Hope Foundation

The Hope Foundation for Research on Ageing is a charitable trust dedicated to sponsoring research on ageing and its effects on the New Zealand community. Preparing New Zealand for an ageing future. The New Zealand population is undergoing a major demographic transformation and is facing an epidemic in ageing. In 1966, 12% of the population was 64 and over, in 2040 it will be 24%. The social impact of a significant proportion of the population being "non-working" has major implications for our society in economic, demographic, town planning, infrastructural and health-related areas. Positive ageing means that older age is both viewed and experienced positively and includes changing attitudes and expectations amongst younger generations regarding ageing and older people. The Foundation’s hope is that by encouraging interest in research in the field of ageing at the start of a career, that interest will be maintained throughout the individual’s productive research life.

Imaging Biomarkers in Parkinson’s disease

Supervisor

Associate Professor Miriam Scadeng

Discipline

Hope Foundation

Project code: MHS012

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

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

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

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

3D structural mapping of the sensory apparatus of balance

Supervisors

Haruna Suzuki-Kerr (09 923 8728)
Rachael Taylor
Peter Thorne

Discipline

Hope Foundation

Project code: MHS017

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

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

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

Skills the student will learn: microCT, tissue dissection, image analysis, 3D image data processing and scientific report writing.

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

Supervisors

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

Discipline

Hope Foundation

Project code: MHS031

Dementia is an emerging global public health challenge for our generation: over 35 million people are affected by this condition worldwide (Alzheimer’s Disease International, 2010). In New Zealand, one-in-three of those over 65 will develop an ageing-related brain disorder (primarily Alzheimer’s disease/dementia) (Brain Research NZ, 2015). Current evidence heavily implicates the involvement of neuroinflammation, an immune response in the brain, as one of the key features of Alzheimer’s disease (AD) pathology.

It has been observed that astrocytes, one the brain’s primary supporting cells, have been implicated in neuroinflammation through a process known as reactive astrogliosis, which involves several changes to astrocytic morphology and phenotype (Sofroniew & Vinters, 2010; Serrano-Pozo et al., 2013). However, the spectrum of astrocytic cell involvement in AD has not been fully dissected, and is still far from being well understood. The objective of this project is to screen for astrocytic changes in the AD human brain with a wide range of immunohistochemical markers for proteins involved in astrocytic function. We will examine markers for astrocytes using human brain tissue microarrays (TMA) comprised of clinically well-characterised AD and control post-mortem cases.

Skills

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

Exploring medication use in the last year of life for people living in residential aged care

Supervisors

Michal Boyd (09 923 3722)
Jo Hikaka
Katherine Bloomfield
Jackie Robinson
Zhiqiang Wu
Aileen Collier
Rosemary Frey
Deborah Balmer

Discipline

Hope Foundation

Project code: MHS040

Almost 40% of all deaths occur in residential aged care (RAC) facilities in New Zealand (NZ). Old age palliative care is complicated by multi-morbidity and advanced frailty, however, little is known about medication use for those who die in RAC. The ELDER study conducted post-mortem surveys in RACs in NZ, and this data will be used to explore end of life medication use. Ministry of Health deidentified pharmacy data has been obtained for all 286 deaths in the ELDER sample.

The summer student will answer these research questions in collaboration with researchers: 1) what medications are used in the last months of life for people dying in RAC, 2) how does medication use correlate with observed end of life symptoms, 3) how does NZ RAC data compare to similar European data. Our previous summer students published their work in high ranking journals, and this study will also be submitted for publication.

You will gain skills in:
• Pharmacy and clinical dataset management
• Descriptive and correlation/regression statistics
• Literature review and academic writing leading to publication

Those that would suit those with an:
- interest in quantitative analysis of existing databases
- interest in honing academic writing skills
- ability to work independently

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

Supervisors

Monica L Acosta (09 923 6069)
Gaganashree Shivashankar

Discipline

Hope Foundation

Project code: MHS043

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

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

Experience in biomedical studies is preferred but is not essential.

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

Supervisors

Dr Monica Acosta (09 923 6069)
Associate Professor Andrea Vincent

Discipline

Hope Foundation

Project code: MHS045

Inherited retinal dystrophies are a large group of diseases that result in death of photoreceptors, the light-sensing cells of the retina. Still largely incurable and progressive with age, protection of surviving photoreceptor cells is imperative. Multiple mechanisms of action have been proposed in the intervention of retinal dystrophies but there are no conclusive studies of the effect of the drugs on vision.

We want to conduct a preclinical efficacy study to determine if it is safe to use anti-inflammatory drugs in damaged retinas. We will assess retinal function and cell survival as a function of drug dose and duration of treatment using rodent models. The study will assess the risk/ benefit of using an anti-inflammatory drugs in the treatment of retinal dystrophies.

