Biomedical

  1. » Molecular mechanisms of heart dysfunction in diabetes
  2. » Prenatal alcohol exposure and infant neurobehaviour
  3. » Prenatal alcohol exposure and genetic/epigenetic interplay
  4. » Project filled: Evaluating the long-term usability of ex vivo bovine corneas for drug delivery applications
  5. » Effect of temperature on the thickness of the human ocular choroid measured with optical coherence tomography
  6. » Project filled: More than surface area: how could cilia on the placental surface impact placental morphogenesis?
  7. » Development of hypoxia activated prodrugs based on the PARP inhibitor talazoparib
  8. » Artificial Sweeteners during pregnancy: friend or foe?
  9. » Monitoring age-related changes of the vitreous of the eye, using MRI
  10. » Does the interaction of inflammation and high fat diet during pregnancy influence male offspring reproductive function?
  11. » Development of tools to measure reactive oxygen species production in the aging eye
  12. » Visualising antioxidant delivery to the ocular lens with imaging mass spectrometry
  13. » Functional characterization of long non-coding RNA in breast cancer cell lines
  14. » Project filled: Understanding GABA Signalling in the Vasculature of Healthy and Alzheimer's Disease Brains
  15. » Project filled: Characterisation of the neuropathological hallmarks of Huntington's disease using human brain tissue microarrays
  16. » Gasping for breath in heart failure
  17. » Does incorrect wiring of the auditory cortex during development contribute to functional deficits in Autism Spectrum Disorder mice?
  18. » Project filled: Clinical and Molecular Characterization of Inherited Optic atrophy from the NZ Inherited Retinal Disease Database
  19. » Understanding the mechanisms through which exercise improves health
  20. » Using human induced pluripotent stem cell-derived kidney organoids to model kidney disease
  21. » Project filled: The assessment of the Comet Assay on fresh versus frozen samples
  22. » PERK up! A cancer drug design project
  23. » Effect of excipients on the stability of extemporaneously compounded levothyroxine oral liquid
  24. » Understanding the interactions between osteoarthritis and gout: does damaged cartilage influence the inflammatory potential of urate crystals?
  25. » Super-resolution imaging of the transverse tubules in ischemic heart failure
  26. » Growth hormone receptor inhibition: identifying key signal transduction pathways
  27. » Formulation and characterization of novel peptide loaded hydrogel for topical delivery
  28. » Cellular identity crisis: understanding the underlying causes of osteoarthritis
  29. » Mechanisms of beta cell destruction during childhood type 1 diabetes
  30. » What can twins tell us about the genetics of keratoconus?
  31. » Topical Delivery of Hyaluronic acid (HA) using microemulsion as a drug delivery system
  32. » Lighting up cancer cells with DAMP signals
  33. » How does raised intracranial pressure drive arterial pressure?
  34. » Understanding and enhancing therapeutic effects of L-DOPA in Parkinson's disease
  35. » Developing gene therapy as a treatment for spinal cord injury
  36. » Using liposomes to target drug delivery in spinal cord injury
  37. » Can we improve treatment of babies with ischemic brain injury?
  38. » Death by a thousand cuts: Drugging the DNA damage response
  39. » Is HMGB1, as one of the most important damage-associated molecular patterns (DAMPs) associated with impaired autophagy seen in preeclampsia?
  40. » Epigenetics and Keratoconus - understanding enigmatic eye disease
  41. » A novel medical device for early warning of severe surgical infections
  42. » Identifying early biomarkers of dementia in human blood
  43. » Does mild fetal asphyxia impair white matter development?
  44. » Can anti-inflammatory medications reduce brain injury after severe fetal asphyxia?
  45. » How does the hypertensive brain protect itself from under-perfusion?
  46. » Project filled: Non-steroidal anti-inflammatory drugs compared to cyclooxygenase 2 inhibitors and risk of adverse cardiovascular event, a systematic review and meta-analysis
  47. » Autonomic control in preserved ejection heart failure
  48. » Project filled: Effectiveness of various intrauterine devices: a systematic review and meta-analysis
  49. » Cannabinoid Receptor Signalling
  50. » Can a nutritional supplement alter oxidative stress in humans-a systematic review
  51. » Beating the superbugs: searching for new antibiotics from New Zealand's fungi
  52. » Targeting the chemoreceptors in hypertension
  53. » Project filled. Erythropoietin and retinopathy of prematurity
  54. » Targeting peripheral inflammation for neuroprotection in infection-related preterm brain injury
  55. » Can SIRT1 be an early marker of gestational diabetes?
  56. » Does excess extracellular hyaluronan affect the developmental morphology of hippocampal and cortical neurons?
  57. » Effects of inhibiting hyaluronan synthesis on development of cortical neurons
  58. » Project filled: Can Magnetic Resonance Imaging (MRI) be used to assess symptoms of malabsorption?
  59. » Viral trigger of human type 1 diabetes
  60. » Project filled: Can we identify prostate cancer patients with a genetic pre-disposition for AKR1C3 over-expressed disease?
  61. » Spheres of influence
  62. » A new broad-spectrum metabolite detection method for discovery metabolomics
  63. » Detecting dysregulation in dynamic metabolomes using network analysis
  64. » Whole genome CRISPR/Cas9 screens to identify tumour hypoxia tolerance genes
  65. » Characterising hypoxia in patient-derived xenograft models of head and neck cancer
  66. » Study of polysialic acid neural cell adhesion molecule in human microglia
  67. » Using induced pluripotent stem cells to identify new drug treatments for cystinosis
  68. » Functional characterisation of novel RNA-binding protein in cultured macrophage cells
  69. » Influence of high glucose and inflammation on barrier properties of primary retinal microvascular endothelial cells
  70. » Understanding the burden of tendon disorders in New Zealand
  71. » Antioxidant eye drops for prevention or delay of cataract formation
  72. » Loss of smell in neurological disorders
  73. » Does mtDNA affect the outcome of IVF?
  74. » Examining receptor trafficking and synapse plasticity in the neural innervation of the heart
  75. » Identification of epigenetic approaches for killing KDM6A-mutant cancers
  76. » Project filled: Creating an Antibody Binding Map for the Group A Streptococcus M protein, a Leading Vaccine Candidate
  77. » Use of gene editing tools to evaluate the role of oxidoreductases in the activation of hypoxia-selective prodrugs
  78. » Can we treat brain damage in preterm babies - a therapeutic role for a2-adrenergic agonists?
  79. » Unravelling mechanisms of lymphatic vessel development
  80. » Project filled: Understanding the metabolism of the hypoxia-activated EGFR inhibitor tarloxotinib
  81. » Understanding the metabolism of hypoxia-activated FGFR inhibitors
  82. » Project filled: Characterization of beta amyloid-induced molecular and cellular changes in an in vivo Alzheimer`s disease mouse model
  83. » Project filled: Which brain cells are affected first in the olfactory bulb in Parkinson's disease
  84. » Project filled: Acute mechanisms of perinatal ischemic brain injury
  85. » Treating cutaneous inflammation by putting skin on a fat-free diet
  86. » Examining changes in patient heart cells with long QT syndrome

Molecular mechanisms of heart dysfunction in diabetes


Supervisor

Kim Mellor

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: 

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

Skills

  • Critical analysis of the literature
  • Molecular biology techniques
  • Experimental models of diabetes
  • Data analysis and presentation

Prenatal alcohol exposure and infant neurobehaviour


Supervisor

Suzanne Stevens

Project type

Biomedical

Department

Psychological Medicine

Location

Auckland

Project code: MHS002

 

Prenatal alcohol exposure (PAE) is an established risk for neurodevelopmental deficits in children and represents a substantial and potentially preventable burden of disease and health care costs. The Prenatal Environment and Neurodevelopment (PEN) Pilot study was set up to investigate the effects of PAE and genetic/epigenetic interplay on infant neurobehavioural development and potential bio-behavioural markers of PAE.

This project aims to investigate the neurodevelopmental and bio-behavioural assessments carried out with infants in our study.

Skills

  • Literature searches
  • Academic writing skills
  • Use of structured infant assessments
  • Experience using bio-behavioural data

 

Prenatal alcohol exposure and genetic/epigenetic interplay


Supervisor

Suzanne Stevens

Project type

Biomedical

Department

Psychological Medicine

Location

Auckland

Project code: MHS003

Prenatal alcohol exposure (PAE) is an established risk for neurodevelopmental deficits in children and represents a substantial and potentially preventable burden of disease and health care costs. The Prenatal Environment and Neurodevelopment (PEN) Pilot study was set up to investigate the effects of PAE and genetic/epigenetic interplay on infant neurobehavioural development and potential bio-behavioural markers of PAE.

This project aims to investigate the genetic/epigenetic interplay with PAE using genotypying and/or epigenetic methylation data from children in our study.

Skills

  • Literature searches
  • Academic writing skills
  • Experience using genetic/epigenetic data

Project filled: Evaluating the long-term usability of ex vivo bovine corneas for drug delivery applications


Supervisor

Sachin Thakur

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS004

This project topic has been filled

Tissue models are an essential tool for ocular drug delivery research. The ex vivo cornea is routinely used in preclinical evaluations for topical formulations such as eye drops and eye ointments. However, very little is known about the post-mortem viability of the cornea, and the tissue is not generally used in evaluations that exceed a few hours. This project aims to analyse and maintain the physiological properties of the cornea post-mortem. Bovine corneas will be collected and maintained under various storage conditions. At set periods following storage; cell viability, tissue structure and biomechanics will be assessed and compared to the baseline. Finally, dye penetration and retention studies will be performed to evaluate retention of tissue permeability and mucoadhesiveness.

Skills

  • UV/Vis spectroscopy
  • Fluorescence spectroscopy
  • Franz cell diffusion studies
  • Tissue staining and fluorescence microscopy
  • Texture analysis

Effect of temperature on the thickness of the human ocular choroid measured with optical coherence tomography


Supervisor

John Phillips

Project type

Biomedical

Department

Optometry and Vision Science 

Location

Auckland

Project code: MHS005

The ocular choroid is the vascular bed supplying blood to the photoreceptors of the retina – one of the highest oxygen-consuming tissues of the body. The choroid has the capacity to change its thickness and blood perfusion in response to a variety of factors including exercise, accommodation, retinal defocus etc. However, the choroid is also important in regulating retinal temperature, although little is known about this function. The aim of this project is to define the time course of the choroidal response (change in thickness) to imposed increases and decreases in temperature applied externally to the eye and surrounding tissues with a simple heating/cooling device. Choroidal thickness will be measured non-invasively using Optical coherence Tomography (OCT) in human volunteers.

Skills

Conducting Optical Coherence Tomography (OCT) scans. Interpretation and analysis of OCT images. Recruiting and managing research Participants. Analysis of the relevant literature.

Project filled: More than surface area: how could cilia on the placental surface impact placental morphogenesis?


Supervisor

Dr Jo James

Project type

Biomedical

Department

Obstetrics and Gynaecology

Location

Auckland

Project code: MHS006

This project topic has been filled

The structural development of the villus tree is key for pregnancy success and adequate fetal growth. During pregnancy, placental villi are bathed in maternal blood, which is delivered via the uterine spiral arteries. Our research group has previously demonstrated a relationship between maternal blood flow from the spiral arteries and the structure of the placenta.  However, we have little understanding of the mechanisms by which this blood flow may affect placental morphogenesis or villus tree branching during pregnancy. 

The outer layer of the placenta is covered by one large multinucleated epithelial cell called the syncytiotrophoblast, which has a large surface area in order to facilitate gas and nutrient exchange between the maternal and fetal circulations.  This surface area is further expanded by ‘microvilli’ on the apical membrane of the syncytiotrophoblast in contact with maternal blood.  The properties of these microvilli are largely unknown and they have been assumed to exist primarily to increase the exchange area of the placenta.  However, in many cell types cilia protrude out from the cell surface and play key roles in detecting mechanical load and shear stress. Therefore, the aim of this project is to determine whether syncytiotrophoblast microvilli express proteins associated with primary cillia that could transduce shear stress generated by maternal blood flow across the placental surface. We hypothesise that if syncytiotrophoblast microvilli do express these proteins, this outer layer of the placenta could sense maternal blood flow and transduce these mechanical signals into the placental villi to regulate villus tree density and development.

