof Kathy Mountjoy (ext 86447)
Dr Gus Grey

Discipline

Biomedical Science

Project code: MHS119

Equine Cushing’s Disease, also known as pituitary pars intermedia dysfunction, is a common endocrine disease in horses. The underlying cause involves damage to the brain pathway that regulates melanocortin hormones produced from pro-opiomelanocortin (POMC) in the pituitary pars intermedia. POMC is cleaved into several peptides in the pituitary pars intermedia and it is unknown how each one of these peptides is affected in Equine Cushing’s Disease.

This project will apply state-of-the-art MALDI imaging mass spectrometry technology to identify and map POMC cleavage products through horse pituitary. MALDI imaging mass spectrometry is a proteomic technique that combines the specificity and sensitivity of mass spectrometry with spatial information to map tissue-wide distribution of multiple analytes simultaneously, directly from a single tissue section.

Research Impact:

Understanding Equine Cushing’s Disease will advance understanding melanocortin hormone physiology and ultimately lead to improvements for horse and human health.

Skills developed include:

  • Cryostat cutting thin pituitary sections from frozen tissue
  • Histology: haematoxylin and eosin staining
  • Light microscopy and documentation of capture images
  • MALDI imaging mass spectrometry
  • Proteomic data searching

Preference will be given to students wishing to continue with honours or Masters degree.

Does the pancreatic beta-cell use IGF-II to fight against diabetes progression?

Supervisors

Dr Kate Lee
Dr Claire Wang

Discipline

Biomedical Science

Project code: MHS121

IGF-II and IGF-II derived peptide hormones have been shown to be secreted from pancreatic islet- beta cells along with insulin. The role that this tissue-specfic IGF-II plays is not fully understood however work done so far indicates it is important in cell protection (lipotoxicity) and in enhancing cell proliferation in times of need (insulin resistance)and therefore would play an important role in protecting the beta cells from failing during diabetes profgression. We have developed conditional IGF-II knockout beta-cell lines in the lab uisng CRISPR-Cas9 technology. This project will use these cell lines to drill down into what role IGF-II has in the beta cell with a specific focus on how IGF-II may be involved in mediating the beta-cell specific effects of the glucagon derived peptide hormone, GLP-1. This is relevant to diabetes therapeutics as GLP-1 mimetics and drugs that upregulate GLP1 make up 3 of the 6 ADA recommended drugs. Our aims for understanding how these drugs affect beta cells is that we can develop more targeted therapeutics that may work along or in conjunction with existing drigs to get a better clinical outcome.

Skellis developed include:

  • Mammalian cell culture
  • Insulin secretion assays
  • Immunocytochemistry
  • Western blot and QPCR
  • Experiemntal design
  • Data analysis
  • Presentation skills

Detecting changes in mood using sensors

Supervisors

Dr Frederick Sundram (09 923 7521)
Dr Amy Chan
Assoc Prof Partha Roop

Discipline

Biomedical Science

Project code: MHS125

Globally, there are increasing rates of mental health disorders such as anxiety and depression. These conditions have significant rates of disability but are often under-recognised, under-diagnosed and under-treated. There is new evidence to suggest that data from digital sensors (e.g. from smartphones, wearables) can be used to monitor and diagnose mood disorders.

This project will focus on personalised approaches to mental health monitoring and diagnosis, with specific focus on the use of digital sensors to detect changes in mood state.

Skills developed include:

  • Developing a literature search strategy
  • Condensing and extracting relevant findings from the key literature
  • Summarising and interpreting findings clearly
  • Working with a multidisciplinary team to design and develop a protocol for testing of digital sensors to monitor mood
  • Testing the mood sensors
  • Developing writing skills and a clear report on the summer studentship work
  • Presentating at various meetings and conferences
  • Publishing a report

Investigating degeneration in the Alzheimer's disease olfactory bulb using high-resolution MRI

Supervisors

Dr Helen Murray
Assoc Prof Miriam Scadeng
Prof Maurice Curtis

Discipline

Biomedical Science

Project code: MHS131

Olfactory dysfunction is a prevalent and early symptom of Alzheimer’s disease. However, it is currently unclear whether this symptom is linked to degeneration of the olfactory bulb. With collaborators at the National Institutes of Health (USA), we have acquired high-resolution MRI (14T/19-25um voxel size) of post-mortem human olfactory bulbs from Alzheimer's disease and control cases. These are the highest resolution MRI images of human olfactory bulbs captured to date and provide a unique opportunity to quantify volume changes in Alzheimer's disease. We are looking for a student with an interest in neuroanatomy and medical imaging to segment structures of interest in these olfactory bulb scans to investigate volume changes in Alzheimer's disease. The student will receive training in olfactory bulb neuroanatomy and MRI segmentation using AMIRA software. The project is highly flexible, with much of the analysis able to be carried out remotely (off-site) if preferred.