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

A randomised controlled trial in retirement villages: Exploring older adults experiences

Supervisors

Katherine Bloomfield (021 159 1580)
Jo Hikaka
Michal Boyd

Discipline

Hope Foundation

Project code: MHS051

Our research group is studying the health, social and functional needs of residents living in retirement villages (RVs). Part of this project included a randomised controlled trial (RCT, n=412) investigating the effect of a multi-disciplinary team (MDT) intervention on healthcare utilisation.
Understanding participant experiences of an intervention is an important step in the development of health services/research design.

This current study is a qualitative study conducted in a subgroup who participated in the intervention arm. The aim is to understand resident experiences of the MDT intervention which will help inform further health service/research development. Non-European participation rate in the RCT was low (<4%). Therefore, ALL non-European RCT participants will be invited into this study, with additional European RCT participants chosen randomly.

The student will conduct semi-structured interviews (in residents’ homes/over the telephone), transcribe the interviews, code the transcripts, participate in the data analysis and collaborate with researchers to draft an academic paper for journal publication.

Skills gained

- Literature review/critical appraisal
- Qualitative research methods including semi-structured interviews, data coding/analysis
- Academic writing
- Working as part of a collaborative, multi-disciplinary research group

This would suit those with

- Excellent communication skills
- The ability to undertake some self-directed work

High Resolution Visualization of Protein Trafficking Machinery in the Lens Fibre Cells

Supervisors

Haruna Suzuki-Kerr (021 118 9953)
Julie Lim

Discipline

Hope Foundation

Project code: MHS055

The ocular lens of the eye is one of two tissues in our body with complete transparency. The lens consists of specialized cell called fibre cells that have elongated shape cell bodies arranged in highly ordered manner. Previous studies in the Molecular vision laboratory have shown that lens fibre cells actively respond to environmental stimuli by altering protein localizations (including purinergic and other receptor proteins), however the mechanisms is unknown.

This project aims to shed light on the protein trafficking machinery in the lens fibre cells. The participating student will prepare rodent lens sample and use immunohistochemistry and super-resolution confocal microscopy to visualize small protein-containing vesicles at subcellular resolution.

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

Skills the student will learn: Tissue dissection, immunohistochemistry, super resolution confocal microscopy, image analysis and scientific report writing.

Purinergic Signalling in the Retina: deciphering glia contribution

Supervisors

Haruna Suzuki-Kerr (021 118 9953)
Monica Acosta

Discipline

Hope Foundation

Project code: MHS057

The retina is the light sensing tissue of our visual system, where several types of neurons communicate with each other to decode visual image information before it is sent to the brain. Studies have identified that a group of purinergic receptors (P2X) expressed in neurons are involved in shaping visual information. However P2X are also expressed in glia and much of their function remains unknown.

This project aims to identify the distribution of P2X in glia and in neurons. The participating student will prepare rodent retinal samples and use immunohistochemistry and microscopy to visualize location of P2X at high resolution. This information will give us clues to the potential function of P2X receptors in mediating neuron-glia interactions.

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

Skills the student will learn

Tissue dissection, immunohistochemistry, confocal microscopy, image analysis, data analysis and scientific report writing.

Glutamate transporter expression in the human Alzheimer`s disease brain

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Hope Foundation

Project code: MHS068

Glutamate is the main excitatory brain neurotransmitter and it plays an essential role in the function and health of neurons and neuronal excitability. Altered glutamatergic signalling plays a key role in a number of pathological conditions affecting the nervous system, including Alzheimer`s disease (AD). AD is characterized by progressive loss of neurons, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD.

Understanding the remodelling of the glutamatergic system in brains of people stricken by AD will help decide what type of drugs to use or design. The gradual neuronal degeneration and decreases of synaptic density in AD affected brain areas precedes increment in aberrant electrical activity. Modulation of the balance between excitatory and inhibitory neurotransmission early in AD is one of the targets of the glutamatergic drugs in the AD brain.

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

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

Skills taught

-neural tissue collection, fixation
-combination of molecular, anatomical and imaging techniques
-data collection, analysis and presentation

Understanding GABA Signalling in the Vasculature of Healthy and Alzheimer’s Disease Brains

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Hope Foundation

Project code: MHS071

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 taught

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

Neuroinflammation in the human Cingulate Cortex in Huntington’s disease

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Hope Foundation

Project code: MHS074

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

The aim of this project is to investigate whether there is significant neuroinflammation in the cingulate cortex of human HD cases using immunohistochemistry on tissue sections of HD cases and controls.

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

Skills taught

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

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

Supervisors

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Hope Foundation

Project code: MHS077

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

The aim of this project is to design an optogenetic stimulation approach to ameliorate neuronal function and behavior in an in vivo Alzheimer`s disease mouse model.