Skills

Dr Clark (Auckland Bioengineering Institute) and Dr James (Department of Obstetrics and Gynaecology) run an interdisciplinary team looking at how the utero-placental circulation impacts pregnancy success. This project aims to provide preliminary data that will feed into a larger proposed project developing computational models of maternal blood flow to the placenta. Therefore, while this project is open to all students, those with a longer term interest in potential interdisciplinary projects combining lab-based biomedical research and computational modelling are particularly encouraged to apply. 

  • Electron microscopy incorporating immunogold labelling
  • Dissection and preparation of primary human tissue (term placentae)

Development of hypoxia activated prodrugs based on the PARP inhibitor talazoparib


Supervisor

Benjamin Dickson

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS007

Talazoparib is the most potent PARP inhibitor currently in clinical development. There is evidence that its ability to ‘trap’ PARP on DNA contributes significantly to its efficacy. Trapping of PARP has been suggested as one of the means by which PARP inhibitors induce off target (normal cell) toxicity. Hypoxia activated prodrugs (HAPs) provide targeted activation of a PARP inhibitor within tumours, reducing off target toxicity. This medicinal chemistry project aims to synthesise analogues of talazoparib and prepare HAPs of these analogues.

The Auckland Cancer Society Research Centre provides a multidisciplinary and collaborative environment.  Opportunities exist for the right candidate to pursue further studies in cutting edge drug discovery.

Skills

  • Organic/Medicinal chemistry (laboratory skills)
  • Drug design (inc. Hypoxia activated prodrugs)
  • Chemistry literature searching (Reaxys, Scifinder)

Artificial Sweeteners during pregnancy: friend or foe?


Supervisor

Clare Reynolds

Project type

Biomedical

Department

Liggins Institute 

Location

Auckland

Project code: MHS008

There is significant evidence that an unhealthy diet greatly increases the risk of complications during pregnancy and predisposes offspring to metabolic dysfunction and obesity. While fat intake is typically associated with the onset of obesity and its comorbidities, there is increasing evidence linking sugar, particularly high fructose corn syrup, to the global rise in obesity rates. Furthermore, the detrimental effects of fructose intake during pregnancy on mother and child have been clearly outlined. Guidelines advising pregnant women to avoid food and beverages with high fat and sugar have led to an increase in consumption of “diet” or “light” options. While these compounds reduce overall caloric load they have been linked to increased gut glucose absorption thereby promoting hyperglycaemia and insulin resistance. Despite their wide availability there is only limited information regarding their impact on maternal pregnancy outcomes, placental/fetal development and long term risk of cardio-metabolic complications in adult offspring. The current project aims to examine the effects of artificial sweetener exposure during pregnancy on maternal glucose homeostasis.

Skills

  • Molecular biology techniques 
  • Experimental model of gestational diabetes
  • Data analysis 
  • Scientific writing

Monitoring age-related changes of the vitreous of the eye, using MRI


Supervisor

Ehsan Vaghefi

Project type

Biomedical

Department

Optometry and Vision Science

Location

Auckland

Project code: MHS009

Our ocular tissues undergo ageing process, similar to other parts of the human body. In the eye, age-related changes of crystalline lens leads to presbyopia, cataract, macular degeneration and in some cases vitreous liquefaction. We are interested in age-related fluid dynamics changes in the vitreous, prior and after the onset of vitreous liquefaction. In order to monitor these changes clinically, we have established a variety of MRI protocols to non-invasively assess the ocular tissue in-vivo. The specific aims will be:

  1. To establish framework for analyzing acquired MRI images
  2. To compare vitreous MRI data from different age-group
  3. To model the age-related trend of vitreous changes

Skills

This project suits for students who have background in Optometry/Biomedical science. You will gain valuable experiences in clinical MRI acquisition, data analysis and processing. Programming skills in MatLab will be an advantage. 

Does the interaction of inflammation and high fat diet during pregnancy influence male offspring reproductive function?


Supervisor

Clare Reynolds

Project type

Biomedical

Department

Liggins Institute

Location

Auckland

Project code: MHS010

Over the last two decades, maternal diet has been exposed as a major driving force in the predisposition to chronic adult onset conditions in offspring including cardiovascular disease and metabolic syndrome. Interestingly, these conditions are strongly associated with a state of persistent low-grade inflammation. IL1R1 is a key signalling mediator which bridges metabolic and inflammatory systems. This study will examine the role of IL-1R1 depletion during pregnancy on high fat diet induced developmental programming of male reproductive organ function. 

Skills

Molecular biology techniques

Histology

Scientific writing 

Data analysis

Development of tools to measure reactive oxygen species production in the aging eye


Supervisor

Julie Lim

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS011

In previous work, we have identified the cystine/glutamate antiporter (CGAP) as a key component in affording antioxidant protection and minimizing oxidative stress in the eye. In vivo examination of the eyes of CGAP KO mouse has revealed these mice develop age related eye pathologies earlier than wild type control mice.  To investigate the role of reactive oxygen species (ROS) formation in this process, we will compare levels of reactive oxygen species between ocular tissues of wild type and CGAP KO using a variety of fluorescent probes coupled with confocal microscopy. The findings from this project will aid in our overall understanding of the role of CGAP in the different tissues of the eye. More specifically it will help us to evaluate the role of ROS production in the series of molecular pathways that lead to the development of eye diseases associated with oxidative stress.

Skills

Dissection of ocular tissues, immunolabelling, confocal microscopy

Visualising antioxidant delivery to the ocular lens with imaging mass spectrometry


Supervisor

Angus Grey

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS012

MALDI imaging is a novel, mass spectrometry-based technique that maps the spatial distribution of proteins, peptides, lipids, metabolites, or drugs in thin tissue sections. Typically, tens to hundreds of biomolecules are detected in a single experiment, and a spatial distribution plotted for each. This technique has been used to study protein and metabolite distributions in the ocular lens, with particular emphasis on characterising proteomic and metabolomic changes that take place with aging and cataract formation. The depletion of glutathione concentration in the lens nucleus is thought to play a central role in age-related nuclear cataract formation. This project aims to map the distribution of exogenous glutathione antioxidant administered in organ culture to an aged lens model to monitor glutathione movement within the lens and its efficacy in preventing proteomic and metabolomic changes that occur with cataract formation.

Skills

Lens dissection, tissue sectioning, MALDI mass spectrometry, MALDI image analysis

Functional characterization of long non-coding RNA in breast cancer cell lines


Supervisor

Marjan Askarian-Amiri

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS013

RNAs were long thought to act mainly as carriers of genetic information between DNA and the protein-synthesising machinery of the cell. Recent whole genome sequencing technology has demonstrated that protein coding open reading frames comprise only about 1.2% of the human genome. On the other hand, 70-90% of the genome is transcribed as non-protein coding RNA (ncRNA). Initially regarded as ‘junk’, these transcripts have been found to possess many regulatory roles and represent a largely unexplored area of cell biology.

The best-known class of ncRNA comprises small regulatory RNAs called microRNAs, but recent studies have revealed that the transcriptome is replete with long ncRNAs (lncRNAs). The emerging role of lncRNAs in different aspects of biology provides encouragement for further studies on their roles in normal cell development and disease.

The major goal of this project is to investigate functional roles of a novel lncRNA  in breast cancer cell lines. We will investigate the dynamic expression of candidate lncRNA species and manipulate the expression of lncRNA using CRISPR/CAS technology and investigate downstream targets as clues to the function of the lncRNA.

Skills

The project involves application of basic molecular biology techniques including mammalian cell culture, RNA and DNA extraction, cloning techniques, PCR and reverse transcription followed by PCR. These techniques will provide the candidate great basic skills required for performing experiments in molecular biology laboratories.

Project filled: Understanding GABA Signalling in the Vasculature of Healthy and Alzheimer's Disease Brains


Supervisor

Dr. Andrea Kwakowsky

Project type

Biomedical

Department

Anatomy and Medical Imaging

Location

Auckland

Project code: MHS014

This project topic has been filled

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

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

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

Skills

  • neural tissue fixation, processing
  • fluorescence immunohistochemistry
  • imaging techniques (light and confocal microscopy)
  • data collection, analysis and presentation

Project filled: Characterisation of the neuropathological hallmarks of Huntington's disease using human brain tissue microarrays


Supervisor

Dr. Malvindar Singh-Bains

Project type

Biomedical

Department

Centre for Brain Research and Department of Anatomy with Radiology

Location

Auckland

Project code: MHS015

This project topic has been filled

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive loss, and psychiatric manifestations. HD is caused by an expansion of polyglutamine trinucleotide repeats in the IT15 [Interesting Transcript 15] gene on chromosome 4, which encodes a mutant protein called huntington. 

The objective of this project is to characterise neuropathological features of Huntington’s disease in a newly constructed human brain cortical tissue microarray comprised of clinically well characterised post-mortem cases from the Neurological Foundation of NZ Douglas Human Brain Bank. We hope to explore the validity of using the tissue-microarray approach, comprising of an array of 2mm samples of human tissue, from several human cases as a tissue conserving method to search for novel biomarkers and mechanisms of neurodegeneration in the human brain.

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 

Gasping for breath in heart failure


Supervisor

Dr. Rohit Ramchandra

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS016

A third of people diagnosed with heart failure die within the first year. The survivors have severely impaired quality of life because even day to day menial activities leave them breathless and incapacitated. Current treatment options include cardiac pacemakers which help to improve the pumping capacity of the heart. However, these pacemakers lead to fixed changes in heart rate, whereas in reality heart rate is rarely static.

Heart rate fluctuates with breathing, and this variability is prominent at birth but lost with the development of heart disease. We will utilise a large animal model of heart disease to explore whether variability in heart rate in tune with breathing is altered in this model. We will also utilise a novel cardiac pace-making approach to re-introduce breathing induced heart rate variability to test the hypothesis that this will improve heart function.

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

Skills

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

Does incorrect wiring of the auditory cortex during development contribute to functional deficits in Autism Spectrum Disorder mice?


Supervisor

Juliette Cheyne

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS017

Autism Spectrum Disorders (ASD) are a set of developmental disorders defined by impaired learning, sensory disorders, communication difficulties, social deficits and stereotyped behaviours. The social and communication difficulties in ASD are thought to be due to the distorted processing of sounds, which in turn impairs language abilities. Because ASD symptoms appear during infancy, it is crucial to examine how brain development is altered, as this could underlie behavioural deficits. We hypothesise that the auditory cortex circuitry develops incorrectly, which results in abnormal neuronal connectivity and impaired ability to process sound. During development, sensory organs and their associated cortical regions are spontaneously active, before the onset of sensory perception. We and others have shown that this activity is crucial for the correct wiring of developing networks in the brain. We will utilize state-of-the-art in vivo cellular recording techniques to examine how spontaneous activity is altered in the auditory cortex during development in an ASD mouse model

Skills

  • Surgery on mice
  • In vivo calcium imaging to record network activity 
  • Data analysis using Matlab
  • Presentation and write up of data

 

Project filled: Clinical and Molecular Characterization of Inherited Optic atrophy from the NZ Inherited Retinal Disease Database


Supervisor

A/Prof Andrea Vincent

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS018

This project topic has been filled

Inherited Optic Atrophy (OA) refers to disease affecting the optic nerve, resulting in significant visual impairment, and due to genetic mutations in genes involved in energy supply to the nerve. In over 40% of cases, the genetic cause is not known. New causative genes are described which may account for one third of these unresolved cases.

This summer studentship project will look specifically at a cohort of inherited Optic atrophy patients without a genetic diagnosis in order to determine the genetic cause.

Project aims

  • To characterize the demographics and of the cohort with Inherited optic atrophy
  • For families, to characterize the clinical spectrum, and non-penetrance of disease
  • To undertake mutational analysis of a candidate gene, which recently is identified in association with the non-syndromic OA phenotype, and establish phenotype-genotype relationships

Skills

This studentship is ideally suited to a medical student or biomedical student with a crossover of interests between clinical characterisation and lab based skills. This combination of skills will foster future clinician-scientists.

