Genetics Otago members Professor Stephen Robertson and Genetics Mātai Ira alumnus Dr Adam O’Neill are part of a group who have discovered how and why some genetic mutations can contribute to the cause of diseases like autism and brain malformations.
Read more in the University of Otago media release
Spatial centrosome proteome of human neural cells uncovers disease relevant heterogeneity
Adam C O’Neill, Fatma Uzbas, Giulia Antognolli, Florencia Merino, Kalina Draganova, Alex Jack, Sirui Zhang, Giorgia Pedini, Julia P Schessner, Kimberly Cramer, Aloys Schepers, Fabian Metzger, Miriam Esgleas, Pawel Smialowski, Renzo Guerrini, Sven Falk, Regina Feederle, Saskia Freytag, Zefeng Wang, Melanie Bahlo, Ralf Jungmann, Claudia Bagni, Georg H H Borner, Stephen P Robertson, Stefanie M Hauck and Magdalena Gotz
Science: DOI: 10.1126/science.abf9088
Genetics Otago member, Dr Silke Neumann has received $250,000 from the Health Research Council’s Emerging Researcher First Grants for the project ‘Treating gastric cancer according to its biology’
Cancers originating from the same anatomical location often display distinct characteristics, which influence their interaction with the immune system, the success of treatments and patient survival. Gastric cancer, treated currently as one disease, displays two main histological forms. We have identified two genes encoding an immunoproteasome regulatory subunit, that impact stomach cancer survival in opposite ways in the two histological forms.
We will determine how these genes tip the balance between anti–tumour immunity and cancer progression and how exploiting these genes may improve patient outcomes in both types of gastric cancer. We will use a novel gene tagging technology to establish where in the cell immunoproteasome regulatory subunit genes and proteins are expressed and can be targeted therapeutically. Overall, our goal is to decipher the mechanism behind the opposing effects these genes play in cancer progression and how they could be exploited to improve survival from gastric cancer.
Read more on the University of Otago Bulletin Board
Genetics Otago members Dr Alex Verry, Dr Keiren Mitchell and Dr Nic Rawlence have used ancient DNA to provide new insight into the distribution of the extinct eastern moa altered their distribution in response to climate change.
Read more in the University of Otago media release and in the publication below.
Genetic evidence for post-glacial expansion from a southern refugium in the eastern moa (Emeus crassus)
Alexander J F Verry, Kieren J Mitchell, Nicolas J Rawlence
The world seems so big at times and at others so small. How could the death of a beautiful baby girl in the USA possibly have an impact on the young people of Aotearoa, half a world away? But it can. Thanks to a generous donation to Genetics Otago by the Aldrich Family who tragically lost their daughter, Claire, to an unknown rare genetic disease at only 8-months old, we have established ‘The Claire Aldrich Legacy’.
“Claire Elizabeth Aldrich was born into this world on April 14th, 2019 – in Charlotte, North Carolina. She was just perfect” says her mother, Sally. Sadly, at 7-months old Claire suffered a seizure that saw her referred to a paediatric neurologist for assessment. Claire never made it to this appointment because she was later admitted to the hospital with a respiratory illness which led to more seizures. An MRI scan showed significant deterioration of her brain and Claire tragically passed away on January 7th, 2020.
Genetic tests revealed that Claire had a mutation in HIVEP2 which explained some symptoms she had experienced prior to the seizures but it was determined that this was not the cause of her death. The geneticist working with the family speculated that there was a second rare mutation that led to Claire’s death but he could not provide an answer for the family. “As a parent, that lack of closure is so hard to live with,” Sally says, “It is a little bit embarrassing to admit, however before Claire, I naively thought that when it came to genetics, most, if not everything, was ‘discovered’. And now I know how wrong I am. There is so much to learn. So much to find.”
Sally and her husband Jeff along with their three children are moving to Dunedin later this year and they wanted to bring Claire with them in some way. So, they have made a donation to Genetics Otago to start ‘The Claire Aldrich Legacy’ a fund that will be used to grow our outreach efforts, helping to educate the next generations of budding scientists about the importance of genetic research. The fund will have a particular focus on rare disease genetics and the impact these diseases have on people’s lives.
