Auckland medical science benefits from major grants

Auckland medical science benefits from major grants

Media Release - University of Auckland - 4 November 2016

A novel peptide delivery system for vaccines, insights into fetal DNA, investigating the lymphatic system, and discovering how diet and exercise affect our cells – these are some of the projects funded by the annual Marsden Fund grants and led by medical scientists at the University of Auckland.

In the latest round announced today, seven new projects in medical and health science at the University of Auckland benefitted from $4.2 million from the Marsden Fund.

Faculty of Medical and Health Sciences Associate Dean (Research), Professor Andrew Shelling, says, “This is a wonderful outcome for the Faculty, and represents another example of our increasing success by researchers in major grant funding rounds.

“These projects will enhance our growing reputation as a leading research faculty and will provide for the development of several exciting fundamental research projects that will directly lead to increased knowledge and understanding of Medical Science.”

Associate Professor Thomas K Proft, (Molecular Medicine and Pathology, School of Medical Sciences), was awarded $825,000 for his project on ‘PilVax - a novel peptide delivery strategy for the development of vaccines’.

His team of researchers will focus on a vaccine against an important infectious disease (tuberculosis) and an anti-tumour vaccine (colorectal cancer).

He proposes to develop a novel peptide delivery system by expressing antigens within the Streptococcus pyogenes pilus on the surface of Lactococcus lactis.

This will have several advantages, including increased peptide stability (rigid pilus structure), biocompatibility (due to no synthetic peptide carriers and adjuvants) and time/cost effectiveness (due to no chemical coupling).

Professor Larry Chamley (Obstetrics and Gynaecology, School of Medicine), was awarded $800,000 for the project, ‘Mum, you are what your babies make you!’

“Our research is investigating whether fetal DNA is permanently taken up by some of the mother’s cells and whether that fetal DNA, like the fetal cells could cause some mothers to develop, or be protected from, diseases in later life,” he says.

During pregnancy the fetus produces large amounts of genetic material (DNA) which is shed into the mother's blood. This fetal DNA in the maternal blood is now being used in a new clinical test to determine whether the fetus is genetically normal, he says.

Since there is so much fetal DNA in the blood of pregnant women his team of researchers hypothesize that some of that DNA might be introduced permanently into maternal cells.

If that does happen, the woman may start to inappropriately produce proteins that are encoded by the fetal DNA.

Research Fellow, Dr Jonathan Astin (Molecular Medicine and Pathology, School of Medical Sciences), was awarded $820,000 for a project entitled, ‘Stop or go? Unravelling the mechanisms behind lymphatic vessel patterning’.

Inappropriate lymphatic vessel growth is an important component of chronic inflammatory disorders and cancer metastasis.

Cancer is the leading cause of death in New Zealand and mortality is frequently caused by the secondary spread of tumour cells to distant organs in the body via ectopic tumour lymphatic vessels.

In contrast, lymphatic hypoplasia or dysfunction causes the painful and incurable accumulation of fluid (lymphoedema) and is a significant survivorship issue for women following axillary lymph node removal during treatment for breast cancer.

Remarkably, we know almost nothing about the guidance cues and molecular mechanisms that dictate where lymphatic vessels grow in different tissues and this knowledge is fundamental to the design of new therapies to treat these lymphatic diseases.

Using a zebrafish model of lymphatic development, we have created the first ever map of the embryonic lymphatic vasculature and used this to identify a lymphatic vessel that grows along craniofacial cartilage.

Laser ablation or genetic disruption of this cartilage inhibits lymphatic growth suggesting that it expresses essential pro-lymphatic guidance factors.

In this project, researchers will use this lymphatic-cartilage interaction to identify novel mechanisms of lymphatic vessel growth regulation and guidance that may be used to develop treatments for lymphatic-related diseases.

Research fellow, Dr Troy Merry (Molecular Medicine and Pathology, School of Medical Sciences), was awarded a Fast-Start grant for $300,000 for a project examining ‘How diet and exercise affect our cells’.

Two major diseases affecting New Zealanders - obesity and type2 diabetes - are known to respond positively to exercise and a calorie-restricted diet. The positive benefits of these interventions are a reduction in the incidence of the disease and extended lifespan.