  • Database searching
  • Collation and review of clinical notes and investigations (history, examination findings, including Optos widefield photos and fundus autofluorescence, OCT, Electrophysiology)
  • Bioinformatics - probing of databases of human variation and protein pathogenicity
  • Literature review
  • Polymerase chain reaction and sequencing

Understanding the mechanisms through which exercise improves health


Supervisor

Troy Merry

Project type

Biomedical

Department

Nutrition

Location

Auckland

Project code: MHS019

Background

Exercise is one of the most potent protective and treatment options for metabolic diseases such as type 2 diabetes. However we do not yet understand how exercise improves our health. If we can understand the mechanisms through which exercise leads to health promoting adaptions then these pathways may be targeted to combat disease. 

Aim

To investigate novel mechanisms/pathways through which exercise our health.  

Skills

This will be dependent on the project we decide on but may involve:

  • Western blot
  • qPCR
  • Cell culture
  • Human experimental trial managment
  • Reviewing litrature 

Using human induced pluripotent stem cell-derived kidney organoids to model kidney disease


Supervisor

Alan Davidson

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS020

Acute kidney injury (AKI) is defined as an abrupt loss of renal function and is commonly caused by ischemia, infection and anti-cancer and antibiotic drugs that damage the renal tubules. AKI, and other forms of renal disease, are a major healthcare issue in New Zealand with ~1:10 people having some form of kidney disease. There are no treatments for AKI and a major shortcoming in the field has been a lack of relevant human models to validate rodent findings. Towards the goal of developing a human model for kidney diseases, we have established a method for converting induced pluripotent stem cells (iPSCs) into kidney organoids (mini kidneys cultured in vitro). These organoids contain multiple kidney cell types and show a high degree of maturation. The aims of our current work comprise:

  1. Optimising the long term culture conditions of the organoids
  2. Establishing a toolset to allow their characterisation
  3. Recapitulating acute kidney disease by administration of nephrotoxic drugs

Our findings will contribute to the overall understanding of the molecular, cellular or pathological basis of acute and chronic kidney disease. More specifically, establishing kidney organoids as disease model will represent a starting point for future analyses including specific gene editing and transcriptional profiling, from which we expect to identify new mediators of kidney disease pathogenesis. 

Please send a CV and academic transcript if interested.

Skills

Students projects will involve treatment and analysis of kidney organoids, and specific techniques learned will include:

  • Administration of fluorescent compounds and/or nephrotoxins to kidney organoids (by incubation or injection, to be tested and optimised)
  • Cryo- and paraffin sectioning
  • Fluorescence immunohistochemistry and imaging (light and confocal microscopy)
  • RNA isolation and qPCR
  • Data analysis and presentation

 

Project filled: The assessment of the Comet Assay on fresh versus frozen samples


Supervisor

Karen Bishop

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS021

This project topic has been filled

It is widely accepted that diet plays a key role in the development of many cancers. DNA damage is associated with the risk of various cancers and this assay is regarded as an ideal marker for the assessment of the influence of foods on cancer as well as the effect of anti-cancer treatments on on-target tissues. The group you will be working with have a wealth of experience with the Comet Assay, the assay used to assess DNA damage. However, we have only ever used fresh samples and there is a need to adapt the assay for use on frozen bloods. We have a couple of methods that need to be established and thereafter they need to be evaluated. If time permits there will be an opportunity for you to perform real-time PCR gene expression experiments.

Skills

Comet assay

Analysis and interpretation of data

Real-time PCR assays for gene expression

PERK up! A cancer drug design project


Supervisor

Dr Lydia Liew

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS022

PERK receptors on the endoplasmic reticulum are involved in a cell's response to stress. The activated PERK pathway produces responses that support the survival of cells under stressful conditions. Tumour cells utilise the PERK pathway to thrive under stressful cellular conditions typical of the tumour microenvironment. We are able to inhibit this survival mechanism by switching-off the PERK receptors in tumour cells. Incidentally, PERK receptors are also highly expressed in the pancreas and are essential for normal functioning. We aim to shut-down the PERK pathway in tumours without affecting the normal function of PERK in the pancreas. We are interested in designing novel PERK inhibitors with the necessary properties for tumour-selective prodrug delivery.

Skills

In this project, you will learn basic research methods and gain experience in the design and synthesis of small drug molecules. The Auckland Cancer Society Research Centre has an international track record in drug development and you will have the opportunity to participate in a multidisciplinary and collaborative research environment.

The preferred candidate should be self-motivated and would be seeking to pursue postgraduate research. Experience working in a chemistry laboratory is essential (minimum CHEM110).

Effect of excipients on the stability of extemporaneously compounded levothyroxine oral liquid


Supervisor

Sara Hanning

Project type

Biomedical

Department

Pharmacy

Location

Auckland

Project code: MHS023

Levothyroxine is a synthetic thyroxine hormone. In New Zealand, three different commercial brands of levothyroxine tablets are fully funded. In instances where it is not feasible for a patient to swallow tablets, such as in paediatrics, a liquid dosage form may be extemporaneously compounded from these tablets. However, guidelines around the compounding of levothyroxine liquid in this way are outdated and a paucity of information exists around the effect of using tablets from different manufacturers. Further, the compatibility of levothyroxine sodium in commercial vehicles such as Oraplus has not been investigated.

This project aims to:

  • Assess the effect of levothyroxine sodium tablet manufacturer on stability of the resulting liquid formulation.
  • Determine the feasibility of using a commercially available vehicle to compound levothyroxine sodium suspension.
  • Make recommendations for future extemporaneous compounding of levothyroxine in light of the above results.

Skills

  • Literature searching and critical review.
  • Formulation and extemporaneous compounding skills.
  • Quantification of drug release using high-performance liquid chromatography (HPLC).
  • Analysis and interpretation of results.
  • Translation of pharmaceutical science to clinical practice.

Please note this project is only available to BPharm students.

 

Understanding the interactions between osteoarthritis and gout: does damaged cartilage influence the inflammatory potential of urate crystals?


Supervisor

Dr Ashika Chhana

Project type

Biomedical

Department

Medicine

Location

Auckland

Project code: MHS024

Gout is the most common inflammatory arthritis affecting New Zealanders, particularly people of Māori and Pacific descent.  Gout is caused by the presence of monosodium urate (MSU) crystals within joints; these crystals can form when serum uric acid levels are elevated.  However, many people with high uric acid levels do not form MSU crystals in their joints and do not develop gout.  In those patients that do form MSU crystals and experience clinical symptoms of gout, there must be other factors present within their joints that promote MSU crystallisation.  MSU crystals are often seen on cartilage surfaces in people with gout and joints affected by previous trauma or osteoarthritis are more likely to be affected by MSU crystal deposition and attacks of gout.  Therefore, osteoarthritic cartilage or specific factors derived from damaged cartilage are likely to have an important role in the formation of MSU crystals and the inflammatory response these crystals induce in vivo

The specific aim of this summer studentship will be to test the inflammatory potential of MSU crystals grown in the presence of healthy or osteoarthritic human cartilage.

Skills

-Basic research methods

-Polarising light microscopy

-Crystallisation assays

-Cell culture and inflammatory assays

-Protein quantification (ELISA)

-Data analysis

 

Super-resolution imaging of the transverse tubules in ischemic heart failure


Supervisor

Dr David Crossman

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS025

The transverse tubules are cylinder shaped extensions of the plasma membrane, approximately ~300 nm in diameter, that penetrate deep into the cardiac myocyte allowing rapid cell wide propagation of the electrical signal that synchronises contraction. Disorganisation of the transverse tubule network is thought to be a major contributor to the loss of contractility in ischaemic heart failure. Previous analysis of transverse tubule structure has predominately utilised confocal microscopy with a resolution limit of ~300 nm. In this project super-resolution microscopy, with 30 nm resolution, will be used to characterise changes in transverse tubule structure in order to provide understanding of the remodelling process at nano-scale.

Skills

Super-resolution microscopy

Fluorescence immunohistochemistry

Image processing

Report writing

Growth hormone receptor inhibition: identifying key signal transduction pathways


Supervisor

Dr Jo Perry

Project type

Biomedical

Department

Liggins Institute

Location

Auckland

Project code: MHS026

Growth hormone (GH) secretion from the anterior pituitary is essential for normal human growth. However, in adults, too much GH can lead to acromegaly, a rare debilitating somatic growth disorder. Expression of GH is also detectable in a variety of different human cancers and is associated with reduced overall survival for breast and endometrial cancer patients. This has led to the development of therapeutic approaches aimed at antagonising GH function. A commercially available GH receptor antagonist, pegvisomant, is Food and Drug Administration (FDA) approved, for the treatment of acromegaly. We are investigating the utility of this inhibitor for applications in oncology and are developing novel therapeutics aimed at neutralising GH action.

With increasing interest in this area there is a need for careful characterisation of the cell lines used if useful data regarding efficacy of inhibition is to be obtained, particularly with reference to the expression of relevant growth factor receptors, autocrine growth factors, and the signal transduction pathways utilised. The aim of this project is to characterise cell lines for components of GH signal transduction in order to identify which are important in determining the response to GH antagonism.

Skills

Techniques will include culture of cell lines and a range of molecular biology techniques including western analysis, AlphaScreen assays, and real-time PCR

Formulation and characterization of novel peptide loaded hydrogel for topical delivery


Supervisor

A/Professor Jingyuan Wen

Project type

Biomedical

Department

Pharmacy

Location

Auckland

Project code: MHS027

Skin, being the largest organ of the body, is an important site for drug administration. Topical delivery offer several advantages such as avoidance of first-pass metabolism, degradation from digestive enzymes, ease of application and improved patient compliance. However, most of the peptide drugs have poor permeability, thus topical delivery of peptide drugs through the skin is very challenging. In this project, a polymeric hydrogel as a novel drug delivery system will be developed for topical delivery of peptide drug, in order to enhance the permeation of peptide across the stratum corneum of skin, thus maximize its therapeutic effect to treat local skin conditions. Characterization of the drug loaded hydrogel such as particle size, zeta potential and drug entrapment efficiency will be determined for optimization of the delivery system.  The rheology and texture profile of the drug loaded hydrogel will be studied to ensure its suitable physical characteristics for topical delivery. In-vitro drug release study will be conducted to demonstrate the drug release behavior of the polymeric hydrogel. Lastly, the ex-vivo drug permeation study across the human skin will be carried out to compare the permeation profiles of drug candidate with or without the hydrogel formulation. The results of these studies will be analysed to evaluate the optimal hydrogel formulation is promising to be used as a topical delivery system for the peptide drugs, to effectively treat local skin diseases  or for various cosmetic applications. 

Skills

  • Screening various polymer for hydrogel formulation and different fabrication techniques
  • Zetasizer to test the particle size and zeta potential
  • Rheometer to study the rheology profiles
  • Texture analyser to analys the hydrogel texture
  • Franz diffusion cell to perform in-vitro drug release studies
  • High pressure liquid chromatography to determine drug concentration

This project is only available for BPharm students.

Cellular identity crisis: understanding the underlying causes of osteoarthritis


Supervisor

Raewyn Poulsen

Project type

Biomedical

Department

Medicine

Location

Auckland

Project code: MHS028

Osteoarthritis develops when normally protective cartilage cells (chondrocytes) undergo a profound behaviour change and begin degrading the cartilage tissue in which they reside. Why this change occurs is unknown. In this project we will examine potential causes of this cell behaviour change.

Skills

This project will provide the student with skills in experiment design, cell culture and standard laboratory techniques such as PCR (for measuring gene expression) and immuno-assays (for measuring protein levels). 

Mechanisms of beta cell destruction during childhood type 1 diabetes


Supervisor

Dr Shiva Reddy

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS029

Type 1 diabetes (T1D), is a serious disorder which can manifest from early childhood, and results from the progressive destruction of insulin-producing beta cells.

There is very little knowledge on the complex immune and non-immune mediated processes involved in beta cell death during human T1D.

The major aims of the study are, therefore, to examine rare pancreatic biopsies from living donors with new-onset T1D, for the expression of candidate protein mediators of beta cell destruction within the islets and determine their cellular source.

Skills

Tissue analysis by bright field and multi-label immunofluorescence microscopy; immunohistochemistry; digital image acquisition; Photoshop and image re-construction; cell analysis and enumeration; molecular and cellular pathology; immunological concepts

What can twins tell us about the genetics of keratoconus?


Supervisor

Verity Oliver

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS030

Keratoconus is a degenerative eye disorder in which the cornea thins and becomes misshapen, blurring vision. The genetics underlying keratoconus is unclear. We have exome sequencing data from two sets of keratoconic twins, who present with different degrees of disease. The aim of this study is to analyse the available exome sequencing data to identify potential genetic variants that contribute to the varying disease severity observed in these twins.