“My wish for the Claire Aldrich Legacy is to help inspire the young minds of New Zealand. The leaders of tomorrow. In our high school years, we are still finding ourselves. I want students to know that they can make a real difference in the world. They can make life-changing discoveries. If I can share Claire’s story, maybe, just maybe, it might plant that seed that could one day grow into ground-breaking findings.” – Sally Aldrich, Claire’s Mother.
Donations to the fund are being accepted through the University of Otago Donations page here.
World Rat Day, yes it is a real thing, was founded 20 years ago by a group that loved their pet rats! Their aim was to challenge the stigma surrounding these creatures and promote their welfare. Dr Catherine Collins (Department of Anatomy, University of Otago) uses ancient DNA (aDNA) to better understand population origins and changes in human populations through time. Here she tells us about her work with the Kiore, and its importance to our understanding of how the Pacific, including Aotearoa, was settled by humans.
The kiore, or Pacific Rat (Rattus exulans), is the smallest of the three rat species found in Aotearaoa (R. exulans, Rattus norvegicus, and Rattus rattus). Today, kiore are the third most widely distributed Rattus species, and are distributed from mainland Southeast Asia, through Island Southeast Asia and throughout the Pacific1. Skeletal remains from kiore first appear in the Pacific, in Remote Oceania in archaeological sites of Lapita settlements and are found in many Lapita, and later Polynesian, archaeological sites in the Pacific2.
Kiore were introduced to Aotearoa around 1280C3, and were the only rat species present here until the introduction of the Norway (R. norvegicus) and Ship rats (Rattus rattus) in the late 18th century. Since the spread of Norway and Ship rats, kiore are now limited to parts of Fiordland, Southland and south Westland, and 18 offshore islands4. Kiore have been eradicated from many offshore islands that they previously inhabited, as part of pest eradication efforts. However, they are also considered to be taonga by some Māori. Consequently, kiore are protected, with Ngātiwai as kaitiaki, on the islands of Mauitaha and Araara off the coast of Northland5. As kiore are taonga, I am fortunate to work with iwi from across Aotearoa to learn more about kiore.
Kiore are poor swimmers, so cannot settle new islands without some assistance – their present day distribution is a result of kiore being carried in the waka of people as they settled islands in the Pacific. Kiore were not the only animals that were introduced to Pacific islands in this way; kuri (Pacific dog), chickens and pigs, along with many plant species, were also important to Pacific peoples and transported with them to new islands. This relationship between kiore and humans means that by studying the genomics of kiore, we can further develop our understanding of the settlement of the Pacific, and ultimately Aotearoa. Matisoo-Smith et al.6 first applied the ‘commensal model’ to the Pacific, by studying a short region of mitochondrial DNA of kiore, to understand the relationships between kiore of different islands. Similarities and differences in genetic sequences of kiore from different islands in the Pacific can tell us how likely it is that those populations are related to one another. This data can then be used to inform hypotheses about the origin of the people in the same waka as the kiore. Genomic data from kiore alone is not sufficient to draw conclusions about these settlement processes, but when interpreted alongside human and other commensal genomic data, archaeological and linguistic data, and indigenous knowledge, we can begin to build a holistic hypothesis about the settlement of this region.
To obtain this data, I sequence DNA extracted from both modern kiore and archaeological kiore bones. The ancient DNA (aDNA) from kiore bones gives us some insight into a ‘snapshot’ in time in the past. With laboratory and sequencing technologies these days we can sequence complete mitochondrial genomes and nuclear markers (or complete nuclear genomes) from both the modern and ancient kiore. This gives us a much higher resolution dataset than what was previously available. You can think of it as the difference between only having a few pieces of a jigsaw puzzle versus having all of the pieces.
Written By Dr Catherine Collins
4. Wilmshurst JM, Ruscoe WA. 2021. Rattus exulans. In The Handbook of New Zealand Mammals. 3rd edn. (Eds CM King and DM Forsyth) Family Muridae, pp. 161-240. CSIRO Publishing, Melbourne.
