RENSHAW PRIZES
The Renshaw Prize is named after one of the founders of the Otago Medical Research Foundation Inc., the late Dr P.K. Renshaw. The prize of $250 is awarded to the Summer Research Student, who in the opinion of the Scientific Committee, amongst the Research Scholars supported, has made the most worthwhile contribution to medical research in that particular year. In recognition of their contribution, prize winners' names are listed below: 1970 - Mr A.G. Yule
1984 - Mr I.L. McLean
1999 - Ms J Pitchforth
1971 - Mr K.J. Davey
1985 - Miss B.C. Galland
1972 - Mr F.M. Patrick
1986 - Mr R.G. Snell
2000 - Mr J Wales
1987 - Mrs T.E. Inder
2001 - Mr M Rahimi
1974 - Mr J.C. Montgomery
1988 - Miss M. Kuipers
2002 - Ms S Jordan
1975 - Mr A.S. McLean
1989 - Miss E.R. Dennett
2003 - Ms E Szymlek-Gay
1976 - Mr N.K. Given
1990 - Miss A. Charlton
2004 - Mr D Kieser
1977 - Miss F.M.F. McQueen
1991 - Mr B. McKenzie
2005 - Mr C Young
1978 - Mr K.D. Jolly
1992 - Mr J.W. Corboy
2006 - Mr C Young
- Mr J.P. Scott
1993 - Ms S.M. Dillon
2007 - Mr S Smart
1979 - Mr R.A. Henderson
1994 - Ms N. Dalbeth
2008 - Ms S Saunderson
1980 - Mr D.W. MacFarlane
1995 - Mr T Zaharic
1996 - Mr M Morrison
1981 - Mr N.E. Dickson
1997 - Mr A Brown
2010 - Mr J Zhang
2011 - Miss E Gavey
1982 - Miss C. Page
1998 - Mr J Mangum
1983 - Mr I.L. McLean
Emma Gavey - Joint 2011 winner
of the Renshaw Prize
CHAIRPERSON'S REPORT
It is with pleasure that I present the 43rd Annual Report on the Otago Medical Research Foundation's activities for the 2011 financial year. During 2011, the Foundation funded $327,875 of medical research in Otago. This brings the total amount funded to $5,993,127 since the Foundation's inception. The extract from the Financial Statements as published further on in the Annual Report show a surplus for the year of $2,042,500. This large surplus arises mainly because of the receipt of a most generous bequest of $2,000,000 from the Estate of the late W. J (Jack) Thomson which is referred to later in the Annual Report on page 27. A condition of the Bequest was that it be used for medical research into the problems and treatment of Arthritis. To enable the Foundation to carry out this wish the capital of the Jack Thomson Arthritis Fund has been invested to provide the necessary income. The bequest sum was received at the end of the financial year so there were no income benefits in the year under review. If we had not received the $2,000,000 our surplus for the year would have been $42,500 and, as noted in previous reports, operating surpluses and deficits arise mainly as a result of the timing of grant payments. The Foundation endeavours to invest surpluses in project grants rather than build up funds but we need further injections of capital to be invested if the Foundation is to continue supporting research at the same rate as we have been. As noted last year, to help achieve this goal, the Foundation has contracted a Director of Development, Steve Davie. The publicity generated, along with the commitment of Steve, has led to some great results in generating additional income for the Foundation, and, while we are receiving additional income now, it is to be hoped that the work done by Steve will result in further additional income over the next few years and beyond. The Investment Sub-Committee has continued to face the challenge of finding suitable low risk investments while acknowledging that income and growth are also important. It is pleasing to report that at balance date, the market value of our Company Securities and Shares shows an unrealised gain on cost of $156,105, which is just over 6% of cost, with the New Zealand and Australian investments being the main contributors. Forward commitments for grants approved but not yet paid at balance date total $227,867 compared with $213,108 last year. As mentioned above, this increase is a reflection of timing issues. At 31 March, 2011, Accumulated General Funds total $355,038 and Special Funds $4,363,617, both these figures comprising Capital and Income. This year marked the 14th year in which the Otago Community Trust awarded an Annual Grant to the Foundation with the details of grants awarded from this year's funding being published further on in the Scientific Committee Report. This brings the total grants received from the Otago Community Trust to $1,080,000, a truly generous contribution. On behalf of all members of the Foundation and all researchers based in Dunedin I would like to sincerely thank the Otago Community Trust for their very generous continuing contributions. The Foundation is deeply indebted to those people who have named the Foundation as a beneficiary in their wills. Medical research is a never ending activity and the role of the Foundation will continue as long as there are medical scientists willing to ask critical questions and people willing to help fund these researchers in their quest for the vital answers. I would ask members to consider the Foundation when preparing their wills. A bequest to the Foundation will be effectively used and your influence will be felt beyond your lifetime.
Thanks
• Firstly, to all those Trusts, Companies, Individuals, Members and Non –Members listed
further on in this Annual Report who have supported the Foundation in the year under review. The period since September, 2010, has seen a huge call on the generosity of the people of New Zealand to support the many disasters that have occurred and the Foundation is very grateful that it has continued to receive the support that it has.
• To Emeritus Professor Barbara Heslop who kindly agreed to become the Foundation's first
Patron. Although this appointment was confirmed after the end of March, it would be remiss of me not to mention it in this report. The Foundation is indeed fortunate to have such an eminent person accept the office
• To my fellow Investment Sub-Committee members, Mike Horne, Ron Lewis and Jenny
McMahon for their wise counsel, advice and time so willingly given to serve on this Sub-Committee. Thank you most sincerely.
• To Steve Davie, our Director of Development, for his commitment to the Foundation in
securing grants and donations from various organisations and Trusts, as well as laying the groundwork for future contributions. We are indeed fortunate to have such a committed person as Steve working for the Foundation, informing people of our presence and what we have done and are doing in the field of medical research.
• Special thanks must be recorded to the members of the Scientific Committee, who,
although all busy with their own career activities, still manage to find the time to provide professional assessment and advice on three rounds of applications and then make their recommendations to the Council. Without this group of dedicated people we would not be able to achieve the object of the Foundation, "The Furtherance of Medical Research in Otago".
• No mention of the Scientific Committee is possible without acknowledging the
contribution of the Chairperson, Associate Professor Patricia Cragg. Having been associated with the Foundation on the administration side for many years I am very much aware of the tremendous amount of work undertaken for the Foundation by Pat since she became Chairperson of the Scientific Committee in November 1992. Pat, your contribution has been immense and we thank you most sincerely.
• To all Council Members, for your contribution and support, my sincere thanks. While
writing this report I was sorry to receive the resignation of Geoff Adams who advised that he will not be standing as an elected member at the AGM. Geoff has been an elected member since November 1992 and served as Chairperson from 23 October, 2007 until 13 December, 2010. Geoff very kindly agreed to take on this position when long standing Chairperson, Mr Peter Gibson was unable to continue for health reasons and the Foundation is grateful to Geoff for doing this. Geoff's contributions around the Council table will be missed and we wish him well for the future and his association with the Dunedin Public Art Gallery Association Council and the Otago Art Society.
• To the Deloitte team, Mike Horne, Louisa Homersham and Jason Grimstrup for continuing
to provide very professional and efficient administration services for the Foundation.
On behalf of the Council
Ken Dempster
Chairperson
REPORT FROM THE DIRECTOR OF DEVELOPMENT
After a solid first 12 months in the role where $162,000 in ‘new' funding
was generated, momentum continued strongly through to the end of the
2010/2011 financial year.
Included in the funding attracted was a $2 million bequest from the estate
of Jack Thomson, this leading to the establishment of the Jack Thomson
Arthritis Fund. Jack's benevolence will result in a significant grant round
being awarded each year (from December 2011) to assist with on-going
research into all manner of arthritis related issues.
The Bequest Society will, in time, play a major role in the continued
growth of the Foundation and its ability to identify and nurture world-class medical research.
While the Jack Thomson Arthritis Fund clearly displays what can be achieved, it is also worth
noting that bequests are affordable to us all and are extremely simple to put in place. No bequest is
too small or unworthy of consideration.
Great strides were made during the year in developing relationships with individuals, businesses
and those in the gaming machine and charity sectors. As a result a number of individuals are now
regular benefactors, business owners have lent their support through ‘sponsoring' annual summer
research scholarships, several gaming machine trusts have made more than one donation, and a
growing number of those within the charitable industry are financially supportive of the
Foundation's vision.