A randomized controlled trial of ketamine-assisted therapy: Does fractal priming improve treatment response in treatment-resistant depression?

Supervisors

Dr Nicholas Hoeh (09 923 9898)
Dr Francesca Fogarty

Discipline

Biomedical Science

Project code: MHS135

Our research team is looking for a summer student with an interest in novel treatments for clinical depression. This is a pilot study exploring the influence of environmental factors influence outcomes with ketamine assisted therapy. The student will be involved with participant recruitment and screening as well as data collection and analysis.

Blood pressure and collateral blood flow in stroke patients

Supervisors

Fiona McBryde (81732)
Dr Douglass Campbell, ADHB

Discipline

Biomedical Science

Project code: MHS138

A recent breakthrough in the treatment of stroke permits the removal of the occluding blood clot from the brain (endovascular thrombectomy). However, this procedure requires patients to be anesthetized during an ongoing occlusion in the brain. The type of anaesthetic drug used for thrombectomy surgeries varies between and even within hospitals, and it is not currently known whether certain approaches may benefit patients. For example, some types of anesthetic may better protect the collateral blood supply to the vulnerable tissues around the stroke infarct, while others may suppress neuronal activity. This translational project will utilize a pre-clinical model of stroke to compare the two most common types of anaesthetic agents used clinically. The ultimate goal is to help determine the best way to manage these vulnerable patients, and improve outcomes.

We are part of the Cardiovascular Autonomic Research Cluster a friendly and supportive team of researchers and clinicians, running a busy and varied program of research. This project would suit a student with an interest and/or background in biomedical science and/or cardiovascular physiology. Our ideal student would be someone with a genuine interest in continuing on into postgraduate research.

Evaluating Dynamic Cerebral Autoregulation in the Conscious Rat

Supervisors

Dr Debra Fong
Dr Tonja Emans
Dr Fiona McBryde

Discipline

Biomedical Science

Project code: MHS142

The brain is our most energy-expensive organ, with a constant and unrelenting demand for blood flow to meet its metabolic needs. Therefore, cerebral blood flow needs to be well regulated at all times, by an intrinsic mechanism known as cerebral autoregulation. Reductions in brain perfusion could lead to dizziness and fainting, and, if prolonged, development of brain pathologies. Currently in our lab, our research focus on the dynamic relationship between cerebral blood flow and fluctuations in blood pressure. This summer student project will be a validation of different approaches to measure cerebral blood flow in a conscious rodent model using a novel technique to alter blood pressure.

Skills developed include:
  • Working in a laboratory research environment 
  • Design and development of scientific protocols
  • Scientific writing
  • Surgical skills (assisting)
  • Collection of physiological data in conscious animals
  • Analysis of data

Synthesis and development of CSF-1R inhibitors

Supervisor

Swarna Gamage (09 923 6268)

Discipline

Biomedical Science

Project code: MHS145

CSF-1, also known as macrophage (M)-CSF, is a hemopoietic growth factor for the mononuclear phagocyte lineage and the primary regulator of macrophage differentiation, proliferation and survival. Expression levels of CSF-1 and CSF-1R correlate with tumour cell invasiveness and adverse clinical prognosis in breast, ovarian and prostate cancers.
Macrophages switch between two main phenotypes M1 (pro-inflammatory and immunostimulatory) and M2 (anti-inflammatory and immunosuppressive). CSF-1R signalling pathway is known to promote recruitment of M2 macrophages to the tumour microenvironment. CSF-1 and CSF-1R promote tumour-associated macrophages (TAMs) which in turn promote tumour progression and metastasis. CSF-1R inhibition targets tumour stroma & tumour itself, preventing tumour growth and metastasis. Designing drugs that can inhibits CSF-1R would reprogram macrophages from M2 to M1 phenotype. Our research group has been developing novel CSF-1R inhibitors as anticancer agents.