Skills

A student with some prior knowledge of next-generation sequencing analysis (theoretical) is sought. The student will gain first hand experience in working with exome sequencing data, in additional to learning laboratory techniques including PCR and Sanger DNA sequencing.

Topical Delivery of Hyaluronic acid (HA) using microemulsion as a drug delivery system


Supervisor

A/Professor Jingyuan Wen

Project type

Biomedical

Department

Pharmacy

Location

Auckland

Project code: MHS031

Hyaluronic acid (HA) is a major component of the skin extracellular matrix and has been widely employed to help the skin to regain elasticity, turgor and moisture. However, HA is a hydrophilic dipolysaccharide with a very high molecular weight of over 200 kDa, thus very difficult to penetrate across stratum corneum. The aim of this project is to develop a novel HA loaded microemulsion for topical delivery of HA effectively across the stratum corneum of skin, thus maximize its application to enhance skin elasticity and moisturization. In this study, a pseudoternary phase diagram will be constructed to select an ideal formulation with large microemulsion region. Characterization of the selected HA loaded microemulsion  such as droplet size, conductivity,  rheology and drug loading capacity will be determined for optimization of the delivery system. In-vitro drug release study will be conducted to demonstrate the drug release behaviour of the drug loaded microemulsion. The ex-vivo drug permeation study across the stratum cornum will be carried out to evaluate the skin deposition between HA solution and HA loaded microemulsion groups.  The ideal HA loaded microemulsion delivery systems should have relative higher HA loading capacity and less amout of surfactants.  Consequently, HA loaded microemulsion could be a promising topical delivery system, and to effectively fight skin aging, improving skin elasticity, hydration and overall skin health.

Skills

  • Screening various oil and surfactants that are suitable for microemuslion formation
  • Pseudoternary phase diagram is constructed by using various ratio combinations of water, oil and surfactant
  • Zetasizer/light microscope to test the droplet size
  • Rheometer to study the rheology profiles
  • Conductivity is measured by using a conductivity metre
  • Franz diffusion cell to perform in-vitro drug release studies
  • High pressure liquid chromatography to determine drug concentration

Lighting up cancer cells with DAMP signals


Supervisor

Sandy Chen

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS032

The body’s immune system is a powerful ‘search and destroy’ tool that reacts not only against infection but also against cancer cells. Unfortunately, some cancers are not recognised by the immune system and continue to grow. Drugs used to treat cancer have long been known to suppress immunity, but it is becoming clear that some of these drugs can potentially enhance immunity. They do this by inducing cancer cells to release signals called DAMPs (damage-associated molecular patterns), which improve the visibility of cancer cells to immune system.

This project will explore a potential mechanism by which DAMP signals are induced by cancer drugs.

Skills

  • Literature review
  • Research experimental design
  • Data analysis and interpretation
  • Cell culture
  • Molecular biology techniques

 

How does raised intracranial pressure drive arterial pressure?


Supervisor

Sarah-Jane Guild

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS033

Intracranial pressure (ICP) is often measured in traumatic brain injury, hydrocephalic or neurosurgical patients. Treatment usually focusses on keeping ICP below 20-25mmHg and while Cushing has described the response to extreme levels of ICP, we have very little understanding of what affect more moderate increases in ICP may have. We have exciting preliminary data to suggest that ramp-like increases in ICP (<20mmHg) are matched by similar increases in arterial pressure via activation of the sympathetic nervous system. We hypothesize that maintenance of cerebral perfusion pressure is the motivation behind the increased arterial pressure but the mechanism behind this increase is as yet unknown. Whatever mechanism is sensing and driving the increased arterial pressure, it must be interacting with, or overriding, the baroreflex. We hope that further understanding of the interactions between ICP and arterial pressure will ultimately allow better clinical decision making in patients with acute and chronically raised ICP.

This project will be mentored by Dr Sarah-Jane Guild and Dr Rohit Ramchandra of the Department of Physiology and will introduce the student to a number of experimental techniques in conscious animals. Preference will be given to students who want to continue on with an Honours or a Masters project.

Skills

Literature review writing skills

Large animal models of disease

Surgical skills (assisting)

Collection of physiological data in conscious animals

Analysis of data

Oral presentation skills

Understanding and enhancing therapeutic effects of L-DOPA in Parkinson's disease


Supervisor

Prof. J. Lipski

Project type

Biomedical

Department

Physiology and Centre for Brain Research

Location

Auckland

Project code: MHS034

Our laboratory investigates the cellular and molecular mechanisms of neuronal damage in models of Parkinson's disease (PD), and the properties of dopaminergic neurons in the Substantia Nigra which are affected by this disease. PD is the second most common neurological disorder linked to the degeneration of nigral dopaminergic neurons and a loss of dopamine. It is most frequently treated with L-DOPA (Levodopa), the precursor to dopamine, which ameliorates motor symptoms by increasing dopamine release from remaining dopaminergic neurons. However, the cellular mechanism of this effect is not well understood, particularly that previous studies have identified a strong inhibitory action of L-DOPA on the firing frequency of action potentials of nigral dopaminergic neurons. So how can L-DOPA increase dopamine release, while at the same time inhibiting the activity of dopaminergic neurons? To address this paradox, this project will simultaneously investigate L-DOPA-induced effects on the electrophysiological activity of dopaminergic neurons and extracellular dopamine levels measured with electrochemistry (‘Fast-scan controlled-adsorption cyclic voltammetry’, a novel technique recently developed in our laboratory in collaboration with the University of Arizona).

The second objective of the study is to test the hypothesis that L-DOPA-induced increase of extracellular dopamine can be boosted by blocking uptake by PMAT (Plasma Membrane Monoamine Transporter) and OCT-3 (Organic Cation Transporter 3). These two recently identified dopamine transporters (collectively referred to as ‘Uptake-2’) are widely expressed in the CNS. Although both have low affinity to dopamine, they are high-capacity, unlikely to be saturated when dopamine levels are enhanced by L-DOPA. Therefore, these transporters may limit the ability of L-DOPA to enhance extracellular dopamine (particularly when the levels of the ‘conventional’ dopamine transporter, DAT, are low as in PD), potentially reducing the efficacy of the drug.

This study will be conducted in brain slices and in anesthetized rats (in vivo). It is expected that it will extend our knowledge of the cellular action of L-DOPA, a drug which remains the ‘gold standard’ in the treatment of PD.

This project will be offered to an enthusiastic student with a cumulative GPA >6.5, with preference given to a student intending to continue in 2018 with studies towards Honours/Masters degree (in BioMed, Physiology or Medicine).

Skills

-  Design of experiments conducted with brain slices and in anaesthetised animals
-  Detection of dopamine release using electrochemistry (fast-scan controlled-adsorption voltammetry)
-  Electrophysiological techniques (microelectrode recordings from Substantia Nigra neurons)
-  Computer data analysis and data interpretation
-  Literature search and scientific writing/oral presentation skills

Developing gene therapy as a treatment for spinal cord injury


Supervisor

Simon O’Carroll

Project type

Biomedical

Department

Anatomy and Medical Imaging/Centre for Brain Research

Location

Auckland

Project code: MHS035

Spinal cord injury (SCI) results in a devastating loss of mobility and other major functions for the victim. A key component of the ongoing response that inhibits recovery after injury is formation of the glial scar by astrocytes. This is a major barrier to functional recovery after injury, and as such is a promising target for treatments to improve outcomes. After SCI, astrocytes upregulate a number of extracellular matrix (ECM) components including chondroitin sulfate proteoglycans (CSPGs), which act to impede neural repair and regeneration. One approach that has shown promise for spinal cord injury is use of the bacterial enzyme chondroitinase ABC (ChABC), which is involved in breakdown of CSPGs. However, chronic delivery of such agents carries risks of tissue damage, inflammation, and infection.

One powerful and safe way to allow continued production of protective molecules is to use viral vector gene therapy. Adeno-associated virus (AAV) gene therapy has been shown to be safe, well tolerated and that relief of symptoms and alteration of disease progression for CNS diseases is achievable.

In our laboratory, we have made an AAV vector that allows gene expression of ChABC preferentially in astrocytes through use of a GFAP (astrocyte-specific protein) promoter. This project will use primary astrocyte cell cultures test the use of astrocyte specific AAV gene therapy to express ChABC and determine if this is an effective means of preventing scar formation following spinal cord injury and developing this approach as an effective treatment for patients.

Skills

Primary cell culture

Immunohistochemistry

Microscopy

Western blotting

Scientific writing/report preparation

Using liposomes to target drug delivery in spinal cord injury


Supervisor

Simon O’Carroll

Project type

Biomedical

Department

Anatomy and Medical Imaging/Centre for Brain Research

Location

Auckland

Project code: MHS036

Spinal cord injury (SCI) results in a devastating loss of mobility and other major functions for the victim. Following SCI, inflammation occurs that leads to activation of glial cells (astrocytes and microglia) and to spread of damage.  A number of potential treatments for spinal cord injury have targeted this inflammation and shown some success. The current clinical treatment for SCI is the use of the glucocorticoid methylprednisolone (MP) but this requires high doses to be affective. Treatment with MP has been controversial, and the high doses cause deleterious side effects. Therefore, targeting inflammation at the site of SCI without inducing systemic side effects, which may occur with drug treatments, would be beneficial. One method to achieve this would be through developing a method that can directly target glia at the site of inflammation following spinal cord injury (SCI), allowing for targeted delivery of drugs to reduce inflammation.  We have developed such a method using nanoparticle-based liposomes that can target a receptor on activated astrocytes that is present after injury.

Our lab has developed small peptides that are able to target connexin43 (Cx43) on astrocytes, which is known to play a crucial role in inflammation in the brain and have shown these peptides are effective in a number of central nervous system conditions including SCI. However, these peptides are delivered via the bloodstream requiring large doses and are short acting.

This project will use primary astrocyte cell cultures to test if we can use liposomes to deliver our Cx43 peptide more effectively to astrocytes as a means of improving drug delivery and developing this approach as a treatment for patients with spinal cord injury.

Skills

Primary cell culture

Immunohistochemistry

Microscopy

Biochemical assays

Scientific writing/report preparation

Can we improve treatment of babies with ischemic brain injury?


Supervisor

Dr Joanne Davidson

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS037

Fetal hypoxia-ischemia, the loss of blood supply before or around the time of birth, can cause death and devastating lifelong disability. Therapeutic hypothermia (cooling of the brain) is currently the only available treatment for infants that have suffered brain injury as a result of ischemia. Whilst it significantly reduces death and disability, many infants still suffer severe brain damage, even when treated with hypothermia. It is not yet clear whether current cooling protocols are optimal and little is known about the ideal rate of rewarming of infants after hypothermia and the effect that this has on outcome. The aim of this study is to determine whether the rate of rewarming after hypothermia has an effect on the development of brain injury.

For this summer studentship, immunohistochemistry, microscopy and cell quantification will be used to assess cell death and inflammation in the brain after hypoxia ischemia followed by treatment with hypothermia with either rapid or slow rewarming. This research will help to establish optimal cooling protocols for treatment of babies suffering ischemic brain injury.

Please send a CV and academic transcript if interested.

Skills

  • Immunohistochemistry
  • Microscopy
  • Cellular quantification
  • Data analysis
  • Statistical analysis

Death by a thousand cuts: Drugging the DNA damage response


Supervisor

Associate Professor Michael Hay

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS038

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. The discovery of new selective inhibitors of DNA-PK would be a dramatic innovation with potential to impact on current cancer treatment.  

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 environment.  The preferred candidate will be a high achiever with synthetic chemistry experience and ambitions to pursue a career in cutting edge drug discovery.

Skills

Medicinal chemistry

Is HMGB1, as one of the most important damage-associated molecular patterns (DAMPs) associated with impaired autophagy seen in preeclampsia?


Supervisor

Qi Chen

Project type

Biomedical

Department

Obstetrics and Gynaecology

Location

Auckland

Project code: MHS039

Preeclampsia, a human pregnancy-specific hypertensive disease, responds to 60,000 young women and their babies’ death each year globally. Although the exact causes of this disease are unclear, there is growing evidence indicating that impaired autophagy contributes to the pathophysiology of preeclampsia. The mechanism is, however, unknown.

Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles. Autophagy responds to the changes in environment for cell survival during stress, starvation, hypoxia and consequently to the placenta implantation and development. During pregnancy, large numbers of trophoblastic extracellular vesicles (EVs) are shed from placenta into maternal blood. It is now well-known that the amount of placental EVs is increased in preeclampsia. The intracellular protein high mobility group box 1 (HMGB1), an important damage-associated molecular patterns (DAMPs) was originally described as a DNA-binding nuclear protein and transcription factor, but more recently, has been shown to be a pro-inflammatory danger signal that causes sterile inflammation when released from necrotic cells or cells under stress. A number of studies including our previous studies have reported increased levels of HMGB1 in preeclampsia. However, whether impaired autophagy contributes to the increased placental EVs in preeclampsia and the increased levels of HMGB-1 associate with the changes of autophagy in placenta are unknown.
The aims of this study are to investigate (1) Whether increased levels of HMGB1 alter the placental EVs shed from placenta; (2) Whether increased levels of HMGB1 alter the expressions of autophagy in placenta; (3) Whether blocking either the function of HMGB1 or autophagy can prevent the increased placental EVs shed from placenta.

Skills

  • Cell and tissue culture
  • Western blotting
  • Immunohistochemistry
  • General laboratory skill

 

Epigenetics and Keratoconus - understanding enigmatic eye disease


Supervisor

Verity Oliver

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS040

Keratoconus is a common degenerative eye disorder causing blurred vision. Whilst both genes and the environment contribute to keratoconus, the mechanisms are unknown. We propose that abnormal DNA methylation is present in the keratoconic cornea and is the missing link in understanding this disease. We aim to identify the epigenetic contribution to keratoconus by performing DNA methylation analysis and epigenetic modification of keratoconic cells. Our research will expose disease mechanisms that have so far remained elusive.

Skills

Over the course of the summer, the student will gain understanding and experience in a variety of lab techniques including PCR, DNA sequencing, data analysis, cell culture and immunohistochemistry.

A novel medical device for early warning of severe surgical infections


Supervisor

A/Prof Gregory O’Grady

Project type

Biomedical

Department

Surgery / Bioengineering

Location

Auckland

Project code: MHS041

This project will involve working with a team of bioengineers and surgeons on a novel medical device.  The goal of the device is to improve the early detection of severe post-operative complications after abdominal surgery, in order to improve patient outcomes.

The nature of the device is currently under non-disclosure (pending intellectual property protection).  The role of the student will be to participate in device refinement exercises, bench-top studies, and to gather experimental data from hospital patients to inform device design and usage.  More specific details will be revealed later.

This project would suit a student interested in abdominal surgery and/or medical devices / bioengineering.  The student will also participate in activities of the Surgical Engineering Lab led by A/Prof O'Grady.

Skills

Literature review, medical device development principles, bench-top and clinical experimental principles, data analysis, study write-up; and hopefully publication and presentation experience.

Identifying early biomarkers of dementia in human blood


Supervisor

Brigid Ryan

Project type

Biomedical

Department

Anatomy and Medical Imaging

Location

Auckland

Project code: MHS042

Our laboratory is searching for early biomarkers of frontotemporal dementia in a human cohort and in a complementary mouse model. The aim of this project is to validate potential microRNA biomarkers that have been isolated from human blood samples and quantified using RNA Seq. The student will use RT-qPCR as an orthogonal technique to validate the utility of specific microRNAs as early biomarkers. The pathological role of validated microRNAs will then be investigated further, by a) identifying predicted mRNA targets and b) using pathway analysis to identify dysregulated pathways.      

Skills

  • RNA isolation
  • RT-qPCR
  • MicroRNA target prediction
  • Pathway analysis
  • Literature searching
  • Oral/written presentation skills

 

Does mild fetal asphyxia impair white matter development?


Supervisor

Prof Alistair Gunn

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS043

Severe oxygen deprivation (asphyxia) before or during birth can cause death or severe motor disabilities, but is thankfully uncommon. However, many babies born prematurely are exposed to more mild asphyxia around the time of birth. It is controversial whether such mild asphyxia affects normal maturation of the brain.

In this study we will assess whether mild asphyxia during fetal life impairs long-term white matter development. This studentship will involve immunohistochemistry, microscopy and cell quantification to examine oligodendrocyte maturation and the extent of inflammation in the brain.

Please send a CV and academic transcript if interested.

Skills

•           Immunohistochemistry

•           Microscopy

•           Cellular quantification

•           Data analysis

•           Statistical analysis

Can anti-inflammatory medications reduce brain injury after severe fetal asphyxia?


Supervisor

Prof Laura Bennet

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS044

Severe oxygen deprivation (asphyxia) before or during birth can cause death or severe motor disabilities. Unfortunately there are no treatments available to treat brain injury and improve outcomes among preterm infants born after asphyxia. Asphyxia triggers long-lasting inflammation of the brain, which reduces the ability of the brain to regenerate and repair itself.

This study will investigate whether novel anti-inflammatory treatment after severe asphyxia can improve long-term development of white and grey matter. This studentship will involve immunohistochemistry, microscopy and cell quantification to examine neuronal survival, oligodendrocyte maturation and the extent of inflammation in the brain.

Please send a CV and academic transcript if interested.

Skills

•           Immunohistochemistry

•           Microscopy

•           Cellular quantification

•           Data analysis

•           Statistical analysis

How does the hypertensive brain protect itself from under-perfusion?


Supervisor

Fiona D McBryde

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS045

The brain is our most energetically "expensive" organ; despite only accounting for 5% of body weight the brain uses 25% of our basal metabolic rate. In addition, our brains have very little metabolic reserve - meaning that a constant supply of blood and oxygen is required to maintain function. Brain tissue is very vulnerable to ischemic damage if the brain blood supply becomes impaired. Therefore, it is not surprising that the brain has evolved ways to protect itself from low blood flow.

In subjects with high blood pressure, the blood vessels to the brain are stiffer and less able to relax (dilate). Normally, the large blood vessels in the brain are innervated by both the sympathetic and parasympathetic nervous system; in hypertension however, the parasympathetic innervation appears to be greatly reduced. Given that sympathetic activity is increased in hypertension, we hypothesize that the hypertensive brain may be less able to protect itself from challenges to brain blood flow.

This project will use cutting edge techniques which let us experimentally "challenge" blood flow to the brain in conscious rats with normal and high blood pressure. By recording changes in blood pressure, brain blood flow and sympathetic nerve activity we evaluate how the brain protects itself from changes in perfusion pressure. We are looking for a summer student with a keen interest in cardiovascular physiology, with a genuine interest in continuing into postgraduate research. Please contact both Dr's McBryde and Barrett by email, and include a copy of your academic transcript.

Skills

  • animal handling, training and care
  • exposure to aseptic (sterile) surgical technique and instrumentation
  • long-term recording, analysis and interpretation of cardiovascular signals
  • presentation and communication of experimental results

Project filled: Non-steroidal anti-inflammatory drugs compared to cyclooxygenase 2 inhibitors and risk of adverse cardiovascular event, a systematic review and meta-analysis


Supervisor

Dr Elissa McDonald

Project type

Biomedical

Department

Nursing

Location

Auckland

Project code: MHS046

This project topic has been filled

Due to recent media coverage and literature regarding NSAIDs and cardiovascular death, it is important to quantify the risk associated with NSAID use and adverse cardiovascular outcome, particularly important in the New Zealand context due to Pharmac fully funding COX 2 inhibitors from June 2017. The aim is determine the risk of adverse cardiovascular event with use of NASIDS compared to COX2 inhibitors.

Skills

  • Systematic review using Cochrane methodology
  • Search strategy development
  • Literature searching
  • Critical appraisal
  • Data extraction
  • Data entry into Cochrane software
  • Data analysis and statistical interpretation
  • Manuscript preparation

 

Autonomic control in preserved ejection heart failure


Supervisor

Dr Carolyn Barrett

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS047

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of all people with heart failure, and, strikingly, nearly 90% of heart failure cases in elderly women. One reason that HFpEF remains poorly understood is a near complete lack of clinically-relevant experimental models.  Our lab has developed a rat model of HFpEF and we have preliminary evidence to suggest that the reflex control of sympathetic activity is very different in this model compared to the more well studied reduced ejection fraction heart failure.  The aim of this project will be to characterize the changes in autonomic reflex control in our model of HFpEF.     This project will involve state of the art techniques for monitoring cardiovascular variables during manipulations of blood pressure and ventricular function.

We are looking for a summer student with a keen interest in cardiovascular physiology, with a genuine interest in continuing into postgraduate research. If interested in this project please contact Dr Barrett (c.barrett@auckland.ac.nz) by email, and include a copy of your academic transcript.

Skills

  • animal handling, training and care
  • exposure to aseptic (sterile) surgical technique and instrumentation
  • long-term recording, analysis and interpretation of cardiovascular signals
  • presentation and communication of experimental results

 

Project filled: Effectiveness of various intrauterine devices: a systematic review and meta-analysis


Supervisor

Dr Elissa McDonald

Project type

Biomedical

Department

Nursing

Location

Auckland

Project code: MHS048

This project topic has been filled

There are numerous intrauterine devices (IUD's) and their effectiveness varies depending on IUD type. This systematic review and meta-analysis will set out to find the most effective IUD in prevention of pregnancy while also taking into account adverse events.

Skills

  • Systematic review and meta-analysis using Cochrane methodology
  • Search strategy development
  • Literature searching
  • Critical appraisal
  • Data extraction
  • Data entry into Cochrane software
  • Data analysis and statistical interpretation
  • Manuscript preparation

Cannabinoid Receptor Signalling


Supervisor

Michelle Glass

Project type

Biomedical

Department

Pharmacology

Location

Auckland

Project code: MHS049

A project will be developed to address an aspect of signalling or function of the cannabinoid receptors.  This will utilise cell signalling or binding assays in transfected cell lines.

Students applying must have a background in GPCR receptor theory (such as MEDSCI 304 Molecular Pharmacology)

Skills

Cell culture

radioligand binding

receptor signalling assays (dependent on exact nature of project that is yet to be determined).

 

Can a nutritional supplement alter oxidative stress in humans-a systematic review


Supervisor

Dr Andrea Braakhuis

Project type

Biomedical

Department

Nutrition

Location

Auckland

Project code: MHS050

To determine whether a particular nutritional supplement will alter oxidative stress markers, based on published literature.

This project would suit a student familiar with producing and conducting a systematic review and meta-analysis.

Skills

-Systematic review protocol development

-Data search 

-Data extraction and possible analysis

Beating the superbugs: searching for new antibiotics from New Zealand's fungi


Supervisor

Siouxsie Wiles

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS051

The discovery of the antibiotic penicillin, made by a fungus, began a golden age for medicine. Since then antibiotics have saved countless lives. Experts predict that within 10 years, antibiotic-resistant superbugs will bring about the end of modern medicine. Common infections will become untreatable and cancer chemotherapy and routine surgery will become life life-threateningly dangerous. We desperately need new antibiotics, but where will they come from?

New Zealand has a treasure trove of unique fungi that have not been exhaustively searched for new antibiotics. In this project, you will use bacteria that glow only when they are alive to rapidly identify fungi that are able to kill microbes, like the hospital superbug Staphylococcus aureus.

For more info watch this video

Skills

  • Basic microbiological skills, including induction into a PC2 lab environment, and the culture of fungi and bacteria 
  • Data collection and interpretation
  • Report writing

Targeting the chemoreceptors in hypertension


Supervisor

Dr. Rohit Ramchandra

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS052

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

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

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

Skills

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

 

Project filled. Erythropoietin and retinopathy of prematurity


Supervisor

Dr Monica Acosta

Project type

Biomedical

Department

Optometry and Vision Science/Physiology

Location

Auckland

Project code: MHS053

This project topic has been filled

The study investigates whether there is a neuroprotective effect of Erythropoietin after asphyxia in preterm fetal sheep. We want to examine the effect of Epo treatment on vascularisation in the eyes. Epo penetrates into the eyes in a dose dependent manner. There is mixed evidence on the effect of Erythropoietin on retinopathy of prematurity. Although recent meta-analysis has shown that Epo treatment is not associated with retinopathy of prematurity, these studies examined low-dose Epo administration. We want to examine if multiple injections of high dose Erythropoietin administered for neuroprotection will increase vascularisation in the fetal eyes. 