After the success of the inaugural Foundation golf tournament last October, the bar has been lifted
through a partnership with OceanaGold, which has signed on as the naming rights' sponsor for the
next three years. The funds generated through the tournament will now open the way for a
significant research grant to be made available annually. In addition to that support OceanaGold
has also agreed to take on an annual summer research scholarship.
Other highlights during the year, or leading into the new financial period, were the appointment of
Emeritus Professor Barbara Heslop as the Foundation's first Patron (Barbara is one of New
Zealand's pre-eminent medical researchers and we are delighted she has agreed to take on the
role), and the establishment of a dedicated fuel card, which offers users a generous discount on
fuel purchases while opening the way for a rebate to the Foundation's capital base.
As noted in last year's report - philanthropy and its process represent a ‘long game' but we are
already seeing the benefits of the building of relationships and the developing of trust.
Steve Davie
Director of Development
INAUGURAL GOLF TOURNAMENT
As the Foundation set about establishing a calendar of events, the inaugural golf tournament was
played on the St Clair course in Dunedin.
A field of 92 assembled for the first-up event with the weather fine and the course in superb condition.
All 18 holes were sponsored, a number of prizes were donated and a profit for the day of just under
$6,000 was recorded.
Our thanks to our hole sponsors – Dunbar Orthopaedics Ltd, Mr Simon McMahon Orthopaedic
Surgeon, Dr John Greaves & Keith Newton (Mornington Health Centre), Associate Professor
Patrick Dawes (Otolaryngology Head & Neck Surgery, University of Otago), Dr David Peart
(Ophthalmologist), Sport Otago, Dr Alan Wright (Southern Neurology Ltd), Associate Professor
Dr Jim Reid (RMC Medical Research Ltd), Orbit Corporate Travel, Forsyth Barr Ltd, Parker
Warburton Team Architecture, Silicon Coach, Deloitte, Southern Colour Print, Dr Brian
McMahon, OceanaGold Ltd, Body Synergy Gym, Speight's Brewery.
Prizes were donated by Remarkable Golf Tours (Queenstown), Rydges Lakeland Resort
(Queenstown), Dr Jenny McMahon, Wattyl New Zealand, The Rugby Channel (Sky Television),
Southern Honda, Speight's Brewery, Liquor King Hillside and Cadbury Confectionery.
The day's results were:
1st – Forsyth Barr, playing off a handicap of 5.75, finishing with a nett score of 54.25
2nd – Sport Otago, 4.627, 54.375
3rd – The Radio Network, 9.25, 55.75
4th – Dr David Peart's team, 10.25, 55.75 (on count back)
5th – Aaron Campbell's team, 9, 56
6th – Speight's Brewery, 4.125, 56.875
7th – Silicon Coach, 9, 57.5
8th – OceanaGold, 9.5, 57.5
9th – Southern Colour Print, 8.5, 57.5 (on count back)
10th – Southern Neurology, 9.75, 58.25
Closets to the pin:
4th – Brent McEwan, 7th – Geoff Long, 13th – Bruce Hodgson, 16th – Ken Rust
Longest drive (18th):
Robert McIntosh
Foundation chairperson Geoff Adams (right) presents members of the winning team at the 2010 Otago Medical Research
Foundation golf tournament with their prize – a voucher for a weekend's golf at Jack's Point and Millbrook Resort. The
team members (from left) are Richard Roberts, Adam Gain, Brent McEwan and Peter Young.
SCIENTIFIC COMMITTEE REPORT
1 April 2010 To 30 September 2011
1. MEMBERSHIP
Chairperson: Associate Professor P.A. Cragg (Nominee of the Otago School of Medical Sciences) Dr S. Bunn (President Otago Medical School Research Society, ex officio) Dr T. Conner (Co-opted) Dr G. Giles Dr P. Gootjes (Nominee Otago Branch of the NZ Medical Association) Dr R.J. Hancox (Nominee Dunedin School of Medicine) Dr N.C.K. Heng (Co-opted) Associate Professor G. Jones (Nominee Otago Medical School Research Society) Dr B. Leitch (Co-opted) Dr D.M. Markie (Co-opted)
Associate Professor R.T.M. Poulter (Co-opted)
Assoc Prof Pat Cragg
Professor T. Rades (Co-opted)
Professor C. Ronson (Co-opted)
Dr P.M.L. Skidmore (Nominee Otago Medical School Research Society)
Professor R.J. Walker (Co-opted)
The Scientific Committee is primarily concerned with adjudicating on applications for Research
Grants and on applications from students for Summer Research Scholarships. To cover the breadth
of topics submitted, the Committee is relatively large to ensure it has representatives from all the
major sub-disciplines of medical research.
In late 2009 there was one retirement from the Scientific Committee, Dr Merilyn Hibma and we
thank her for all her contributions since she joined the committee in 2008 initially as a nominee of
the Otago Medical School Research Society (OMSRS) and then as its President. For 2010 we
welcomed Dr Stephen Bunn the new President of OMSRS.
Note: Most, but not all research projects, have protocols that require approval by the appropriate
Ethics or Safety Committee prior to commencement of the research. Agreement by the Foundation
to fund research projects is thus subject to receipt by the Scientific Committee's Chairperson of a
letter from the University of Otago Animal Ethics Committee, the University of Otago Human
Ethics Committee or the Ethics Committee of the Health Funding Authority indicating that the
research has received full ethical approval. Work involving genetically modified organisms
requires evidence of approval from ERMA or from the University of Otago's Institutional
Biological Safety Committee.
The scientific activities of the Foundation (advertising of up-coming grants and listings of awards)
can be found on the following web site
2. SUMMER RESEARCH SCHOLARSHIPS 2010/2011
One hundred and thirty-seven applications (compared with 123 the previous year) were received
from the University of Otago, of which 20 were recommended for funding by the OMRF (and 113
gained scholarships from other funding bodies). Of the 20 students funded by the OMRF, eight are
studying medicine, six science, one biomedical science, two a postgraduate diploma, one dentistry,
one physical education and one medical laboratory science. It should be noted that the ten-week
summer research is not part of the study required in a student's tertiary qualification and any data
obtained during the summer research cannot contribute to the dissertation or thesis of such a
qualification.
Due to matched funding from the University the Scholarships were each worth $5,000 including
the two highest scorers who were awarded named Summer Research Scholarships – named in
honour of the late Allan Wilkinson and the late Emeritus Professor Garth McQueen. Allan was
Secretary of the Foundation from its inception in 1967 until his retirement in 1993 and Garth was a
foundation member of the Foundation and one of the instigators of the formation of the
Foundation's Auxiliary. One of the projects was funded from the Foundation's Iverach Fund and another was administered by the OMRF but sponsored by the Otago Diabetes Research Trust. Due to the sponsorship drive of the OMRF seven of the other 16 OMRF scholarships were funded by Deloitte Touche Tohmatsu Limited, Foodstuffs Community Trust, Kingston Sedgfield Charitable Trust, OceanaGold (2), Otago Service Clubs Medical Trust and WHK. This new source of funding and the involvement of Otago commercial companies and the community in supporting summer research by tertiary students is a wonderful initiative. All scholars returned good to excellent reports. The Renshaw Prize ($250) for the best report was awarded this year to three students: Emma Gavey, who worked under the guidance of Dr James Crowley of the Department of Chemistry; Edward Ottley, who worked under the guidance of Dr Elspeth Gold of the Department of Anatomy; and William Parkyn, who worked under the guidance of Professor Andre van Rij of the Department of Surgical Sciences. The following is a list of the summer scholars and summaries of the projects undertaken – additional information on these projects can be obtained from the Chairperson of the OMRF Scientific Committee or from the supervisor concerned.
Emma Gavey (Dr James Crowley, Department of Chemistry)
Title: Development of a molecular cage for the targeted delivery of cisplatin
(Garth McQueen Summer Scholarship and Renshaw Prize Winner)
Cisplatin is the most widely used platinum(ll)-based anticancer drug, but its administration is limited by
resistance and toxicity. To help circumvent these issues, this project aimed to develop a palladium-based
molecular cage for the targeted delivery of cisplatin. Targeting was to be achieved by the attachment of
biological groups to the cage. I initially investigated the binding of a variety of biologically-substituted
molecules to palladium, before successfully synthesising a ligand (side of the cage) which was
functionalised by the attachment of a sugar group. This provided proof of principle that the cisplatin-
containing cage may be bio-targeted.
Edward Ottley (Dr Elspeth Gold, Department of Anatomy)
Title: Are activins a potential therapy for advanced prostate cancer?
