Major Project Grants 2021: $865,000 in research funding awarded

Eight local medical researchers have been awarded a total of $865,000 in funding from the Canterbury Medical Research Foundation (CMRF) as part of their annual Major Project Grants round.

This year’s research topics include Huntington’s Disease, cannabis use in pregnancy, stuttering in children, tuberculosis, mental health as well as prostate and breast cancer. 

Foundation Director Melissa Haberfield says the team at CMRF are delighted that the annual grants process has been able to continue despite Covid-19 lockdowns as a number of similar funding programmes have not. Researchers rely on securing funding to enable them to undertake their research projects. Supporting Canterbury based health and wellbeing research is CMRF’s reason for being.

“Being able to award these grants this year is testament to the hard work of our team and the dedication of our loyal supporters who have donated to fund these world class research projects” she says. “Research is incredibly important and shouldn’t stop because of things like Covid-19. In fact, it’s more important than ever.”

CMRF received the highest number of applications on record this year which illustrates the demand for health and medical research funding. All researchers are aligned with one of CMRF’s host institutions including University of Canterbury, University of Otago Christchurch and New Zealand Brain Research Institute. Ms Haberfield says several research programmes from prior funding rounds are already producing important findings and interim results.

The successful researchers are:

“Being able to award these grants this year is testament to the hard work of our team and the dedication of our loyal supporters who have donated to fund these world class research projects” said Ms Haberfield. “Research is incredibly important and shouldn’t stop because of things like Covid-19. In fact, it’s more important than ever.”

Dr Vanessa Morris, University of Canterbury – $109,923
A new inactivation mechanism of a crucial tumour suppressor: investigating amyloid formation in cancer

Cancer is the leading cause of death in Aotearoa New Zealand. It contributes to approximately 30% of all deaths, with the incidence increasing as our population ages. Cancer involves uncontrolled cell growth and cell division. Tumour suppressors are proteins that strictly control cell division in healthy cells. These proteins are very often mutated in cancer cells, leading to uncontrolled cell division and tumour development. p16 is a tumour suppressor protein that is amongst the most frequently mutated in cancer patients. We recently discovered that under stress conditions, p16 can change its structure and forms large fibrillar aggregates called amyloid. In this amyloid state, p16 is unable to carry out its normal protective function.
We will investigate this alternative p16 state by identifying which part of the protein is involved in amyloid formation, and if tumour-associated mutations promote amyloid formation. Amyloid proteins have been well studied in relation to dementias; our study will be the first to characterise amyloid proteins involved in cancer, promising novel insights into tumour biology. A thorough understanding of how these proteins function and the mechanisms cancers use to inactivate tumour suppressors will be crucial for development of novel treatments.

Dr Daniel Foley, University of Canterbury – $109,946
Chemical tools to reveal the roles of splicing-associated kinases in breast cancer

Pharmacological inhibitors are small molecules that bind to specific biomolecules and prevent them from performing their biological functions. They are useful tools towards the development of new therapeutics, and for developing our understanding of biochemical pathways. Our project aims to prepare selective inhibitors for biomolecules (CLKs) involved in the ‘spliceosome’, a complex molecular machine found in all human cells that enables correct formation of proteins. Proteins perform almost all the important cellular functions in our bodies. When the spliceosome malfunctions, mutant proteins are generated that promote cancer development and progression. Therapeutic targeting of the spliceosome by selective CLK inhibition may prevent rogue functioning, and in the longer term will be key in developing molecular tools that can deconvolute its roles in cancer. The CLKs are implicated to play roles in a range of cancers, notably including breast cancer – the most common cause of cancer for New Zealand women. Every day, breast cancer takes the lives of two New Zealand women. Māori women have one of the highest incidences of breast cancer worldwide – 60% higher than Pākehā. Further, the Canterbury region has a notably higher number of cancer registrations than the national average. Increasing our understanding of breast cancer development and progression at the molecular level is paramount to discovering the next generation of effective personalised treatments.

Dr Campbell Le Heron, New Zealand Brain Research Institute – $109,870
Understanding apathy in Huntington’s disease – from cognitive mechanisms to longitudinal trajectories

Apathy (loss of motivation) is commonly seen in people with Huntington’s disease (HD), but remains poorly understood. Dr Le Heron’s team will study people with HD in Canterbury using novel behavioural tasks, to determine whether apathy is caused by disruption of normal brain decision-making processes.  Furthermore, by combining these insights with analyses of international HD datasets – which researchers and patients in Canterbury have been contributing to for the last eight years – we will deepen understanding of how apathy evolves in relation to other aspects of HD. By doing so, the study will provide new understanding of the mechanisms underlying apathy. This will open two new avenues for improving clinical management. Firstly, it will pave the way for treatments that specifically target apathy itself, thereby improving quality of life for patients. Secondly, the combined mechanistic and trajectory information will provide an important step towards an apathy-based behavioural biomarker, to be used to guide management in clinical settings and as an outcome of trials.