In this project, you will be involved in the chemical synthesis of series of potential inhibitors, starting with commercially available chemicals. Characterization of compounds you make by NMR, LC-MS/MS.

Skills developed include:
  • Organic/Medicinal chemistry in drug development
  • Compound synthesis, purification (chromatography techniques) and structure
  • identification (nuclear magnetic resonance (NMR) spectroscopy)
  • The use of scientific data bases (Scifinder, Chemdraw)

Second year chemistry knowledge would be helpful.

Astrocytes as a cell target for gene therapy

Supervisors

Debbie Young (09 923 4491)
Angela Wu

Discipline

Biomedical Science

Project code: MHS153

Astrocytes are key players in brain information processing because of their roles in blood flow regulation, synapse formation and plasticity, and energy metabolism as well as in many neurological disorders. NURR1 is a transcription factor important in regulating the expression of endogenous target genes that are important in the survival and maintenance of the dopamine neurons that are susceptible in Parkinson's disease. NURR1 also inhibits inflammatory gene expression in glial(microglia and astrocytes) cells. This project aims to determine whether pathogenic stimuli capable of increasing calpain activation and reactive astrogliosis can be harnessed to drive NURR1-regulated gene therapy strategies in astrocytes.

Skills developed include:
  • Mammalian tissue culture
  • Immunocytochemistry
  • Imaging
  • Western blotting  

We are seeking a motivated student with an interest in neuroscience, gene therapy and the testing of new therapies.

Feasibility study of a 10-week advanced anatomical visualisation project

Supervisors

Angela Tsai (09 923 1552)
Prof Maurice Curtis
Assoc Prof Miriam Scadeng
Dr Sue McGlashan
Dr Beau Pontre
Peter Riordan

Discipline

Biomedical Science

Project code: MHS156

The Department of Anatomy and Medical Imaging is in the exciting process of developing a new major in Anatomy. As a pivotal cornerstone of this new major, a new and ambitious Stage 3 course in “Advanced Anatomical Visualisation” (MEDSCI 300) is currently being designed and will be offered for the first time in semester 2, 2021. Students enrolled in the MEDSCI 300 course will undertake a semester-long visualisation project that produces a tangible and useful ‘output’ that showcases the applicability of anatomical imaging in creative, diverse and interdisciplinary contexts.

The overall aim of this project is for the Summer Scholar(s) to work closely with the course personnel to test the practicalities of the current project design and timeline milestones, critically evaluate these against “good practice” published in the relevant literature, and recommend research-informed, practical suggestions for improving the design of the project (and therefore the course learning outcomes). This feasibility study is critical for ensuring that the expectations of our novel approach to assessing MEDSCI 300 are realistic and practicable.

The Summer Scholar(s) will undertake an anatomic visualisation project following the milestones that are currently established. They will journal their reflection after each aspect of the project/activity, and meet with the course personnel on a weekly basis to discuss their reflections and to answer additional questions from the course personnel. At the end of the project, the Summer Scholar(s) will submit a written report summarising the process of involving the student voice in course co-development and improvement.

Useful pre-requisite course (but not essential): MEDSCI 201

Skills developed include:
  • Search strategies to identify relevant and appropriate journal articles
  • Creating a Library of suitable articles using a reference management tool (e.g. EndNote / Zotero / RefWorks)
  • Drafting a literature review
  • Communicating using educational theory and principles
  • Reflective journaling
  • Providing criticism and practical suggestions in a constructive manner

The role of SHANK3 in insulin secretion regulation

Supervisors

Dr Waruni C Dissanayake (ext 85702)
Prof Peter R Shepherd

Discipline

Biomedical Science

Project code: MHS169

Pancreatic ß-cells are the only cells in the body that can produce insulin hormone. Type-2 diabetes arises when these cells are unable to release enough insulin hormone to properly control glucose homeostasis. During the process of insulin secretion, insulin granules move to and fuse with the plasma membrane of ß-cells in response to glucose stimulation.

