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More than $28 Million for Auckland health research

More than $28 Million for Auckland health research
Media Release

University of Auckland

11 June 2014

More than $28 Million for Auckland health research

Health research grants totalling more than $28 million for University of Auckland research projects, programmes, feasibility studies and work by emerging researchers, were announced by the Health Research Council of New Zealand this week.

The largest grant was for nearly $5 million to a research programme led by Professor Bill Wilson into developing new prodrugs to combat hypoxia in cancer tumour cells and for investigation into biomarker-guided drug targeting of the tumour microenvironment in radiotherapy.

The HRC 2014 funding round of University of Auckland projects included:

Professor Frank Bloomfield (Liggins Institute) - ProViDe RCT: Does better early nutrition in preterm babies improve development? (HRC Project funding $1,194,159, 60 months).
Providing adequate nutritional intakes, especially of protein, in extremely low birth weight (ELBW, birth weight < 1,000 g) infants in early life is extremely challenging.
Consequently, the majority of ELBW babies have faltering postnatal growth. Poor growth in ELBW babies is associated with adverse neurodevelopmental outcomes.
This project proposes a randomised, double-blind, placebo-controlled multi-centre trial of a simple, inexpensive and practical intervention to determine whether, in ELBW babies, an extra 1 g/day of intravenous protein in the first five days after birth will improve survival free from neurodisability at 2 years' corrected age.
This trial will provide the first evidence on the long-term outcomes of increased protein intake in ELBW babies in early life. If the intervention is effective, it could be introduced immediately into neonatal units at very little cost with health benefits for these highly vulnerable babies and providing economic benefits for New Zealand.

Professor Winston Byblow (Sport and Exercise Science) - Individualised neuromodulation for motor recovery after stroke (HRC Project funding $1,179,896, 36 months).
Stroke is the leading cause of adult disability worldwide. Inhibitory tone in the brain is altered by stroke and dictates how plasticity and recovery of function occur after stroke, but this varies from one individual to the next.
The study objective is to identify factors that predict how best to apply non-invasive brain stimulation to modulate inhibitory tone and facilitate motor recovery in the initial days and weeks after stroke. To do this, advanced neuroimaging and neurophysiological assessments will be undertaken to establish links between inhibitory function, effects of brain stimulation on recovery, and patient outcomes.
This project will increase the understanding of the molecular, cellular and neurophysiological mechanisms of recovery of motor function in human patients after stroke, and reduce inequalities in stroke outcomes for people who are more likely to suffer stroke earlier and live with disability longer.

Associate Professor Leo Cheng (ABI) - Mechanisms of gastric dysmotility: Advances from cell to clinic(HRC Project funding $1,189,475, 36 months).
As in the heart, an underlying electrical activity termed the 'slow wave' regulates stomach contractions. Stomach wave dysrhythmias (abnormalities in the slow wave) have been associated with common and significant diseases such as functional dyspepsia and gastroparesis.
Post-operative complications have also been attributed to disruption to the normal slow wave conduction due to surgical removal of the natural slow wave pacemaker region of the stomach.
This project has an international, interdisciplinary team to develop and apply a range of new generation slow wave recording methods, to critically advance the fundamental understanding and therapy of gastric dysrhythmias.
The team will develop new innovative slow wave recording capabilities across multiple platforms and integrate them with advanced signal processing tools that will allow accurate identification of gastric dysrhythmias. These methods will offer high-fidelity and/or minimally-invasive slow wave recordings for translation to improve diagnosis and therapy of these diseases.

Dr Melanie Cheung (Anatomy and Radiology/CBR) - Augmenting neuroplasticity in the Huntington's disease brain (HRC Project funding $1,189,942, 36 months)
There is evidence to suggest Huntington’s disease (HD), (a progressive neurodegenerative disease that results in deterioration of movement, personality, thinking and eventually death), is at least twice the rate in Māori than non-Māori.
We have been working in partnership with a large Taranaki Maori HD whanau, who after six years of building relationships, is eager for us to begin developing treatments together.
To date the most promising brain disease treatments harness neuroplasticity, the brain's powerful ability to change and adapt itself.
This research project brings together Taranaki Māori whanau, HD scientists and clinicians from the Centre for Brain Research (Auckland University) and Brain Plasticity Institute (San Francisco) to develop computer-based brain exercises that augment neuroplasticity in the brains of people with Huntington’s disease to ultimately slow the course of the disease.
Methods will include Kaupapa Māori approaches to brain imaging, neuropsychology and clinical care (neurology, psychiatry and nursing).

