Faculty Research Development Funding covers 10 projects in 2013

09 September 2013

Associate Professor Andrew Shelling, FMHS Associate Dean (Research), reports that 10 of the 47 applications to this year’s Faculty Research Development Fund (FRDF) were approved, these being awarded a total of $1,263,000. FRDF funds come from the University’s annual budget, including funding derived from the Performance Based Research Fund (PBRF) with the annual faculty allocation determined by the office of the Deputy Vice-Chancellor (Research), calculated on faculty PBRF performance. The fund is designed to assist and promote the research careers of faculty staff members at all stages of their careers and across all disciplines, and as the successful projects listed below show, those principles are certainly being followed. FRDR funding can only be awarded to maximum level of $80k/annum and projects will be funded for a maximum of two years.

Successful 2013 FRDF projects and summaries of the research involved are:

Dr Marcus Henning, Associate Professor Jennifer Weller, Associate Professor Andy Wearn The impact of Progress Testing in the University of Auckland MBChB program on students’ approaches to learning and levels of stress ($155,617)

Background: The MBChB programme aims to produce graduates with a deep, applied understanding of their subject and high-quality learning strategies needed for life-long learning. To this end, Progress Testing (PT), which purports to promote deep learning strategies, was introduced in 2013. It is a comprehensive knowledge test sampling across all content areas of the curriculum, assessed at graduate outcome levels, and administered periodically to all students across all years of the program. By its comprehensive nature, it is intended to discourage students attempting to prepare specifically for that test, and thus discourage the use of superficial learning strategies such as rote learning (van der Vleuten 1996). However, the impact of PT on student learning can vary with context and curriculum structure (Wade 2012), and the extent to which PT fulfills its theoretical promise is untested in our MBChB program. Furthermore, assessments are stressful for students, and the extent to which PT will affect students’ stress levels is also unknown. Aim: To determine the effect of Progress Testing on medical students’ approaches to learning and stress.

Methods: Mixed methods, using previously validated questionnaires and student focus groups; comparison of student cohorts exposed or not exposed to Progress Testing. The Revised Study Process Questionnaire (R-SPQ-2F) evaluates learning approaches and the Perceived Stress Scale (PSS) evaluates levels of stress. Focus group questions will provide in-depth understanding of any changes to learning approach or stress scores and the relationship to PT.

Analysis: Comparison of mean cohort scores derived from questionnaire instrument; correlations between R-SPQ-2F, PSS and PT scores; thematic analysis of focus group transcripts.Significance: Results will inform ongoing development of the MBChB curriculum, inform PT theory, inform the international community on educational impact of PT, and contribute to a program of evaluative research in medical undergraduate education in FMHS.

Dr Nicola Anstice Improving the efficacy of the B4 School Vision Screening Check; ($79, 716) Abstract: The B4 School Vision Check attempts to screen all NZ children at 4-5 years of age to prevent detrimental effects of vision disorders on educational and developmental outcomes by triggering early intervention.

There is strong evidence that early treatment produces better visual outcomes in children. However, in the area of preschool screening, there is a lack of consistent evidence regarding the best screening tests to use, the most appropriate referral criteria and which personnel to utilize. Our recent retrospective analysis of records from Counties Manukau District Health Board revealed high rates of false positive referrals (40-50%) which place an unnecessary economic burden on health care systems. It is unclear whether this is due to the screening test used or the training of the lay screeners using the test. Currently no data exist, in NZ or elsewhere, that allow for the calculation of false negative rates (children with vision disorders who are missed by vision screening). Furthermore, no previous studies have investigated the use of alternative screening tools within a NZ context. This study aims to provide a prospective evidence base that will support improvements in NZ preschool vision screening.

This will be accomplished in three phases:

  • Phase 1: a) development and evaluation of a training protocol for lay screeners
  • b) development of automated software to standardize the scoring of vision tests
  • c) piloting of prospective data collection using a range of candidate vision tests.
  • Phase 2: Fully powered prospective evaluation of the sensitivity and specificity of paediatric vision tests for detecting important vision disorders (amblyopia, strabismus, refractive error and unexplained reduced visual acuity)
  • Phase 3: One year follow up of children who failed screening to assess long-term outcomes.
  • This application is for funding to support Phase 1. Applications will be submitted to external funding bodies to support Phases 2-3.

