Biomedical Science

Mapping functional connectivity of human visual cortex

Supervisors

Sam Schwarzkopf
Catherine Morgan
Reece Roberts
Alex Puckett

Discipline

Biomedical Science

Project code: MHS002

The human visual cortex is organised into a topographic visual field maps. Functional MRI can reveal this architecture non-invasively. However, such retinotopic mapping experiments require stable fixation and repetitive visual stimulation without cognitively engaging the participant. Such experiments are tedious even for healthy neurotypical adults. It is exceptionally difficult to do this in children, the elderly, patient populations, or any groups who cannot endure these conditions for a prolonged period. Naturally it is impossible to use these methods at all when the participant’s eyes are closed.

However, recent advances in imaging analysis enable us to construct a map of functional connectivity between brain areas. Here we will use data collected while participants freely viewed movies or when their eyes were closed and thus reconstruct retinotopic architecture without the use of explicit mapping stimuli. First, we will compare this approach with traditional mapping in normal healthy adults and test its robustness when participants move their eyes or when their vision is blurred. Then, we will apply this method to data from special populations, such as young children, individuals with autism spectrum disorder, schizophrenia, and patients with glaucoma, achromatopsia, and amblyopia.

Examining the cellular underpinnings of autism spectrum disorders in human cells

Supervisors

Johanna Montgomery (09 923 9828)
Kevin Lee

Discipline

Biomedical Science

Project code: MHS003

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder which results in behavioural deficits including repetitive behaviours, learning deficits, communication deficits, and sensory issues. Genetics studies from people affected by ASD show a significant number of ASD-related mutations occur in the Shank family of synaptic proteins in the brain. We have previously shown that ASD-Shank mutations weaken synaptic transmission and alter synaptic plasticity, and moreover, increasing dietary zinc can prevent these changes and also reverse ASD-related behavioural deficits in rodent ASD models. We now aim to progress this research into human cells. The aim of this summer studentship is to begin this transition by establishing stem cell cultures from people affected by ASD that carry a Shank3 deletion. We will mature these cells into neurons and examine the effects of zinc on these cells. Techniques involved for this project include cell culture, immunostaining, and microscopy. This work will be in collaboration with our Minds for Minds network, an Auckland-based collaborative network of scientists, clinicians, and people affected by ASD.

Examining plasticity in the neurons of the heart

Supervisors

Johanna Montgomery (09 923 9828)
Jesse Ashton

Discipline

Biomedical Science

Project code: MHS004

Plasticity is a key feature of neurons, defined as their ability to change their level of synaptic strength in response to specific stimulation paradigms. Synaptic plasticity is known to underpin learning and memory, as well as sensory and motor function. Large populations of neurons also exist outside of the brain, innervating major organs including the heart. On the heart surface are clusters of neurons, termed ganglionated plexi (GP), that are the last point of neural control of the heart. We hypothesise that these neurons also express plasticity, and that the changes in synaptic strength occurring then alter heart rhythm. We are particularly interested in the role of plasticity in atrial fibrillation (AF), the most common heart arrhythmia, as GP neuron activity is known to contribute to this arrhythmia. In this project we will examine these GP neurons to determine how stimulation alters their structure and function in both normal and arrhythmic tissue. Techniques involved include immunostaining in human and rodent tissue, and cellular imaging.

Understanding the anatomy of the pulmonary lymphovenous junction (LVJ)

Supervisors

Ali Mirjalili (09 923 7487)

Discipline

Biomedical Science

Project code: MHS006

Literature review of the anatomy and physiology of pulmonary lymphatic system. Examining 20 LVJ under the confocal and electron microscope.

Can we treat brain injury in preterm babies by repairing the extracellular matrix?

Supervisors

Dr. Kenta Cho ( ext. 81452)
A/Prof Justin Dean

Discipline

Biomedical Science

Project code: MHS009

Brain injury caused by reduced oxygen and blood flow (hypoxia-ischemia) to the brain is very common in premature babies. This pattern of brain injury typically involves damage to developing oligodendrocyte and neuronal cells. Our group has recently found evidence of damage to the brain regions that surround cells (i.e., the extracellular matrix or ECM) in preterm brain injury. Further, this ECM damage seems important for controlling the survival and development of brain cells after injury. Thus, reducing injury to the ECM may be a novel treatment strategy to promote or restore brain function after preterm brain injury.

This preclinical experimental study will examine whether pharmacological blockade of abnormal ECM degradation after preterm hypoxia-ischemia is an effective therapeutic strategy to reduce brain injury.

This study will utilize a clinically-relevant model of preterm brain injury that closely mimics the common pathological feature of brain injury seen in the human preterm infant.

Skills learnt:

  • Analysis of neurophysiological data, including EEG, heart rate, and blood pressure.
  • Immunohistochemistry
  • Microscopy
  • Data analysis
  • Report writing
  • Presentation skills

Better than a hole in the head? Magnetic Resonance Imaging (MRI) of brain motion as an indicator of raised intracranial pressure

Supervisor

Miriam Scadeng (027 515 6901)
Samantha Holdsworth
Sarah-Jane Guild

Discipline

Biomedical Science

Project code: MHS015

The medical or surgical management of several conditions, characterized by high intracranial pressure (ICP), is hampered by the lack of a reliable, non-invasive technique to confidently determine if the pressure is elevated. Raised ICP can severely compromise brain perfusion. Currently, the only way to definitively determine ICP is to measure it directly, requiring a highly invasive skull burr hole in the skull. What if there was a way to determine the ICP with a non-invasive Magnetic Resonance Imaging (MRI) scan? We have developed a method called amplified MRI (aMRI), which can detect changes in brain motion with changes in ICP. Together with our capability to directly measure and modulate ICP in a clinically-relevant large animal (sheep) model, we now have a means to model the brain physiology across a range of ICPs.

The goal our research is to see if aMRI can provide a diagnostic index of ICP which will remove the necessity for invasive surgical intervention.

We are looking for a curious student with interest in brain imaging, and can learn and assist with analysis and interpretation of our MRI data in a sheep model of brain pressure.

They will get to experience working in a cross-disciplinary team between medical imaging, physiology, and biomechanical engineering.

Skills: Interest in data analysis and computation. Ability to work in a team.

The impact of short chain fatty acids on regulatory T cells in term and premature neonates

Supervisor

Gergely Toldi

Discipline

Biomedical Science

Project code: MHS016

The neonatal immune system rapidly needs to adapt to the extrauterine environment in the first few weeks of life. Regulatory T cells (Tregs) play an important role in fine-tuning the appropriate level of immune reactivity and tolerance in this period. In previous animal experiments, short chain fatty acids (SCFAs), in particular propionate and butyrate, were described to play an important role in promoting Treg differentiation and proliferation.

In this project, we aim to identify how various SCFAs influence the suppressive capacity of Tregs and the development of their subtypes in cord blood samples of term and premature neonates in comparison with a control group of healthy adults.

Peripheral blood mononuclear cells will be isolated and cultured in the presence of SCFAs under various experimental conditions. Regulatory T cells will be phenotyped using flow cytometry. Mixed lymphocyte reactions (MLRs) will be used to assess the suppressive capacity of Tregs.

The above experiments will help us better understand the development of the adaptive immune system with a specific focus on factors orchestrating the expansion of the Treg pool in the early neonatal period.

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

Topical medicated spray for wound application

Supervisors

Manisha Sharma (09 923 1830)

Discipline

Biomedical Science

Project code: MHS017

NZPERF Funded project:

Delivering therapeutic agents to wound bed remains a challenge. Traditional dosage forms such as creams and ointments not only require repeated application but are also very difficult to apply to the wound site, affecting patient compliance. This project aims to develop a sprayable drug delivery system to achieve ease of application on to the wound site, with the ability to provide slow release of the therapeutic agents, thus reducing the need for repeated application. Thermoresponsive polymer, poloxamers will be investigated for developing sprayable in-situ gel system. Poloxamers are liquid at room temperature, easy to spray and gels at body temperature to form a slow release gel depot. Main aim is to develop and evaluate sprayable characteristics of thermoresponsive in-situ gel system for the controlled delivery of therapeutic agents.

  • To develop and optimize poloxamer based sprayable in-situ gel system.
  • To evaluate spray characteristics of the developed system along with other gel properties.
  • To evaluate in vitro release profile of the selected optimized system.

More suitable for Pharmacy-BPharm Year 2 and 3 students

Exploring novel analogues of ketamine as non-opioid analgesics

Supervisors

Dr Ivo Dimitrov
Manisha Sharma

Discipline

Biomedical Science

Project code: MHS018

Managing severe and chronic pain in the hospital has become an increasingly challenging task. Opioids have been the traditional mainstay for treatment of severe pain, however decades of over prescription and abuse especially in the Western World has led to increasing number of opioid dependent patients who are resistant to opioid treatment. The financial burden of the opioid epidemic has been estimated to be $72 billion in the USA alone. Opioid overuse can lead to hyperalgesia and analgesic tolerance, which result in ineffective pain control. Ketamine is a widely used non-opioid anaesthetic with profound analgesic properties and is known to reduce opioid hyperalgesia. Ketamine however produces psychotomimetic side-effects which limit its clinical potential.
 