One of the main aims in our lab is to identify how insulin secretion regulates normally and what will go wrong when type-2 diabetes develops. As a part of a big project we have previously identified that modulating the level of Shank3 protein has functional consequences on ß-cell insulin secretory capacity and the protein level of SHANK3 is changed with glucose stimulation. What we do not yet understand is the mechanism by which how SHANK3 regulates insulin secretion process. In this project we are aiming to define how exactly SHANK3 modulate insulin release, particularly focusing on actin cytoskeleton remodelling.

Skills developed include:
  • Cell culture
  • Western blot
  • Cell based assays (insulin secretion assays, Calcium flux assays, Actin polymerization assays)
  • Protein-protein interaction studies (co-immunoprecipitation)
  • Actin cytoskeleton imaging with confocal microscopy

Characterisation of an in vitro model for screening novel immunotherapies for Alzheimer's disease

Supervisors

Angela Wu (09 923 1907)
Debbie Young

Discipline

Biomedical Science

Project code: MHS171

Our lab has developed a novel immunotherapy that improves learning and memory in aged mice. To determine the clinical applicability of our treatment for conditions associated with cognitive decline, we want to determine whether our immunotherapy would be useful in the context of Alzheimer's disease. To further this work, the aim of this project is to develop and characterise an in vitro model that will be used to screen and fine-tune our immunotherapy.

Techniques taught will include:
  • Mammalian cell culture
  • Immunocytochemistry
  • Imaging and microscopy
  • Image analysis

We are seeking highly motivated and enthusiastic individuals with a passion for neuroscience and the development of novel therapies for neurodegenerative diseases

Quantification of exchange proteins activated by cAMP (Epac) in rat hearts with right ventricular hypertrophy

Supervisors

Dr Marie-Louise Ward (09 923 4889)
Dr Sarbjot Kaur

Discipline

Biomedical Science

Project code: MHS179

Heart disease is a global burden, responsible for 31% of all mortalities worldwide. However, little is known of the contribution of the right ventricle to heart disease that progresses to heart failure and premature death. Right heart disease frequently arises as a result of increased right ventricular afterload in response to pulmonary arterial hypertension. Research using an animal model of pulmonary artery hypertension suggests that the development of right ventricular hypertrophy results in subcellular changes in the cardiomyocytes that impair cardiac function. Recent studies have shown that exchange proteins activated by cAMP (known as “Epac”) induce alterations in intracellular Ca2+ regulation when activated in many cell types, including cardiomyocytes. Cyclical changes in intracellular Ca2+ are key in controlling cardiomyocyte contraction and relaxation, which enables the heart to function as a pump. Previously we have shown that Epac activation of healthy cardiomyocytes causes Ca2+ leak from the sarcoplasmic reticulum, which is the intracellular Ca2+ store. This in turn means less Ca2+ is available for activating the cross bridges and force production.

The aim of this summer studentship project is to quantify the relative abundance and distribution of Epac proteins in ventricular tissue from healthy control hearts and in hearts with right ventricular hypertrophy. Fixed tissue samples will be sectioned and antibody labelled with specific Epac antibodies and key excitation-contraction coupling proteins. Images will be taken using confocal microscopy and quantification carried out.

This project would ideally suit a student with a strong background in cardiac muscle physiology who are considering a research career.

Skills developed include:
  • Cryosectioning
  • Immunolabelling 
  • Confocal microscopy
  • Data collection and statistical analysis
  • Literature review and scientific report writing 
  • Presentation of results

Nanoscale fibrosis and intracellular remodelling of cardiac myocytes in heart failure

Supervisor

David Crossman (89964)

Discipline

Biomedical Science

Project code: MHS183

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 (https://www.fmhs.auckland.ac.nz/en/sms/about/our-departments/physiology/research-groups/cardiac-nanobiology-group.html) 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 microscopy to characterise fibrosis and myocyte remodelling at the nanoscale. This will provide new insight on the structural changes that drive heart failure.

Epileptiform transients as a prognostic biomarker for perinatal brain damage?

Supervisors

Dr Guido Wassink (ext 55384)
Prof Alistair Gunn

Discipline

Biomedical Science

Project code: MHS189

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 (https://www.fmhs.auckland.ac.nz/en/sms/about/our-departments/physiology/research-groups/cardiac-nanobiology-group.html) 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 microscopy to characterise fibrosis and myocyte remodelling at the nanoscale. This will provide new insight on the structural changes that drive heart failure.