    Dr Darren Svirskis Novel polymer implant for on-demand ocular drug delivery; ($159,903) Abstract Treatment of retinal disorders such as age-related macular degeneration (AMD) involves frequent injections of a drug-containing solution into the eye, an unpleasant procedure that can lead to surgical complications, and equally importantly, requires frequent specialist visits with the need currently exceeding capacity. Existing scleral implants used in practice passively release drug at a fixed rate and once exhausted, between six months and three years, require surgical procedures to replace them throughout the period of treatment. This project aims to develop an innovative rechargeable ocular implant based on conducting polymers (CPs) that passively releases the drug at a constant rate over at least six months, but also allows for doseindividualisation using non-invasive electrical stimulation with wireless communication technologies which currently exist, removing the need for an invasive procedure. Like existing implants, the proposed system will be non-biodegradable, however, its design allows it to be recharged with drug during the biannual check-up visit, reducing the number of surgical procedures and significantly reducing the treatment burden of retinal disease on patients. To meet the research objectives in this novel and translational proposal, funding is sought for a postdoctoral research fellow. Our proposed research fellow, Ali Seyfoddin, has the relevant background knowledge and expertise to solely focus on this project, generating high quality research outputs and aiding in the development of successfully external funding bids. This ground-breaking research will bring us to the forefront of ocular drug delivery technology and has great intellectual property and commercialization potential. By bringing researchers from multiple disciplines such as chemical, pharmaceutical and biomedical sciences together to address poorly met clinical needs, this innovative translational research project can reduce the burden of treatment for a growing patient group with debilitating eye diseases.

    Professor John A. Windsor Cross-species communication: how insects might promote surgical wound healing; ($159,853) Abstract: Background: Medicinal maggots, the larvae of the green bottle blowfly, are used in the clinic to improve healing of chronic wounds. The maggots secrete a cocktail of proteins, fatty acids and lipids with known roles as antibiotics and as enzymes to digest away the dead tissue. Another molecule can directly alter the phenotype of skin cells to promote healing. An exciting new field in biology is the discovery of small non-protein coding RNAs as regulatory molecules which can be transported between cells as signals to alter recipient cell characteristics. We hypothesise that in our scenario, small RNAs secreted by medicinal maggots can promote healing by being taken up into wound cells and directly modifying their gene expression and phenotype.

    Proposal:To investigate the ability of maggot derived small RNAs to promote wound healing through a new collaborative surgical research program involving the insect and cell culture resources of the School of Biological Sciences (SBS), Bioinformatics, and Surgery. Significance: The promotion of healing by application of maggot small RNAs to wounds opens the way for an exciting new class of therapeutics for the treatment of disease. Furthermore, this study will be the first to explore small RNAs as novel signalling molecules between the two diverse multicellular organisms of insects and mammals and has wide reaching implications for the fundamental biological communication between many other species such as plants, pests, mammals and parasites.

    Associate Professor Mervyn John Merrilees New approach to improving the quality of cultured skin for grafting; ($64,834) Abstract:A significant drawback to cultured human skin for the grafting of burns and other wounds is the fragile nature of the skin, especially during early culture over the first month. Longer periods of culture allow for greater structural integrity but lengthy culture times are not clinically feasible. Our research has demonstrated that integrity of skin sheets, and importantly the elastin content, is significantly increased by overexpression of a normally inactive matrix gene called V3. Recently we have discovered that treatment of growing skin with a fragment of V3, the N terminal G1 domain (38KDa), appears to be even more efficient at increasing the strength of the sheets, and induces an ordered structure to the cells and matrix of the cultured dermis, with the advantage that it can be applied topically as a recombinant protein. Preliminary data indicate that G1 binds to the pericellular hyaluronan-rich cell coat, compacting the HA and changing the physical relationship between the dermal fibroblasts. Further, while this treatment does not appear to increase soluble elastin production, we have evidence that it may promote enhancement of elastic fibre deposition. Collagen content appears to be increased which may account for the increased strength.