(OceanaGold – Prostate Cancer Scholar; and Renshaw Prize Winner)
Prostate cancer (PCa) is a worldwide health concern of which there are two types, organ-confined and
aggressive-metastatic disease. Activin A is a negative growth regulator in the prostate, whose bioactivity is
regulated via antagonists. Activin C is a novel antagonist of activin A, and overexpression leads to mouse
prostate pathologies. Thus we proposed increased activin C is associated with aggressive PCa. Via
immunohistochemistry and stereological methods this mechanism was examined in the mouse and human.
Results indicate increased expression of activin C is associated with advanced PCa and may therefore offer
novel therapeutic options for the treatment of aggressive PCa.
William Parkyn (Professor Andre van Rij, Department of Surgical Sciences)
Title: Skin problems in the lower legs of morbidly obese patients and the possible role of
bariatric surgery
(OceanaGold – Obesity Scholar; and Renshaw Prize Winner)
Bariatric surgery appears to cure skin problems in the legs of morbidly obese people. This study compared
the prevalence of symptoms before and after bariatric surgery. The prevalence of symptoms such as
swelling, itchiness, eczema and ulcers was established in a group of morbidly obese patients awaiting
surgery and then compared with those having had bariatric surgery. Rates of all problems were significantly
lower in the post-surgery group except for the prevalence of varicose veins. Morbidly obese people do have
significant problems with the skin in their legs for which bariatric surgery provides a cure in over half of the
cases.
Julia Aratmonova (Dr Nick Heng, School of Dentistry)
Title: Finalising the genome sequence of the oral bacterium Streptococcus salivarius strain
M18
Streptococcus salivarius, an important human oral bacterium usually associated with good oral health, is a
suitable species for development as oral probiotics. In this project, the existing draft genome sequence of S.
salivarius Ml8, an oral probiotic candidate, was verified with respect to its genetic annotation. In addition,
several genomic gaps were closed by sequencing of gap-bridging PCR amplicons. The newly-obtained
sequence data indicates that the organisation of the S. salivarius M18 chromosome differs significantly from
that of the Streptococcus thermophilus and S. salivarius SKI26 reference genomes. These organisational
differences may have resulted from chromosomal inversion events.
Isaac Bernhardt (Professor John Highton and Dr Simon Stebbings, Department of Medicine; and
Dr Sarah Young, Department of Pathology)
Title: Dendritic cell responses to bacteroides in ankylosing spondylitis
(J.A. Iverach Summer Scholar)
Ankylosing spondylitis is a disease that causes spinal inflammation and significant disability in younger
people. Treatment options for this disease are currently limited or have potentially serious adverse effects.
Previous work by our group and others has shown that the cause of ankylosing spondylitis may be related to
an abnormal immune response to normal bacteria in the intestine. In this project we attempted to compare
the interaction between normal bowel bacteria and dendritic cells in patients with ankylosing spondylitis and
normal controls. Technical difficulties with the dendritic cell culture meant that limited data was produced.
Further work is thus required to answer our research question.
Caillan Crowe-McAuliffe (Dr Elisabeth Poole and Professor Warren Tate, Department of
Biochemistry)
Title: Can cellular location indicate the function of a highly unusual human gene involved in
embryo development and cancer?
Paternally Expressed Gene 10 (PEG10) is a highly unusual gene found in placental mammals. It is essential
for placental development and can function inappropriately to enhance growth in some cancers. Although
some functions of PEG10 have been discovered, it is still largely unknown what this gene does in the cell.
This study developed a method that uses microscopic fluorescence to look at where within cultured liver
cancer cells PEG10 is localised. This will allow a closer assessment and understanding of aberrant PEG10
activity in cancer.
Sijing Feng (Dr Torsten Kleffmann, Associate Professor Sally McCormick and Dr Anne von
Zychlinski Kleffmann, Department of Biochemistry)
Title: Quantitative comparison of lipoprotein(a)-associated proteins by mass spectrometry in
subjects with and without cardiovascular disease
An increased amount of lipoprotein (a) [Lp(a)] in plasma has been found to be a significant contributor to an
increased risk of developing cardiovascular disease (CVD). In this project, I performed mass spectrometry-
based analyses to identify and quantify Lp(a)-associated proteins between CVD and non-CVD subjects
which may contribute to a higher risk of developing CVD. Complement protein C8 was found only in the
non-CVD subject and there was an increased apoE level in the HDL fraction in the CVD subject compared
with the non-CVD subject. These findings suggested a set of complex relationships between Lp(a)-
associated proteins and CVD pathogenesis.
Joseph Foster (Dr Geoffrey Tompkins, School of Dentistry; Dr Jo-Ann Stanton and Dr Hallie
Buckley, Department of Anatomy)
Title: Can ancient dental deposits provide archaeological clues?
(Deloitte Touche Tohmatsu Limited Scholar)
This project aimed to develop a method for extracting bacterial DNA preserved in prehistoric dental
calculus. Oral bacterial DNA sequence information could be useful in indicating interactions between
contemporary individuals. Calculus was removed from extracted teeth and demineralised. Released bacterial
DNA was amplified by polymerase chain reaction and DNA fragments of the expected size were generated
from some but not all samples. It was evident that the calculus was not fully demineralised and therefore
may not be releasing DNA from all samples. These initial results will encourage further studies, initially
aimed at improving calculus demineralisation to increase DNA release.
Melanie Grant (Dr Sarah Young, Department of Pathology)
Title: Activating cancer patients' immune systems against their tumours: Dendritic cell
activation of antigen-specific T cells
This study aimed to investigate the ability of different antigen-primed dendritic cell (DC) populations to
activate antigen-specific CD4+T cells. The key results were that CD11c+DCs exposed to LPS or OVA
antigen take on activated phenotype and that antigen-specific T cells can be activated by these DCs. The
study results concurred with current knowledge but more time was needed for experimental refinement and
looking at other DC sub-populations.
Kimberley Hughes (Dr Heather Brooks, Department of Microbiology & Immunology, and Dr Jon
Cornwall, Department of Surgical Sciences)
Title: Potential infectious agents that exist on non-sterile gloves in a hospital setting
The aim of this study was to isolate and identify potential infectious bacteria found contaminating unused
nonsterile disposable gloves in a hospital setting. Fresh boxes of gloves were placed in various rooms in
Dunedin Public Hospital and samples were taken every 72 hours for 9 days. A total of 12 boxes were
sampled allowing for 41 glove sets to be analysed for bacterial contamination, 39 of which were found to be
contaminated by various bacteria. Bacterial counts and identification were carried out using standard
microbiological procedures. Common hospital-acquired infectious bacteria isolated included coliforms,
staphylococci, enterococci, streptococci and Pseudomonas species. This study highlights the importance of hand
and environmental hygiene in the hospital and shines light on a potential new source of hospital-acquired
infections.
Victor Komarovsky (Professor Gregory Cook and Dr Jenny Robson, Department of Microbiology &
Immunology)
Title: Uncovering the mode of action of TMC207: a new drug in the fight against tuberculosis
(Allan Wilkinson Summer Scholarship)
A new anti-tuberculosis drug currently in clinical trials, Tibotec Medicinal Compound 207 (TMC207), exhibits
high bactericidal activity against mycobacterial strains. While the molecular target of TMC207 is known (F
1F0-ATP synthase), the mechanism whereby the drug kills mycobacterial cells remains unknown. This study
investigates the msmeg_6554 and msmeg_6553 genes, previously identified as being important to the TMC207
susceptibility of Mycobacterium smegmatis, by producing markerless knock-outs of each, forming the basis of
further investigation. This information may lead to a better understanding of the mechanism of killing of
Mycobacteria, and to the development of better anti-TB drugs to combat the global threat of TB.
Beom Jun Lee (Dr Noelyn Hung and Dr Tania Slatter, Department of Pathology)
Title: Telomere damage and chrosomal instability in early breast cancer
(WHK Scholar)
Hypoxia is a well recognised microenvironmental selection force during somatic evolution in breast
carcinogenesis and links DNA damage responses and genomic instability, especially in the guanine-rich
telomere regions. The onset of hypoxia was to be demonstrated by the correlation of hypoxia markers, e.g. CA9,
in proliferative to neoplastic breast tissues with telomere damage/repair shown by γH2AX/ 8-oxo-G foci
immunohistochemistry but unfortunately the results for CA9 and 8-oxo-G staining were not appropriate for
interpretation for reasons explained in the report, making it impossible for further analysis. As for γH2AX
staining, the cases that showed positivity, including one benign case, seemed to be of younger population with
less aggressive features of carcinogenesis leading to an implication that could be further investigated by another
study with bigger sample size.
