Genetics Otago members Dr Ludovic Dutoit and Dr Nic Rawlence have been featured across several media platforms recently for their paper on the evolutionary origins of the pygmy whale Caperea marginata.
Publication details
Convergent evolution of skim feeding in baleen whales
Ludovic Dutoit, Kieren J. Mitchell, Nicolas Dussex, Catherine M. Kemper, Petter Larsson, Love Dalén, Nicolas J. Rawlence, Felix G. Marx
Marine Mammal Science https://doi.org/10.1111/mms.13047
Congratulations to our members who were successful in their HRC Grant applications this year. The five successful members received a total of almost $6 million. You can read the details of their projects below.
Professor Julia Horsfield Fighting leukaemia colonisation of the haematopoietic niche
Acute myeloid leukaemia (AML) has a low survival rate of 22 per cent in New Zealand. Treatment options for AML are limited and new strategies are needed to combat this disease. Understanding the function of AML-associated gene mutations is required to develop new therapies. Mutations in genes of the cohesin complex are present in ~12-20% of AML. Leukaemia stem cells can survive and evade treatment through interaction with the surrounding microenvironment known as the ‘niche’. We found that cohesin mutation enhances adhesive characteristics of leukaemia cells. We propose that these characteristics could promote increased interaction and colonisation of the leukemic cells into the niche. Zebrafish are an excellent model to study leukaemia development in vivo. This project will utilise cohesin mutant zebrafish models to examine the interaction and invasion potential of cohesin mutant cells within the niche, and determine whether niche interactions can be targeted for therapeutics.
Dr Euan Rodger Identifying epigenetic markers for early detection of colorectal cancer
Colorectal cancer (CRC) death rates are particularly high in Aotearoa New Zealand and are increasing in younger people (age <50 years) and Māori, who are more likely to present with advanced stages of disease. Prognosis and survival of CRC patients rely heavily on the stage at diagnosis. Therefore, there is an urgent need for accessible and easily clinically-deployable biomarkers that enable early diagnosis and improve CRC outcome. Recent work demonstrates that DNA methylation patterns could be used as a powerful tool for highly specific and highly sensitive early tumour detection. We aim to use unbiased whole genome-scale analysis to identify DNA methylation markers in the blood that can be used for minimally invasive early detection of CRC patients. In the future, our work will contribute further to enhanced surveillance for relapse and treatment response to improve CRC outcomes in New Zealand.
Dr Rachel Purcell Targeting the tumour microenvironment to improve outcomes in rectal cancer
The incidence of rectal cancer is increasing in NZ, particularly in younger people (< 50 years). Radiotherapy is often used to treat rectal cancer but patients have varying response, and currently, there are no predictive biomarkers of response available. Our recent work has identified an immune signature in rectal tumours that is predictive of response to radiotherapy, and, based on this, we will validate a biomarker test in an international cohort to predict response to radiotherapy and better direct treatment for rectal cancer patients. In addition, we found that the immune signature is linked to a specific tumour microbiome. We will use state-of the art techniques to determine the tumour immune-cell microenvironment that co-operates with radiotherapy and explore the potential of microbiome-based interventions to improve response to radiotherapy. This work will lead to the development of novel tests and microbiome-based treatments for rectal cancer, and ultimately improve outcomes for cancer.
Dr Htin Aung Understanding inequitable tuberculosis transmission in Aotearoa
In Aotearoa New Zealand tuberculosis (TB) disproportionally affects Māori and Pasifika particularly children under five and 5-14 years, suggesting ongoing transmission is occurring in these communities. Adding to this problem, there are variants of TB-causing Mycobacterium tuberculosis bacteria which predominate in these communities. Our research project will investigate TB transmission in Māori and Pasifika communities, by combining the expertise of bacterial genetics, epidemiology, and social science research teams. This will involve working alongside communities and combining expertise from public hospitals, New Zealand universities and Te Whatu Ora in a collaborative approach. Utilising this culturally-responsive, transdisciplinary approach, our research project also aims to serve as a blueprint to tackle other infectious diseases in New Zealand and promote better health outcomes for New Zealanders.
Professor Merilyn Hibma A molecular triage test to reduce colposcopy referrals after HPV testing
In 2023, the primary test for cervical screening will change to human papillomavirus (HPV) testing. HPV testing can be carried out on a self-collected swab, improving accessibility of screening for Māori and other women. However, a follow-up invasive triage test may be required. Additionally, many women referred to colposcopy following an HPV+ test do not have disease and would be better managed with monitoring. The purpose of this research is to develop a triage test for HPV+ women using the cells from a self-collected vaginal swab that will distinguish high-grade disease requiring treatment from low-grade disease that can be monitored. RNA sequencing will be used to identify disease-associated changes in gene expression and an assay will be developed and evaluated for its diagnostic effectiveness in a cross-section of HPV+ women. If successful, this test will have a significant impact on women’s health and on health delivery nationally and globally.