5. Department of Conservation (2010) DOC and Ngatiwai Trust Board sign management agreement for two of the Marotere (Chicken) Islands http://www.doc.govt.nz/news/media-releases/2010/doc-and-ngatiwai-trust-board-sign-management-agreement-for-two-of-the-marotere-chicken-islands.
Who are you?
The Epilepsy Research Group, led by Professor Lynette Sadleir, is a research team based in the Paediatrics department of the University of Otago, Wellington. Professor Sadleir is a paediatric epileptologist at Wellington Children’s Hospital, as well as being the director of our group and heavily involved in epilepsy research. The team consists of our bioinformatician, research assistants, and PhD students.
What is the main objective of your research?
In the Epilepsy Research Group, our main objective is to improve the quality of life for people who have epilepsy. We undertake research that aims to understand the spectrum of epilepsy syndromes and their underlying genetic causes. Currently, we are particularly focused on the most severe group of epilepsies: developmental and epileptic encephalopathies. In these catastrophic disorders that present in childhood, the seizures and ongoing abnormal brain activity between seizures cause brain damage and result in intellectual disability, physical disability, autism and behavioural problems. We aim to use clinical and genetic approaches to identify new and emerging epilepsy syndromes in these children and then sequence their DNA to identify the genes responsible. When we identify novel epilepsy genes, we can then define the clinical presentation of people who have genetic abnormalities in those genes. Our findings are quickly put into clinical practice and help with the diagnosis and management of children who present have these severe disorders.
How is Genetics important to the research?
Epilepsy has a variety of causes however, the majority of epilepsy is caused by changes in the genetic code of an affected individual. These genetic changes cause abnormalities in the way the brain functions which ultimately result in seizures. There are a multitude of benefits that come with identifying the genetic change causing an individual’s epilepsy, which help improve the lives of children with epilepsy and their families.
Why should others be interested in your work?
Epilepsy is the most common serious neurological disorder worldwide. It is characterised by recurrent, unpredictable seizures. Over a lifetime, 1 in 20 people will have a seizure and ~38, 000 New Zealanders will be diagnosed with epilepsy. Epilepsy is a group of disorders, each with varying seizure types and outcomes. Many individuals live a relatively normal life but one third have treatment-resistant seizures which negatively impact their quality of life. The developmental and epileptic encephalopathies, in particular, can have a devastating impact on the trajectory of a child’s life. Our work, therefore, has the potential to help those individuals who are seriously impacted by their seizures.
Written by Brittany Jones
Victoria Sugrue, University of Otago PhD candidate in Anatomy, is the winner of the People’s Choice Science Communication award at the recently held Genetics Otago Symposium, for a video about her research on the effect of sex hormones on DNA methylation.
Lab Supply was the sponsor of the annual event, which showcased and recognised the latest research from across the Centre. Lab Supply also sponsored the Science Communication prize, which highlights the value of communicating science in a way that informs and inspires audiences.
Read the full article and learn more about Victoria’s research here.
Republished with permission. This story was first published by Lab Supply.
For those of you unable to attend our recent Symposium and who have not yet managed to get your hands on a physical copy of this years magazine, we have an electronic version you can view.
If you would like a physical copy, please get in touch and we will arrange a delivery to you.
A huge thank you to all who have contributed to this year’s magazine and to the events, research and activities that fill its pages!
The 2021 NZ International Science Festival was both the biggest and most diverse festival yet, with a jam-packed programme that included over 100 events from 8th – 18th July. This biennial festival was enjoyed by the smallest budding scientists all the way through to those working in science but curious to find out more about other disciplines. Genetics Otago was lucky enough to be involved with two events over the 10 days.
Together with the Department of Biochemistry and the Genetics Teaching Programme (Genetics Mātai Ira) we hosted a hands-on display at the University of Otago Science Expo on the 9th and 10th of July. This huge 2-day event, in the atrium of the Business school, included displays and activities from 23 University departments and research centres. Children and adults alike had a great time exploring our stations; trying their hand at pipetting and gel loading, observing and drawing fruitflies and lysozyme crystals with mini microscopes and, our tried and true favourite, extracting DNA from bananas (a staggering 200 DNA extractions were performed over the 2 day period!)
