SAGC Collaborative Projects

2023 saw the establishment of the South Australian node of the Australian Alliance for Indigenous Genomics (ALIGN), on the back of the successful 2021 Genomics Health Futures Mission grant to advance the benefits of Genomic Medicine for Aboriginal and Torres Strait Islander peoples.

Key priorities of the SA node, which is partially led by SAGC, revolve around extensive multi-omics analyses in the PROPHECY (Predicting Renal, Ophthalmic and Heart Events in the Aboriginal Community) study, Aboriginal-led policy development for Indigenous Genomics projects in SA and capacity development of a SA Indigenous genomics workforce. To help facilitate and guide this work, a South Australian Aboriginal Governance Committee has been established to provide Aboriginal insight and oversight into culturally safe genomics research practices so that we can work towards prioritising community benefit, health and wellbeing. The PROPHECY study is the largest longitudinal study of diabetes in Aboriginal Australians ever conducted. PROPHECY aims to understand why Aboriginal people get type II diabetes at a much younger age, and why they experience associated complications such as kidney disease and blindness at a much younger age than non-Aboriginal Australians.

People who have COVID-19 will excrete fragments of the SARS-CoV-2 virus through faecal waste or other bodily fluids into the wastewater stream through the sewerage system. A wastewater surveillance program therefore provides another mechanism through which community transmission can be monitored to complement clinical surveillance. The point of difference for wastewater surveillance is that it does not rely on clinical presentation by individuals. Wastewater surveillance will detect virus fragments from people who are weakly symptomatic or asymptomatic. The use of wastewater surveillance for detecting and quantifying the presence of SARS-CoV-2 virus fragments was expanded in 2022 to identify the variants of the virus circulating in the community in a manner that is independent of clinical presentation by individuals.

The aim was to provide a complementary source of information to analysis of variants detected from sequencing of clinical isolates. In South Australia, SA Water, SA Health and the SAGC ran a PCR-based screening wastewater surveillance program over the course of a year, whereby samples were collected from the major metropolitan wastewater treatment plants twice a week. These plants service about 65% of the SA population. PCR products from these samples were submitted to SAGC for sequencing. The resulting data produced was used by SA Health to assess changes in prevalence of variants and to monitor the appearance of new variants of concern (results are shown in the figure 1).

Emergence of COVID-19 and the ensuing pandemic has demonstrated the continued threat infectious diseases can pose to our health, economy, and lifestyle and highlighted the importance of vaccines as a countermeasure. COVID-19 vaccines were developed and approved in approximately 350 days, which was 5-10 times faster than ever before. However, even greater speed is needed, and 100-days for vaccine development is the current target. Achieving this goal will require a shift in current vaccine paradigms and development of new flexible, rapid, scalable technologies.

The Sementis viral vector vaccine platform (SCV) has been designed to deliver safe, versatile, and scale-able vaccines and is being positioned for pandemic preparedness. Sementis and the Experimental Therapeutics Laboratory at the University of South Australia (UniSA) have worked together to develop a multi-pathogen Chikungunya and Zika virus vaccine and a first-generation COVID-19 vaccine to demonstrate the immunogenicity of the vaccine platform and utility in infectious disease. UniSA has further collaborated with Sementis, as part of a broader global network to position the vaccine platform for pandemic preparedness. This included supporting the introduction of new technology to enable rapid construction and characterisation of new vaccines.

Dust and soil were collected from three sites with differing soil properties across South Australia. The resulting ITS and 16S sequencing data, generated at the SAGC, showed that it was possible to perform analysis from a single swabbed sample and that there were unique biological and chemical signatures between sites. When modelling bacterial and fungal diversity, Dr. Jennifer Young and team found samples were correctly predicted using dust 67% and 56% of the time and using soil 56% and 22% of the time for bacteria and fungi communities respectively. This proof-of-concept study found that metabarcoding of dust samples can generate bacteria and fungi community profiles that are unique to sites. While there is still a long way to go in this field, both metabarcoding and biogeochemical analyses of dust samples show potential for applications in forensic science.

Nicole R. Foster et. al, 2023, The secret hidden in dust: Assessing the potential to use biological and chemical properties of the airborne fraction of soil for provenance assignment and forensic casework, Forensic Science International: Genetics, Volume 67

Irritable Bowel Syndrome (IBS) is a chronic disorder of the gastrointestinal tract affecting ~11% of the global population. Chronic visceral pain (CVP) is the most debilitating symptom associated with IBS. Despite this burden of disease, effective therapies for CVP associated with IBS are lacking. The first step in finding new treatments is understanding how pain from the gut is generated and transmitted to the brain via the microbiome-gut-brain axis and determining how these processes change in IBS. The Visceral Pain Research Group, led by Professor Stuart Brierley at SAHMRI is working in conjunction with SAGC to fill this knowledge gap. The goal is to identify changes in the molecular profile of precise cell types within the microbiome-gut-brain axis to determine how changes to these molecular profiles drive altered function and generate the abnormal pain signalling characteristic of IBS.

The genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) are mutated in brain cancer and leukaemia and drive the production of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). However, specific differences between these two mutations with targetable implications have not been described. Dr Dan Thomas is a clinician and researcher who runs the Myeloid Metabolism Laboratory at SAHMRI. His team has recently discovered a novel susceptibility specifically for IDH1 mutation (mIDH1) by identifying the lipid synthesis enzyme ACC1 (acetyl CoA carboxylase 1) as a synthetic lethal target, published recently in Cancer Discovery and highlighted as one of the most important papers for 2023 by the European Cancer Association. By analyzing the metabolome of primary patient cells, his team identified a mIDH1-specific reduction in fatty acids compared to healthy progenitor cells that was not observed in IDH2-mutant cancer. Moreover, mIDH1 cells exhibited an increase in acyl-carnitine linked fatty acids destined for the mitochondria, indicating a switch to beta-oxidation. Overall, their data show that mIDH1 cancer cells have a higher dependency on both exogenous and de novo fatty acids than mIDH2 cancers.