Skills

ex-vivo fundus imaging and optical coherence tomography of the eye

tissue processing and sectioning

immunohistochemistry

confocal imaging and figures preparation

data analysis including statistical tests and report writing

Targeting peripheral inflammation for neuroprotection in infection-related preterm brain injury


Supervisor

Dr Justin Dean

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS054

Preterm birth is a major cause of neonatal morbidity and mortality, with very preterm infants exhibiting high rates of injury and impaired growth of white and grey matter, which are highly associated with subsequent neurodevelopmental impairment. There is strong evidence for a link between brain injury and exposure to low-level infection or inflammation around the time of birth. At present, there are currently no effective treatments to prevent or reduce brain injury in these infants.

The aim of this project is to investigate how infection affects cortical brain development and to determine whether anti-inflammatory drugs can be used to prevent or reduce cortical brain injury in a preterm-equivalent rodent model. Specifically, this summer studentship will involve analysis of brain tissues collected from our newborn rodent model of inflammatory-brain injury, including neuronal survival and neuronal dendritic growth.

Skills

This project will involve a range of methodologies including tissue collection, immunohistochemistry, stereology, and microscopy. 

 

Can SIRT1 be an early marker of gestational diabetes?


Supervisor

Anna Ponnampalam

Project type

Biomedical

Department

Liggins Institute

Location

Auckland

Project code: MHS055

Early onset GDM or unrecognised Type II diabetes is associated with a significant proportion of maternal and perinatal complications and occurs in 11% of all pregnancies. In New Zealand, the prevalence of GDM is particularly high among the non-European population. Data from Auckland’s National Women’s Hospital 2012 survey identified GDM was diagnosed in over 20% of Indian, almost 16% of Asian, and over six percent of Pacific Island and Māori women (groups known to have high rates of Type II diabetes), compared with three percent of NZ European women. Age and body mass index (BMI) are also risk factors for GDM with a 7-10 fold higher incidence among pregnant women older than 24 years of age, which is elevated further if these women are obese. There is also growing evidence that GDM significantly increases the risk of a number of short and long-term adverse consequences for the fetus and neonate, as well as the mother, the most significant of which is a predisposition to the development of metabolic syndrome and Type II diabetes. Sirtuin 1 (SIRT1) is a nutrient sensing protein deacetylase and major regulator of metabolic pathways. SIRT1 is involved in glucose and insulin metabolism through regulation of the activity of several regulatory transcription factors, co-regulators and enzymes- resulting in enhanced gluconeogenesis and repressed glycolysis in the liver, reduced adipogenesis in adipose tissue and increased release of insulin by pancreatic beta cells. SIRT1 is down-regulated in cells that have high insulin resistance, while over-expression of SIRT1 increases insulin sensitivity and protects mice against high-fat diet induced glucose intolerance. SIRT1-transgenic mice have lower blood glucose levels and are more glucose tolerant. Variants in the SIRT1 gene have been shown to affect diabetes risk, insulin and obesity resistance. 

Placental physiology is adversely affected in GDM pregnancies and placental glucose transporters are aberrantly regulated. We and others have also shown that SIRT1 is expressed in human placenta and our preliminary data show that SIRT1 gene and protein expressions are significantly reduced in placenta from GDM pregnancies The overall aim of this proposed research is to determine, via a pilot study, whether circulating SIRT1 concentrations can be used as an early marker for gestational diabetes. This would allow early intervention to potentially treat or alleviate GDM in later pregnancy, as well as reducing the risk of the women of developing Type II diabetes following a GDM pregnancy. Risks to the fetus and new born also would be attenuated. Therefore the main objective of this studentship is to establish whether differences in SIRT1 concentrations are evident we early as 15 and 20 weeks of pregnancy.

Skills

ELISA

Data analysis

Does excess extracellular hyaluronan affect the developmental morphology of hippocampal and cortical neurons?


Supervisor

Dr Justin Dean

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS056

In the nervous system, neurons and glia are surrounded by a complex arrangement of extracellular proteins and sugars. These matrix molecules may play critical roles during neuronal development. Our group is interested in the role of hyaluronan, an unbranched sugar, in the extracellular vicinity of developing cortical and hippocampal neurons. We propose that neurons express critical hyaluronidase enzymes, which degrade excess levels of hyaluronan during extension of neurites (initially as lamellopodia and growth cones).

The aim of this study is to characterise how the degradation of excess extracellular hyaluronan relates to the morphological development of cortical and hippocampal neurons in dissociated cultures. The student will analyse the morphological properties of neurons grown on hyaluronan-coated surfaces. Comparisons will be made between cultures grown in the absence or presence of hyaluronidase inhibitors.

Skills

This project involves work with dissociated cultures of hippocampal and cortical neurons. The student will experience immunocytochemistry and confocal imaging. This study will have a strong focus on image processing and analysis methodology. The student will also gain skills necessary to design and conduct hypothesis driven-experiments.

Effects of inhibiting hyaluronan synthesis on development of cortical neurons


Supervisor

Dr Justin Dean

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS057

In the nervous system, neurons and glia are surrounded by a complex arrangement of extracellular proteins and sugars. Our group studies the role of the sugar hyaluronan, a major component of the extracellular matrix throughout the body. Hyaluronan is produced by three enzymes called hyaluronan synthases, and is known to be important for cell structure, differentiation and signalling in many cell types. Our lab has recently shown that cortical neurons can produce their own hyaluronan matrix, and that this hyaluronan is located on structures that are critical for outgrowth of neurons. We propose that neuronal production of hyaluronan is important for controlling the growth of neuronal processes and that blocking the activity of hyaluronan synthase enzymes will impair neuronal growth.

Aims

Understand the functions of the three hyaluronan synthase enzymes in neuronal morphological development. Expression of individual hyaluronan synthase enzymes will be reduced using plasmid vectors transfected into primary cortical neuronal cultures. Neurite outgrowth analysis will be performed to assess effects of gene knockdown on neuronal growth.

Skills

This project involves work with dissociated cultures of cortical neurons. The student will experience immunocytochemistry, neuronal transfection, fluorescence and confocal imaging, image processing and analysis methodology, including neuronal tracing. The student will also gain skills necessary to design and conduct hypothesis driven-experiments.

Project filled: Can Magnetic Resonance Imaging (MRI) be used to assess symptoms of malabsorption?


Supervisor

Amber Milan

Project type

Biomedical

Department

Liggins Institute

Location

Auckland

Project code: MHS058

This project topic has been filled

Malabsorption of carbohydrates (e.g. lactose, fructose) causes a range of digestive symptoms such as bloating, abdominal pain, and flatulence. While malabsorption of lactose in foods like milk results in negative digestive symptoms in those unable to tolerate lactose (i.e. lactose intolerant), alternate products (e.g. yogurt) may be able to reduce these symptoms. To assess the benefits of different options for those with lactose intolerance, appropriate measures are required.

Malabsorption can be measured objectively by methods such as breath hydrogen production; however, most symptoms are recorded by subjective questionnaires. The development of an objective measure to quantify subjective symptoms of digestive malabsorption offers a useful tool in the assessment of digestive tolerance. MRI offers a non-invasive means to capture information about the gastrointestinal digestive process, and may provide the opportunity to measure features such as gastric emptying, intestinal transit, and gas production.

The current project aims to use MRI imaging to assess symptoms of malabsorption.

Skills

Medical imaging analysis

Data analysis

Reviewing literature

Viral trigger of human type 1 diabetes


Supervisor

Dr Shiva Reddy

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS059

Certain viruses have been implicated in beta cell destruction during the initiation of type 1 diabetes. Such viruses may invade beta cells of diabetes-prone subjects and may be associated with the expression of interferon-alpha. 

The aim of this project is to examine  and analyse the expression of interferon-alpha and related molecules linked with viral infection, in rare pancreatic biopsies from new-onset human type 1 diabetic diabetic donors.

Skills

Immunohistochemistry; bright field and fluorescence microscopy; digital imaging; dual and triple immunostaining ; cell enumeration; data analysis; immunological concepts; disease pathogenesis

Project filled: Can we identify prostate cancer patients with a genetic pre-disposition for AKR1C3 over-expressed disease?


Supervisor

Nishi Karunasinghe

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS060

This project topic has been filled

Aldo-keto reductase 1C3 (AKR1C3) is an enzyme with multiple functions including the production of extra-testicular androgens.  Increased expression of AKR1C3 is associated with advancing prostate cancer. Treatment failures with abiraterone acetate and enzalutamide used to treat castrate resistant prostate cancer patients have an association with AKR1C3 over-expression.

Preliminary data from our laboratory has shown that this enzyme level in leukocytes increases with age only among patients carrying the GG genotype of the AKR1C3 rs12529 single nucleotide polymorphism. It is only those with this genetic polymorphism that shows a correlation between the serum prostate specific-antigen level and the leukocyte AKR1C3 level. We have also looked at detailed histopathology records of 130 prostate cancer patients undergone prostatectomy. These data also show trends of various parameters associated with the same AKR1C3 rs12529 genetic polymorphism.
The proposed study intends to increase our data collection to build up a substantial data base to produce robust results.

Skills

1. Understanding post-prostatectomy histopathology reports.

2. Spectrophotometry to measure AKR1C3 enzyme level adjusting for levels of other AKR1C family enzymes

3. Data analysis skills

 

Spheres of influence


Supervisor

Trevor Sherwin

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS061

This project will utilise spheres of human adult stem cells derived from limbal tissue from the eye.

These stem cell spheres are currently being investigated for their potential to regenerate the human cornea:

The project aims to determine several variables:

  1. Are human stem cell spheres obtained from different donors able to interact with each other?
  2. Do the cells within the sphere have an idea of self?
  3. Do stem cells from female donors have greater potential than their male counterparts?

Skills

  • Human adult stem cell culture.
  • Immunofluorescence microscopy
  • Quantitative and digital PCR

 

A new broad-spectrum metabolite detection method for discovery metabolomics


Supervisor

Dr Elizabeth J. McKenzie

Project type

Biomedical

Department

Liggins Institute

Location

Auckland

Project code: MHS062

Metabolomics is the study of the totality of small (<1KDa) biomolecules present in any given biosample. The metabolite profile represents a snapshot of the metabolism of an organism, and reflects the combined effects of the genome, the microbiome, and the environment. Discovery metabolomics looks for biomolecules associated with health or disease states in an unbiased, untargeted manner. Suitable methods for metabolomics detect a wide range of metabolites.

Currently, trimethylsilylation via N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) is widely used in metabolomics because of its ability to derivatise a broad spectrum of biomolecules. However, this method suffers from lack of reproducibility and derivatives are sensitive to environmental factors like temperature and humidity.

Project aims

The aim of this project is to develop and test a fully-automated, high-throughput extraction and analysis method for metabolomics using trimethylsilyl cyanide derivatisation. A set of reference standards will be run and metabolite profiles will be obtained from plasma, serum and urine using the new technique.

This project would suit a second, third or fourth year undergraduate student with basic chemistry/biochemistry laboratory experience and an interest in metabolomics.

Skills

Skills that will be taught:

  • Safe handling of laboratory reagents
  • Storage and handling of temperature sensitive samples
  • Metabolite extraction from biofluids
  • Instrumental analysis (Gas Chromatography-Mass Spectrometry)
  • Mass spectrometry data extraction and identification
  • Strategies for handling high-dimensional data

Candidate preferences:

  • Hepatitis B immunisation preferred, but can be arranged
  • Preferred start: November 2017
  • Science/Biomedical major
  • Creative thinker
  • Self-motivated
  • Attention to detail

 

Detecting dysregulation in dynamic metabolomes using network analysis


Supervisor

Dr Elizabeth J. McKenzie

Project type

Biomedical

Department

Liggins Institute

Location

Auckland

Project code: MHS063

The metabolite composition of certain biosamples, such as faeces or urine, is highly variable and depends on what the subject has been eating or doing just prior to sample collection. This can obscure differences in the average levels of metabolites between healthy and diseased individuals. The levels of some metabolites are closely associated with each other, because one compound is derived from the other, or both are produced when particular pathways are active. The covariance matrix can describe how sets of metabolites increase and decrease together, and can measure the strength of that relationship. This means that it is able to detect dysregulation that is not obvious from differences in mean metabolite levels.