The aim of this project is to synthesise novel analogues of ketamine, which retain its desired analgesic properties while eliminating its undesired side-effects. At the same time, we wish to test a novel delivery mode for the most successful analogue using a microneedle array system. The project will expose the student to synthetic organic chemistry techniques and methods involved in development and evaluation of a novel drug delivery system. No prior experience necessary

Death by a thousand cuts: drugging the DNA damage response

Supervisors

Michael Hay
Lydia Liew

Discipline

Biomedical Science

Project code: MHS021

Cancer cells use DNA repair mechanisms to escape the full effects of cytotoxic chemotherapy and radiotherapy. DNA-Protein Kinase (DNA-PK) plays a crucial role in repairing DNA damage caused by radiotherapy and some chemotherapy drugs. Consequently, DNA-PK represents a new drug target where inhibition will potentiate cytotoxic therapy. Currently, there are few selective inhibitors of this enzyme or strategies for their selective delivery to tumours. We have recently discovered a new class of DNA-PK inhibitor and are exploring its potential to sensitise radiotherapy in models of head and neck cancer and lung cancer.

This project will explore novel pharmacophore models to design, synthesize and evaluate new inhibitors of DNA-PK.

The Auckland Cancer Society Research Centre provides an exciting, multidisciplinary and collaborative research environment. This project would particularly appeal to students contemplating a higher research degree in drug discovery.

Skills: Medicinal or organic chemistry.

Assay validation for local anaesthetics for use in clinical pharmacokinetic studies

Supervisor

Jacqui Hannam (09 923 2869)
Malcolm Tingle

Discipline

Biomedical Science

Project code: MHS026

Lignocaine, ropivacaine and bupivacaine are commonly used local anesthetics. Although their use is well established, the optimal concentration that provides safe and effective pain relief is unknown. Overdose of local anaesthetics is associated with neurological symptoms such as convulsions , CNS depression and cardiovascular depression. Pharmacokinetic models, which can be used to identify the appropriate dose to achieve a target concentration, are lacking. To develop these models, we need to be able to quantify both total and unbound concentrations of the drug in the laboratory.

The Department of Pharmacology and Clinical Pharmacology is seeking a motivated student to assist with the refinement and validation of lab protocols for measuring total and unbound concentrations of lignocaine, ropivacaine and bupivacaine, as well as an active metabolite of lignocaine. This work will allow us to conduct pharmacokinetic studies of these drugs in patients and in turn, promote their safe and effective use in clinical practice.

Aims:
To validate assays for total and unbound concentrations of lignocaine, bupivacaine and ropivacaine, and the metabolite monoethylglycinexylidide (MEGX).

Skills learnt:

  • Approaches to quantification of drug concentrations
  • Standard curve validation techniques
  • Ultrafiltration techniques
  • HPLC and Mass Spec analysis
  • Presentation skills
  • Working as part of a professional team

Regulation of lymphatic vessel growth

Supervisor

Jonathan Astin (09 923 4480)

Discipline

Biomedical Science

Project code: MHS032

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:

  1. imaging lymphatic vessel growth in mutant fish.
  2. Isolating genomic DNA for use in mutation mapping
  3. experiments focused on the validation of candidate mutations.

Skills:

  • Model organism genetics
  • Live cell imaging
  • Zebrafish husbandry

Delaying the onset of age related cataract: understanding antioxidant regulation in the lens

Supervisors

Julie Lim (09 923 2591)
Haruna Suzuki-Kerr

Discipline

Biomedical Science

Project code: MHS034

The lens is a remarkable tissue in its ability to uptake, synthesise and regenerate millimolar concentrations of the antioxidant glutathione (GSH). This enables the lens to withstand oxidative insults and remain transparent over decades of life. Previous work in the lab has shown that the lens contains circadian clock proteins which suggest that GSH levels may be regulated in a circadian manner. Since circadian rhythms are disrupted with age, and the depletion of glutathione in the lens is a known initiating factor in the development of age-related cataract, this may explain why GSH levels become depleted with advancing age. To test this idea, the aim of this project to is determine whether GSH levels in the lens are altered during the day and night in young animals and whether these levels change with aging.

Skills:

  • Understanding of eye anatomy
  • Lens dissection
  • Biochemical assays to measure GSH levels.

Biased melanocortin hormone signalling via G-protein coupled receptors

Supervisors

A/P Kathy Mountjoy
Shree Kumar

Discipline

Biomedical Science

Project code: MHS036

Melanocortin hormones play pivotal roles in numerous physiological responses, including the stress response, immune response, appetite, body weight, metabolism, brain and adrenal development, and pigmentation. Melanocortin hormones are prodced from the large precursor protein, pro-opiomelanocortin, through a co-ordinated, tissue-specific series of proteolytic cleavages and post-translational modifications. These hormones can similarly bind one or more of 5 G-protein coupled receptor subtypes known as melanocortin 1-5 receptors, resulting in different physiological effects. Specific physiological functions for the different melanocortin hormones are largely unknown. This project will investigate biased agonist signalling for specific melanocortin hormones activating specific melanocortin receptors expressed exogenously in cultured HEK293 cells. Ultimately, we will identify specific signalling mechanisms associated with specific melanocortin hormone physiological responses. In the future, this may lead to identification of new therapeutics for human diseases (e.g. obesity, diabetes, neurodegenerative, cardiovascular, acute inflammation) without unwanted side-effects.

Skills taught:

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

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

Supervisors

A/P Kathy Mountjoy
Dr Gus Grey
Shree Kumar

Discipline

Biomedical Science

Project code: MHS037

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 hormones in the pituitary pars intermedia and it is unknown how each one of these 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.

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

Skills taught:

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

Building a Comprehensive Map of the Little Brains on the Heart

Supervisors

Jesse Ashton (021 841 318)
Johanna Montgomery
David Crossman
Greg Sands

Discipline

Biomedical Science

Project code: MHS038

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 serious abnormal heart rhythms, such as atrial fibrillation (AF), in conditions of cardiovascular disease. Nerve stimulation which reverses this "neuronal plasticity" has emerged as a viable therapeutic strategy for treating AF. This project will help advance this treatment strategy by improving our understanding of how AF affects cardiac ganglia structure and function.

We take ganglia from patients with AF undergoing open heart surgery at Auckland Hospital and from spontaneously hypertensive rats (SHRs) which are genetically predisposed to AF. Then we make electrophysiological recordings from the ganglia to determine how their neurons function and communicate. We also use so-called tissue clearing techniques to render the samples transparent so we can examine the cellular makeup of ganglia with deep 3D imaging. This exciting project will involve scaling up our methods to map much larger areas of the cardiac nerve network. The student will develop skills in immunolabelling, 3D confocal microscopy, tissue clearing and a new “super-resolution” imaging method called Expansion Microscopy.

How do Gain-of-Function Melanocortin 4 receptors variants protect humans from developing obesity?

Supervisor

A/P Kathy Mountjoy (09 923 6447)
Shree Kumar

Discipline

Biomedical Science

Project code: MHS039

Obesity, a global health problem and disease, that disproportinately affects more than a third of all New Zealanders, has limited effective treatment options. A more complete understanding of the molecular mechanisms that regulate body weight should give rise to more effective and safe anti-obesity treatments. Understanding how two Gain-of-Function MC4R variants protect humans from developing obesity could be key to developing new therapies. There are two Gain-of-Function human MC4R variants that associate with protection from obesity but over 150 Loss-of-Function MC4R variants that associate with causing obesity. Loss-of-Function MC4R variants have defective MC4R signalling. Little is understood about how Gain-of-Function MC4R variants signal compared with Wild-Type MC4R.

This project will investigate melanocortin hormones activating Gain-of-Function MC4R variants compared with Wild-Type MC4R signalling, using melanocortin receptors expressed exogenously in cultured HEK293 cells. We predict that Gain-of-Function MC4R variants will have preferred signalling responses compared to Wild-type MC4R. In the future, this may lead to identification of new therapeutics for human obesity.

Skills taught:

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

Using super resolution microscopy to study the three-dimensional distribution of the water channels AQP5 and AQP0 in the mouse lens.

Supervisors

Rosica Petrova (021 389 923)
Paul Donaldson

Discipline

Biomedical Science

Project code: MHS042

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 the aquaporins (AQP) or water channels of the lens have a major involvement in supporting the circulating fluids in the lens which in the absence of blood supply delivers nutrients to and removes waste products from its deepest parts. Therefore, the aim of this summer project is to visualise the three-dimensional distribution of the two main AQPs- AQP5 and AQP0 in an effort to understand how each channel contribute to the differential movement of water. This will be achieved by using super resolution functional imaging to resolve the molecular association of AQP5 and AQP0 in the fiber cells of the outer cortex, inner cortex and core regions of the mouse lens.

Skills that will be taught in this project include:

  • Fixation of the mouse lens.
  • Cryosectioning of the lens tissue.
  • Labeling with specific membrane marker wheat germ agglutinin (WGA).
  • Super resolution imaging that will involve using ZEIS 800 airy scan microscopy to allow visualisation of the AQPs localization throughout the mouse lens.

Investigating exercise intolerance in heart failure with preserved ejection fraction

Supervisors

Rohit Ramchandra (09 923 5183)

Discipline

Biomedical Science

Project code: MHS043

Heart Failure with preserved ejection fraction now represents around half of all patients with heart failure. Unfortunately, none of the treatments that are currently used appear to show benefit in this cohort. Thus there is a unmet clinical need to find better treatments for this disease and this starts with better understanding the mechanisms of disease progression. The aim of this summer studentship is to further establish a large animal model of heart failure with preserved ejection fraction and then to determine the mechanisms behind exercise intolerance in this model. Using a large animal model will enable preclinical translational studies to be carried out which have more relevance to the clinical condition.