Professor Phillip Crosier (Molecular Medicine and Pathology)- Uncovering mechanisms and inhibitors of tumour-induced lymphangiogenesis (HRC Project funding $1,199,342, 36 months).
Cancer is now the most common cause of death in New Zealand. Mortality is frequently caused by the secondary spread of tumour cells (metastasis) to distant organs in the body via the lymphatic vasculature.
One of the first steps in lymphatic-mediated metastasis is the growth of lymphatic vessels (lymphangiogenesis) towards and within the primary tumour; a process that could be targeted by drugs and form a new approach to cancer treatment.
Many of the signalling pathways that underlie lymphangiogenesis remain unknown and require identification to progress this work.
This project team will use a zebrafish model of lymphangiogenesis to identify new genes and pathways that regulate lymphatic vessel growth. They will also conduct a chemical screen to identify anti-lymphatic compounds that inhibit tumour-induced lymphatic vessels in zebrafish and in mammalian models.
This work will form an important first step in developing therapies to prevent or limit lymphatic-mediated metastasis.

Professor Caroline Crowther (Liggins Institute) - Optimal glycaemic targets for gestational diabetes: The randomised trial TARGET (HRC Project funding $1,198,858, 36 months).
Gestational diabetes (GDM) is a significant health problem affecting one in every 12 pregnant women or over 5,200 women in New Zealand annually. GDM has a major, negative impact on maternal and perinatal health with lifelong consequences. It is unclear what intensity of glycaemic control during GDM treatment is best for mother and infant.
The TARGET randomised Trial will evaluate the implementation of tighter treatment targets for blood sugar control compared with current less stringent targets in women with GDM.
Researchers will compare the risk of the infant being born large for gestational age, which is strongly associated with significant early life and later health problems.
Other relevant outcomes will be assessed. This unique trial will allow for the sequential implementation of the new, nationally recommended tighter treatment targets for women with GDM and, for the first time, establish if there are true benefits, without harm, to tighter treatment targets.

Professor Caroline Crowther (Liggins Institute) - Gestational diabetes trial of detection thresholds: Impact on health and costs (HRC project funding $1,199,330, 36 months).
Gestational diabetes (GDM) is a significant health problem affecting one in every 12 pregnant women or over 5,200 women in New Zealand annually.
GDM has a major, negative impact on maternal and perinatal health with lifelong consequences. There is no consensus as to the degree of high blood glucose needed for the diagnosis of GDM or when treatment will be beneficial, due to a lack of high quality evidence.
Our unique, randomised trial compares important health outcomes for mothers and babies of treating women with GDM by the current criteria used in New Zealand with newly proposed criteria, that use a lower threshold and will diagnose more women as having GDM.
Our results will show which diagnostic criteria is best for the health of mothers and babies and which is more cost-effective, and so provide the necessary information to guide clinical practice and policy in New Zealand, with global relevance.

Professor Caroline Crowther (Liggins Institute) - Antenatal magnesium sulphate: Mechanisms of fetal neuroprotection (HRC Project funding $1,199,011, 48 months).
Children who survive preterm birth face life-long health problems and increased educational needs, often related to abnormalities of brain development around the time of birth.
Magnesium sulphate given to women immediately prior to preterm birth at or before 30 weeks' gestation protects the fetal brain, so fewer babies die or develop cerebral palsy. It is not known exactly how magnesium exerts this benefit.
The MagNUM Study, a nested study within a multicentre randomised trial of antenatal magnesium sulphate prior to preterm birth at 30 to 34 weeks' gestation, will assess the possible mechanism of effect of magnesium treatment, by a MRI scan of the baby's brain at term equivalent age.
This project will assess whether magnesium reduces brain injury, particularly in brain regions that control movement, learning and behaviour, and relate these changes in brain structure to later development.