The 17th and 18th of July saw us ‘set up shop’ for the Outside Inside Forest in the Meridian Mall. The Forest had a wide variety of activities over the 10 days including land and sea conservation, climate science and animal education. Genetics Otago brought along a modified version of our ‘Who Killed the Kiwi?’ school resource for the first time, adding another successful community outreach resource to our belts. Young detectives helped to identify suspects using footprint analysis and hair samples, they then learnt about the power of DNA in determining the true culprit (the naughty dog!) using gel electrophoresis. The use of a microscope and loading of gels were both hits with children of all ages. The activity provided a great reminder of why it is so important to keep our dogs under control while out walking in the bush and on beaches (this activity could easily have been ‘Who Killed the Penguin?’).
With almost 100 entries to our detective prize draw by the end of the weekend, we drew two lucky winners to take home a prize pack of Genetics merchandise. Congratulations to Quinn (5) from Invercargill and Siraj (6) from Mosgiel and thank you to all the young (and not so young) detectives who helped us solve the mystery.
Events like this are not possible without the support of volunteers to run the activities and answer the many questions from the public, so a huge thank you to the members of our Outreach hub who helped out over the two weekends, we hope you enjoyed the experience!
Genetics Otago and Allan Wilson at Otago (University of Otago Research Theme) supported the second Ira Rangahau symposium, held on the 3rd and 4th of June 2021. This event was planned following the initiative of Phil Wilcox (Department of Maths and Statistics), who organised the inaugural Ira Rangahau in 2018. With Phil’s guidance, Alana Alexander and Catherine Collins (both Department of Anatomy) planned the format of Ira Rangahau 2021, with assistance from Rebecca Oliver (Genetics Otago) and Jane Reynolds (Division of External Engagement). The event was a great success, with 30 people, including Māori undergraduate students, staff and other interested colleagues at the University of Otago, registering to attend across the two days in addition to 23 colleagues and whānau listening via zoom.
‘…thank you to you all for organising everything and for inviting me along to share my mahi. I had an amazing time and got to talk to some truly inspirational people. I felt very privileged to be a part of it all!’ – Blaise Forrester-Gauntlett (invited speaker).
Participants were welcomed by Ben Te Aika (Ngati Mutunga, Te Ati Awa, Kati Wairaki, Kati Mamoe, Waitaha) with a mihi whakatau on the morning of the 3rd. We were then fortunate enough to hear from nine Māori kaikōrero (speakers) from across Aotearoa, and from a variety of host institutions (universities, CRIs and a DHB) about their research applying genetics. Many of the speakers were early career researchers and in addition to sharing their science, speakers spoke often of their experiences and journeys as Māori scientists. Over kai and inu during the breaks, participants networked and engaged in whakawhanaungatanga, strengthening relationships between genetic scientists at the University of Otago and elsewhere.
We then heard from Mere Roberts (Ngāti Apakura, Ngāti Hikariro, Pākehā), as our keynote speaker, on the morning of the 4th. Mere delivered a fantastic keynote, sharing her experiences straddling genetics and Te Ao Māori over the course of her career. Following a final break for kai and the chance to chat to one another, those who were interested visited Stephen Robertson’s lab in the Department of Women’s and Children’s Health, to hear about his research and experiences working with whānau who gift tākoha to study rare genetic diseases. Rebecca Oliver then led a small group through a hands-on workshop, in the Genetics undergraduate teaching lab.
‘Thoroughly enjoyed the conference… because the speakers were excellent, I was able to follow and learn’ – Mere Roberts (keynote speaker).
Overall, Ira Rangahau provided the opportunity for us to demonstrate Otago’s commitment to supporting Māori kaiputaiao. Many of the speakers were early career researchers from Otago, showcasing the talent in Māori researchers and the potential for these scientists to become leaders in their field, while working with Māori communities, here at Otago.
Written by Catherine Collins and Alana Alexander