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

Skills that will be taught and mentored through this studentship include:

  • Literature review writing skills
  • Surgical skills (assisting)
  • Collection of physiological data in conscious animals
  • Analysis of data
  • Oral presentation skills

Microglial Contribution to Synapse Loss During Neuroinflammation

Supervisors

Kevin Lee (Ext83259)
Michael Dragunow
Johanna M. Montogmery

Discipline

Biomedical Science

Project code: MHS048

Neuroinflammation, the brain's immune response to harmful stimuli, is a major pathogenic contributor to many neurological disorders such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and traumatic brain injury. One of the earliest hallmarks of neuroinflammation is the activation of brain's immune cells called microglia and a loss of neuron-to-neuron communication sites called synapses. Therefore, identifying the link between microglial activation and synapse loss is central to advancing our knowledge of disease mechanisms and thereby facilitating the development of effective therapies for neurodegenerative diseases.

The aim of this summer studentship is to examine how neuroinflammation shapes the structure of excitatory and inhibitory synapses of cortical neurons and analyse the microglial contribution. With our recent establishment of a research platform that enables the maintenance of live adult human brain tissues for more than a week in a dish, the student will also assist in identifying and validating a human-specific mechanism that underlies human neuroinflammation. Techniques involved in the project include brain slice culture, secretome profiling assay, immunohistochemistry, and confocal microscopy.

Stretchable micro-electrode arrays to model neural damage in spinal cord injury

Supervisors

Brad Raos
Darren Svirskis

Discipline

Biomedical Science

Project code: MHS049

Background: Spinal cord injury is a devastating condition and can result in permanent disability that compromises quality of life through paralysis, sensory deficit and neuropathic pain. The body only has a limited capacity to heal such devastating injuries and currently there are a lack of clinically meaningful treatments available. Our research group is currently developing novel electrical treatments to enhance the body’s natural capacity for self-repair. We test these treatments using in vitro cultures of neurons that are grown on micro-electrode arrays (MEAs). These MEAs can sense and stimulate electrical activity in the neurons.

Aims: This is a hands-on lab-based project where you will develop MEAs that can be stretched to simulate a mechanical injury to in vitro neuronal cultures. You will be using techniques that we have established in our lab to create conductive polymer stretchable surfaces that you will fabricated into MEAs. You’ll gain lab experience and skills in rapid prototyping, conducting polymer fabrication and the mechanical and electrochemical characterisation of materials.

Human Pericyte Tone and Cerebral Blood Flow in Neuroinflammation

Supervisor

Kevin Lee (Ext83259)
Michael Dragunow
Rebecca Johnson

Discipline

Biomedical Science

Project code: MHS050

Although only accounting for 2% of the body's mass, the human brain requires over 20% of the cardiac output to accommodate nutrient and oxygen demand for normal functioning. To deliver blood flow effectively to the brain, a special group of cells called pericytes, positioned at an interface between the brain and blood vessels, regulate blood flow by actively contracting and relaxing their bodies. Moreover, pericytes play a pivotal role in blood-brain barrier formation, clearance of toxic compounds from the brain, and brain's immune response. However, these mechanisms have been examined extensively using non-human-based research models. Therefore, it is unclear whether the same cellular pathways and mechanisms underlie human pericyte physiology and neurovascular function.

Here we aim to identify the human-specific cellular mechanisms that underlie pericyte-dependent neurovascular dysfunction during neuroinflammation, a brain's immune response to detrimental stimuli. Specifically, the current summer studentship will examine how the tone of adult human pericytes change in response to protein aggregates, including amyloid ß, that have been implicated in the pathogenesis of Alzheimer's disease. Moreover, we will investigate which signalling pathways underlie the contraction and relaxation of pericytes during neuroinflammation. Techniques involved in the project include cell culture, immunocytochemistry, microscopy and xCELLiGence electrical impedance assay.

Re-defining the origin of the embryonic kidney

Supervisors

Zhenzhen Peng

Discipline

Biomedical Science

Project code: MHS051

The kidney plays a crucial life-sustaining role in the purification of blood. New Zealand has a high rate of kidney disease and there is an urgent need to develop new therapies to treat renal failure. The development of regenerative kidney therapies, such as the use of renal progenitor cells (RPCs) or the bioengineering of transplantable kidneys, relies on a fundamental understanding of how the kidney forms in the embryo and the therapeutic potential of different types of RPC. Using the zebrafish, we have identified a unique class of RPC that can be transplanted into damaged kidneys where it forms new functional tissue. By investigating the origin of this cell, we discovered that it arises from the same embryonic tissue lineage as the muscle. As the muscle and kidney have not been previously linked in this way, our findings radically change the textbook understanding of embryonic kidney formation.

Skills learnt:

  • Zebrafish Husbandry
  • Fluorescent Immunohistochemistry
  • Microscopy and histology
  • Imaging

Can CRISPR/Cas9 knockout of MFSD12 prevent a rare kidney disease?

Supervisors

Jennifer Hollywood (09 923 1223)

Discipline

Biomedical Science

Project code: MHS055

Aims:
The rare kidney disease, cystinosis, is responsible for kidney failure in children and young adults. Cystinosis occurs when the gene CTNS is mutated resulting in defective transport of the amino acid, cystine out of the lysosomes. This leads to an abnormal accumulation of cystine resulting in a build-up of cystine crystals which cause damage to many organs and tissues. The kidneys and eyes are especially affected by this damage and there is currently no cure for this disease.

Recently, it has been shown that when another gene, MFSD12, that is involved in skin pigmentation is missing in cystinotic cells there is no accumulation of cystine. This implies that if we can disrupt this gene in cystinosis patients using drugs or small molecules then we can stop the build-up of cystine and prevent kidney failure.

Here we aim to test this idea as a possible new therapeutic approach by generating a double-knockout cell line for CTNS and MFSD12 and measuring the cystine levels in these cells. Specifically, the current summer studentship will use CRISPR/Cas9 gene editing technology to disrupt the MFSD12 gene in our already established cystinosis stem cell lines. They will then use HPLC-Mass spectrometry to determine how the cystine levels in these cells compare to control cell lines.

Techniques and skills involved:

  • CRISPR/Cas9 gene editing
  • Induced Pluripotent Stem Cell culture
  • HPLC-MS/MS (Mass spectrometry)

Protein binding and internal standard use during unbound drug concentration analysis

Supervisors

Malcolm Tingle (09 923 4949)
Conor O'Hanlon
Jacqueline Hannam

Discipline

Biomedical Science

Project code: MHS057

Many commonly administered drugs bind to plasma proteins in our blood. However it is only the unbound (free) drug that is active and exerts a pharmacological effect. This means unbound drug measurements are most suitable for quantitative studies in pharmacology.

Drug concentrations in the blood (or other fluids) are be measured in the laboratory using analytical techniques. Internal standards are used to account for possible analyte loss during assay procedures. However in vitro protein binding displacement reactions between the analyte and internal standard may mean biased or imprecise measurements of unbound drug concentration.

The Department of Pharmacology and Clinical Pharmacology is looking for a motivated student to investigate in vitro changes in protein binding across a range of drugs, and in turn provide guidance for appropriate use of internal standards when measuring unbound drug concentration.

Aims: To investigate the impact of in vitro protein binding displacement reactions on the quantitation of unbound drug

Skills learnt:

  • Approaches to quantitation of drug concentrations
  • Standard curve validation to FDA guidelines
  • Ultrafiltration techniques
  • Protein precipitation/liquid-liquid extraction techniques
  • Analytical chromatography (HPLC-UV)
  • Presentation skills
  • Working as a part of a professional team

Involvement of the inflammasome pathway in uveitis

Supervisors

Ilva Rupenthal
Avik Shome

Discipline

Biomedical Science

Project code: MHS058

Uveitis is an ocular inflammatory disease responsible for 10-15% of all cases of blindness worldwide. We have recently established a mouse model of the disease to further investigate the inflammatory pathways involved in as well as to test novel treatments for uveitis.

This project will investigate the involvement of the inflammasome pathway in uveitis by labelling ocular tissue sections of treated and untreated animals for markers such as NLPR3, caspase-1 and connexin43.

The ideal candidate will have a keen interest in understanding the inflammatory pathways involved in uveitis.

Skills gained include tissue sectioning, immunohistochemistry, confocal microscopy, image analysis and report writing.

Characterising the Neuropathology of the X-linked Dystonia Parkinsonism Human Brain

Supervisors

Dr. Christine Arasaratnam (Ext86053)
Dr. Malvindar Singh-Bains
Assoc Prof Henry Waldvogel
Distinguished Professor Sir Richard Faull

Discipline

Biomedical Science

Project code: MHS059

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

Skills:

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

Development and characterisation of oxygen-loaded injectable hydrogels

Supervisors

Sachin Thakur (09 923 7199)
Darren Svirskis
Zimei Wu

Discipline

Biomedical Science

Project code: MHS062

Solid tumours are characterised by hypoxic cores which render them resistant to chemotherapy and radiotherapy. Reoxygenation of tumour cores has allowed restoration of tumour sensitivity to these therapeutic approaches. Unfortunately, current methods of tumour reoxygenation are non-specific with risks of adverse effects due to over-oxygenation of the blood. This may be remedied by developing an oxygen-loaded hydrogel that can be injected directly into solid tumours and releases the oxygen specifically at the target site.

In this project we will:

  1. investigate the amount of oxygen that can be loaded into hydrogels
  2. determine how oxygen loading affects the viscoelastic properties of the hydrogels
  3. assess the rate of oxygen diffusion from the formulated systems under physiological conditions.