    We propose to investigate this new finding as it has the potential to confer significant benefit to our cultured skin sheets (and to other cultured tissues), and help overcome the structural weakness that is a problem for grafting. We need to confirm and expand on this new finding in order to provide the evidential basis for a much larger application for external funds, to the Department of Defense, USA, who see rehabilitation medicine for wounded military personnel as a priority. Clinical applications for an agent that improves tissue structure, of course, extend to the wider community for treatment of wounds due to trauma and burns.

    Associate Professor Nicola Dalbeth The osteocyte: a mediator of bone erosion in gout? ($157,903) Abstract: Gout is the most common form of inflammatory arthritis, with very high rates of disease in Māori and Pacific men. Bone erosion is a frequent manifestation of chronic gout and leads to joint deformity and musculoskeletal disability. Our research has previously demonstrated that monosodium urate (MSU) crystals (the crystals that cause gout) promote formation of bone-resorbing osteoclast cells and inhibit survival and function of bone-forming osteoblast cells. It is likely that these interactions contribute to development of bone erosion in gout. Recently, it has become apparent that osteocytes, the most abundant cells of the skeleton, play a central role in regulation of bone mass in the postnatal skeleton.

    This project aims to understand the role of osteocytes in development of bone erosion in gout. The project will examine interactions between osteocytes and MSU crystals in vitro, and will also examine the relevance of these interactions in patients with gout. This project will extend our understanding of the mechanisms of bone erosion in this important and debilitating condition, and may provide an experimental platform for assessing treatment options for bone erosion in gout for future work.

    Dr Peter Freestone and Professor Janusz Lipski Lighting up endocannabinoid research with optogenetics; ($159,821) Abstract: Optogenetics is a recent, powerful neuroscience research methodology which has been quickly expanding worldwide, allowing neuroscientists to control neuronal activity using specific light activation. This project will be the first to establish optogenetics in the FMHS, enabling us and other researchers in the Faculty to answer new questions which cannot be resolved using conventional electrical stimulation techniques, and to keep up to date with this novel global trend in neuroscience research.

    Specifically, we will use optogenetic techniques both in-vitro and in-vivo to study the role of endocannabinoids in regulating basal ganglia circuitry in the brain – a region involved in motor control in health and disease, including Parkinson’s disease (PD). Endocannabinoids are cannabis-like substances produced in the brain where they inhibit synaptic transmission between neurons. Photo-stimulation of neurons in the Subthalamic nucleus (STn), a basal ganglia region which excites dopaminergic neurons in the Substantia Nigra (SN), will be achieved by selectively expressing the light-activated protein channelrhodopsin. This will allow us to test the specific involvement of the STn in driving endocannabinoid production in SN neurons, building on our recent discovery of a novel endocannabinoid action in this region. Optogenetics will also be used to map functional connectivity in-vitro (in brain slices) – a novel technique which the PI learnt during his recent visit to Prof. G. Augustine’s laboratory at Duke-National University of Singapore. This will enable us to precisely pinpoint the location of endocannabinoidmodulated neurons in the basal ganglia circuitry.

    In addition, we will conduct preliminary invivo experiments in freely moving rats, in which optical fibers will be implanted to activate STn neurons expressing channelrhodopsin. This approach will allow us to study the role of the STn in controlling the behavioral (motor function) outputs.

    Future study will investigate the STninduced endocannabinoid modulation of behavior in normal rats and in PD animal models (rats with 6-OHDA lesion of the nirgo-striatal pathway). This novel approach will allow us to study the role of endocannabinoids in modulating the function of the basal ganglia, and should lead to novel therapeutic strategies for PD and other basal ganglia disorders based on targeting the endocannabinoid system. In addition, introduction of these novel tools will facilitate work of several other groups within our Faculty which require specific neuronal activation.