Epileptiform transients as a prognostic biomarker for perinatal brain damage?

Supervisors

Dr Guido Wassink (ext 55384)
Prof Alistair Gunn

Discipline

Biomedical Science

Project code: MHS189

In babies with hypoxic-ischemic encephalopathy (HIE), treatment with therapeutic hypothermia (i.e. brain cooling) reduces death, moderate-severe brain damage, and neurological disabilities. However, cerebral cooling needs to be started within 6 hours after hypoxia-ischemia to be neuroprotective, whereas perinatal brain injury develops and worsens over 72 hours. Ideally, a prognostic biomarker rapidly identifies those infants for hypothermia treatment to minimize brain damage. Epileptiform transients on the electroencephalogram (EEG) are pathological discharges that indicate abnormal excitatory or inhibitory neuronal function, and develop within 6 h after hypoxia-ischemia. However, it is unclear whether they predict damage in subcortical structures commonly injured in term babies with HIE. This research project will investigate whether epileptiforms after severe hypoxia-ischemia are associated with changes in hippocampal excitatory and inhibitory neuronal phenotypes.

For this summer studentship, immunohistochemistry, microscopy and cell quantification will be used to determine changes in hippocampal neuronal phenotypes after hypoxia-ischemia in near-term fetal sheep. This research will advance knowledge on biomarkers for hypoxic-ischemic brain damage.

Please send a CV and academic transcript if interested.

Skills developed include:
  • Immunohistochemistry
  • Bright-Field Microscopy
  • Cellular quantification
  • Computerized data analysis
  • Graphing and statistical analysis

Can we prevent brain damage in babies with mild hypoxic-ischemic encephalopathy?

Supervisors

Dr Guido Wassink (ext 88543)
Dr Joanne Davidson

Discipline

Biomedical Science

Project code: MHS192

In babies with hypoxic-ischemic encephalopathy (HIE), treatment with therapeutic hypothermia (i.e. brain cooling) reduces death, moderate-severe brain damage, and neurological disabilities. However, it remains unknown whether hypothermia also works for babies that experience less severe hypoxia-ischemia (i.e. oxygen deprivation) around birth. Historically, these babies with mild HIE were thought to not develop significant brain damage, and thus were excluded from the original clinical trials that examined therapeutic hypothermia for term infants with moderate-severe HIE. This research project will investigate whether cerebral cooling provides neuroprotection after mild hypoxia-ischemia, and help establish the working parameters for therapeutic hypothermia in infants with mild HIE.

For this summer studentship, immunohistochemistry, microscopy and cell quantification will be used to determine neuronal and white matter survival, and the degree of inflammation in the parasagittal cortex after mild hypoxia-ischemia in near-term fetal sheep, following hypothermia or no treatment.

Please send a CV and academic transcript if interested.

Skills developed include:
  • Immunohistochemistry
  • Bright-Field Microscopy
  • Cellular quantification
  • Computerized data analysis
  • Graphing and statistical analysis

Building a new module for Metwork: Identifying stable isotope labelled compounds in Imaging Mass Spectrometry research

Supervisors

George Guo (021 0246 7916)
Gus Grey

Discipline

Biomedical Science

Project code: MHS195

Metabolomics research with Imaging Mass Spectrometry is very powerful. Distributions of hundreds of small molecules are detected simultaneously from thin tissue sections, and displayed in two dimensional images. This leads to data complexity, especially when analysing the relationships between different compounds and metabolic pathways. To address this, a stable isotope labelling (SIL) approach is introduced to replace endogenous compounds, allowing a focus on a specific metabolic pathway. While common SIL metabolites can be readily identified, detection and identification of more obscure SIL compounds is challenging. The objective of this project is to develop an automated analysis module to detect and rate signal from SIL molecules in imaging mass spectrometry data and incorporate that into our existing in-house Metwork analysis pipeline. While this approach has many different biomedical applications, initial work will focus on ocular lens function and lens cataract formation.