Dr Merry and colleagues from the University of Otago and ETH Zurich in Switzerland will focus on recently identified mitochondrial-derived peptides such as humanin which have been linked with protective effects in age-related neurological damage.

They will focus also on how these molecules may protect us from metabolic stress and oxidative stress.

Dr Merry and his team are interested in the effects of short-term (acute) and long-term (chronic) changes of diet or exercise on peptide levels in blood and muscle tissue.

Specifically, they will investigate how these interventions, and the resultant changes in peptide levels, contribute to restoring metabolic balance, focussing on obesity.

They theorise that acute increases in metabolic activity (e.g. short bursts of exercise, change in diet) raise peptide levels to protect against metabolic stress and oxidative stress. In contrast, chronic metabolic stress (e.g. obesity) may result in a drop in peptide levels and a loss of protection.

This project will pioneer an exciting new field of metabolic research and provide a better understanding of the biological processes underlying diseases like diabetes and obesity.

Research fellow Dr Jie Zhang, (Ophthalmology, School of Medicine) was awarded a Fast-Start grant of $300,000 for a project ‘Determining the potential of the corneal transition zone for corneal transplants’.

Disease, damage or loss of the innermost layer of the cornea (the corneal endothelium), can result in blindness, and methods to repair the affected cornea involve corneal transplantation using donor endothelium.

As there isn’t a sufficient supply of donor cornea, limiting the number of patients that can be treated, there is an increasing demand for corneal donors in New Zealand, partly driven by an ageing population and increased life expectancy.

The ultimate aim of this project is to increase the number of patients who can be treated from a single donor.

Dr Zhang will investigate a particular type of adult stem cell that has recently been found in a specific area of the cornea called the transition zone. This type of cell looks to have the potential to regenerate the corneal endothelium.

The purpose of this research is to understand and manipulate these corneal cells, with the goal of treating corneal disease. If successful, each donor cornea could be a source for several transplants.

Dr Juliette E Cheyne (Physiology, Medical Sciences) was awarded a Fast-Start grant of $300,000 to investigate ‘Measuring in vivo activity in the prefrontal cortex and its link to Autism Spectrum Disorders’.

Autism Spectrum Disorders (ASD) are developmental disorders defined by learning difficulties, social deficits, sensory changes and stereotyped behaviours.

In the brain, the prefrontal cortex (PFC) plays a major role in these higher level functions, and researchers hypothesise that the neuronal wiring in the PFC develops incorrectly in ASD.

They will utilise state-of-the-art in vivo cellular recording techniques to measure how network activity is altered during development of the PFC in a mammal model and how this affects sensory processing later in life.

As spontaneous and sensory-driven activity both play key roles in developing neuronal connectivity researchers will also examine whether altering sensory experience, by sensory deprivation, affects network function.

By directly linking sensory stimulation with recordings of neuronal activity, this work will determine how observed activity changes in vivo could underpin ASD-related impairments in high-level sensory processing and behaviour that are mediated by the PFC.

Professor Paul Donaldson (HOD, School of Medical Sciences) was awarded $810,000 for a three year project entitled ‘Your eyes: more than just windows to your soul’.

When you read, the lens of your eye must maintain both clarity and the correct shape to focus on the text and refract the light to the back of your eye. If you get distracted and glance outside, your eye performs an amazing feat of physics to refocus on objects that are further away.

But the lens of your eye is made of living cells. So how do they stay clear and maintain their shape to precisely focus light from both near and far?

Professor Donaldson and colleagues from both the University of Auckland and the State University of New York, are working on an answer.

Professor Donaldson’s Marsden-funded research will build on their earlier work, to determine exactly how the cells of the eye regulate the water pressure to maintain clarity and change the focal length of the lens.

They will also investigate whether applying mechanical tension to the lens, to mimic lens refocusing, alters water transport and lens power. This research will also provide clues as to why the process sometimes goes wrong, for example in cataract formation in the ageing eye.

The ultimate goal of this project is to come up with non-invasive, early intervention methods of improving vision and delaying the onset of cataracts.

ENDS

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