Keith LEE (Dr Andrew Bahn, Department of Physiology)
Title: Characterisation of primary human kidney cell lines as a model to study the control of
urate transporters by miRNAs
The purpose of my summer research was to determine the endogenous expression of urate transporters GLUT9,
OAT2 and ABCG2, which are essential for maintaining urate homeostasis, using Human Renal Cortical
Epithelial (HRCE) cells which resemble the proximal tubule in the human kidney, and examine the effect of
miRNAs in regulating the expression of these urate transporters. Results showed that GLUT9 was highly
expressed in HRCE cells in comparison to OAT2 and ABCG2 which may indicate its cellular specificity.
Endogenous expression of miR-153 was inversely proportional to that of GLUT9 indicating that miR-153 could
be involved in down-regulation of GLUT9.
Sze Ying Leong (Professor Indrawati Oey, Department of Food Science)
Title: Evaluation of phytochemical compounds in seasonal fruits and vegetables grown in the
Otago region during summer
(Foodstuffs Community Trust Scholar)
The purpose of this study was to evaluate the content of phytochemicals (anthocyanins, carotenoids, vitamin C)
in fruits and vegetables (e.g. cherries, nectarines, apricots, peaches, plums and peppers) grown in the Otago
region (e.g. Cromwell, Roxburgh, Mosgiel and Clinton). These commodities
contained different types and contents of phytochemicals. Furthermore, different food preparation methods, i.e.
blanching (98°C, 10 minutes), freezing (-20°C) and freeze-drying, affected the retention of phytochemicals. In
general, freezing resulted in the highest retention of phytochemicals. Hereto, consumption of varied fruits and
vegetables in daily diet is highly recommended to provide sufficient access to numerous phytochemicals for
their potential health benefits.
Annie Manning (Associate Professor Patrick Manning and Dr Claire Robertson, Department of
Medicine)
Title: Diabetes and abnormal glucose tolerance in women with previous gestational diabetes in
New Zealand
(Otago Diabetes Research Trust Scholar)
Gestational diabetes mellitus (GDM) is a condition in which women exhibit high blood glucose levels during
pregnancy. These women are at increased risk for the future development of Type-2 diabetes and should
undergo diabetes screening annually. After investigating women in the Otago region with GDM, we found that
65.6% underwent screening for Type-2 diabetes postpartum with a mean time to the first screen of 17.2 months.
The prevalence of Type-2 diabetes in our study was 1.9% at 6 weeks after birth increasing to 15% by 20
months. These results indicate that future diabetes is prevalent amongst women with previous GDM and that
improvements in postpartum screening are required.
Bridget Mcilraith (Dr Sandy Mandic, School of Physical Education)
Title: Physical activity habits and physical function in older adults participating in
community-based cardiac rehabilitation
(Otago Service Clubs Medical Trust Scholar)
While short-term benefits of cardiac rehabilitation (CR) are well documented in cardiovascular disease
(CVD) patients, less is known about long-term effects of CR. We compared the physical activity habits and
physical function in elderly individuals participating in community-based CR (with CVD (CR-CVD, n = 61)
and without
CVD (CR-noCVD, n = 16)) and 25 apparently healthy individuals (NoCR). NoCR participants had better
functional capacity and muscular strength but not physical function compared to CR groups. No significant
difference in functional capacity, physical function and physical activity habits was found between CR-CVD
and CR-noCVD. Therefore, elderly individuals should be encouraged to participate in community-based CR.
Nicole Neverman (Dr Stephanie Hughes, Department of Biochemistry)
Title: Investigating a new link between the transcription factor Fezf2 and the anti-epileptic
drug valproic acid
(Kingston Sedgfield Charitable Trust Scholar)
Fezf2 is a protein critical in the development of a subset of neurons in the brain. Evidence suggests that
alterations in Fezf2 expression during development, caused by either genetic polymorphisms or certain
environmental factors, contribute to autism, one such environmental factor being valproic acid (VPA). This
study aimed to determine whether VPA-induced autistic mice show changes in Fezf2 expression in the
motor region of the brain. Fezf2 expression was able to be visualised using transgenic mice that express
green fluorescent protein (GFP) under the control of the Fezf2 promoter. The results showed that VPA
exposure lead to different effects in different animals including the absence of Fezf2, an ill-defined Fezf2
positive band in the motor cortex, incorrect neuron location, and disruptions to neuronal dendrites. These
findings suggest that VPA leads to major motor cortex defects and is therefore a dangerous drug for women
in the early stages of pregnancy and suggest a mechanism whereby VPA can induce autistic phenotypes.
Heather Norton (Dr Roland Broadbent, Department of Women's and Children's Health, and
Professor Gerald Tannock, Department of Microbiology)
Title: Probiotics for preterm babies: how and why would we start a new treatment regime?
This research explores the process involved in initiating a probiotic regime in the Neonatal Intensive Care
Unit of Dunedin Hospital, as well as investigating the bacteria that colonise the pre-term gut. This study
aims to make comparisons between 6 pre-term and 4 full-term infants, analysing their stool to determine the
complexity of the bacterial colonisation of the gut. Microbiological study showed that all infants, regardless
of gestational age, have few types of bacteria in their gut, but these types varied. Full-term infants had a
higher proportion of Bifidobacterium, a bacterium found in probiotics, which may be protective against the
development of disease.
Bernard Teo (Dr Mary Jane Sneyd and Associate Professor Brian Cox, Department of Preventive
& Social Medicine)
Title: The effect of latitude on the incidence and mortality of melanoma in New Zealand
The effect of latitude on the incidence and mortality of melanoma in the non-Maori population in New
Zealand during 1996-2006 was examined. Registrations and deaths from melanoma, and population counts
were grouped into four regions defined by latitude. The incidence and mortality rates were compared using
Poisson log linear regression. The most southern region had 16.9% lower incidence rates compared with the
most northern region. Incidence increased over time for all latitude regions except the most northern region.
Mortality rates only increased in most southern region. The latitude gradient seen previously in New Zealand
for melanoma incidence is no longer so clear-cut.
Matthew Versteeg (Professor Cliff Abraham and Dr Bruce Mockett, Department of Psychology)
Title: Exploring abnormal brain function in Alzheimer's disease
Alzheimer's disease (AD) is a progressive, fatal neurodegenerative disorder that is associated with low levels
of neuroprotective protein secreted amyloid precursor protein-alpha (sAPPα). The aim of this study was to
investigate the sAPPα role in an aspect of synaptic plasticity regulation (metaplastcity). This was done by
utilising TNF-α protease inhibitor-1 (TAPI-1), a drug that prevents sAPPα activation, and
dihydroxyphenylglyceine (DHPG), the drug used to induce metaplastic priming (expressed by an initial
synaptic depression). TAPI-1 caused a reduction in the transient synaptic depression caused by DHPG.
However sAPPα involvement in the persistent expression of metaplastic priming could not be assessed due
to experimental limitations.
3. RESEARCH GRANTS AWARDED
(a) Annual grants and Otago community trust grants
These one-year grants are for research concerned with human health and the scientific basis of
medicine. In June 2010 there were 34 applications from the University of Otago (cf 27 the previous
year) totalling $785,228 and ten of these were funded at a total expenditure of around $185,000 of
which $75,000 was provided most generously by the Otago Community Trust.
(i) Annual Grants
Dr H. Hussaini, Professor G. Seymour and Associate Professor A. Rich (School of Dentistry)
Potential benefit of immunological biomarkers in predicting oral
cancer progression and spread – AG 290
Oral cancer cells establish themselves after gaining the ability to escape from
the immune system. Various escape mechanisms have been proposed, but the
precise means of evasion are not fully understood. Our study investigated
these escape mechanisms in archival tissues of primary oral cancer as well as
in the lymph nodes of the neck, the usual site of oral cancer nodal metastasis,
by the analysis of gene expression on cancer cells and tumour-associated
immune cells. We were able to derive informative gene expression data from
archival tissues. Early results indicated, for the first time in oral cancer, that
there was an equal or more profound escape mechanism in place in
metastatic lymph nodes, in comparison with the primary oral cancer site. The
difference in the escape mechanisms between the primary site and the lymph
nodes creates a gradient that might facilitate the progression of cancer cells
to cervical lymph nodes.