Skills taught: hydrogel formulation and evaluation, oxygen microvesicle formulation and evaluation, oxygen measurement, ultrasound imaging.

Prerequisites: only Part 2 and 3 BPharm students are eligible to apply as the project is NZPERF funded.

Characterisation of pathogenic proteins in the Huntington’s disease human brain

Supervisors

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

Discipline

Biomedical Science

Project code: MHS063

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

Skills:

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

Computational Modelling of Neurocognitive Responses to Havening Therapy

Supervisors

Zohreh Doborjeh
Grant Searchfield

Discipline

Biomedical Science

Project code: MHS065

Havening is an innovative psychosensory intervention for the psychological trauma that utilises nurturing touch and is used by therapists worldwide. However, very little empirical evidence exists to understand the psychological and biological mechanisms through which Havening might work. Our work investigates the role of nurturing touch during Havening therapy for psychological trauma on wellbeing. Participants (n=27) who had experienced mild psychological trauma underwent a Havening intervention that included either a touch component (H+, n=15) or no-touch component (H-, n=12). H+ showed greater improvement in subjective wellbeing than H-. Brain function, as assessed using electroencephalography (EEG), has also been collected before and after the intervention. We propose to use machine learning methods to 1) Understand the brain response to H+ compared to H- conditions; 2) Predict response to H+ and H-.

We have previously used Spiking Neural Networks (SNN) to investigate the effect of other interventions (e.g. Mindfulness) on brain function in which we predicted response to intervention with 93% accuracy, and demonstrated that improvement in mood paralleled improvement in functional connectivity. We will apply similar methods to our Havening data to understand neurocognitive mechanisms by which nurturing touch improves wellbeing and who might benefit most from such interventions.

It's a Trap! Comparing the trapping ability of PARP inhibitors using in situ proximity ligation assay.

Supervisors

Benjamin Dickson
Tet Woo Lee

Discipline

Biomedical Science

Project code: MHS070

PARP inhibitors have swiftly become a mainstay of BRCA mutant cancer therapy, however their use outside this synthetic lethal context is limited by on-mechanism toxicity in non-target tissues. This has precluded use of PARP inhibitors in combination with cytotoxic chemotherapeutics and radiotherapy, despite this being the initial rationale for their development. PARP inhibitor activity is typically considered to be the intersection of two distinct modalities - catalytic inhibition of PARP and trapping of PARP to DNA. Thus PARP inhibitors with similar catalytic inhibition of the isolated enzyme can vary markedly in cell-based cytotoxicity experiments.

During the course of our work investigating prodrugs of clinical PARP inhibitors we prepared an analogue of olaparib with significantly improved efficacy in cell culture experiments despite very high structural similarity. Recent reports use proximity ligation assay to detect chromatin-trapped PARP and provide a tool for comparison between various PARP inhibitors. This project will establish the proximity ligation assay in our laboratory and use it to compare trapping between a set of clinical PARP inhibitors as well as our olaparib analogues and prodrugs thereof.

Neuroinflammation in the human Cingulate Cortex in Huntington’s disease

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull
Thulani Palpagama

Discipline

Biomedical Science

Project code: MHS074

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 taught:

  • human post-mortem tissue processing
  • immunohistochemistry
  • light and confocal microscopy
  • data collection, analysis, and presentation

Investigating the effect of tonabersat in an experimental mouse model of Multiple Sclerosis

Supervisor

Dr Andrea Kwakowsky
Prof Helen Danesh-Meyer
Prof Colin Green

Discipline

Biomedical Science

Project code: MHS075

Multiple sclerosis (MS) is a neurodegenerative disease marked by the chronic inflammation of the central nervous system. Connexin 43 (Cx43) hemichannel blockade has been shown to prevent inflammasome activation and secretion of disease-driving inflammatory cytokines.
The aim of this project is to investigate whether tonabersat, a Cx43 hemichannel blocking drug, can reduce inflammation in various regions of the mouse brain in an Experimental Autoimmune Encephalomyelitis (EAE) mouse model of MS and improve behavioural outcomes.

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 taught:

  • 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

Supervisor

Dr Andrea Kwakowsky

Discipline

Biomedical Science

Project code: MHS076

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 taught:

  • animal handling
  • stereotactic brain surgery
  • mouse behavioural testing
  • neural tissue collection, fixation
  • combination of molecular, anatomical, and imaging techniques
  • data collection, analysis, and presentation

Alpha synuclein in Parkinson’s disease. Are ‘strains’ the solution for novel therapeutics?

Supervisors

Dr Victor Dieriks (09 923 1920)

Discipline

Biomedical Science

Project code: MHS077

Parkinson’s disease (PD) is the fastest-growing chronic neurological disorder affecting 10 million people worldwide. Current therapies are symptomatic and do nothing to stop disease progression. We know that a-synuclein aggregate formation plays a crucial role in toxicity and progressive neurodegeneration. Still, it does not explain the variability in cell types affected and symptoms observed in patients with PD. The recent identification of fibrillar a-synuclein aggregates with noticeable differences in structural and phenotypic traits led to the hypothesis that different a-synuclein 3D conformations or ‘strains’ may be in part responsible for the heterogeneous nature of PD. We hypothesize that the variability that occurs in PD can be stratified based on the a-synuclein strains and that effective treatment requires a strain-specific approach. Novel key genes and proteins linked to the Fibrils and P91 strain have been identified through RNA sequencing. Modification of these targets could lead to the development of novel therapeutics to treat the underlying mechanisms in PD.

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

Validating novel therapeutic targets for Parkinson’s disease: a strain-specific approach

Supervisors

Dr Victor Dieriks  (09 923 1920)
Dr Helen Murray

Discipline

Biomedical Science

Project code: MHS078

Parkinson’s disease and Multiple System Atrophy are neurological disorders affecting 10 million worldwide. Central in these conditions is the formation of toxic clumps of alpha-synuclein protein. Previous research suggests that the building blocks of these clumps are the same but that the resulting 3D structure can vary, giving rise to unique alpha-synuclein 'strains'. We hypothesise that these ‘strains’ may be in part responsible for the varied nature of PD and that future treatments will require a strain-specific approach. We identified the most important gene changes for each strain by exposing brain cells to different alpha-synuclein strains. This project aims to validate the changes linked to the ribbon strain in human brain tissue from patients affected by these diseases. Ultimately the goal is to identify therapeutic targets that reduce the burden of alpha-synuclein in the brain.

Techniques used

  • Multiplex immunofluorescent labelling of human brain tissue
  • High throughput fluorescent microscopy
  • Image processing
  • Data analysis

Application of neurocomputational methods to evaluate brain functional connectivity in relation to depression, systemic inflammation and gut microbiome

Supervisors

Zohreh Doborjeh
Grant Searchfield

Discipline

Biomedical Science

Project code: MHS079

New Zealand has one of the highest 12-month prevalence rates for depression in the world. Depression may be a disease of inflammation. That is, whilst inflammation is critical to our immune response, excessive inflammation damages organs, and may underpin white matter (i.e., myelin) degeneration in depressive disorders, resulting in impaired communication between brain regions. The immune system is, in part, regulated by communities of microbiota that inhabit the intestines. Our previous work applies novel machine learning methods, spiking neural networks (SNN), to brain electrical signals (electroencephalography, EEG), in order to measure communication between various brain regions. Using SNN, we have generated ‘connection weights’ that indicate the degree to which brain regions underlying a scalp site are receiving or sending information to other brain regions. Moreover, we have shown that connection weights can be used to identify individuals vulnerable to depression. We have data (n=30, student and general population) on depression, inflammation (from blood), gut microbiome (from faecal samples), and EEG (64 channels). We want to use SNN to generate connection weights across scalp regions and identify relationships between connection weights and 1) depression; 2) inflammation; 3) gut microbiome.

Exploring the effect of undernutrition and growth restriction on fetal brain development

Supervisor

Dr Joanne Davidson

Discipline

Biomedical Science

Project code: MHS080

Fetal development in utero is a fascinating and highly complex process, with many internal and external factors contributing to the health and development of the fetus. This project will examine how maternal undernutrition and/or prolonged in utero growth restriction induced by insufficient blood supply during gestation affect the developing brain. This study is part of an international collaboration and the results obtained will be correlated with our collaborators MRI findings.

During this summer studentship, the student will master key transferable techniques such as image analysis, cell counting, data analysis and basic statistics. This research will extend our understanding of how fetal brain development is affected by intrauterine growth restriction and maternal undernutrition.

Synthesis and Evaluation of Anti-TB Drug Candidates

Supervisors

Leon Lu (09 233 717)

Discipline

Biomedical Science

Project code: MHS082

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

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

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

Experience working in a chemistry lab would be an advantage (CHEM230 or above).

Autonomic control of heart rate during fetal life

Supervisors

Christopher Lear

Discipline

Biomedical Science

Project code: MHS083

The assessment of fetal heart rate patterns during labour is essentially the only way to tell if a baby is or is not tolerating the stress of labour. This is important in determining whether it is safe for labour to continue, or if an urgent intervention such as a caesarean section is needed. Despite this being used everyday across the world, there are still sizable gaps in our knowledge of what fetal heart rate patterns actually mean or reflect on a physiological level. This project will dissect the sympathetic and parasympathetic contributions to fetal heart rate patterns, and further seek to understand how fetal behaviour and brain activity contribute to heart rate patterns.