Professor Peter Davis (Compass) - Life-course predictors of mortality inequalities (HRC Project funding $1,091,258, 36 months).
Life-course socio-economic influences on mortality have different implications for intervention but have not been established in the New Zealand context. The team will analyse mortality records linked with the historic longitudinal census dataset (linked records across the 1981-2006 Censuses) to fulfil four research aims:

• To test which life-course hypotheses best explain associations between socio-economic status and mortality: accumulation, sensitive period, social mobility, or instability?
• To test whether social and cultural capital protects against socio-economic risk.
• To assess ethnic disparities in mortality and test whether these are explained by the greater experiences of long-term harsh and unstable environments among some ethnic groups (e.g., Māori, Pacific).
• To test life-course hypotheses among siblings discordant on socio-economic risk, and among siblings discordant for social and cultural capital (thus controlling for family background factors).
This research will be both methodologically innovative (e.g., discordant sib-pair analyses), and important for the understanding of ethnic inequalities in New Zealand.

Professor Paul Donaldson (Optometry and Vision Science) - Delivering lens anti-oxidants: A strategy to develop anti-cataract therapies (HRC Project funding $1,198,171, 36 months).
The goal of this research is to reduce the incidence of cataract by developing effective strategies to delay its onset, thereby alleviating the need for surgical intervention.
Since age related nuclear (ARN) cataract is associated with oxidative damage, the use of antioxidant supplements has been advocated as a therapeutic approach to slow cataract progression. However, the efficacy of antioxidant supplements is unproven, due to a lack of knowledge on how antioxidants accumulate in the lens nucleus, the region of the lens specifically affected in ARN cataract.
To address this, researchers will study how the levels of the natural lens antioxidant glutathione and nutrients required to maintain it in its reduced state are delivered, accumulated and utilised in the nucleus of normal and cataractous lenses.
This will allow targeted strategies to restore and enhance the natural defence systems of the lens to be developed, thereby affording increased protection against ARN cataract.

Dr Natasha Grimsey (Pharmacology) - Characterising cannabinoid receptor 2 polymorphisms implicated in mental illness (HRC funded Project $149,732, 36 months).
Mental illnesses such as depression, bipolar disorder and schizophrenia affect around 16% of New Zealanders and are difficult to diagnose and treat effectively. Continued research is required to better understand these disorders and develop new medicines. Individuals with small alterations in their DNA, called polymorphisms, can produce different versions of the same protein which might work differently. A few specific versions of Cannabinoid Receptor 2 (CB2), one of the proteins that mediates the effects of cannabis, are more common in patients suffering from mental illness than in the general population. These may play a role in disease cause or progression. In this research we plan to investigate what is different about the function of these versions of CB2 at a cellular level. This will include studying cells donated by patients with schizophrenia. This information will provide insight into the causes of mental illness and may assist with designing new therapies.

Professor Alistair Gunn (Physiology) - Protecting brain development after clinically silent infection before birth (HRC Project funding $1,151,828, 36 months).
Premature babies have a high risk of neurodevelopmental disability and there is no effective treatment. Although multiple factors are involved, disability is closely linked to infection and inflammation around the time of birth.
In this study, we will first test in preterm fetal sheep whether exposure to a clinically silent dose of a key part of bacterial cell walls for just five days will impair growth of the branches (dendrites) that connect brain cells together, and so reduce the growth and function of the brain.
Researchers will then test whether blocking one of the key inflammatory pathways in the brain will help restore normal maturation of brain cells and brain activity, and determine the window of opportunity for treatment.
This new knowledge will help us understand how cognitive deficits develop in preterm infants, and provide a new way of protecting normal brain development.