Project aims

The previous summer project successfully trialled a graphical method for producing a covariance models. Now it needs to be applied to real data. Network analysis will be used to estimate covariance matrix differences in case-control studies, for both public and Liggins-collected metabolomic data sets. The insights gleaned will be interpreted with reference to those based on mean comparisons. Other graphical methods will be explored for visualizing covariance, model optimisation and assessment of model validity.

This project would suit a second, third or fourth year undergraduate student with an interest in high-dimensional data and some background in statistics.  The ideal candidate would have experience using R, or Matlab, or other computer programming languages. 

Skills

Skills that will be taught:

  • Intermediate to advanced use of R
  • Fundamentals of  (inverse) covariance modelling
  • Techniques for preserving data integrity while handling large datasets
  • Publication-standard data plots using R

Candidate preferences:

  • Preferred start date – November 2017.
  • An interest in statistics
  • Programming skills
  • Self-motivated
  • Creative thinker
  • Attention to detail

Whole genome CRISPR/Cas9 screens to identify tumour hypoxia tolerance genes


Supervisor

Dr Stephen Jamieson

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS064

The disorganised and immature vasculature in tumours results in unstable and inefficient blood flow generating regions of hypoxia, which are much more prevalent and severe in human tumours than normal tissue. Tumours must adapt to this lack of oxygen to survive and do so through changes in gene regulation. However, the genes responsible for promoting survival of tumour cells within the hypoxic tumour microenvironment (TME) are poorly understood. We are attempting to address this by using whole genome CRISPR/Cas9 technology to knock out every gene individually (i.e. one gene per cell) in head and neck cancer cells exposed to hypoxia to identify the genes that facilitate tolerance to hypoxic TME stress. This project will involve exposing head and neck cancer cells transduced with a CRISPR/Cas9 library to cycles of hypoxia to induce growth inhibition. Genomic DNA will be isolated and PCR amplified prior to sequencing to identify genes that promote survival under hypoxia.

Skills

A range of cell and molecular biology techniques including cell culture, DNA extraction and PCR amplification

 

Characterising hypoxia in patient-derived xenograft models of head and neck cancer


Supervisor

Dr Stephen Jamieson

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS065

The inefficient blood supply within tumours gives rise to severe hypoxia, which can drive the growth and spread of tumours and promote their resistance to chemotherapy and radiotherapy. This is particularly evident in head and neck cancer, where there is compelling evidence that hypoxia limits standard-of-care chemoradiotherapy. As part of a 5-year Health Research Council programme grant, we have recently developed novel xenograft models of head and neck cancer using patient tumour specimens from Auckland City Hospital. In this project, we plan to characterise these models for their hypoxia status by staining tumour sections with the hypoxia marker pimonidazole and by analysing mRNA expression of hypoxia signature genes by qRT-PCR. 

Skills

Immunofluorescence

Fluorescence and brightfield microscopy

Image analysis

RNA extraction

qRT-PCR

Study of polysialic acid neural cell adhesion molecule in human microglia


Supervisor

Natacha Coppieters

Project type

Biomedical

Department

Anatomy and Medical Imaging

Location

Auckland

Project code: MHS066

The neural cell adhesion molecule (NCAM) is a receptor involved in the regulation of major biological processes including cell-cell adhesion and synaptic plasticity. The function of NCAM can be modulated by the addition of polysialic acid (PSA-NCAM) which reduces cell-cell adhesion and promotes cell migration. In the central nervous system, PSA-NCAM is expressed at the cell surface of neurons. However, it has recently been reported that PSA-NCAM is also expressed in the Golgi apparatus of rodent microglia, the immune cells of the brain. This recent finding questions the role of PSA-NCAM in those cells and remains to be validated in human.

The objective of this project will be to investigate PSA-NCAM in microglia from human brain tissue using fluorescent immunohistochemistry. Markers specific for the Golgi apparatus and confocal imaging will enable us to confirm the sub-cellular localization of PSA-NCAM in those cells.

Skills

  • Immunohistochemistry
  • Confocal Imaging
  • Image analysis

 

Using induced pluripotent stem cells to identify new drug treatments for cystinosis


Supervisor

Jennifer Hollywood

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS067

Induced pluripotent stem cells (iPSCs) have the ability to become any cell of the body. These cells are quickly becoming a state of the art tool to study genetic diseases.

We have generated iPSCs to model the genetic kidney disease cystinosis. The cause of this disease remains largely unknown and although there is a drug treatment, cysteamine, available to patients, most will develop end stage kidney.

We have established a cystinotic iPSC line using CRISPR/Cas that is genetically matched to the parental control making it an ideal model to identify new drug treatments. Using this new model we wish to perform RNA Seq analysis to identify new pathways involved that result in the pathogenesis of this disease. The aim of this summer project will be to further analyse any potential targets using qPCR in order to discover new drug treatments.

Please send your C.V. and transcripts if interested.

Skills

  • Extraction of RNA from cultured cells
  • cDNA preparation
  • Perform qPCR
  • Analysis of qPCR data

 

Functional characterisation of novel RNA-binding protein in cultured macrophage cells


Supervisor

Associate Professor Alan Davidson

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS068

Inflammatory responses provide protection to tissue stress, injury, and infection. However, chronic inflammation can be maladaptive and is a component of many illnesses including kidney disease, diabetes, cancer and neurodegenerative disorders.

Cytokines are key regulators of inflammation and are regulated by RNA-binding proteins that control their translation and stability. Our laboratory has identified a new RNA-binding protein with anti-inflammatory features that destabilises and downregulates proinflammatory cytokines.

The aim of this project is to identify downstream targets of this new protein in response to inflammation in cultured macrophage cells.  

Skills

Cell culture

Genome editing using CRISPR/Cas9

RNA isolation and quantitative PCR

Western blotting

Fluorescence immunocytochemistry and imaging (by light and confocal microscopy)

Data analysis and presentation

Influence of high glucose and inflammation on barrier properties of primary retinal microvascular endothelial cells


Supervisor

Ilva Rupenthal

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS069

Diabetic retinopathy is a chronic disease that develops due to high glucose-induced vascular disruptions in the retina characterized by blood-retinal barrier leakage, pericyte loss, endothelial cell death and neovascularization. Recent findings from our lab have shown that exposing retinal microvascular endothelial cells to high glucose and inflammatory cytokines simultaneously can induce vascular changes similar to the in vivo condition. This study will assess how high glucose and inflammation, alone or together, change the blood retinal barrier properties of retinal microvascular endothelial cells. 

Skills

  • Cell culture
  • Confocal microscopy
  • Immunohistochemistry
  • Barrier permeability assays (FITC-dextran permeability studies, ECIS technology)

 

Understanding the burden of tendon disorders in New Zealand


Supervisor

Dr David Musson

Project type

Biomedical

Department

Medicine

Location

Auckland

Project code: MHS070

Tendons connect muscles to bones, and with over 4000 tendons in the human body, they are fundamental to our ability to move and function in a way we take for granted. Injuries to tendons severely affects our quality of life, reducing our ability to work and limiting our recreational activities.

Recent data from the UK suggests one type of tendon disorder alone (tennis elbow) cost the UK healthcare system over £27 million GBP in 2012, and resulted in an average of 29 days sick leave taken per year. In New Zealand, however, the true burden of tendon injuries is unknown. Therefore, the aim of this summer studentship is to collect data on the incidence, cost and demographics of tendon injuries within New Zealand. Specifically, this project will use data sourced from the ACC, as well as information from local DHBs, and format them into an article to be published in a peer-reviewed journal.

One of the focusses of our research group is tendon biology. We collect tendon biopsies and tendon cells from orthopaedic surgeon colleagues, and run experiments to understand the mechanisms of tendon disease and to test novel therapeutics aimed at improving tendon healing. Understanding the burden of tendon disease in New Zealand will contribute to this research and build connections between academic research and healthcare providers.

Skills

• Communication skills

• Gaining knowledge in interdisciplinary research/healthcare

• Review of databases and data analysis

• Writing for academic publication

There is scope to follow this summer studentship with a lab-based Honours project, if interested.

Antioxidant eye drops for prevention or delay of cataract formation


Supervisor

Ilva Rupenthal

Project type

Biomedical

Department

Ophthalmology

Location

Auckland

Project code: MHS071

Cataract formation is associated with reduced levels of antioxidants in the lens core, making lenses particularly susceptible to oxidative damage. As a result proteins become crosslinked and aggregate, leading to scattering of light and therefore loss of lens transparency. Increasing the level of antioxidants in the lens core is therefore thought to prevent cataract formation. This project aims to formulate antioxidant eye drops and measure their penetration across the cornea and into the lens using an ex vivo eye model. 

Skills

  • Formulation and characterisation of various eye drops
  • Penetration studies across bovine corneas
  • Tissue processing
  • Fluorescence spectroscopy
  • Immunohistochemistry
  • Confocal microscopy

Loss of smell in neurological disorders


Supervisor

Dr Victor Dieriks

Project type

Biomedical

Department

Anatomy and Medical Imaging

Location

Auckland

Project code: MHS072

Losing the sense of smell (anosmia) has long been considered a side effect of aging. However, we now know that anosmia is closely linked to a wide range of neurological diseases. In Parkinson’s disease 95% of patients have an impaired sense of smell, which is observed 5-10 years before the other typical motor symptoms start to appear. It is currently unclear how the disease mechanism leads to the loss of smell.

This project will examine various sub-regions of the human olfactory bulb and compare the expression of neurochemical markers between control, Alzheimer’s, Parkinson’s, Huntington’s and Motor Neuron disease. As these diseases all present with an impaired sense of smell, we suspect the mechanism of anosmia may be similar.

Skills

This project involves work with tissue sourced from the human Brain Bank. The student will assist with processing human brain tissue and learn immunohistochemistry, fluorescence and confocal imaging as well as image processing and analysis. The student will also gain skills necessary to design and conduct hypothesis driven-experiments.

Does mtDNA affect the outcome of IVF?


Supervisor

Dr Lynsey Cree

Project type

Biomedical

Department

Obstetrics and Gynaecology

Location

Auckland

Project code: MHS073

Recent estimates suggest that 1 in 5 couples in New Zealand will suffer from infertility, with this number likely to increase as women delay childbearing for social reasons. Female fertility declines with age. Despite many advances in assisted reproductive technologies, procedures such as IVF are unable to overcome this decline.

This project will be part of a study investigating the role of mitochondria in ovarian ageing to identify strategies aimed at reversing ovarian ageing. Mutations in the mitochondrial DNA (mtDNA) are associated with ageing in addition to several hereditary disease. Mitochondrial function is key to many cellular processes, including during oocyte and early embryo development. In this project, we will investigate whether maternal ageing and the procedure of hormonal stimulation can have a significant impact on the mtDNA of the patient's oocytes, and therefore resulting embryos.

Skills

Real-time quantitative PCR

Digital PCR

Analysis of embryo development by time-lapse microscopy techniques

Cell dissection techniques, including micromanipulation

Literature review

Data analysis

Examining receptor trafficking and synapse plasticity in the neural innervation of the heart


Supervisor

Associate Professor Johanna Montgomery

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS074

The heart receives rich innervation from the central and peripheral nervous sytems. Located on the surface of the heart are "little brains" - clusters of  neurons that are thought to play a major role in controlling heart rate and rhythm. Little is known about the function and plasticity of these neurons. In this research project, we will utilise our expertise studying synapses in the central nervous system and apply this to the little brains of the heart to determine how their function and plasticity could contribute to development of life-threatening cardiac arrhythmias.

Project aims:

1. Examine the expression of critical synaptic scaffolding proteins in the little brains of the heart and in the cardiomyocytes using fluorescence imaging

2. Investigate how expression profiles differ in experimental models of cardiac arrhythmia

Please send a CV and academic transcript if interested.

Skills

Students can expect to gain experience with tissue sectioning, immunocytochemistry, histology, fluorescence and confocal microscopy, and advanced image processing and quantification methodologies. 

Identification of epigenetic approaches for killing KDM6A-mutant cancers


Supervisor

Dean Singleton

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS075

Tumour growth depends on the continuous proliferation and self-renewal of cancer cells. This state of immortality requires remodelling of the chromatin landscape to silence differentiation and activate pluripotency gene expression programmes. Cancer cells acquire both focal and widespread changes in epigenetic reorganisation, including alterations in post-translational histone modifications. Ultimately, this remodelled chromatin state acts to restrict binding of lineage-specific transcription factors to their DNA binding sites.