Required Skills:
  • A basic background in biology and chemistry
  • Basic skills in R or Python programming
  • Understanding of data processing and visualization will be preferable

Skills developed include:

  • Documentation skills in computer programming
  • Data processing and visualization

Identifying adult stem cells in bone

Supervisor

Brya Matthews

Discipline

Biomedical Science

Project code: MHS196

Bone has a tremendous healing capacity, and fractures generally heal to restore the original functionality of the bone. However, in severe cases, or in patients who are elderly or have other complications healing may be delayed or blocked. The periosteum is a rich source of stem cells that go on to form bone, however, there are no well-established ways to identify these cells. In addition, the processes by which they activate and differentiate are also poorly defined. In this project we will evaluate growth of different potential stem cell populations. We will also examine events following injury in a mouse model by histology and immunohistochemistry.

You will perform or be exposed to techniques including: cell culture, tissue dissection, flow cytometry and cell sorting, immunohistochemistry, image analysis.
 
Hands on experience in some lab techniques preferred. Students who are considering continuing with a research-based degree (honours or masters) are particularly encouraged to apply.

What happens to bones of preptin knockout mice as they age?

Supervisors

Emma Buckels
Brya Matthews

Discipline

Biomedical Science

Project code: MHS197

Osteoporosis is a serious public health problem, characterised by low bone mass and micro-architectural deterioration of bone tissue. The risk of osteoporotic fracture increases with aging, with these fractures being a significant contributor to mortality in the elderly.
 
The pancreatic hormone preptin was discovered at the University of Auckland. Our previous studies have indicated that preptin has positive effects in bone, however, the function of preptin in the skeleton in vivo is unknown.

We have generated a preptin knockout mouse to assess the in vivo function of preptin. You will help to test the hypothesis that in vivo, preptin deficiency has a negative effect on bone microarchitecture. To date, our preliminary data indicate that these mice have increased bone mass, but we do not know why.

This project will involve investigating the mechanism of bone gain in preptin knockout mice as they age. We have samples from 6-week, 14-week, and 1-year old mice, with this studentship focusing on the latter. These studies will further inform researchers that are involved with the development of therapeutics against osteoporosis.

Techniques will include: histology and histomorphometry, immunostaining and imaging, microCT analysis, gene expression.

Novel neurodevelopmental roles for the extracellular sugar hyaluronan: is hyaluronan metabolism altered in developing nerve cells after early hypoxia

Supervisors

Dr Rashi Karunasinghe (09 923 9964)
Assoc Prof Justin Dean

Discipline

Biomedical Science

Project code: MHS200

The targeted growth of neurons is a key event that occurs during brain development, but can become disrupted in infants exposed to low oxygen (hypoxia) near the time of birth. As a result, brain regions such as the cerebral cortex and hippocampus show abnormal neuron growth and activity (typified by seizures and learning problems), affecting functions throughout later life. Yet, scientists and clinicians are still challenged by why and how low oxygen affects neuron development.

Hyaluronan is an extracellular sugar that wraps around brain cells. We recently found that young neurons produce hyaluronan, and this normally regulates the extension of axons and dendrites. However, experimentally restricting blood flow, and thereby limiting oxygen and glucose supply, caused a loss of brain hyaluronan. We hypothesise that an early hypoxia-evoked loss of hyaluronan will lead to abnormal neuronal development.

Using neuronal cultures as a model of development, the main objective of this study is to evaluate the changes evoked by hypoxia on the expression of hyaluronan, the enzymes that regulate hyaluronan metabolism (synthesis and degradation), and hyaluronan receptors.

Skills developed include:
  • Neuronal cell culture
  • Molecular biology
  • Live-cell microscopy
  • Data analysis
  • Report writing
  • Presentating

Exploring the effects of preptin deficiency on the skeleton following metabolic dysfunction

Supervisors

Brya Matthews
Emma Buckels
Kate Lee

Discipline

Biomedical Science

Project code: MHS201

Individuals with type 2 diabetes mellitus (T2DM) have a higher incidence of osteoporotic fracture than patients with an otherwise similar risk profile. However, the mechanism that links these two disorders is unknown.

The pancreatic hormone preptin was discovered at the University of Auckland. Our previous in vitro studies have indicated that preptin improves insulin secretion, and has positive effects on cultured bone cells. Furthermore, individuals with T2DM have increased circulating preptin concentrations. Due to its dual action on pancreatic and bone cells, preptin has been identified as a hormone that could connect the risk of osteoporotic fracture with T2DM.