Dr Joanna James (Obstetrics and Gynaecology) - Growing better placentas for healthy babies (HRC funded Emerging Researcher First Grant $139,550, 36 months)
In pregnancy disorders such as intrauterine growth restriction (IUGR) a poorly functioning placenta is a major component of the disease process. Placentae from IUGR pregnancies often have poor vascular development, which limits their ability to absorb nutrients from the maternal blood.
While IUGR affects 8-14 per cent of pregnancies, we currently have no effective treatment for this disorder. Mesenchymal stem cells (MSCs) have shown exciting therapeutic promise in regenerating a range of tissue types, in part by stimulating blood vessel development.
This research aims to determine whether MSCs could be a viable treatment for IUGR by determining 1) whether IUGR is associated with differences in placental MSC function, 2) whether transplanted MSCs can survive in placental tissue, and 3) how MSCs may contribute to successful placental vascular development.
This will allow us to determine whether MSCs could be successfully transplanted or targeted therapeutically to fix failing placentae from the inside out.

Associate Professor Andrew Jull (Nursing) - Low dose aspirin for venous leg ulcers: A randomised trial(HRC funded $1,199,722, 36 months).
Leg ulcers are a common, costly and debilitating condition and the burden will increase as the population ages. Venous leg ulcers (VLU) are the most common leg ulcer, can be painful, and limit work, lifestyles and activity, especially in older patients.
There are few effective treatments - compression therapy (tight bandaging or stockings) helps healing, but about half the people with a VLU remain unhealed even after 12 weeks of treatment. Research suggests taking aspirin as well as using compression may speed up healing for VLU, but the current evidence is not enough to change clinical practice.
Researchers will conduct a randomised controlled trial to test whether using low dose aspirin really does speed up healing. If aspirin does speed up healing, it is an inexpensive treatment that could quickly be put into clinical practice.

Professor Ross Lawrenson (Waikato Clinical School) - How to improve outcomes for women with breast cancer in New Zealand (HRC funded $1,175,663, 36 months).
New Zealand has the seventh highest mortality rate from breast cancer (BC) in the world. Māori and Pacific women fare even worse.
Data on 12,500 women with BC (including 1200 Maori and 850 Pacific women) from the Waikato and Auckland Breast Cancer Registries will be used to explore the differences in characteristics of women with BC, their access to care and quality of treatment comparing Māori, Pacific and non-Māori/non-Pacific.
Researchers will examine the impact these differences have on BC survival and recurrence. Based on the findings they will pilot improved and targeted care coordination for a group of women with newly diagnosed BC.
Working with local breast cancer care co-ordinators, the strategy will be to address key issues such as patient understanding, timeliness and adequacy of treatment, adherence to medication, and appropriate tailoring of treatment to specific sub types of breast cancer such as HER-2 positive.

Dr Simon Malpas (ABI) - Improving hydrocephalus management through an implantable device (HRC funded $1,188,597, 36 months).
Imagine you are the parent of a child with water on the brain (hydrocephalus). A shunt catheter was surgically placed to divert excess fluid from the brain to the stomach.
This means that instead of being a fatal condition, the child can lead a normal life…with one proviso; that the shunt continues to work. Unfortunately 50 per cent of shunts will fail within two years.
The symptoms of early shunt failure are often very similar to a simple headache or non-related infection which necessitates many costly CT or MRI scans to resolve.
Now a team of engineers and neurosurgeons at the University of Auckland want to remove that stress, reduce cost and radiation exposure and the likelihood of missing shunt malfunction by developing a tiny implant which will sense and wirelessly transmit the pressure and temperature inside a person's brain and the flow of fluid through the shunt.

Dr Rinki Murphy (Medicine) - Factors affecting gut micro biota establishment and function during infancy (HRC funded $150,000, 12 months).
Types of gut microbiota (microorganisms living in our gut) and their function is thought to be important for enhancing health and wellbeing.
Understanding early life determinants of gut micro biota colonisation, and the extent to which this is modified by exposure to probiotics while in the womb and after birth is important for developing more effective gut micro biota targeted therapies to promote resilience to many inflammatory and metabolic diseases.
Researchers propose a detailed study of the gut micro biota composition and function using longitudinal faecal samples collected from infants within a randomised controlled trial of probiotics given to mothers (during pregnancy and breastfeeding) and their infants.
Prior to embarking on this study, researchers want to undertake a feasibility study to ensure that the faecal DNA samples are of acceptable quality, estimate technical variability in gut micro biota sequencing, establish biological variability in faecal micro biota function and establish scalable, integrative, computational analysis methods.