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

Skills taught

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

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

Supervisors

Jesse Ashton (093737599 ext 83259)
Johanna Montgomery

Discipline

Hope Foundation

Project code: MHS093

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

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

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

Supervisors

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

Discipline

Hope Foundation

Project code: MHS110

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

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

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

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

Supervisors

Dr. Helen Murray
Associate Prof Miriam Scadeng
Prof Maurice Curtis

Discipline

Hope Foundation

Project code: MHS130

Olfactory dysfunction is a prevalent and early symptom of Alzheimer’s disease. However, it is currently unclear whether this symptom is linked to degeneration of the olfactory bulb. With collaborators at the National Institutes of Health (USA), we have acquired high-resolution MRI (14T/19-25um voxel size) of post-mortem human olfactory bulbs from Alzheimer's disease and control cases. These are the highest resolution MRI images of human olfactory bulbs captured to date and provide a unique opportunity to quantify volume changes in Alzheimer's disease.

We are looking for a student with an interest in neuroanatomy and medical imaging to segment structures of interest in these olfactory bulb scans to investigate volume changes in Alzheimer's disease. The student will receive training in olfactory bulb neuroanatomy and MRI segmentation using AMIRA software. The project is highly flexible, with much of the analysis able to be carried out remotely (off-site) if preferred.

The impact of Covid-19 on intergenerational social contact among people over 70

Supervisors

Professor Merryn Gott (021 246 2197)
Tessa Morgan
Dr Lisa Williams

Discipline

Hope Foundation

Project code: MHS132

The Covid-19 lockdown had particular implications for people over 70 who were identified as most vulnerable to the virus and singled out as needing to take special precautions. We received funding from the Auckland Medical Research Foundation to explore older people's experiences during this time. One phase of the project involves people over 70 (and Maori and Pacific people over 60) writing letters about their experiences of Lockdown. At the time of writing we have over 160 letters and are anticipating many more.

We are seeking a summer student to explore the issue of inter-generational social contact during lockdown as described in the letters. Letters will be analysed using thematic analysis to address the following objectives: 1) What was the impact of lockdown upon the extent of inter-generational contact people over 70 had during lockdown? 2) Did the nature of that contact change? 3) What was the role of technology in facilitating contact? 4) Has lockdown had any long term impacts upon inter-generational contact for people over 70?

We have permission to recontact letter writers to further explore aspects of their recorded experiences. The final part of the project will involve contacting a sample of letter writers to discuss findings. This will ensure older people are included at every stage of the project.

We are seeking a student with good analytic and inter-personal skills and a commitment to social justice, particularly in relation to older people. The project is part of the programme of research being undertaken by the bicultural Te Arai Palliative Care and End of Life Research Group.

Women Wellness Program after Stroke Project

Supervisors

Julia Slark (09 923 8471)
Bobbi Laing

Discipline

Hope Foundation

Project code: MHS148

Women Wellness Program after stroke project -administration and transcribing duties, data collection and entry, clean and code data; undertake preliminary data analysis under supervision of team members.

Astrocytes as a cell target for gene therapy

Supervisors

Debbie Young (09 923 4491)
Angela Wu

Discipline

Hope Foundation

Project code: MHS152

Astrocytes are key players in brain information processing because of their roles in blood flow regulation, synapse formation and plasticity, and energy metabolism as well as in many neurological disorders. NURR1 is a transcription factor important in regulating the expression of endogenous target genes that are important in the survival and maintenance of the dopamine neurons that are susceptible in Parkinson's disease. NURR1 also inhibits inflammatory gene expression in glial(microglia and astrocytes) cells.

This project aims to determine whether pathogenic stimuli capable of increasing calpain activation and reactive astrogliosis can be harnessed to drive NURR1-regulated gene therapy strategies in astrocytes.

Skills taught

Mammalian tissue culture
Immunocytochemistry
Imaging
Western blotting

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

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

Supervisors

Angela Wu (09 923 1907)
Debbie Young

Discipline

Hope Foundation

Project code: MHS170

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

Techniques taught will include:

Mammalian cell culture
Immunocytochemistry
Imaging and microscopy
Image analysis

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

An iPad-based assessment of reading performance

Supervisors

Prof S Dakin (027 836 5800)
Geraint Phillips
Joanna Black

Discipline

Hope Foundation

Project code: MHS180

The COVID-19 pandemic has highlighted the need for effective home-based monitoring of patients’ vision. This includes older adults who need to be monitored for changes in their vision that might signal a deterioration in long-term conditions such as age-related macular degeneration (AMD).

Although patients complain about problems reading, there is currently no means of their measuring their own reading performance on a regular basis. To address this we have developed an eReader application, that runs on Apple iOS devices, and leverages these devices’ imaging capabilities to measure where the patient is looking during reading. This allows us to make detailed, daily, automated assessment of patients reading while they enjoy their preferred reading material.

In this project we will validate this approach by comparing the measures made using the iPad to (a) results from an infra-red eyetracker and (b) gold-standard measures of reading speed made in the clinic. We will do this for people with normal vision and a variety of simulated visual problems (e.g. AMD).

The project would suit a student with a background in optometry, psychology and/or programming (e.g. Matlab, Swift).