During this summer studentship, the student will be involved in the analysis of multiple complex physiological parameters, including fetal heart rate, heart rate variability, body movements, breathing movements as well as EEG activity (brain activity).

This project will provide important information to help guide the assessment of fetal wellbeing during labour by obstetricians and midwives.

Charactersing pulmonary lymphatics

Supervisors

Prof Anthony Phillips (09 923 2037)
Prof John Windsor 

Discipline

Biomedical Science

Project code: MHS085

Scope: Pulmonary lymphatics have only been superficially described to date. In this project the intention is to complete a systematic review of the literature as well as undertaken anatomical and histological analysis using human tissue specimens. A particular focus is charactersing the lymphatic path and anatomical composition of the lymphatics in different lung regions.

Skills: Literature searching; interest in human anatomy. Some familiarity with histological preparation of tissues is an advantage but is not a prerequisite and the successful candidate will be taught these skills when this is required.

Evaluation of a non-aqueous eyedrop

Supervisors

Priyanka Agarwal (021 333 817) 

Discipline

Biomedical Science

Project code: MHS087

Delivery of poorly soluble drugs to the ocular surface is challenging, especially as aqueous solutions are the preferred eyedrops type. Our previous studies have demonstrated that non-aqueous eyedrops may result in higher drug penetration into the ocular tissues, especially when formulated as suspensions.

Therefore, this project will evaluate the safety and efficacy of a non-aqueous eye drop suspension and compare it to an aqueous eyedrop using in vitro and ex vivo models. Ocular irritation potential and drug concentration in ocular tissues will be determined via analytical and imaging methods.

Skills gained: eye drop formulation and characterisation, in vitro toxicity, tissue penetration, drug quantification, microscopy, image analysis and report writing

Dementia in contact sport athletes – assessing tau pathology in different neuronal populations

Supervisors

Dr. Helen Murray
Prof. Maurice Curtis

Discipline

Biomedical Science

Project code: MHS088

Repetitive mild traumatic brain injury in sport can lead to a progressive neurodegenerative disorder called chronic traumatic encephalopathy (CTE). CTE pathology involves the accumulation of toxic clumps of tau protein within neurons that surround blood vessels in the cortical sulci. However, we do not know whether specific neuronal populations are more susceptible to tau accumulation.

The aim of this project is to identify whether specific neuronal populations are affected by tau in CTE lesions. We will label different types of neurons and tau pathology using multiplexed fluorescent immunohistochemistry on brain tissue from former athletes diagnosed with CTE. The results will provide important new insights into the pathological signature of CTE and how it differs from other forms of dementia.

Skills that will be taught in this project:

  • How to review literature
  • Multiplexed fluorescent immunohistochemistry and microscopy
  • Image acquisition, processing and analysis
  • Scientific report writing and figure making

Neuroinflammation and aggregate pathology in Alzheimer’s disease

Supervisors

Dr. Helen Murray 
Prof. Maurice Curtis

Discipline

Biomedical Science

Project code: MHS090

Protein aggregation and neuroinflammation are the hallmark pathologies of neurodegenerative disorders. In Alzheimer’s disease, neurofibrillary tangles are aggregates are made up of different isoforms of the tau protein, and the composition changes as the disease progresses. It is currently unclear whether changing aggregate composition is associated with increased cell stress and/or neuroinflammation.

The aim of this project is to examine the composition of tau aggregates in Alzheimer’s disease brain tissue as well as markers of cell stress and neuroinflammation. We will use multiplexed fluorescent immunohistochemistry to label all proteins of interest. The results will provide new insights into the role of protein aggregates in disease progression.

Skills that will be taught in this project:

  • Multiplexed fluorescent immunohistochemistry and microscopy
  • Image acquisition, processing, and analysis
  • Scientific report writing and figure making

Characterisation of a TRPV4 variant impact on insulin secretion and apoptosis of pancreatic cells

Supervisors

Claire Wang (09 923 5702)
Professor Peter Shepherd

Discipline

Biomedical Science

Project code: MHS091

Type-2 diabetes (T2D) is a major health problems, the incidence of which are rising rapidly both in New Zealand and globally in recent years. T2D develops slowly and is preceded by insulin resistance where major insulin target tissues fail to respond properly to insulin, resulting in impaired glucose uptake in muscle and fat and increased hepatic glucose production. A key determinant of the development and progression of type 2 diabetes is pancreatic beta-cell dysfunction, including the loss of cell mass, the impairment of insulin biosynthesis and inadequate exocytosis. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), a Ca2+ -permeable non-selective cation channel, is involved in pancreatic beta-cell replication, insulin production and secretion.

We recently identified a Maori and Pacific population specific TRPV4 variant which has been found has dysfunctional impact on TRPV4 channel function. This project will investigate the impact of this TRPV4 variant on beta-cell insulin secretion, proliferation as well as insulin exocytosis compared with Wild-Type TRPV4. In the future, this will contribute to personalised therapy by using the TRPV4 variant as a therapeutic target for T2D and related conditions in the Maori and Pacific community.

The work will involve mammalian cell culture, insulin secretion assay, immunocytochemistry, western blot and qPCR, experimental design, data analysis and presentation skills.

Note: This project can take up to 2 students.

Vitreous extracellular vesicles as markers of ocular disease

Supervisors

Ilva Rupenthal
Henry Louie

Discipline

Biomedical Science

Project code: MHS093

Extracellular vesicles (EVs) are small membrane-bound vesicles, secreted by most cells, which exhibit immunomodulatory properties in inflammatory and neurodegenerative diseases. Our previous studies in human donor vitreous have shown that the EV concentration was significantly increased in diseased compared to healthy eyes with protein content also altered. While these results are exciting, limitations associated with post-mortem tissue, including variable processing time and cause of death, hamper clinical translation. Therefore, this study aims to analyse EVs in vitreous collected during vitrectomy.

The ideal candidate will have an interest in understanding ocular disease mechanisms and inflammatory processes.

Skills gained include the isolation and purification of EVs, nanoparticle tracking analysis (NTA), biochemical assays, western blotting, statistical analysis and report writing.

Nanoscale fibrosis and intracellular remodelling of cardiac myocytes in heart failure

Supervisors

David Crossman (021 072 0166) 

Discipline

Biomedical Science

Project code: MHS094

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

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

Novel methods to treat bacterial biofilm infection

Supervisor

Jian-ming Lin (09 923 3193)
Brya Matthews
Simon Swift

Discipline

Biomedical Science

Project code: MHS096

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 or Staphylococcus aureus 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.

Techniques will include: microbiology in a PC2 lab, colony enumeration assays, testing of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC) assays for different combinations of drugs.

Localisation of calcium-binding proteins in the human peripheral nervous system – potential role in neuropathic pain

Supervisor

Simon O'Carroll (09 923 9664)

Discipline

Biomedical Science

Project code: MHS101

Calcium is crucial for many cellular processes. The activity of calcium is regulated by a number of proteins called calcium binding proteins (CBPs), which play important physiological roles through regulating the amount of free intra-cellular calcium. In the peripheral nervous system (PNS) CBPs are involved in pain and proprioception signalling. Animal models show that peripheral nerve injury leads to changes in CBPs in dorsal root ganglia (DRG), and they are a target for pain relief. Little is known about the localisation of these molecules in the human PNS - understanding their expression in humans is crucial in determining if these are potential targets for debilitating conditions of neuropathic pain such as trigeminal neuralgia.

This project will use immunohistochemistry to determine CBP expression and cellular localisation in human DRG and trigeminal ganglia (TG). This project will provide novel data on the localisation of these proteins with neuronal populations involved in pain signalling and whether these are potential targets for treatment. Future work will study the expression and localisation of CBPs in tissue from individuals who suffered from neuropathic pain to understand if this may be a target for treatment.

Skills learnt:

  • Immunohistochemistry
  • Brightfield and fluorescence microscopy
  • Preparation of a scientific report

Fishing for endometrial cancer biomarkers in extracellular vesicles

Supervisors

Dr Cherie Blenkiron
Anastasiia Artuyants

Discipline

Biomedical Science

Project code: MHS102

Endometrial cancer (EC) is the most common gynaecological cancer in New Zealand. Our research focuses on discovering minimally invasive assays for accurate diagnosis and monitoring of females with EC. For that, we isolate extracellular vesicles (EVs) directly from tumour tissue and aim to identify present biomarkers. All living cells, including cancer cells, release EVs into the surrounding environment. These nanosized particles carry a bioactive molecular cargo of protein, nucleic acids and metabolites that reflect their parent cell. Once taken up by the target recipient cells, EVs can alter these cells' behaviour, promoting cancer survival and metastasis. Importantly, EVs are also released into the blood circulation and therefore can be exploited as minimally invasive liquid biopsies.

We are currently profiling EVs isolated from the tumour tissue. This summer student project will aim to compare EVs profile from tumour tissue with those produced from EC cell lines. The main experiments will include – establish endometrial cancer cell lines; isolate and characterise EVs from several EC cell lines; compare biomarkers found in EC cell lines EVs with tumour tissue EVs.

Skills taught:

  • Cell culture;
  • Ultracentrifugation;
  • Nanoparticle Tracking Analysis;
  • Protein quantification;
  • Electron microscopy;
  • Immunostaining.

Building a pioneering child health study with community participation

Supervisors

Samantha Holdsworth (021 834 164)
Robby Green
Graham Wilson

Discipline

Biomedical Science

Project code: MHS103

Paediatric imaging studies help understand human anatomy as we grow and develop. They can inform our understanding of normal anatomy and the epidemiology of disease, and help us identify early biomarkers of diseases.