Associate Professor Adam Patterson (ACSRC) - Colonising tumour necrosis with Clostridium sporogenes for precision therapy (HRC funded $1,186,308, 36 months).
Most solid cancers contain regions of necrotic (dead) tissue. The extent of necrosis is associated with poor survival, most likely because it reflects aggressive tumour outgrowth and inflammation.
The harmless anaerobic bacteria Clostridium sporogenes, upon injection as spores, will germinate and thrive in these necrotic regions, providing cancer-specific colonisation.
Through an international collaboration we have "armed" C.sporogenes with a chemotherapy-activating gene that enables the bacteria to be imaged by positron emission tomography.
Researchers will characterise the interaction of armed clostridium plus 'masked' chemotherapies developed in our laboratories.
They will validate the relationship between tumour necrosis and anti-tumour efficacy and also design next generation 'masked' agents that release inhibitors of DNA repair and investigate their ability to enhance radiation therapy in combination with armed C.sporogenes. This will, for the first time, exploit necrosis in solid cancers, turning this pathological feature associated with treatment failure into a target for precision therapy.

Dr Helen Petousis-Harris (SOPH) - Effectiveness of maternal pertussis booster in pregnancy - outcomes in infants (Partnership Programme Funders HRC and Ministry of Health. $104,142, 12 months).
Whooping cough is a difficult disease to control and is particularly serious in infants, especially those too young to vaccinate. This research investigates the effectiveness of providing pregnant women a dose of whooping cough vaccine to prevent or lessen the disease in their infants.
Transfer of antibodies through the placenta in pregnancy is expected to offer some passive protection until the infant is protected by childhood immunisation starting at six weeks of age.
The study will firstly use data for all births between 2011-2013, all infants who were diagnosed with whooping cough and whether or not their mothers received the vaccine in pregnancy.
Secondly, it will take a small blood sample from a subgroup of infants at several time points to see how well they respond to their own vaccinations.
Knowledge from this research will help inform the New Zealand immunisation programme and better control of whooping cough.

Dr Helen Petousis-Harris (SOPH) - Feasibility study of human papillomavirus (HPV) infection, awareness and vaccine acceptability in men (HRC funded $149,588, 12 months).
As well as causing cervical cancer in women, human papillomavirus (HPV) is associated with other cancers including cancers of the mouth, throat, penis and anus in men, with a particularly high incidence among men who have sex with men (MSM).
Many issues relating to HPV and vaccination in males are poorly understood in the New Zealand context.
The objective of this feasibility study is to estimate HPV prevalence, awareness, and vaccine acceptability among three subpopulations of interest: HIV positive MSM, other MSM, and heterosexual males.
Participants will be recruited from primary health care and outpatient settings in Auckland via screening and sequential sampling with quotas, because sexual orientation data is not routinely collected.
The estimates of HPV prevalence and response rates will inform the design (sample size, duration) of a larger study to measure baseline HPV prevalence and monitor vaccine impact among these populations in the absence of alternative surveillance sources

Dr Anthony Phillips - Re-thinking the cross talk between bacteria and host cells (HRC funded Explorer Grant $150,000, 24 months).
The successful interaction between bacteria and their host during infection is complex. A range of signals mediated by protein, peptide and small molecule effectors are well-recognised mechanisms for bacterial manipulation of the host.
In this study we are proposing a new type of molecular communication system based on combinations of nucleotides (building blocks of DNA and RNA) that act as signals being released by bacteria to alter the way the host cell nucleus and associated machinery make proteins.
Researchers will screen profiles of the nucleotide based molecules released from bacteria for combinations that we will then show can alter human cells. It offers two major outputs.
The first is a new paradigm in biology related to nucleotide communication between bacteria and host. Secondly it promises to provide the basis for developing a completely new class of anti-infective directed at disrupting this novel bacteria-to-host signalling pathway.