Mutations in genes encoding epigenetic modifiers are common in cancer and this finding has prompted the development of epigenetic inhibitors, many of which have proved to be highly effective cancer treatments.

Our work investigates Lysine (K)-Specific Demethylase 6A (KDM6A), a tumour suppressor gene that is frequently mutated in bladder cancer. We identified cancer cell lines with loss of KDM6A and have engineered these cells so that they re-express KDM6A. In this project the candidate will treat these cell line pairs (KDM6A null, KDM6A WT) with a library of potent and selective epigenetic inhibitors and determine effects on cell survival. These studies seek to identify new epigenetic vulnerabilities in KDM6A mutant cancer cells.

We are looking to recruit a summer student with an interest in continuing on to postgraduate research. 

Skills

Cell culture, drug sensitivity assays, fluorescence microscopy, western immunoblotting, RT-qPCR

Project filled: Creating an Antibody Binding Map for the Group A Streptococcus M protein, a Leading Vaccine Candidate


Supervisor

Nikki Moreland

Project type

Biomedical

Department

Infection and Immunity, Molecular Medicine and Pathology

Location

Auckland

Project code: MHS076

This project topic has been filled

Aim

To purify and characterise antibodies that bind to the Group A Streptococcus antibody.

Acute rheumatic fever and rheumatic heart disease are autoimmune sequela that follows an untreated Group A streptococcus infection. Rheumatic heart disease causes over 350,000 deaths globally per annum and the rates of ARF in Māori and Pacific children in New Zealand are amongst the highest in the world. A GAS vaccine to prevent development of ARF is urgently needed. The most promising vaccine candidates are strain-specific vaccines based on the GAS M protein. However very little is known about how antibodies interact with the M protein and which epitopes confer protection. This project will investigate M protein immunogenicity using both human serum and M-protein specific monoclonal antibodies and will produce clinically relevant data for vaccine design.

Skills

Recombinant expression of proteins and antibody fragments, immunoassays

Use of gene editing tools to evaluate the role of oxidoreductases in the activation of hypoxia-selective prodrugs


Supervisor

Chris Guise

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS077

A characteristic feature of the tumour microenvironment is the presence of a dysfunctional and irregular blood supply, resulting in the creation of hypoxic tumour regions. Hypoxia-selective prodrugs have the potential to eliminate these hypoxic tumour cells. The activation of these prodrugs requires both a low oxygen environment and the presence of oxidoreductases that catalyse prodrug activation. This project aims to characterise the role of known prodrug-activating enzymes through use of gene knockout studies.

Skills

This project will involve in vitro culturing of cancer cell lines. CRISPR/Cas9 genome editing will be used to create knockout cell lines which no longer express prodrug-activating enzymes. Once gene knockout has been confirmed, the role of the enzyme in prodrug activation will be characterised using techniques such as IC50 assays and prodrug metabolism studies. You will have the opportunity to participate in a multidisciplinary research environment and gain essential skills required for further postgraduate studies in drug discovery.

This project would suit a biomedical student with an interest in drug discovery and development. Practical laboratory experience (e.g. undergraduate teaching laboratories) is preferred.

Can we treat brain damage in preterm babies - a therapeutic role for a2-adrenergic agonists?


Supervisor

Dr Guido Wassink

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS078

Perinatal asphyxia is a major contributor to neonatal death and poor long-term neurodevelopmental outcomes in preterm babies. The predominant pattern of brain damage in these neonates are diffuse, non-destructive lesions in the periventricular and surrounding white matter, with moderate injury to subcortical neural structures. There are currently no proven therapeutic interventions that can treat such brain damage in preterm neonates. Catapres (clonidine hydrochloride), a α2-adrenergic agonist with potential anti-excitotoxic properties, is a medication clinically used to treat high blood pressure and attention-deficit hyperactivity disorder. In preterm fetal sheep and newborn rats, clonidine also reduced subcortical neuronal injury after hypoxia-ischemia. However, its potential therapeutic effect on white matter lesions remains unknown. The aim of this project is to determine whether clonidine can improve periventricular white matter damage after hypoxia-ischemia in the preterm brain.

For this summer studentship, immunohistochemistry, microscopy and cell quantification will be used to determine immature and mature oligodendrocyte cell survival and the degree of inflammation in white matter tracts of the preterm brain after prolonged hypoxia-ischemia, following treatment with either vehicle (control) or clonidine-hydrochloride. This research pioneers therapeutic treatment for preterm babies with brain damage from perinatal hypoxia-ischemia.

Please send a CV and academic transcript if interested.

Skills

Skills Taught

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

 

Unravelling mechanisms of lymphatic vessel development


Supervisor

Jonathan Astin

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS079

Lymphatic vessels are components of the vascular system, and play a key role in immune cell trafficking. Inappropriate lymphatic vessel growth contributes to the pathogenesis of many chronic inflammatory disorders and in cancer metastasis. Remarkably, we know almost nothing about the guidance cues that dictate where lymphatic vessels grow in different tissues and this knowledge is fundamental to the design of new therapies to treat these diseases.

Using transgenic zebrafish embryos in which lymphatic vessels are fluorescently labeled we have created the first map of the embryonic lymphatic vasculature. We used this map to identify lymphatic vessels that develop along cartilage or sensory neurons. The aim of this project will be to identify novel molecules involved in lymphatic vessel guidance by examining mutants in cartilage and neuronal development in which lymphatic vessels do not develop correctly. This work will uncover novel mechanisms of lymphatic vessel guidance that may be applied to develop treatments for lymphatic-related diseases.

Skills

Molecular Biology

Zebrafish Husbandry

Genetics

Confocal Imaging

Genome Editing

Project filled: Understanding the metabolism of the hypoxia-activated EGFR inhibitor tarloxotinib


Supervisor

Dr. Matthew Bull

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS080

This project topic has been filled

Tarloxotinib is a first-in-class hypoxia-activated EGFR antagonist for the treatment of cancer and was developed in-house at the Auckland Cancer Society Research Centre. The metabolic breakdown of tarloxotinib in patients is an important determinant of its duration and intensity of effect.  This pharmacology project aims to investigate the major mechanisms of metabolism, and resultant metabolites, of the clinical stage anti-cancer hypoxia activated prodrug tarloxotinib.

Skills

This project involves application of in vitro pharmacology and bio-analysis techniques, including optimisation and use of microsomal stability assays, liquid chromatography and tandem mass spectrometry. You will have the opportunity to participate in a multidisciplinary research environment and gain essential skills required for further postgraduate studies in drug discovery.

This project would suit a pharmacology or biomedical student with an interest in drug discovery and development. Practical laboratory experience (e.g. undergraduate pharmacology teaching laboratories) is preferred.

Understanding the metabolism of hypoxia-activated FGFR inhibitors


Supervisor

Dr. Matthew Bull

Project type

Biomedical

Department

Auckland Cancer Society Research Centre

Location

Auckland

Project code: MHS081

Building on the pre-clinical success of tarloxotinib (a first-in-class hypoxia-activated EGFR antagonist developed at the Auckland Cancer Society Research Centre), the development of hypoxia-activated prodrugs as FGFR antagonists for the treatment of cancer has resulted in the selection of a lead pre-clinical candidate. The metabolic breakdown of this candidate and, indeed, all hypoxia-activated prodrugs prior to their activation in patient tumours is an important determinant of their duration and intensity of effect. This pharmacology project aims to investigate the major mechanisms of metabolism, and resultant metabolites, of a preclinical stage anti-cancer hypoxia activated prodrug.

Skills

This project involves application of in vitro pharmacology techniques and bio-analysis techniques, including optimisation and use of microsomal stability assays, liquid chromatography and tandem mass spectrometry. You will have the opportunity to participate in a multidisciplinary research environment as part of an international collaboration,  and gain essential skills required for further postgraduate studies in drug discovery.

This project would suit a pharmacology or biomedical student with an interest in drug discovery or development. Practical laboratory experience (e.g. undergraduate teaching laboratories) is preferred.

Project filled: Characterization of beta amyloid-induced molecular and cellular changes in an in vivo Alzheimer`s disease mouse model


Supervisor

Dr. Andrea Kwakowsky

Project type

Biomedical

Department

Anatomy and Medical Imaging

Location

Auckland

Project code: MHS082

This project topic has been filled

Alzheimer's disease (AD). AD is characterized by progressive loss of neurons, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD. A feature of the pathogenesis of AD is the increased concentration of neurotoxic soluble oligomers of beta amyloid peptides.

The aim of this project is identifying the mechanism of beta amyloid-induced changes 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

-neural tissue collection, fixation

-combination of molecular, anatomical and imaging techniques

-data collection, analysis and presentation

 

Project filled: Which brain cells are affected first in the olfactory bulb in Parkinson's disease


Supervisor

Maurice Curtis

Project type

Biomedical

Department

Anatomy and Medical Imaging

Location

Auckland

Project code: MHS083

This project topic has been filled

The aim of the project is to study the various cell types in the Parkinson's disease olfactory bulb and to identify which ones accumulate the pathological protein the most and the earliest. The student will use immunohistochemistry and high throughput image screening to identify the cell types based on known cell markers and to identify alpha synuclein, the hall mark of Parkinson's disease.

Skills

Immunohistochemistry, microscopy, confocal microscopy, metamorphosis analysis, histology.

Project filled: Acute mechanisms of perinatal ischemic brain injury


Supervisor

Dr Joanne Davidson

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS084

This project topic has been filled

Fetal ischemia, the loss of blood supply before or around the time of birth, can cause death and devastating lifelong disability. Therapeutic hypothermia (cooling of the brain) is currently the only available treatment for infants that have suffered brain injury as a result of ischemia. Whilst it significantly reduces death and disability, many infants still suffer severe brain damage, even when treated with hypothermia. In order to develop better treatment options we need to improve our understanding of the cellular and molecular mechanisms underlying the development of ischemic brain injury and how these are affected by therapeutic hypothermia.

For this summer studentship, western blotting, immunohistochemistry and microscopy will be used to investigate the cellular and molecular changes occurring after ischaemia and whether these changes are attenuated by therapeutic hypothermia. This research will help to identify novel injury pathways which contribute to the development of brain damage after hypoxia ischaemia.

Please send a CV and academic transcript if interested.

Skills

  • Western blotting
  • Immunohistochemistry
  • Microscopy
  • Data analysis
  • Statistical analysis

Treating cutaneous inflammation by putting skin on a fat-free diet


Supervisor

Dr Chris Hall

Project type

Biomedical

Department

Molecular Medicine and Pathology

Location

Auckland

Project code: MHS174

Persistent accumulation of immune cells within the skin is damaging and contributes to inflammatory dermatoses like atopic dermatitis and psoriasis. Understanding what regulates this immune response is fundamental to designing new therapies to treat inflammatory dermatoses. By live imaging epidermal cell metabolism during cutaneous inflammation, in transparent zebrafish embryos, we have shown epidermal cells utilise fatty acid metabolism to ‘fuel’ immune cell accumulation. We propose inhibiting uptake and metabolism of fatty acids within epidermal cells, during skin inflammation, represents a new strategy to block/suppress the persistent immune response that underlies cutaneous inflammation. We have identified drugs that we predict target this metabolic-immunological interface to suppress inflammation. By exploiting the live imaging potential of the zebrafish model system, this project will further explore the mechanism through which these drugs operate.

Skills

  • Molecular biology
  • Zebrafish husbandry
  • Live confocal imaging

Examining changes in patient heart cells with long QT syndrome


Supervisors

Dr Annika Winbo
A/Prof Johanna Montgomery
Prof Jon Skinner

Project type

Biomedical

Department

Physiology

Location

Auckland

Project code: MHS175

Long QT syndrome is a cardiac arrhythmia that can cause fatal ventricular arrhythmia.

In this project we will examine differences in ion channel expression and localisation in heart cells derived from patient blood cells.

Project aims

  • Examine the growth and differentiation of heart cells
  • Investigate how potassium channel expression differs with different LQTS associated mutations

Skills

Students can expect to gain experience with cell culture, immunocytochemistry, fluorescence and confocal microscopy, and electrophysiology.