Haizal Hussaini extracting genetic
information from paraffin embedded
Dr P. Jones (Department of Physiology)
blocks of oral cancer using PCR
Understanding the molecular mechanism by which mutations in
RyR1 lead to malignant hyperthermia – AG 291
Malignant hyperthermia (MH) is an autosomal dominant, life-threatening, pharmacogenetic disorder. It affects
the skeletal muscle of patients (1:15000-50000) in response to volatile anaesthetics during surgery. It has
particular importance in New Zealand, as some regions have an incidence as high as
1:200. The most commonly mutated protein in MH is the skeletal muscle ryanodine receptor (RyR1). How
mutations in RyR1 lead to MH is poorly understood. Using in vivo muscle electroporation we have successfully
expressed MH mutant RyR1 proteins in rat skeletal muscle. We have also used this technique to express a
variety of probes used to measure the impact of RyR1 MH mutations on skeletal muscle function. We have,
therefore, established a novel model for studying RyR1 MH mutations in situ. Accordingly, we are now using
this model to study the impact of the most common RyR1 MH mutation. Understanding the molecular
mechanism underlying MH may lead to improved treatments for this life-threatening disease.
Dr R. Kemp (Department of Microbiology & Immunology)
How do immune memory cells stay alive? – AG 292
During infection, an immune response is generated that clears the invading pathogen. At the end of this process,
a memory population of T cells remains, and these cells are faster to respond to a re infection by the same
pathogen. The memory T cell population is maintained by a family of cytokines that control survival and
proliferation at a molecular level. Our research investigated how these cytokines signal the memory cells to stay
alive or to proliferate by looking at the downstream signaling pathways that are triggered. We found different
roles for the cytokines in maintaining memory T cells – these could be manipulated to improve memory
responses to vaccines.
Dr D. Schwenke (Department of Physiology)
Blood vessel dysfunction in pulmonary hypertension – AG 293
The pulmonary blood vessels are finely regulated intrinsically by the vessel endothelium, which releases various
vasoactive substances to act upon the surrounding smooth muscle layer to either dilate or constrict vessel calibre
and, thus, regulate pulmonary blood flow. Impairment of these signalling pathways either within the
endothelium or the vessel smooth muscle can potentially culminate in the development of pulmonary
hypertension (PH). This project aimed to assess specifically the nitric oxide (NO) vasoactive pathway of the
pulmonary endothelium, as well as the Rho-kinase pathway within the vascular smooth muscle, for modulating
pulmonary blood flow distribution during the development of PH. Experiments were conducted at the SPring-8
facilities in Japan, which provides the use of synchrotron radiation microangiography for visualising the
pulmonary micro-vessels of normal and PH rats, in vivo. We assessed dynamic changes in the internal diameter
(ID) of pulmonary vessels (ID range 80 – 500 µm) in response to intravenous administration of i) the Rho-
kinase inhibitor, fasudil (10 mg/kg), ii) acetylcholine (ACh, 3 µg/kg/min), iii) sodium nitroprusside (SNP, 5
µg/kg/min) and iv) Nω-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg). The results showed that fasudil
improved pulmonary blood flow distribution and reduced pulmonary pressure in PH rats, not only by
dilating already-perfused vessels (ID >100 µm), but also by restoring blood flow to vessels that had
previously been constricted closed (ID <100 µm). Endothelium-dependent vasodilation (i.e. in response to
ACh) was impaired in PH-rats primarily in vessels with an ID <200 µm. Moreover the vasoconstrictor
response to NO inhibition (i.e. by L-NAME) was accentuated in PH-rats, but only in the 200-300 µm
vessels. These results highlight the importance of Rho-kinase-mediated control and endothelial control of
pulmonary vascular tone in PH. Indeed, an effective therapeutic strategy for treating PH should target both
the smooth muscle Rho-kinase and endothelial pathways.
Dr J. Tyndall (Department of Pathology), Professor R. Cannon and Dr E. Lamping (School of
Dentistry)
New azoles for emerging fungal pathogens – AG294
Our aim is to investigate the structure of the important enzyme CYP51, the target for azole antifungal drugs.
We have successfully manipulated the CYP51 gene from Candida albicans in order to express the protein in
E. coli. This has proved problematic as the protein is degraded. However, using S. cerevisiae as an
expression host has proven to be far more promising. We have successfully expressed and purified soluble
CaCYP51 protein. We have also shown this to be relatively stable. In addition we have had some success in
expressing and purifying the same enzyme from a similar fungal species. Crystallisation of both enzymes
will be commenced following production of sufficient quantities of protein with a view to structure
determination.
Dr S. Young (Department of Pathology), Dr C. Jackson and Associate Professor M. Thorn
(Department of Medicine)
Enhancing tumour-associated immune responses in cancer – a new treatment strategy – AG
295
Colorectal cancer (CRC) is New Zealand's most common (non-skin) cancer, and the second leading cause of
cancer-related mortality, ahead of both prostate and breast cancer. Current treatments for tumours include
surgical resection, radiotherapy and chemotherapy (including monoclonal antibodies). Whilst these therapies
have resulted in improved survival, over 80% of patients with metastatic disease remain incurable and
therapies are aimed at life extension and palliation. Immunotherapies are a new candidate for the treatment
of cancer and are based on the principles of vaccination. Harnessing the immune system to combat cancer is
an attractive strategy because it has the potential to (a) selectively destroy only tumour cells bearing specific
tumour-associated antigen and (b) to generate immunological memory for that particular tumour and thus
prevent reccurrence.
This project investigated ways to harness the immune system and target it against CRC. We aimed to isolate
a population of immune cells important for tumour destruction, called T cells, then to activate these T cells
against the tumour and then transfer them into the tumour-bearing host to assess whether they could kill the
tumour. In cancer patients we have pioneered a way to identify the sentinel lymph node(s) draining the
primary tumour site and the metinel node(s) draining metastasis from liver, lung and skin. In addition we
have shown that T cells isolated from these nodes are predominantly populated by CD4+ Th cells. This
research proposal aimed to mimic these studies in an animal (mouse) model of CRC. This model is
advantageous as immunologically the response seen in humans is similar in mice. However with the mouse
model we have the capacity to utilise different strains of mice to determine a number of different aims.
These included to define the best way to activate the Th cell in vitro; to treat the tumour in various ways
before activating the T cells, to determine the mechanism of action of the T cells and to assess the best time
to administer the T cell therapy after chemotherapy.
To date we have determined the best mix of immune hormones (cytokines) required to activate Th cells in
vitro. We have shown that addition of a combination of IL-2, IL-7 and IL-15 induces specific proliferation of
Th cells and also drives them into a memory Th cell. This means that the Th cells will be long-lived when
transferred into the host. We have also shown that irradiating the tumour cell before lysate production
enhances the T cell response. We are currently determining whether these T cells can control tumour growth
after adoptive transfer and how well this therapy works with chemotherapeutic agents oxaliplatin and
capecitabine.
(ii) Otago Community Trust Grants
Associate Professor Anita Nolan (School of Dentistry) and Dr Rebecca Roberts (Department of
Biochemistry)
Can the pain and cost of Crohn's disease be reduced by examining the mouth? – CT 294
The significance of the relationship between oral lesions and intestinal lesions in Crohn's disease (CD)
patients is unknown, although it is reported that oral signs may reflect disease activity in CD. The aim of this
study is to establish the prevalence of oral lesions in CD patients and to evaluate the accuracy of a Patient
Self Reporting Questionnaire (PSRQ) to screen for oral lesions in CD patients. This study will investigate if
patients who manifest the oral lesions of CD are genetically different from those without such lesions.
Nearly 80 CD patients attending Gastroenterology Clinics in Otago have already completed a PSRQ on current
and past history of oral lesions and have had an oral mucosal examination undertaken.
These participants have also consented to have genetic testing undertaken and have completed questionnaires on
Oral Health Related Quality of Life and Environmental Factors. The preliminary results from this research show
that 60% of these CD patients report a history of mouth lesions that could be described as "Oral Crohn's".
Within this group, 73% stated that their mouth lesions occurred before or around the time of onset of bowel
symptoms and 25% experience Oral Crohn's when a relapse of their intestinal CD occurs. The results of
genotyping are not yet available, although DNA has been extracted from samples.
The preliminary results of this project suggest that "Oral Crohn's" is a significant marker of intestinal activity in
CD. The results of the genotyping may give us further insight into the relationship between oral lesions and CD.
The PSRQ is not yet validated, but could potentially be a practical and cost-effective screening tool for oral
lesions in CD patients. In the future, detection of Oral Crohn's lesions may be regarded as an indication for
early medical intervention in CD management and might reduce future patient suffering and healthcare costs.