Professor Sally Poppitt (Nutrition) - Seeking new insights and new routes to diabetes prevention: PREVIEW New Zealand (HRD Project funded $1,120,603, 36 months).
There is growing concern about the diabetes epidemic and the health of New Zealanders. While many therapies treat diabetes, far more important is prevention.
We are participating in a large scale, long-term global program, PREVIEW: Prevention of Diabetes through Lifestyle Intervention in Europe, New Zealand and Australia; recruiting two and a half thousand (2,500) overweight adults and children known to be at high risk.
The study will test whether a higher protein diet is more successful for weight loss and diabetes prevention than current international best practice of a higher carbohydrate diet, and also the additional effect of moderate/higher exercise.
This will be the first large international study to follow participants long-term to discover who develops diabetes and who does not, what are the most important risk factors, and how can they best be modified through diet and exercise.
This is a landmark study which will inform international diabetes recommendations.

Professor Peter Shepherd (Molecular Medicine and Pathology) - Regulating hormone secretion via dynamic modulation of beta-catenin levels (HRC funded $1,187,711, 36 months).
Type-2 diabetes mellitus is reaching epidemic proportions. Relatively little is known about the exact mechanisms by which the disease develops. One key step leading to development of type-2 diabetes is that cells lose the ability to release insulin in response to glucose but the reason for this is unknown, although recent genetic studies have provided clues.
One of the most prominent genetic risk factors is in the TCF7L2 gene but it is not known how this leads to diabetes. Our recent work has identified a novel way by which glucose controls insulin release by regulating a protein called catenin.
This has led researchers to develop a highly novel hypothesis as to how the TCF7L2 gene defects might affect insulin secretion.
They will use cell based and transgenic animal studies to test this hypothesis and believe this will solve an important missing link in understanding how type-2 diabetes develops.

Associate Professor Cathy Stinear (Medicine/CBR) - Accelerating recovery after stroke with neuromodulation: A feasibility study (HRC funded project $149,950, 12 months).
Stroke is a leading cause of adult disability. The ability to live independently after stroke depends on the recovery of motor function. This research will investigate whether trans cranial direct current stimulation (tDCS) can increase the rate and extent of motor recovery after stroke.
TDCS is a safe, painless and non-invasive way to increase the activity of the stroke side of the brain. Previous studies have shown that applying tDCS during physiotherapy can enhance the benefits of therapy. However, little is known about its effects with patients at the sub-acute stage.
This feasibility study will evaluate patient and therapist acceptance of tDCS, and estimate effect size and recruitment rate. If feasible, tDCS will be integrated with rehabilitation after stroke in a multi-centre, double-blind, randomised controlled trial.
This research has the potential to improve the recovery of motor function and independence for the approximately 6,000 New Zealanders who experience stroke each year.

Professor Boyd Swinburn (Epidemiology and Biostatistics) - Food environments in New Zealand: Policies and impacts on health and equity (HRC funded $1,162,422, 36 months).
An International Network for Food and Obesity/non-communicable diseases (NCDs) Research, Monitoring and Action Support (INFORMAS) has been established to monitor and benchmark food environments globally and support actions to reduce obesity, NCDs and their related inequalities. INFORMAS will be fully implemented in New Zealand as the first national survey of the healthiness of food environments and the degree of implementation of the policies that influence them.
In addition, for four key modules (food prices, provision, promotion and retail), 'environmental equity' indicators will be developed to assess progress towards reducing diet-related health inequalities.
New Zealand food environments will be compared with those of other countries as a first step towards global benchmarking of food environments and their related policies.
Effective policy responses will be identified to improve the healthiness of food environments, and this baseline INFORMAS database will ensure that the impact of future food and nutrition policies can be evaluated.

Dr Ruth The (Nursing) - Transforming ways of living and ageing (HRC Feasibility study funded, $149,303, 12 months).
Maintaining function and quality of life (QOL) are preferred over longevity. Combinations of healthy lifestyle behaviours benefit QOL and function however physical activity is low and nutrition risk high in older people.
This study examines the feasibility of a large trial testing the effectiveness of nutrition and physical activity to improve QOL and function. This feasibility randomised trial tests two synergistic components; nutrition, Senior Chef, and physical activity and green prescription, and facilitates participation for both Maori aged 60+ and non-Maori 75+ through primary care and community organisations.
Those at high risk of losing independence will be enrolled, change in food eaten and physical activity undertaken will be measured and compared between the intervention and control group over 2 months.
If this study is successful a large trial will test the sustainability and effectiveness in improving QOL and function, and thus impact on reducing health services and prolonging healthy life expectancy.

