Imogen McNeill
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PROJECT SUMMARY
Dinogunellins are a class of four toxic phospholipids found in the roe of four fish with a unique and modular structure. To date, they have only been extracted rather than synthesised, resulting in small quantities of compound and limiting the ability to test their properties. This project aims to build on ongoing research in the Green group by utilising a click-chemistry approach to synthesise a library of dinogunellin analogues and subsequently test their biological activity. As numerous other toxic natural compounds have demonstrated biological activity and drug-like properties, dinogunellins and analogues are anticipated to behave similarly, and therefore show serious promise as a starting point for developing drugs to fight infectious diseases.
RESEARCH IMPACT
New Zealand will always have to face serious infectious disease threats and will therefore require a range of effective drugs for these situations. Dinogunellins have a unique structure, especially with regard to the phosphoramidate bond, that strongly suggests that analogues will be biologically active and possess drug-like properties. Synthesis of a variety of analogues with the aim of finding a drug lead is a critical step in developing our understanding of these compounds. Moreover, the widespread availability of the starting materials necessary means that synthesis of dinogunellin analogues will not be limited by rarity or expense of the required building blocks. Combined with the straightforward click chemistry approach, the synthesis of these potentially very useful compounds is uncomplicated, easily replicated, and therefore remarkably useful for New Zealand's ability to respond to infectious disease threats.
RESEARCH PERSONNEL
- Dr Nick Green | Supervisor
Claudia Priddey
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PROJECT SUMMARY
Acute respiratory infections are the most common reason preschool-aged children present to primary care and are the most frequent cause of hospital admission in this age group. Within New Zealand, acute respiratory infection hospital admission rates are higher for tamariki Māori and for Pacific children and children living in socioeconomically deprived households.
Many acute respiratory infection hospitalisations are preventable or avoidable by access to high quality preventive and primary care. Access to such care varies greatly between population groups in New Zealand. One group with notably poorer access are rural Māori.
The aims of this project are to:
- To engage with waahine Māori at one or more kōhanga reo in the Waikato region.
- To engage in kōrero with these wāhine to gain an understanding of their experiences with chest infections in their tamariki and of their healthcare access decision making and utilisation.
- To use this information to help inform the development of child health services in the Waikato region.
This project will be conducted within the ARROW study. It will utilise qualitative research methodologies.
RESEARCH IMPACT
The ARROW study is a clinical trial of a novel intervention that aims to prevent recurrent hospital admissions for wheezy chest infections. Te Niwha are funding a community and primary care component of this project in the Waikato, Auckland and Bay of Plenty region.
Wheezy chest infections are a very frequent cause of visits to GP practices and to hospitals. For Māori children wheezy chest infections are a more frequent cause of hospital admission than non-Māori children. Is this because of barriers to them accessing primary care or due to the quality of the primary care they receive?
This project will help our understanding of how healthcare is accessed by wāhine Māori for their tamariki nohinohi. This will help inform the development of healthcare delivery in the north Waikato region. This region is acknowledged by the children’s health team at Waikato Hospital as being one where healthcare delivery needs to be improved.
We aim to submit a draft/summary of the project findings in June 2025. This date aligns with the milestones and deliverables of the parent project (ARROW).
RESEARCH PERSONNEL
- Prof Cameron Grant | Primary Supervisor
- Dr Simone Watkins | Supervisor
- Marisa van Arragon | Supervisor
Myles Landon
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PROJECT SUMMARY
Malonyl-CoA Decarboxylase (MCD) is a crucial enzyme in the fatty acid biochemical pathway. MCD is responsible for the breakdown of malonyl-CoA to acetyl-CoA, which can be synthesised into new fatty acids and ultimately energy production. The regulation of MCD is highly integral to one’s health in controlling the concentrations of malonyl-CoA present within a cell. A mutated or defunct MCD can lead to serious health problems as the synthesis and transport processes for fatty acids will be stopped, leading to a lack of energy production and a build-up of fats, toxins, and waste products that can severely impact the cardiovascular system.
Coacervates are membranelles organelles that localise enzymes and their substrates to increase their relative concentrations and thus improve catalytic activity. Incorporating MCD and malonyl-CoA inside a coacervate increases the reaction leading to an increase in the fatty-acid biochemical pathways.
This project will give great insights into how coacervates can alter catalytic reactivity to be used in further health research.
RESEARCH IMPACT
This project aligns with Te Niwha's mission to ensure that Aotearoa has world-class research facilities and the capability to respond to the sudden event of an infectious disease threat. It is important for us here in Aotearoa as a small relatively isolated country to stay connected to and at the forefront of global health research. Using coacervates in the medical sector is very new and largely unexplored. This project will aim to provide critical research information on how enzymes such as MCD can be integrated with coacervates to alter catalytic activity, with the potential of being used in a medical sense to aid in both protection and recovery from enzyme-targeting diseases. This project will aim to ensure that our response to an infectious disease is treated equally among ethnicities and will take the diversity of our country, and the different effects diseases can have on our community into account. The critical information gathered by this research will be shared with the scientific community, with a particular focus on the Maori community to ensure that the knowledge can be applied throughout all our communities.
RESEARCH PERSONNEL
- Prof Renwick Dobson | Primary Supervisor
- Dr Natalia (Amy) Yewdall | Supervisor