Genetics Otago members Associate Professor Aniruddha Chatterjee, Dr Rachel Purcell and Dr Euan Rodger have pinpointed a key feature that leads to the aggressive spread of colon cancer. Colorectal (bowel) cancer is Aotearoa’s second highest cause of cancer death.
Euan J. Rodger, Gregory Gimenez, Priyadarshana Ajithkumar, Peter A. Stockwell, Suzan Almomani, Sarah A. Bowden, Anna L. Leichter, Antonio Ahn, Sharon Pattison, John L. McCall, Sebastian Schmeier, Frank A. Frizelle, Michael R. Eccles, Rachel V. Purcell, Aniruddha Chatterjee, An epigenetic signature of advanced colorectal cancer metastasis,
iScience,
Volume 26, Issue 6,
2023,
106986,
ISSN 2589-0042, https://doi.org/10.1016/j.isci.2023.106986
Two GO members Associate Professor Christopher Brown (Department of Biochemistry) and Associate Professor Aniruddha Chatterjee (Department of Pathology) have been named as the only Otago University academics to receive Health Research Council Explorer Grants.
Associate Professor Christopher Brown Department of Biochemistry
Explorer Grant
There is an urgent need for replacements for antibiotics. During evolution bacterial viruses have evolved to manipulate or destroy specific human pathogens. There are huge and rapidly increasing numbers of sequences from bacterial viruses in the public domain, but this wealth of data has not been able to be fully utilised. We believe that it has now become possible to mine this data for new antibiotics. In preliminary studies we have identified thousands of potential anti-bacterials – the difficulty is choosing the best ones. To select these we propose to develop novel computer methods to predict their hosts, biophysical, functional, and expression properties. If successful, this research will provide proof of principle by discovering and testing pre-clinically new anti-bacterials. It will open up a novel and flexible computational approach to transform antibiotic discovery.
Associate Professor Aniruddha Chatterjee Department of Pathology
Explorer Grant
Although about 90% of cancer deaths are caused by metastasis, the underlying molecular events that drive it are poorly understood. This limited understanding hinders the development of effective cancer treatments. Initially thought to be driven by genetic mutations, our work indicates that epigenetic changes such as DNA methylation may be responsible for driving metastasis. Until recently it has not been possible to directly demonstrate that specific methylation changes alter metastatic potential. However, the development of precision editing tools now provides an opportunity to specifically edit epigenetic states target genes and to exclusively investigate the effect of these changes on cancer cell function. Our proposed research will further develop CRISPR/Cas technology to enable high-throughput interrogation of epigenetic drivers of metastasis. We aim to demonstrate that epigenetic mechanisms drive metastasis. This will open new avenues for understanding metastasis biology, lead to better outcome prediction, and identify new therapeutic targets to treat metastatic cancers.
The full Otago University recipient list for HRC grants can be read here.
Genetics Otago member Hamish Spencer is Sesquicentennial Distinguished Professor in the Department of Zoology at the University of Otago who writes a column for the ODT ‘Biological Taonga’. Read his latest article here.
Professor Jon Waters (Genetics Otago member, Department of Zoology) shares research authored by fellow GO members Dr Felix Vaux (Department of Zoology) and Associate Professor Ceridwen Fraser (Department of Marine Science) and other colleagues describing how kelp genomics can aid in revealing the impacts of ancient earthquakes.
Genetics Otago researcher Dr Matthew McNeill (Department of Microbiology and Immunology) and his group has featured in the media recently for their work on treating antibiotic-resistant strains of tuberculosis (TB).
A global study led by GO co-director Associate Professor Logan Walker has discovered a gene, that when modified, could reduce the risk of breast cancer.
A group of GO members who were the Otago Innovation’s Proof of Concept Grant winners in 2021, Dr Erin Macaulay, Dr Chi Lynch-Sutherland and Professor Mike Eccles, of the Department of Pathology, along with Dr Sarah Diermeier, of the Department of Biochemistry and founding Chief Scientific Officer of Amaroq Therapeutics, have gained entrepreneurship qualifications from Stanford Online.
Congratulations to our members who have had academic promotions announced!
Professor: Stephanie Hughes (Department of Biochemistry) David Orlovich (Department of Botany) James Ussher (Microbiology and Immunology)
Associate Professor: Louise Bicknell (Department of Biochemistry) Lynette Brownfield (Department of Biochemistry) Heather Cunliffe (Department of Pathology) Matthew Parry (Department of Mathematics and Statistics)
You can read more about the promotions on the Otago Bulletin.