Auckland University and Matai Medical Research Institute are developing an ambitious, long term study to follow up a cohort of children in Tairawhiti district. Advances in MRI technology make this an opportunity to understand the human body in greater detail than before.

This study is being developed with community and academic collaborators. A small pilot study is being carried out over winter 2021, following which the research team will be building collaboration and designing the full study. Kaupapa Maori values will be central to the full study.

The research student will assist in designing the full study, building relationships with community stakeholders in the district along with academic collaboration. We are looking for a student who is interested in child health and Maori health, community participation, and research design. Being a strong communicator will be essential.

The student will be based in Gisborne.

Skills gained:

  • Understanding research processes
  • Working with community stakeholders
  • Academic writing

For more details, please contact r.green@matai.org.nz

Investigating the role of novel physiological pacing rhythms in heart failure

Supervisors

Rohit Ramchandra (09 923 5183)

Discipline

Biomedical Science

Project code: MHS104

In New Zealand, heart failure affects around 80,000 people. Patients living with heart failure have a poor quality of life because day to day tasks leave them breathless and incapacitated. There have been few new developments in management of heart failure in the last decade. Thus, there is a pressing and substantial unmet clinical need for improved treatment of heart failure. We are currently investigating whether a novel heart pacing device incorporating physiological feedback can improve cardiac function in an ovine model of heart failure. This summer studentship will involve examining heart tissue collected from these studies to determine if particular proteins can affect heart function.

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

Skills that will be taught and mentored through this studentship include:

  • Literature review writing skills
  • Immunohistochemistry and histological analysis
  • Collection of physiological data in conscious animals
  • Analysis of data
  • Oral presentation skills

Characterising lymphatic muscle

Supervisors

Professor John Windsor (021 901 930)
Professor Anthony Phillips

Discipline

Biomedical Science

Project code: MHS105

Scope: Lymphatic vessels undergo phasic contractions like the heart, as well as tonic contractions like arteries and vein. The structure and function of this muscle layer is unique and incompletely described to date. This project aims to advance our understanding of lymphatic muscle in health and disease, and will form part of a larger project on this topic, aimed towards drug modulation of lymphatic function to reduce oedema and improve organ function.

Skills: Literature searching, data analysis and some lab work, such as immunohistochemistry (some familiarity with this procedure is an advantage but not a prerequisite).

Identifying novel inhibitors that target growth hormone receptor signalling

Supervisors

Jo Perry
Yue Wang

Discipline

Biomedical Science

Project code: MHS109

Expression of growth hormone (GH) is detected in a variety of different human cancers and is associated with reduced overall survival for breast and endometrial cancer patients. Despite the growing body of evidence implicating GH in cancer, preclinical studies investigating the therapeutic potential of inhibiting the GH receptor for the purposes of treating cancer have been hindered by a lack of an effective GH inhibitor suitable for in vivo studies. This summer student project is part of a wider drug discovery effort aimed at developing novel GH receptor antagonists. In this project you will purify a series of novel GH receptor antagonists and determine whether they can neutralise GH action in cell-based and molecular biology assays.

Skills taught: mammalian cell culture, protein purification, cancer cell biology and western blot assays, experimental design and data interpretation.

Design and Synthesis of Novel Xanthenone based Molecules to control Kinase Cell Signalling in Disease.

Supervisor

Swarna Gamage (021 235 2370)

Discipline

Biomedical Science

Project code: MHS111

We discovered xanthenone-based chemistry is a novel and highly effective way of developing new molecules that can inhibit the activity of a tyrosine kinase enzyme called Lck involved in the survival of T-cell leukaemias.

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

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

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

Second year chemistry knowledge would be helpful but not essential.

More than meets the eye

Supervisors

Trevor Sherwin (09 923 6748)

Discipline

Biomedical Science

Project code: MHS114

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

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

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

Supervisors

Lola Mugisho (09 923 8274)
Charisse Kuo

Discipline

Biomedical Science

Project code: MHS117

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.

Ideal candidate: The ideal candidate will have a keen interest in understanding disease mechanisms and pathways.

Skills gained: Human donor eye processing, immunohistochemistry, confocal microscopy, western blotting, statistical analysis.

Characterization of a novel neovascularisation model using human donor choroids

Supervisors

Lola Mugisho (09 923 8274)
Charisse Kuo

Discipline

Biomedical Science

Project code: MHS118

Neovascularisation, the formation of new but unhealthy blood vessels, is a key feature of several sight-threatening diseases. A clinically relevant preclinical model of neovasularisation is required to further our understanding of underlying disease mechanisms and for the development and characterization of novel therapeutics. This project aims to develop a 3D vascular model that mimic abnormal vessels formed in neovascularisation using endothelial tubules which sprout from cultured human donor choroid.

Ideal candidate: The ideal candidate will have a keen interest in understanding disease mechanisms and pathways.

Skills gained: tissue culture, microscope imaging, quantification, statistical analysis

Histological characterisation of kidney development in sheep

Supervisors

Veronika Sander (022 383 6428) 

Discipline

Biomedical Science

Project code: MHS119

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, microtome 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.

This summer studentship can be continued towards Honours, Masters or PhD studies, see also https://www.findathesis.auckland.ac.nz/research-entry/10459767

Using human kidney organoids to study disease

Supervisors

Veronika Sander (022 383 6428) 

Discipline

Biomedical Science

Project code: MHS120

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, microtome 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.

This summer studentship can be continued towards Honours, Masters or PhD studies, see also https://www.findathesis.auckland.ac.nz/research-entry/10459767

Systematic quantification of aortic flow from 4D flow MRI

Supervisor

Kat Gilbert  (021 834 164)
Robby Green
Samantha Holdsworth

Discipline

Biomedical Science

Project code: MHS124

The aorta is the largest blood vessel in the body and is responsible for carrying blood from the heart to the circulation system.

We are collecting 4D MRI datasets of the flow down the aorta, and in this project you’ll be helping us setup a protocol for the measurements we’ll be doing. Additionally, in this project we will be qualitatively assessing flow profiles. This project is in collaboration with Matai Medical Research Institute in Gisborne and will ideally take place in Gisborne, however it would be possible to complete it in Auckland.

Data will be collected as part of the Tairawhiti study pilot. The full study will use pioneering MRI techniques to capture paediatric anatomy in greater breadth and depth than has previously been achieved, following a cohort of children as the grow and develop. Ten children will be scanned during the pilot to develop MRI protocols, processing and modelling.

Skills developed will include:

  • In depth knowledge of cardiac anatomy and functional assessment
  • Science communication – communicating your results to the community, engineers and clinicians
  • Statistical techniques in R

COSMOS and Diabetes

Supervisors

Sakina Bharmal
Professor Max Petrov

Discipline

Biomedical Science

Project code: MHS125

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

Skills Taught:

  • Working in a clinical research team environment
  • Management of a clinical study
  • Laboratory bench work 
  • Preparation of a manuscript for publication in an international peer-reviewed journal

Feed the World .... using cellular agriculture!

Supervisors

Trevor Sherwin (09 923 6748)
Laura Domigan

Discipline

Biomedical Science

Project code: MHS128

How can we produce enough food to feed the ever growing world population?

How can we provide more nutritious food at lower cost to fight the diabetes epidemic?

How can we reduce the environmental impact from conventional farming?

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

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

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

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

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

Understanding the Molecular Pharmacology of Novel Compounds Targeting Cannabinoid Receptor 2

Supervisors

Natasha Grimsey (09 923 1886)

Discipline

Biomedical Science

Project code: MHS129

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.

Working with medicinal chemists, we are developing novel CB2 ligands with particular interest in modifying physicochemical properties and determining influence on signalling profiles and targeting different subcellular receptor populations.

This project will characterise a set of novel compounds in one or more signalling pathways to assist in understanding the compound properties and potential in therapeutically targeting CB2.

Skills Taught/Utilised

  • 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, 319) 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

New Friends (or Enemies?) for Cannabinoid Receptors

Supervisor

Natasha Grimsey (09 923 188) 

Discipline

Biomedical Science

Project code: MHS130

Cannabinoid Receptors (CBRs) are G Protein-Coupled Receptors (GPCRs) expressed in a wide range of tissues and implicated in various disorders. CB1 is one of the most highly expressed GPCRs in the central nervous system and CB2 is highly coveted as an immune system target, whereas orphan putative cannabinoid receptor GPR18 and GPR55 remain under-characterised.

Accessory proteins such as RAMPs and MRAPs are known to markedly alter the function of various GPCRs, but have not yet been studied in the context of CBRs.

This project will contribute to follow-up studies from our pilot data indicating interactions between CBRs and accessory proteins, particularly in the context of whether CBRs can influence expression and signalling of other co-expressed receptors which depend on accessory proteins for normal function.

Skills Taught/Utilised

  • 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, 319) is preferred, but this would also be suitable for students with general interests in mammalian cell biology, medicinal chemistry / drug development and/or CNS and immune-related therapeutic application.

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

Building Virtual Cochlea 3D Model for Hearing Research

Supervisors

Haruna Suzuki-Kerr (09 923 8728)
Vicke Shim
Peter Thorne

Discipline

Biomedical Science

Project code: MHS131

Our sense of hearing originates in the inner ear organ called the cochlea. Cochlea is a pea-sized organ taking shape similar to snail shell, containing complex networks of vasculatures, innervations, sensory cells and neurons. To better understand the complex tissue physiology and fluid dynamics within the cochlea, this summer studentship project aims to build anatomical models of sheep and human cochlea.