We have generated a preptin knockout mouse to assess the in vivo function of preptin. This mouse was fed a high-fat diet to induce metabolic dysfunction. High-fat diets promote decreased bone formation and increased bone resorption.

This studentship is part of a larger body of research exploring whether preptin deficiency has a negative effect on bone microarchitecture and whether preptin deficiency protects against the negative effects of a high-fat diet on bone. These studies will further inform researchers examining the relationship between metabolism and bone. The long-term goal of this research is to lessen the burden of osteoporotic fractures in individuals with T2DM.

Skills developed include:
  • Histology and histomorphometry
  • Immunostaining and imaging
  • MicroCT analysis
  • Analysing gene expression

CRISPR/Cas9 technology to advance anticancer strategies

Supervisor

Dr Barbara Lipert (09 923 6803)

Discipline

Biomedical Science

Project code: MHS202

From the chemotherapy drugs through radiotherapy to the most advanced immunotherapy strategies, the efficacy of a treatment is defined by the genetic makeup of the targeted cells. Mutations and perturbed expression of numerous genes gained on the way of tumour evolution establish defensive mechanisms of cancer but also its weak points. We are applying whole-genome and focused CRISPR/Cas9 screens to get insight into genetic determinants of sensitivity to selected anticancer treatments, including radiation, antibody-drug conjugates, genotoxic agents and modulators of DNA repair. This summer project will help to determine the exact role of candidate genes in cancer cells response to treatment and provide hands-on experience in CRISPR/Cas9 knockout generation, tissue culture and cell viability assays.

Novel methods to treat bacterial biofilm infection

Supervisors

Jill Cornish
Jian-ming Lin

Discipline

Biomedical Science

Project code: MHS203

Most antibiotic and antimicrobial drug discovery is done in rapidly growing planktonic cultures. But in reality, most bacteria reside in communities known as biofilms where they grow much more slowly and produce protective slime-like matrix. These biofilms are very resistant to treatment, and can cause chronic infections like prosthetic joint infection and infection in contaminated fractures that respond poorly to antibiotic treatment. In this project, you will use both standard microbiology, and a bioreactor system to grow biofilm to investigate sensitivity of Pseudomonas aeruginosa to antibiotics and lactoferrin. Lactoferrin is a milk protein that shows promise as an antibiofilm agent. This is part of an exciting project funded by the US Department of Defence.

Skills developed and techniques include:
  • Microbiology in a PC2 lab
  • Colony enumeration assays
  • Testing of minimum inhibitory concentration (MIC)
  • Minimum bactericidal concentration (MBC)
  • Minimum biofilm eradication concentration (MBEC)
  • Assays for different combinations of drugs.

Targeting biofilm infection in osteomyelitis

Supervisors

Jill Cornish
Simon Swift

Discipline

Biomedical Science

Project code: MHS205

Osteomyelitis is a severe infection localised to the bone. It generally occurs in growing children, and is a particular problem in New Zealand due to high prevalence in Maori and Pacifica children. Treatment often involves surgery and long-term antibiotic treatment. Some children require treatment in intensive care, and in some of these cases, the infection proves fatal. Infections generally become chronic or treatment-resistant because bacteria form biofilm on hard surfaces like bone, which makes them very resistant to treatment. Traditional microbiology techniques do not examine bacterial sensitivity to treatment when they are grown as a biofilm. In this project, you will test the effect of various treatments on biofilms grown from clinically relevant strains of Staphylococcus aureus which is the most common bacteria found in osteomyelitis. We ultimately hope to understand more about the organisms that cause this devastating disease, and develop more effective treatments to rapidly clear the infection.