Associate Professor Tony Poole (Department of Medicine) and Professor Michael Eccles
(Department of Pathology)
Primary cilia defect in kidney disease – CT 295
Meckel-Gruber syndrome (MKS) is a lethal recessive disorder involving kidney, liver, central nervous system and limb malformations. Recent studies show the disease proteins in MKS are associated with the primary cilium, a single, hair-like, cellular organelle that projects into the kidney nephron and is mechanically deflected by urine flow to mediate renal function. Defects in proteins involved with ciliary structure and function perturb a range of cell signalling mechanisms, resulting in cyst formation and extensive fibrotic scarring. We have now characterised an Otago-based sheep flock that carries a mutation in the MKS3 gene coding for the ciliary
Professor Tony Poole
protein meckelin, and has a clinical presentation very similar to human patients with MKS3 mutations.
Our studies indicate that the ovine model we have developed is the first large animal model of Meckel-Gruber
syndrome, and that it offers the potential to interrogate the role of primary cilia defects in human disease. In
particular, new collaborations developed during the course of this project will begin to examine neurological
defects in the brains of these animals, since animal models such as C. elegans, zebrafish, and even rodents, do
not offer sufficient neural complexity to fully study the neurological defects associated with Meckel-Gruber
syndrome in humans.
Associate Professor Rhonda Rosengren (Department of Pharmacology & Toxicology)
Development of a drug therapy for aggressive breast cancer: a new use for an already
established drug – CT 296
We have previously shown that raloxifene, a drug that is approved for the prevention of osteoporosis decreases
the growth of breast cancers that are resistant to standard drug treatment (termed ER negative). In this project
we explored this effect further. Specifically, we showed that a very low dose of raloxifene ( 12 times lower than
the dose prescribed to women) caused human tumours implanted in mice to decrease in size and weight by
75% compared to untreated tumours. Importantly the tumours from raloxifene-treated mice were also 10%
smaller after 10 weeks of treatment, compared with their size at the start of drug treatment. This shows not only
suppression of tumour growth but also shrinkage of tumour size. Tumours were then removed and analysed and
the results showed that there were fewer blood vessels within the tumour following raloxifene treatment. This is
likely to be a reason for less growth because the tumour cannot get the nutrients and oxygen it needs for growth.
Other results showed that there were fewer actively dividing cells and more dead cells in the tumours from
treated mice. Lastly, key proteins in the tumour that cause cells to grow were also decreased following
raloxifene treatment. These findings are important because new drugs are desperately needed. This is because
women with ER negative breast cancer have a poorer prognosis due to the aggressive nature of the cancer and
the fact that it is resistant to drug treatment. Before raloxifene can proceed to clinical trials, the next aspect that
needs to be examined is whether or not raloxifene can decrease cancer spread to other organs. We are currently
examining this aspect.
Professor Mark Stringer (Department of Anatomy)
New Zealand Gall Stones – CT 297
Gallstone disease is a worldwide problem that consumes considerable healthcare resources. In New Zealand
more than 3,000 patients have their gallbladder removed each year for symptomatic gallstone disease, at a total
annual cost of approximately $30M (Ministry of Health data). There are several different types of gallstones,
distinguishable by their chemical composition, and each associated with different causative factors. The aim of
this study was to investigate the spectrum of gallstone types in New Zealand and relate these to established risk
factors. Between June 2009 and June 2010, gallstone samples were collected from 107 patients undergoing
surgery for gallstone disease at Auckland City Hospital. Their average age was 51.7 ±
18.1 years (range 19 - 88), 75 (70%) were female, and mean body mass index was 29.5 ± 7.9 (≥25 is
overweight, ≥ 30 is obese). The major ethnic groups were European (51%), Asian (23%) and Maori/Pacific (17%). A family history of gallstone disease was elicited in 40% of cases. A single gallbladder stone was present in 11% of patients and more than 10 stones in 50%. Detailed chemical analyses using Raman spectroscopy revealed three major gallstone types: 75% were pure or mixed cholesterol stones, 16% black pigment stones, and 8% brown pigment stones. In common with previous studies, female sex, obesity, and a positive family history were strongly associated with gallstone disease in New Zealand. However, a greater proportion of patients had pigment gallstones compared to many other countries. Further analysis of the data should allow us to explore associations
Major Gallstone types of various sizes
between specific gallstone types and individual risk factors, such as ethnicity.
(b) Laurenson Awards
Laurenson Awards are one-year grants for research concerned with the effects of diet and/or drugs on human
health. In December 2010 there were 16 applications (compared with 9 the previous year) from the
University of Otago totalling $374,528 and five of these were funded at a total expenditure of around
$100,000. Work in progress is summarised below:
Dr John Ashton (Department of Pharmacology & Toxicology)
Opioid-induced hyperalgesia and chronic pain syndrome – LA 298
This study aims to investigate whether loss of motor function in chronic pain is
caused or worsened by opioid treatment through inflammation of spinal motor
neurons. We have made progress on answering this question with respect to each of
our specific hypotheses. (i.) Opioid treatment following chronic constriction injury
(CCI) causes long-term loss in motor function - we have determined that CCI does
impair rat motor performance, but have evidence that this may be residual pain
sensitisation. We are working on this problem. We have not yet tested whether this is
exacerbated by opioid treatment. (ii.) Opioid treatment following CCI causes loss of
spinal cord motor neurons. Initial results have shown that motor neurons enclosed by
activated microglia (inflammatory mediators) undergo a loss of neurofilament heavy
protein and chromatin staining. Oddly, the nuclear envelop of these cells is still intact, so it is possible that these neurons are remodelling rather than dying. We are working on this question. Opioid treatment following CCI causes intensified inflammation in the spinal cord ventral horn motor region. We have repeated initial results showing micogliosis around motor neurons, but have not yet quantified this.
Dr Gregory Giles (Department of Pharmacology & Toxicology)
Photoactivated nitric oxide donor drugs as anti-cancer agents: designing light-activated
cancer drugs – LA 299
Photodynamic therapy is a rapidly emerging technology that promises to revolutionise cancer treatment. The
technique uses light to activate a drug inside a tumour, the activated drug then proceeds to destroy the
tumour from within. We have used our Laurenson Award to design new light-activated drugs which display
promising activity against lung cancer, the leading cause of death in New Zealand. We initially synthesised a
pool of five structurally related molecules, based on the photoactive S-nitrosothiol functional group. Our
measurement of their activation rates enabled us to derive a theoretical model, which now allows us to
predict drug action. We then optimised the parameters for maximum anti-cancer activity by investigating the
means of light delivery. We examined a ranged of light activation strategies including pulsed versus
continuous light activation, and incremental step increases in light intensity. Based on these conditions, we
are currently conducting mechanistic studies to determine how our drugs cause damage to cancer cells, and
whether the nature of cellular injury changes with different light delivery strategies. Our research discoveries
have formed the basis of a Project Grant application to the Health Research Council for funding to trial our
new therapy in vivo.
Dr Shelia Skeaff (Department of Human Nutrition) and Associate Professor Ted Ruffman
(Department of Psychology)
The effect of iodine supplementation on cognition and well-being in young adults: a
randomised, placebo-controlled, double-blind study – LA 300
Iodine deficiency during periods of brain development can result in detrimental effects on cognitive ability.
In school-aged children with mild iodine deficiency, improvements in cognitive test scores have been seen
with iodine repletion. The brain continues to develop throughout young adulthood and into the fifth decade
of life, however, there is little research into the effect of iodine deficiency on cognition in young adults.
The aim of this study was to investigate the effect of daily iodine supplementation in mildly iodine deficient young adults on cognition. A double-blind, randomised, placebo-controlled trial is being conducted from July 2010 to September 2011 in young adults aged 18-30 years who usually ate <2 servings of bread per day.
Participants were randomised to receive 150 µg potassium iodate daily, or placebo, for 32 weeks. At baseline, seven cognitive tests from the Wechsler Adult Intelligence Scale were administered and participants asked to provide a casual urine sample for the measurement of urinary iodine concentration (UIC). All measurements will be repeated at the end of 32 weeks. At baseline, 205 young adults (mean age = 21.4 years) participated in the study. The median UIC of these subjects was 65 µg/L (25th, 75th percentile: 33, 101), between 50-99 µg/L indicating mild iodine deficiency.