High resolution microCT datasets of human and sheep cochleae are already available in our laboratory (the department of Physiology). In collaboration with the Virtual Brain Group (ABI), the student will take series of image data through image processing to build 3D computational model of cochleae with features including bones, nerve fibres, sensory epithelium and different cochlear fluid compartments.

The successful applicant will have strong interests in biology/physiology, have keen eyes for anatomy and in learning new skills. Please enquire to find out more details on the project.

Skills: Image analysis & processing by filtering and segmentation, 3D modelling and visualization, literature review and report writing.

Vascular Biology of the Sheep Cochlea

Supervisors

Haruna Suzuki-Kerr (09 9238 728)
Joanne Davidson
Peter Thorne

Discipline

Biomedical Science

Project code: MHS132

Our sense of hearing is critical for daily communications and activities. Some early-onset hearing loss caused by congenital or secondary to infection are known to manifest as bilateral hearing loss that are slowly progressive in nature. The pathological mechanism is unknown, however the involvement of vascular inflammation has been suggested. This summer studentship project aims to characterize the mature and developing sheep cochlea, focusing on cochlear vasculatures.

The student will be trained to conduct lab-based work in the department of physiology to prepare tissue samples from adult or foetal sheep cochlea, and study the histological and anatomical features of the cochlear vasculature by microscopy techniques. This study will lay a foundation for using sheep as large animal model for studying the role of vascular inflammation in progressive hearing loss.

The successful applicant will have strong interests in biology/physiology, and in learning laboratory skills. Please enquire to find out more details on the project.

Skills: Tissue dissection, tissue sectioning, immunohistochemistry, fluorescent microscopy, image processing, report writing, literature search.

How does Shank3 regulate Pancreatic beta-cells?

Supervisors

Dr. Waruni C. Dissanayake (093737599 ext 85702)
Prof. Peter R. Shepherd

Discipline

Biomedical Science

Project code: MHS135

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. Calcium influx via voltage gated Calcium channels plays a major role during insulin secretion process.

One of the main research themes 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 its potential role in the modulation of calcium influx.

During this project you will learn several techniques including cell culture, cell based assays (insulin secretion assays, Calcium flux assays) and protein-protein interaction studies (co-immunoprecipitation).

Biomarker detection in melanoma extracellular vesicles

Supervisors

Dr Cherie Blenkiron
Marcella Flinterman

Discipline

Biomedical Science

Project code: MHS138

Melanoma is the third most common cancer in New Zealand and accounts for more than 80% of all skin cancer deaths. Extracellular vesicles (EVs) are nanosized particles that are produced by all cell types and which can be released in the blood circulation. EVs are representative of their parent cells and play an important role in disease pathology including cancer. Expression levels of certain proteins in melanoma patient plasma EVs can be used as a biomarker to detect early response/non-response to immunotherapy.

We are currently investigating EVs isolated from melanoma patient plasma samples for biomarker expression. The aim of the student project will be to isolate and characterise melanoma cell line EVs for biomarkers and compare the results with the data from melanoma patient plasma EVs.

Techniques taught:

  • Cell culture
  • Ultracentrifugation
  • Size exclusion chromatography
  • Nanoparticle tracking analysis
  • Protein quantification
  • Western blot analysis
  • Electron microscopy

Architectural Assessment in Heart Valve Tissue Engineering

Supervisors

Professor Jillian Cornish
Dr Steve Waqanivavalagi
Mr Marcus Ground
Mr Paget Milsom

Discipline

Biomedical Science

Project code: MHS140

Valvular prostheses in current clinical use each face some limitation precluding their routine use in surgery. We have developed a prototype collagen scaffold for use as a tissue engineered heart valve. Our work to date has involved basic architectural assessments of the scaffold and immunogenic testing in a subcutaneous rat model that we developed in house.

We are now in a position where we want to optimise our product further my interrogating the architectural effects of our tissue engineering process. We have previously developed a soft tissue imaging protocol using microCT. That imaging technique has advantages over other extended-volume imaging techniques such as microMRI and confocal laser-scanning microscopy in that it is not as costly, does not require tissue destruction, and is readily accessible.

We are offering a project in which the microCT imaging protocol will be optimised and then used to examine the difference between our prototype scaffold and both native and industry-standard, glutaraldehyde treated scaffolds.

This project will involve work in our laboratory in Grafton and the microCT suite at the Auckland Bioengineering Institute on Symonds Street. Academic writing, tissue handling, laboratory skills, imaging skills, and presentation techniques will be learned.

Note: This project can take up to 2 students.

New dopamine pathways in the brain – better understanding of Parkinson’s disease

Supervisors

Peter Freestone (021 072 8589)

Discipline

Biomedical Science

Project code: MHS151

The precise timing and location of release of the brain chemical dopamine underlies many brain functions including movement, memory/learning and cognition processes. Indeed, disruption to the normal release of dopamine is the key pathological feature of many neuropsychiatric and neurological disorders. Parkinson’s disease is one such example – a debilitating movement disorder currently affecting ~12,000 New Zealanders.

While much is known about the brain regions and pathways affected by Parkinson’s disease, exciting recent research by our group has unveiled a new dopamine pathway that could be crucial in the development of the disease and be a target for novel treatment strategies. This novel dopamine pathway originates with the dopamine neurons in the substantia nigra pars lateralis (SNL), and project to the tail (caudal) region of the striatum. Both the SNL and tail striatum are poorly studied and require careful examination. The aim of this project is to characterize the dopamine neurons in the SNL using electrophysiological techniques, and build our knowledge of these unique neurons.

Skills:

  • Electrophysiological recording of neuronal activity (action potential firing)
  • Brain slice preparation
  • Retrograde labelling of SNL neurons.
    Experience in neuroscience (e.g. MedSci206), ideally electrophysiology (e.g. MedSci309) would be favorable.

This project has the potential to continue to a Hons/Masters/PhD project.

Neurocardiac view on the Long QT Syndrome

Supervisors

Dr Annika Winbo
A/Prof Johanna Montgomery

Discipline

Biomedical Science

Project code: MHS152

Long QT Syndrome, the most common cause of sudden death in New Zealand youth, is characterised by life-threatening abnormal heart rhythms triggered by the sympathetic “fight-or flight” response. It is unknown whether the sympathetic triggering of abnormal heart rhythm in the Long QT Syndrome is isolated to an abnormal response in the heart cells, or if there is also an abnormal stimulation by the nerve cells.

Recent breakthroughs make it possible to model the interactions between nerve cells and heart cells when they are grown together in vitro. We have established a functional neurocardiac model, using stem cells reprogrammed from human blood to grow sympathetic nerve cells and heart cells together.

We are offering a project in which the cellular composition of novel neurocardiac cocultures will be characterized, using cocultures derived from Long QT Syndrome patients and healthy controls. This project will involve work in the Montgomery laboratory at FMHS in Grafton. Academic writing, tissue handling, laboratory skills, imaging skills, and presentation techniques will be learned.

Identifying novel drug candidates for treating kidney diseases using "mini kidneys in a dish"

Supervisors

George Chang

Discipline

Biomedical Science

Project code: MHS153

Podocytes, a specialised type of kidney cells, are the main targets of injury in various kidney diseases. However, current treatments for kidney diseases are not curative but act indirectly to mitigate podocyte injury. As a result, these treatments can only slow, but not stop, the disease progression and cause adverse side effects. This summer student project is part of a wider drug discovery effort aimed at identifying novel therapeutic agents for podocyte injury. In this project, the summer student will be testing different drug candidates using "mini kidneys in a dish" generated from inducible pluripotent stem cells.

Techniques and skills involved:

  • Mammalian cell culture
  • Histology (paraffin embedding, microtome sectioning, H&E- and trichrome staining)
  • Immunohistochemistry and confocal microscopy
  • RNA isolation and qPCR
  • Data analysis and presentation

Imaging, analyzing and modelling neurons in the subthalamic nucleus

Supervisors

Peter Freestone (021 072 8589)
Mark Trew

Discipline

Biomedical Science

Project code: MHS154

Networks of neurons in the subthalamic nucleus of the brain are implicated in the development and symptoms of Parkinson’s disease. Mapping the electrical and physical connectivity of these networks will give new insights into Parkinson’s and eventually direct the focus of potential treatments.

High resolution, “smart” electrophysiology mapping in slices of subthalamic nucleus is done using lasers and an array of micro-mirrors. These data are collected from genetically modified mice with brain tissue that responds to laser light stimulation. After the experiment the tissue is optically cleared and high-resolution line scanning confocal microscopy is used to build 3D structure images of the neuron bodies in the tissue. The combination of electrical maps and 3D structure images form the basis of inferred neuron network connections.

This project contributes to the 3D imaging, image analysis and inferred functional linkages back to the experimental electrical data.

While there will likely be some tissue handling, most of the project will be algorithmic and computationally based, working with confocal images of the subthalamic nucleus, extracting useful information through image filtering and training data models (machine learning) to identify neuron bodies, and analysing the shapes and sizes of the neurons. Finally, Sherlock Holmes logic and deduction will be needed to propose the inter-neuron linkages that could be inferred from the electrical and structural data sets.

Most of the project is based in the Auckland Bioengineering Institute and will give the successful candidate experience interacting with other students and researchers there. However, there will also be exciting opportunities to meet students and researchers in the Centre for Brain Research and observe the intricate experimental work that takes place there.