    Professor Boyd Swinburn Benchmarking food environments: Establishing the International Network for Food and Obesity/non-communicable diseases (NCD) Research, Monitoring and Action Support (INFORMAS) and pilot testing it in New Zealand; ($156,710) Abstract. Food environments are major contributors to the increasing global burdens of obesity and noncommunicable diseases (NCDs), but are virtually absent from existing WHO global monitoring frameworks. In light of this, the applicant developed the International Network for Food and Obesity/NCDs Research, Monitoring and Action Support (INFORMAS) and launched it at the Bellagio Rockefeller Centre in November 2012. INFORMAS aims to monitor and benchmark food environments globally, and is coordinated by the applicant. The foundation papers for all monitoring modules will be published in 2013 as a supplement of Obesity Reviews.

    This application is to support the establishment of INFORMAS, to develop the protocols for its 10 modules and to pilot test six of the modules (food composition, labelling, promotion, prices, food in public sector settings and food retail) in New Zealand. The international module leaders will work with the applicant to develop the protocols and the links between modules and finalize these in a workshop in New Zealand in early 2014. Databases will be developed concurrently, and piloted using New Zealand data. This will ensure that the databases are ready to accept data from multiple countries when INFORMAS offers the protocols internationally from 2015-6.

    Having the coordinating centre for this ambitious, international research network based within the Faculty will bring benefits through increased: international funding, peer-reviewed publications and citations, impacts of research on policy and practice, reputational enhancement, projects for postgraduate students, visiting researchers, and international students. Several major foundations (Wellcome Trust, Rockefeller Foundation, Bloomberg Philanthropies, BUPA Foundation, Robert Wood Johnson Foundation) will be targeted for funding, as well as the European Union, overseas aid and national research agencies. This research program will be a major component of a proposed Centre for Global Health based in the School of Population Health and will contribute to the Global Health teaching program.

    Dr Bridget Kool Utilising a regional web-based trauma registry to support trauma quality improvement and injury prevention in the Midland region - a research collaboration; ($159,264) Abstract: The social and economic costs of injury in New Zealand are estimated to be $10 billion annually. The Midland Regional Trauma System (MRTS) is a regional network established in 2011 to ensure best practice in trauma care for patients from point of injury to optimal function. The system includes a trauma registry which enables multi-facility patient tracking with time-based measures on all significant interventions. The Trauma Quality Improvement Project (TQIP) uses data from the MRTS registry and other sources to improve the patient experience; to reduce the burden of trauma in the community; and to enable quantitative analyses of cost versus benefit for service provision.

    This project will explore the feasibility of using the MRTS data as a foundation for a programme of research that can investigate the burden of injury and the quality and appropriateness of care across the injury continuum. The project strands include investigating: 1) the completeness and comprehensiveness of the MRTS registry data and explore ways to refine, update, or expand the information base; 2) robust mechanisms to link MRTS data with emergency response team, post-discharge and rehabilitation data (ACC claims) leading to the generation of a real-time prospective injury cohort study; 3) IT processes that can increase the quality and efficiency of registry data collection; and 4) imbedding clinical decision support systems into the MRTS registry enabling the establishment of a timely and responsive quality improvement mechanism facilitating evidence-based trauma care that minimizes variations in practice and unexplained disparities in care.

    This project will strengthen existing relationships between the University and the MRTS to support the development of local capacity to collect and analyse injury related information that can be used to inform system development, focus prevention strategies, guide resource planning, and build a programme of research in this field.

    Dr Vanessa Jordan-Cole Epidemiology of randomised controlled trials of fertility treatments; ($14,600) Abstract: Although systematic reviews are considered to be gold standard source for information on the effectiveness of healthcare interventions, the methodology that is behind these reviews continues to be improved. We are interested in investigating the role that blinding and quasi randomisation plays within fertility research, included in systematic reviews. We are also interested in determining the most accurate and informative primary outcome for this research. At the moment some research assesses pregnancy rate, some live birth and more recently some research has looked at cumulative pregnancy rate. This research will add to the knowledge base that informs the methodology behind these gold standard reviews.