Investing in Research
Canterbury Scientific’s aim is to be a sustainable company, with high potential and growth opportunities. Having emerged from the Canterbury District Health Board (CDHB), and with close relations with local science and health organisations, we’re committed to encouraging the continued success of science in New Zealand.
To support this endeavour we put aside twenty percent of our annual profit for new research initiatives, summer studentships and grants, in addition to our own internal R&D commitment to further product development.
2012 Summer Studentships
Over the 2011-2012 summer period we sponsored five students, who had just completed their undergraduate degrees, to work on a number of research projects. The first four students were co-supervised by members of the Biomolecular Interaction Centre at the University of Canterbury and Maurice Owen of CSL. The fifth student worked at the Department of Medicine, University of Otago, Christchurch campus and was supervised by Drs Barry Palmer and Chris Pemberton.
Briefly the projects were as follows:
- The development of a potential new universal liquid stable HbA1c control. Charunya Nanayakkara prepared a new haemoglobin derivative and characterized its spectrum and its chromatographic profile on the BioRad variant 2 and TOSOH G8 instruments. An accelerated heat stability test was done comparing the new material with CSL’s existing liquid control. This was co-supervised by Assoc Prof Richard Hartshorn.
- Lettitia Gilmour looked at the development of a bioassay for angiotensinogen to Identify women prone to pre-eclampsia. This used surface plasmon resonance to attempt to measure the kinetics of interaction between renin and the different redox forms of angiotensinogen. This was co-supervised by Prof Conan Fee.
- David Carter, a chemical and process engineering graduate, worked on the development of a preparative chromatographic method to purify HbA1c from HbA0. This compared two candidate ion exchange resins and optimized the pH and buffer conditions to obtain a rapid and efficient resolution. He also designed an Excel spreadsheet to calculate scale-up quantities and economies. This was co-supervised by Prof Conan Fee.
- Sian Davies looked at the biophysical assessment of the stability of haemoglobin controls and derivatives. This involved using differential scanning calorimetry, circular dichroism spectroscopy, differential scanning fluorimetry, size exclusion chromatography, and laser light scattering. Liquid HbA1c controls that had been stored under real-time conditions of 4⁰C for times ranging from 6 months up to 5 years were compared with controls that had been subject to accelerated stability aging at 35⁰C for up to 42 days. The samples were examined using the above methods for evidence of protein unfolding and/or aggregation. This was co-supervised by Dr Grant Pearce.
- Tim Wilkinson looked at a protein in the blood called soluble Flt (sFlt). When a heart attack occurs, the blood supply to part of the heart is blocked. A normal response to this would be the development of new blood vessels to supply the heart. A question that this study addresses is whether the level of sFlt can be a measure of cardiovascular disease. In other words, the reason why some people develop heart failure is because they have high levels of sFlt in their heart, preventing the blood supply to the heart muscle from increasing when it needs to. This was indeed one of the findings of this study and it may eventually help doctors identify those patients most at risk of developing heart failure.
There are plans for two of these projects to continue with Lettitia carrying on the development of a bioassay for redox forms of angiotensinogen using surface plasmon resonance as part of her MSc degree, and discussions with the Ministry of Science and Innovation about the possibility of funding further study on the soluble Flt and heart disease.
1. Pre-eclampsia screening test
Angiotensinogen is a blood protein which provides the active angiotensin peptide that raises blood pressure. The crystal structure of angiotensinogen has recently been determined by Aiwu Zhou in Robin Carrell’s group in Cambridge University, UK. From this work they identified a redox switch that modulates the release of angiotensin. CSL is funding the development of an assay that can measure the redox state of the molecule. This is a two–year study to develop a new predictive biomarker for blood pressure in collaboration with Cambridge University, Canterbury Health Laboratories, and the University of Otago, Christchurch.
The goal is to create a test that can measure the ratio between oxidised and reduced angiotensinogen in the blood, and can potentially predict conditions, such as pre-eclampsia in pregnant women. Participants in the study include Research Fellow Darrell Wang, Canterbury Health Laboratory’s Peter George, Steve Brennan and Scientific Consultant Tim Yandle of the University of Otago, Christchurch.
Listen to Radio NZ interviewer Ruth Beran speak with Neil Pattinson and Maurice Owen from Canterbury Scientific, and collaborators Peter George, Darryl Wang and Tim Yandle about the angiotensinogen research project.
We are also developing an SPR-based assay to detect redox state of angiotensinogen in blood. The longer term idea here is to attach renin or another bio-specific molecule to the SPR chip and expose to blood samples of interest to detect pre-eclampsia. Firstly, fully reduced samples of angiotensinogen alone would be used to establish proof of principle that the methodology was valid. Secondly, oxidised samples would be trialed to establish the extent to which oxidation of the key cysteine residues impacts on binding. If oxidation alters the binding, then the method could be developed to provide a quantitative analysis of blood samples. The SPR chip and angiotensinogen samples to be supplied by CSL. The study is led by Conan Fee at the University of Canterbury.
2. Chromatography Method to Deplete HbA1c from Hb
This study is to develop a chromatography method to do large scale depletion of HbA1c from a Hb solution. Method scouting will be performed on new Capto S cation ion exchange media, followed by scale-up. Chromatography media and HbA1c samples to be provided by CSL. This project is led by Conan Fee.
3. Stability Assessment of Hb Samples
This study entails the biophysical assessment of the stability of Hb preparations using DSC, CD and perhaps DSF. The idea here would be to establish thermodynamic parameters for protein unfolding and aggregation at different temperatures and to use these measurements to inform shelf life predictions for Hb standards stored in solution at 4C. Hb samples to be supplied by CSL. This project is led by Grant Pearce.
4. Ligand Stabilisation of Hb
This project will investigate the use of other ligands that enter the heme pocket to help stabilize the molecule. Richard Hartshorn of the Chemistry department at the University of Canterbury who has an interest in cytochrome P450 is looking at any parallels with Hb oxidation.
Watch Dr Maurice Owen discuss the serpin α1-Antitrypsin and its connection to emphysema on Canterbury Television’s “The Body, The Research, The Professor” from November, 2011. The programme is hosted by John Dunn and Canterbury Medical Research Foundation’s Prof Rob Fraser.