Exploring hippocampal deficits in a mouse model of Autism Spectrum Disorder using miniscopes

Supervisors

Juliette Cheyne (027 720 3490)
Yewon Jung
Johanna Montgomery

Discipline

Biomedical Science

Project code: MHS155

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

Skills that will be learned through the project:

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

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

Python interface for EEG studies

Supervisors

Matthew Moore (09 923 2899)
Shashikala Ramakrishna

Discipline

Biomedical Science

Project code: MHS157

The candidate will refine and test an interface between a stimulus display computer and another machine recording a high-definition electroencephalogram (EEG). The stimulus display computer will be running OpenSesame in Python 3, and the EEG recording machine EGI NetStation 5 under MacOSX. Timing will then be tested using a photodiode and signal processing techniques in Matlab.

The package is currently working in a rudimentary fashion (https://github.com/mattmoo/PyNetStation), but needs refinement. A fully operational package with published timing data has the potential to be widely cited.

The candidate will need advanced programming skills, preferably in Python.

Targeting biofilm infection in osteomyelitis

Supervisors

Simon Swift
Jingyuan Wen

Discipline

Biomedical Science

Project code: MHS158

In a biofilm infection bacteria grow on tissue or implanted devices. Biofilms are responsible for about 65% of all human infections and are especially associated with chronic infections. Biofilms exhibit high levels of antibiotic tolerance and without specific resistance genes can be 1000× less sensitive to an antibiotic than cells in broth cultures grown from the biofilm bacteria. Biofilms therefore are often a factor in the failure of antibiotic treatments and new therapies are needed to target biofilms. Specifically, there is a need for drugs that can penetrate or disrupt the biofilm polymeric matrix and provide efficacy against the phenotypically variable cells within the biofilm, including the recalcitrant persister cell population.

One example of a biofilm infection is osteomyelitis, a severe infection localised to the bone. It generally occurs in growing children, and is a particular problem in New Zealand with a high prevalence in Maori and Pasifika 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. 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 antibiofilm formulations on biofilms grown from clinically relevant strains of Staphylococcus aureus, which is the most common bacteria found in osteomyelitis. We ultimately hope to develop more effective treatments to rapidly clear the infection.

Techniques will include: Microbiology in a PC2 lab, growth and characterisation of S. aureus biofilms, biofilm eradication assays for different the formulations, microscopy of biofilms to visualise the penetration of the formulations prepared. Depending on time and student interest/skills there may be an opportunity to prepare and characterise antibiofilm formulations.

What floats your boat? CSF and blood flow analysis to improve novel MRI method

Supervisors

Eryn kwon (021 977 118)
Samantha Holdsworth

Discipline

Biomedical Science

Project code: MHS161

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

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

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

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

Investigating mild traumatic brain injury - Virtual brain project

Supervisors

Eryn Kwon (021 977 118)
Vickie shim
Samantha Holdsworth

Discipline

Biomedical Science

Project code: MHS162

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

This project will build on a pre-existing large animal MRI database, collected both before and after a controlled impact. There are two major parts: the first is to perform a manual segmentation of the sheep brain with a matching skull. The second part will use the segmented geometry from the first part, run a simulation of the impact, and validate the result with the experimental data.

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

All software and simulation training will be provided.

The effect of preptin deficiency on the bone in aging mice

Supervisors

Emma Buckels
Brya Matthews

Discipline

Biomedical Science

Project code: MHS164

Osteoporosis is a serious public health problem, characterised by low bone mass and micro-architectural deterioration of bone tissue, resulting in bone fragility and increased risk of fracture. 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. This studentship is part of a larger body of research testing 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. 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, data analysis and interpretation.

Hollow Microneedles Array for Painless Blood Extraction

Supervisors

Manisha Sharma (09 923 1830)
Andrew Taberner
James McKeage

Discipline

Biomedical Science

Project code: MHS165

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

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

Manipulation of astrocyte function for gene therapy

Supervisors

Angela Wu (09 231 907)
Deborah Young

Discipline

Biomedical Science

Project code: MHS166

AAV vectors are the vector-of-choice for human gene therapy and whilst neurons are the major cell target for gene therapy strategies, other non-neuronal cell types could also be involved in driving the pathogenesis of neurodegenerative diseases. This project is aimed at characterising the functionality of a simple NURR1-based gene regulation system in astrocytes, as an alternative gene therapy strategy for Parkinson's disease.

We are looking for a motivated, enthusiastic student who has a strong interest in neuroscience and biomedical research.

Skills learnt:

  • Mammalian cell culture
  • Immunocytochemistry
  • Imaging
  • Basic molecular cloning/ plasmid preparation

Improve the solubility of CoQ10 using advanced drug delivery technology

Supervisors

Jingyuan Wen (09 232 762)

Discipline

Biomedical Science

Project code: MHS168

Coenzyme Q10 (CoQ10) also known as Ubiquinone, is an essential component in all membranes throughout the cell. It is a highly lipophilic molecule that is naturally present in all membranes of human cells. CoQ10 plays a central role in shuffling electrons through the initial stages of the electron transport chain. Other functions of CoQ10 include free radical scavenging, cell signalling and gene expression. The antioxidant activity of CoQ10 has a protective role on lipid proteins and DNA mostly due to its proximity to oxidative events within the cell. CoQ10 deficiencies can occur in patients with diabetes, cancer and cardiovascular and neurodegenerative diseases. CoQ10 supplementation has shown positive results in multiple clinical trials for these disease states; however, the success of treatment is dependent on sufficient CoQ10 bioavailability. The high molecular weight (863.34 g/mol) and high lipophilicity (logP = 21) of CoQ10 makes it poorly water soluble and consequently leads to low systemic availability (<10%). It is also chemically unstable when exposed to air, UV light and temperatures over 40°C.

The aim of the project is to improve the aqueous solubility of CoQ10 using advanced drug delivery techniques, such as encapsulating CoQ10 into mico-/ nanoemulsions and nanocrystals systems.

Techniques will include: Emulsions systems of CoQ10 will be developed and characterised using ternary phase diagram methods. Droplets size will be measured by Zetasizer. And in vitro drug release will be evaluated using Franz diffusion cells and the samples will be analysed by High Performance Liquid Chromatography.

3D MRI Atlas of Dolphin and whale Neuroanatomy

Supervisors

Miriam Scadeng (09 923 9659)
David Dubowitz

Discipline

Biomedical Science

Project code: MHS170

Aims: 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.

Collateral damage? Improving brain blood flow during stroke

Supervisors

Fiona McBryde
Tonja Emans

Discipline

Biomedical Science

Project code: MHS173

Background: New clinical procedures (endovascular thrombectomy) to remove blood clots from the brain have had a huge impact on the prognosis of stroke patients. The level at which blood pressure (BP) is maintained during endovascular thrombectomy may affect the collateral blood supply to vulnerable parts of the brain. We have developed an advanced imaging protocol using high resolution ultrasound to let us “see” what is happening to brain perfusion during stroke, in real time. Our ultimate goal is to determine whether elevating blood pressure can improve the collateral blood supply, and whether this is altered in subjects with hypertension.

Research Skills: The successful student will work with a preclinical model of ischemic stroke, including testing the functional sensorimotor recovery from stroke. Other skills include the acquisition and analysis of photoacoustic and contrast-assisted ultrasound imaging of the brain, to quantify changes in regional perfusion.

Student Requirements: We seek a bright and motivated student to join us for the summer, and hopefully beyond. We offer a friendly and supportive team environment, with world-leading expertise and cutting-edge translational research programs. This project would particularly suit a student with an interest in medical imaging.

Harnessing inhaled argon to protect the brain during stroke.

Supervisors

Tonja Emans
Fiona McBryde

Discipline

Biomedical Science

Project code: MHS174

There is an urgent need for strategies to help protect brain tissues during ischemic stroke, until the occluding blood clot can be removed or dissolved. The inert gas argon has been identified as having neuroprotective properties, which in combination with its ready availability and potential to be given in an ambulance/emergency setting, make it a promising candidate for use in stroke patients. However, a convincing case needs to be built before a clinical trial of argon in stroke patients can be justified – consideration needs to be given to a summary of the current literature and designing appropriate preclinical studies to test the in vivo efficacy of inhaled argon in stroke.

This summer project will evaluate whether inhaled argon can help protect the brain and reduce neuronal death during ischemic stroke.

Research Skills: The successful student will work with a preclinical model of ischemic stroke, including testing the functional sensorimotor recovery from stroke and histology to confirm infarct volume.

Student Requirements: We seek a bright and motivated student to join us for the summer, and hopefully beyond. We offer a friendly and supportive team environment, with world-leading expertise and cutting-edge translational research programs. This project would particularly suit a student with an interest in physiology and neuroscience.

Novel targets within the carotid body for treating diabetes.

Supervisors

Julian Paton
Pratik Thakkar

Discipline

Biomedical Science

Project code: MHS175

Cardiovascular diseases such as high blood pressure and heart failure combined with diabetes cause the highest number of deaths per year in Aotearoa. For both diseases, sympathetic nerve activity (SNA) is raised and offers a potential common target for improving the outcome for patients. Recent studies discovered that carotid bodies (CB) senses blood sugar and/or insulin and causes increases in SNA, whereas their removal lowered blood sugar, blood pressure, and SNA. We have discovered two novel receptors within the CB control blood sugar via modulating SNA. These data will advance our understanding of the mechanisms of diabetes and will inform unique treatment strategies for treating cardiometabolic disease.