Dr Jenni Manuel, University of Otago – $95,049
Evaluating a peer-led residential service for severe mental illness

Concerns have been raised about the clinical effectiveness and patient experiences of the current model of inpatient psychiatric care. Peer-led community-based treatment is a new alternative model of care, whereby acute treatment is provided in a homelike environment with a peer model of support. This project aims to evaluate one of these initiatives.  It will compare the outcomes for people who have had care in a peer-led unit with people who were admitted to hospital before the unit existed. Detailed interviews with staff and with people who have experienced admission to the unit will be used to understand their experience.

Dr Elisabeth Phillips, University of Otago – $110,000
Adipocyte markers as predictors of progression in men with prostate cancer

When a man presents with prostate cancer it is difficult to tell whether his cancer is aggressive and needs immediate treatment to prevent it growing and spreading, or whether it is likely to remain dormant and may never need treatment. Recent research has shown fat cells surrounding the prostate can stimulate tumour progression, and we have identified a panel of proteins released by cancer-associated fat cells that promote tumour survival, growth and spread. The overall aim of this study is to test this panel of proteins to see if they can be used to distinguish between dormant and aggressive prostate cancers, and ultimately help men with prostate cancer to undergo fewer unnecessary treatments.

Dr Catherine Theys, University of Canterbury – $109,798
Brain changes associated with treatment effects in children who stutter

Communicating effectively with others is essential for a person’s hauora (physical, emotional, social and spiritual wellbeing). For those who kikikiki (stutter), everyday communication is a struggle. At least one in twenty pre-schoolers in Aotearoa (New Zealand) develops stuttering. While many recover, spontaneously or with early speech-language therapy, a significant proportion do not. For the 1% of the population with persistent kikikiki, there is currently no cure. Treatments are demanding and effects are often not maintained. Today, more than 50,000 New Zealanders live with the burden of stuttering and the well-documented academic, emotional (e.g., fear of speaking) and social (e.g., isolation) challenges that result. After centuries of research, the cause of stuttering remains unknown. Recent studies provide evidence for a neural basis, reflected by differences in brain function between those who stutter and fluent speakers. However, we do not yet understand the causal mechanisms underlying these differences nor how we can change them with treatment. Our study will, for the first time, investigate how stuttering therapy changes brain function in children who stutter. With these findings, we aim to improve treatment, and have a positive impact on the lives of the 80 million people who kikikiki and their whānau (family) worldwide.

Dr Timothy Allison, University of Canterbury – $110,000
The assembly of the exotoxin secretion system in Mycobacterium tuberculosis 

The growing resistance of microbes to medicines used to prevent and treat infections is a global health threat. The pathogenic bacterium Mycobacterium tuberculosis already kills >1 million people per year and is increasingly developing resistance to the few available treatments we have. One way that M. tuberculosis survives in humans is by secreting a toxin that kills immune cells. This toxin relies on proper and efficient secretion at the right time for effective killing, therefore making the machinery that secretes it a good target for drug discovery efforts. This project seeks to understand the role of a crucial component of the system that exports this toxin from the bacteria, by uncovering how this component is structured and assembled. The understanding of this system will give us the knowledge that may help to develop the urgently needed new treatments for tackling this global pandemic.

Dr Amy Osborne, University of Canterbury – $107,119
The impact of maternal cannabis use during pregnancy on neurodevelopment genes in exposed offspring

Substance use during pregnancy is a large driver of health inequalities in exposed children. Globally, cannabis use in pregnant women is increasing, yet there is limited understanding of its effects on offspring exposed during development. Epidemiological and associative research from humans and animals shows increasing evidence that maternal cannabis use during pregnancy can have a negative influence on the brain development of exposed offspring. However, it is not yet established whether this relationship is causal, partly causal, or only correlational. We do know, however, that developmentally-induced health inequalities are often driven by environmentally-induced genetic change. Thus here we aim to determine whether maternal cannabis use impacts the genome of exposed offspring at genes involved in neurodevelopment. This would fill the knowledge gap around the association between maternal cannabis use in pregnancy and offspring neurodevelopment.  It will also provide clarity around the potential risks of maternal cannabis use during pregnancy, and what this might mean for the health outcomes of exposed children.

For more information about Canterbury Medical Research Foundations Grants click here.

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