There were no significant differences in UIC (P = 0.144) and cognitive test scores for the block design (P = 0.639), backward digit span (P = 0.172), matrix reasoning (P = 0.364), symbol search (P = 0.465), visual puzzles (P = 0.641), coding (P = 0.740) and letter-number sequencing (P = 0.158) between the placebo and supplemented group. At baseline, despite mandatory fortification of bread, young adults who consumed <2 servings of bread per day were mildly iodine deficient. At the conclusion of the study (i.e. September 2011) an improvement in cognitive test scores in the supplemented group will provide evidence for the continuing role of iodine in brain development in young adults.
Dr Cherie Stayner (Department of Pathology) and Professor Michael Eccles (Department of
Pathology)
Developing a therapy for recessive polycystic kidney disease – LA 301
Polycystic kidney disease (PKD) is a common component of a large spectrum of human diseases, some of
which can be caused by mutations in the Mks3 gene. We have a unique sheep model of PKD that carries a
mutation in Mks3, causing kidney cysts to develop in utero and lambs to die shortly after birth. We have shown
that treating PKD mice in utero with rapamycin reduces their cystic disease. Our objective is to treat our PKD
sheep with rapamycin in utero, the first such trial in a large animal model of polycystic kidney disease.
One aim of our study was to optimise the delivery of rapamycin in our sheep. Our initial bioavailability studies focused on oral delivery as the preferred route of drug administration. Oral doses are the least invasive option but the nature of the sheep rumen appeared to further limit the bioavailability of this compound, such that ten times the oral dose of rapamycin normally given to humans was required to achieve a similar blood trough level. We have tested a variety of potential delivery agents to help improve uptake of the drug, but only a small improvement with the phospholipid-based phosal 50 PG was obtained. However, two short trials using subcutaneous delivery in wildtype non-pregnant sheep, was able to achieve blood trough levels in the therapeutic range using less rapamycin. It was decided to use subcutaneous delivery in our treatment of pregnant PKD carrier ewes.
A further aim of our study was to increase our current carrier ewe pool by genotyping ewes from the source farm of our PKD sheep. We have developed an assay that successfully identifies those sheep carrying the mutation in the Mks3 gene. Blood collected from just over 100 ewes from the source farm were processed and genotyped. In a group of 50 older ewes we identified 11 carriers for the mutation in the Mks3 gene. We were able to purchase 10 of these ewes. A group of 52 younger ewes showed an incidence of 10% carriers. With 2400 ewes on the farm, there are likely to be many more carriers amongst the flock.
We were not able to purchase more ewes at this time, but we are likely to be able to acquire more carrier ewes in the future for larger trials. In preparation for our drug treatment, a total of 22 carrier ewes in our research flock were mated with a carrier ram in April this year. All ewes were confirmed as pregnant by ultrasound scan in July, and by August we had identified those ewes that were carrying PKD lambs. Of the ten ewes identified, 5 commenced treatment with rapamycin (by daily subcutaneous injection) and the other 5 are receiving delivery agent alone. We continue to monitor kidney size by ultrasound scanning and, following birth, tissues will be collected from the treated lambs and analysed for the effect of treatment on renal cystogenesis and markers of kidney cyst development.
Professor Rob Walker and Dr Tracey Putt (Department of Medicine) and Professor Stephen
Duffill and Associate Professor Paul Fawcett (School of Pharmacy)
The impact of renal tubular function on drug handling in the elderly – LA
302
The kidney plays a major role in the handling of most drugs by several mechanisms
including filtration and tubular secretion/reabsorption. With renal impairment,
modification of drug doses are required. In clinical practise, changes in renal function
are estimated according to the creatinine clearance (CrCl) (estimate of glomerular
filtration rate [GFR]). The formulae used include age as a variable that assumes that
renal function declines with age alone. It is also assumed that changes in tubular
function parallel changes in GFR, but this may not be correct.
Given that many drugs are organic acids, tubular secretion/reabsorption are important variables that in the setting of impaired kidney function may significantly alter drug
Professor Rob Walker
Using a simple drug cocktail given simultaneously to measure tubular secretion and reabsorption, along with accurate measurement of the GFR, we are comparing a normal (normal plasma creatinine, no known medical conditions) older age group (aged >65 years) with a matched-aged group with known renal impairment (GFR < 60 ml/min) as well as a younger normal group (20-40 years).
To date we have completed studies on 46 individuals with a further 8-10 remaining to complete the clinical
studies. Analyses of the plasma and urine samples will continue over the next 3 months. Once the results are
available, the clearances can be calculated and analysed. Completion of the study is planned for the end of
March 2012. Our expectation is that this will provide a more accurate estimate of the contribution of renal
tubular function for drug handling in the older population. This in turn will allow safer drug prescribing
especially in the older age group.
4. OTHER ACTIVITIES OF THE SCIENTIFIC COMMITTEE
OMRF Student Speaker Awards at the Otago Medical School Research Society:
At the May 2010 scientific meeting of the Otago Medical School Research
Society (OMSRS) there were ten candidates (selected from 24 applicants based
on their submitted abstracts). All were summer research scholars and two of
the ten had been sponsored by the OMRF. The first prize ($500) funded by the
OMRF was awarded to John Zhang (supervisor Professor Mark Stringer,
Department of Anatomy), a student who had received an OMRF summer
research scholarship in 2009/10 and been the recipient of the 2010 Renshaw
Prize. The topic of his talk was "Absence of valves in the facial and ophthalmic
veins: an anatomical myth". The other OMRF-sponsored summer research
scholar presenting at the meeting was Maria Polak (supervisors Dr Sandy
Mandic, School of Physical Education, and Dr Paula Skidmore, Department of
Human Nutrition).
At the July 2010 meeting of the OMSRS there were ten presentations from
PhD students and the OMRF funded the second prize ($750) won by Evan
Tan (supervisor Dr Barbara Galland, Department of Women's and Children's Health) on the topic of
"Effectiveness of a sleep hygiene programme, developed with youths, on sleep hygiene, daytime
somnolence, sleep quality and body mass index".
At the May 2011 meeting of the OMSRS there were nine candidates (selected from 23 applicants based on
their submitted abstracts). All were summer research scholars and two of the ten had been sponsored by
the OMRF. The first prize ($500) funded by the OMRF was awarded to Clare Burn (supervisor Dr
Merilyn Hibma, Department of Microbiology & Immunology) on the topic of "Human papillomavirus
virus-like particles and their potential as gene delivery vectors in the skin". The second prize, jointly
funded by the OMRF and the OMSRS, was shared ($200 each) by Michael Fleete (supervisor Dr Ping Liu,
Department of Anatomy) for "Effects of aging on arginine metabolism in the striatum and spinal cords in
rats" and Edward Ottley (supervisor Dr Elspeth Gold, Department of Anatomy) for "Activin C: a possible
therapeutic target in prostate cancer progression". Edward was an OMRF summer scholar (funded by
OceanaGold) and one of the recipients of the 2011 Renshaw Prize. The other OMRF-sponsored summer
research scholar presenting at the meeting was William Parkyn (supervisor Professor Andre van Rij),
funded by OceanaGold and one of the recipients of the 2011 Renshaw Prize.
At the September 2011 meeting of the OMSRS there were ten candidates selected from 27 applicants based
on their submitted abstracts. All were PhD students. The first prize ($1,000) was funded by the Otago
Postgraduate Medical Society and the second prize ($500) by the OMRF. This second prize was shared
($250 each) by Zarina D'Costa (supervisor Professor Andrew Mercer and Dr Merilyn Hibma, Department
of Microbiology & Immunology) for "Human paillomavirus type 16 E6 regulates E-cadherin in a
DNA methyltransferase-dependent manner" and Yanfeng Zhang (supervisors Professor Cliff Abraham,
Department of Psychology, and Associate Professor John Reynolds, Department of Anatomy) for "Timing
dependent effects of reinforcement on visual responses in the superior colliculus".
Each Student Speaker award is given to the student speaker who, in the opinion of a panel of five judges,
gives the best oral presentation – based on both the components of the presentation and its scientific merit.
To be eligible the candidate must report work that has been performed under the auspices of the University
of Otago and, in the case of PhD students, the candidate must not be more than 1 year post-doctoral.
OMRF-sponsored Invited Speaker for the Otago Medical School Research Society:
The Foundation was not asked by the OMSRS to sponsor the Annual Review Lecture in 2010. The
opportunity for such sponsorship occurred in May 2011 when the Annual Review Lecture was given by
Professor John McCall, McKenzie Chair of Clinical Science, Department of Surgical Sciences, University
of Otago on the topic of "Nutrition and liver disease: a decade of clinical research".