Dr John Thompson (Paediatrics) - Quality of care and outcomes in children with cleft lip and/or palate
(HRC project funded 48 months, $1,005,314)
This study has two main objectives in relation to cleft lip and palate (CLP). Firstly it will investigate the health care delivery pathways from the time of diagnosis to the primary surgery for children with a cleft lip and/or palate and their families.
This will ensure that CLP patients are receiving health delivery to the standard expected and required. Secondly it will provide the first consistently collected outcome data in relation to cleft lip and palate in New Zealand, including surgical outcomes, speech, dental care and importantly quality of life.
This data will be compared to a parallel study in Australia, as well as to data from the UK to determine how cleft lip and palate patients in New Zealand fare compared to their contemporaries worldwide. This will allow any deficiencies to be identified and processes put in place to ensure improved outcomes in the future.

Dr Ehsan Vaghefi (Optometry and Vision Science) - Digital design of therapies to combat age related nuclear cataracts (HRC funded Emerging Researcher first grant, $141,000, 36 months).
Age-Related Nuclear (ARN) cataract is associated with oxidative damage to the lens core and is initiated by an age-dependent deterioration of the lens transport system. In the absence of a blood supply, this system maintains lens homeostasis by delivering nutrients and antioxidants to its core.
In this application, they will facilitate efforts to develop anti-cataract therapies by continuing the development of a 3D computer model of lens structure and function that can predict the effects of aging on the individual components of this lens transport system.
To complement this modelling approach, MRI will be used to non-invasively measure water diffusion rates in human lenses.
By feeding these values back into the model, it will be possible to determine how lens functionality changes with age, an important first step in the development of therapeutic strategies to combat ARN cataract by up regulating the delivery of protective antioxidants to the core of older lenses.

Dr Siouxie Wiles (Molecular Medicine and Pathology) - Evolution in action: A novel model for studying pathogen adaptation in vivo (HRC funded Explorer Grant $150,000, 24 months).
We are locked in an arms race with opponents who are capable of evolving faster than we can. These microbes place a huge burden on the New Zealand health system; a staggering one in four overnight hospital admissions are infection-related. So how do infectious microbes adapt to live and cause disease in their hosts? And what factors influence this arms race?
Researchers will investigate these questions using a bacterium that naturally infects laboratory mice. The knowledge gained from this study will transform the field of pathogen evolution from one which relies on anecdote and observation, to an experimental science in which the consequences of genetic change of both pathogen and host may be precisely defined and tested.
Such an understanding will allow the evolution of infectious microbes to be anticipated and should highlight new 'chinks' in our opponents’ armour. In the fight against an ever changing foe, forewarned is forearmed.

Professor William Wilson (ACSRC) - Biomarker-guided drug targeting of the tumour microenvironment in radiotherapy
(HRC funded programme $4,918,968, 60 months)
The inefficient blood supply within tumours gives rise to severe hypoxia and extracellular acidity.
This abnormal microenvironment drives growth and spread of tumours, and their resistance to chemotherapy and radiotherapy.
Our primary objective is to develop new prodrugs that selectively target anticancer drugs (cytotoxins, DNA repair inhibitors) to these refractory cells.
The programme focuses on head and neck squamous cell cancer (HNSCC), the sixth most common human malignancy and the tumour type with the most compelling evidence that hypoxia limits standard-of-care chemoradiotherapy.
We will develop three chemical classes of prodrugs using preclinical models of HNSCC including 3D cell cultures and tumour xenografts derived from individual cancer patients. A central aspect of the Programme is co-development of predictive biomarkers, using genomic and proteomic tools, to identify patients who will benefit from these prodrugs.
Our longer term objective is to support first-in-human clinical trials in New Zealand in HNSCC and other cancer indications


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