Skills developed and techniques include:
  • Microbiology in a PC2 lab
  • Colony enumeration assays
  • Minimum biofilm eradication concentration (MBEC)
  • Assays for different combinations of drugs

Assessing brain blood vessel health using MRI arterial spin labelling

Supervisors

James P Fisher
Catherine Morgan
David Dubowitz

Discipline

Biomedical Science

Project code: MHS208

The brain possess critical regulatory mechanisms to ensure adequate compensatory blood vessel dilation and increased perfusion (known as “cerebrovascular reactivity”). Cerebrovascular reactivity is impaired in a number of cerebrovascular diseases and neurological disorders, and is an established independent predictor of cardiovascular mortality. Magnetic resonance imaging (MRI) using arterial spin labelled (ASL) perfusion is a state-of-the-art approach for non-invasively acquiring whole brain blood flow images by using water in arterial blood as a tracer. The purpose of this project is to establish a new approach for assessing cerebrovascular reactivity using ASL at the University of Auckland, that can be applied to a clinical population. The studentship will provide an opportunity to gain an understanding of how MRI images are acquired/processed, insights into human brain physiology, experience of working with human participants in a clinically relevant context, along with general literature reviewing, writing and oral presentation skills. Relevant skills or experience with the following would be advantageous: MATLAB/Python, image processing, data analysis, working with human volunteer study participants.

Examination of the immunogenicity of a tissue engineered heart valve using a novel surgical model in rats

Supervisors

Professor Jillian Cornish
Dr Steve Waqanivavalagi
Mr Paget Milsom

Discipline

Biomedical Science

Project code: MHS219

Background

Our group is tissue engineering a novel heart valve that we hope will outperform and outlive prostheses currently used for valve replacement surgery. A preliminary scaffold has been engineered using bovine pericardium and decellularised to remove the genetic material of the animal. This scaffold has surpassed preliminary laboratory investigations and is now at a point where its immunogenicity must be interrogated.

Project

To answer this question, experimental samples will be surgically implanted subcutaneously in rats and then harvested at designated time points. Experimental tissue samples will be compared to industry standard samples using histological, biochemical, and architectural techniques that have been perfected within our laboratory.

A surgical rat model has been designed specifically for this project last summer and animal ethics application has been initiated.

Outcomes

The main aim of the study is to prove that the surgical rat model can be used to satisfactorily examine the immunogenicity of experimental tissue engineered heart valves. This summer project will set the scene for a strong Honours project. The project will suit biomedical students interested in regenerative medicine and translational science or clinical students interested in Cardiology or Cardiothoracic Surgery.

The promise of clinical cancer genomics in addressing cancer outcomes in Aotearoa New Zealand

Supervisors

Kimiora Henare

Discipline

Biomedical Science

Project code: MHS220

Despite heightened attention, Māori continue to experience substantial cancer survival inequities (1). This is the take home message from a recent update by Gurney et al (2020) (1) using national data from 2007-2016, following on from Robson et al (2010) (2), pointing out that inequities across the cancer care continuum contribute to the persistence of these inequities (1). Clinical cancer genomics seeks to improve outcomes for cancer patients through gaining a better understanding of tumour biology and through the development of clinical genomic tools for utility across the continuum, including; screening, diagnosis, treatment-matching, and disease monitoring. However, a critical review of existing evidence demonstrating the potential of cancer genomics and alignment with cancers that are most important to Māori health has not been done systematically. For this project, the candidate will conduct a review of published clinical research and clinical trial data involving cancer genomics with a focus on the most common causes of cancer death for Māori. The resulting review will link with existing cancer genomics projects (3) currently underway within the Faculty to best inform research and clinical priorities in oncology in Aotearoa NZ in order to address these untenable inequities.

The project may best suit a medical, health science, or biomedical science student particularly with, but not limited to, an interest in oncology, Māori Health, genomics, immunotherapy, or cancer research.

References

1. Gurney J, Stanley J, Mcleod M, Koea J, Jackson C, Sarfati D. (2020) Disparities in Cancer-Specific Survival Between Maori and Non-Maori New Zealanders, 2007-2016. J Clin Oncol.;
2. Robson B, Cormack D, Te Ropu Rangahau Hauora a Eru Pomare. (2010) Unequal Impact II: Māori and Non-Māori Cancer Statistics by Deprivation and Rural–Urban Status, 2002–2006. Available from: http://www.moh.govt.nz
3. Henare KL, Parker KE, Wihongi H, Blenkiron C, Jansen R, Reid P, Findlay MP, Lawrence B, Hudson M, Print CG. (2019) Mapping a route to Indigenous engagement in cancer genomic research. Lancet Oncol. Jun 1;20(6):e327–35.