OMRF-sponsored prizes at the Otago School's Science Fair:
The Foundation sponsors prizes each year in the Special Prize category (four awards at $50 each) at the
Otago Schools' Science Fair for projects involving medically orientated topics. In August 2010 the
recipients were "On Sugar" by Will Ferguson (Year 7), "Sensing Memory" by Lily Thomas-Milne (Year 7),
"Sleep: Is it really necessary?" by Baily Brandham (Year 8), and "Jumpstart Your Heart" by James Manson
Year 8). The Foundation's judges for 2010 were Associate Professor Greg Jones, Dr Bob Hancox and Dr
Paula Skidmore. In August 2011 the recipients were "We Taste With Our Eyes" by Romany McLaren (Year
7), "Does Coca-Cola Raise Your Heart Rate?" by Jessica Powell (Year 8), "The Beat Goes On" by Ronald
Poon (Year 9) and "Useful Killers" by Ghasaleh Dousti and Ye Ji Lee (Year 13). The Foundation's judges
for 2011 were Associate Professor Greg Jones, Dr Tamlin Connor, Professor Thomas Rades and Dr Paula
Skidmore.
ACKNOWLEDGEMENTS
The Foundation continues to play an ever increasing role in funding Medical Research in Otago –
may I thank the Scientific Committee for its dedicated efforts in the arduous, though satisfying,
work of assessing the scholarship and merit of the many summer research projects and grant
applications that it receives. We thank the Council of the Foundation for the support, advice and
enthusiasm with which our funding recommendations are endorsed and the many Benefactors of
the Foundation whose financial support has made all this possible.
Patricia A. Cragg
Chairperson, Scientific Committee
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Receipts should be attached to the Donations Rebate Form in support of the claim. From 1 April, 2008 taxpayers are able to claim a 33.33% tax rebate on all donations up to their annual net income.
Gift and Death Duties:
• No gift duty is payable by an individual on gifts to the Foundation.
Remembrance Donation:
• When you consider this substitute in place of a floral tribute, write or telephone the
Secretary giving the name of the deceased, the relationship to the deceased, the relationship to the bereaved, and the name and address of the bereaved. A letter of condolence will be sent to the bereaved notifying them that you have made a donation in place of a floral tribute. An acknowledgement, with a receipt for your donation (which may be tax deductible), will be sent to you. This is a dignified and practical way of expressing your condolence, which is invariably appreciated by the bereaved.
Membership:
• A form for membership application or donations is included on page 2 of this report .
Further information or brochures will be supplied on request to the Secretaries, Deloitte, P.O. Box 1245, Dunedin. Telephone (03) 474-8630.
FUNDING PATHWAY
The Otago Medical Research Foundation made steady progress as it applied a conscious and deliberate funding strategy during the 2010/2011 financial year. A number of charitable Trusts, organisations and companies joined the Foundation in partnership with the details as follows: Adinstruments . $150
Otago Service Clubs Medical Trust. $4,000
Deloitte . $4,000
Pub Charity . $10,000
Farry Group of Companies . $500
Progressive Enterprises. $50
Foodstuffs Community Trust . $4,000
Southern Trust. $10,000
JAD Iverach Memorial Fund. $2,000
Southern Victorian Charitable Trust . $35,000
Kelliher Charitable Trust . $25,000
St Kilda Community Sports Society . $12,000
Kingston Sedgefield Charitable Trust . $4,000
The Community Trust of Otago . $75,000
MM & JH Hughes Family Trust . $2,500
The J N Lemon Charitable Trust . $35,000
Oceana Gold . $8,000
WHK Otago . $4,000
Otago Diabetes Trust . $4,000
During the 2010/2011 financial year, the following individuals have made donations to the Foundation:
Rev Dr J R Brinsley
Prof D C G Skegg
Mr E J Chronican
Mr & Mrs L P Chronican
Mrs S M Willkinson
Mrs J W McChesney
Prof J G Mortimer
Assoc Prof D J Perez
BEQUESTS
William John "Jack" Thomson
The generosity of the late William John ‘Jack' Thomson will be of
enormous benefit to Dunedin-based research into arthritis. Mr Thomson,
a former Dunedin chartered accountant and company secretary, died in
Dunedin in September 2008 aged 83 and his estate has released a $2
million dollar bequest to the Otago Medical Research Foundation.
As a result, the Foundation will administer the Jack Thomson Arthritis
Fund with the first research grant from the fund to be made later this
year. A grant round in the vicinity of $70,000 to $80,000 will be awarded annually from 2012 for
specific research into the cause and treatment of arthritis.
"Jack was a gentleman who was intensely interested in people," Foundation Director of
Development, Mr Steve Davie said. "He was extremely generous with his time, helping many
clubs and societies with honorary accounting and auditing services. And he had many friends from
a wide cross-section of Dunedin society.
"Jack was a successful fly fisher and was always keen to display photos of his latest catch or tell
the stories behind the trophies on display at his home. He loved travel and had a passion for
cricket, golf, tennis and bowls. He was also an avid photographer."
Mr Davie said the bequest is a real fillip for the Foundation which began a highly successful
fundraising campaign last year, with all money raised to date being immediately directed back into
research projects and scholarships.
Mr Thomson attended Kaikorai and Maori Hill Primary Schools before three years at Otago Boys'
High School, 1939 to 1941. Having studied successfully at night for his accounting degree while
employed by Provident Life Assurance with whom he spent 20 years, Mr Thomson worked for
WEC Reid & Co (now Deloitte) and Tomkinson Wood Adams (now Wilkinson Adams Lawyers)
before retiring in 1985.
He was a member of a number of associations and societies including the Dunedin Photographic
Society, Balmacewen Bowling Club, Otago Anglers Club, Otago division of the Arthritis and
Rheumatism Foundation, Otago Acclimatisation Society, Otago Golf Club and Pakeke Lions.
"Jack suffered from debilitating arthritis in his latter years and often talked about how he would
like to help with research into a disease which robbed him of his mobility but certainly not his
enthusiasm for life," Mr Davie said. "The Foundation is delighted to be able to retain his name in
perpetuity through his terrific generosity."
LIST OF MEMBERS
ORDINARY MEMBERS
Prof W.C. Abraham
* Prof D.G. Palmer
N. & E.S. Paterson Ltd
Prof A. Goulding
Assoc Prof D.J. Perez
Prof. G.B. Petersen
Mrs S. Armstrong
Prof. B.F. Heslop
* Mr J.H. Heslop
Prof. A.E. Reeve
Assoc Prof M.A. Baird
Assoc. Prof. J.J. Reid
Prof. J. Highton
Prof. L.R. Robinson
Dr R.S.J. Highton
Dr C. McK. Holmes
Rev Dr John R Brinsley
* Prof. J.B. Howie
Prof. D.C.G. Skegg
Caversham Pharmacy
Prof. D.T. Jones
Mr & Mrs S.D. Jones
Prof. R.D.H. Stewart
Dr W. Sutherland
* Mr E.J. Chronican
Assoc Prof I.L. Lamont
Clutha District RSA
Dr Liz Ledgerwood
Mr M Thompson-Fawcett
Assoc Prof P.A. Cragg
Mrs J.W. McChesney
Prof. A.M. van Rij
Waihemo Pharmacy Ltd
Mr K.G. Dempster
* Mr N.Y.A. Wales
* Mr G.G. Dunckley
Dr T.D. Medlicott
* Fairmaid Chance &
Prof A C B Molteno
* Mrs S.M. Wilkinson
Prof. J.G. Mortimer
Mr T.J. Williams
* Prof. F.N. Fastier
* Dr N.W. Fitzgerald
Assoc Prof D. Oorschot
RESEARCH PATRONS
AMI Insurance Limited
Hope & Sons Limited
Asthma Society Inc.
Respiratory Research Unit
Wickliffe Limited Otago
(University of Otago)
LIFE MEMBER
Cadbury Confectonery Ltd
Marsh Family Trust
HealthCare Otago Ltd
Northern Southland
Cerebos Gregg Ltd
Dr R S Henderson
Janssen-Cilag Pty Ltd
Schering (NZ) Limited
Ciba-Geigy NZ Ltd
Lions Club Dunedin South
Roche Products NZ Ltd
Donaghys Industries Ltd
St Margaret's College Council
Dunedin City Council
Farra Dunedin Engineering
* Indicates Founder Member
HONORARY LIFE MEMBERS
Rotary Club of Dunedin South
Rotary Club of St Kilda
Source: http://sites.mythwebdesign.co.nz/omrf/wp-content/uploads/2012/08/OMRF-AnnualReport2011.pdf
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