Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A be ....Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A better understanding about the genetic architecture for complex traits will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will lead to more efficient selection programs in agricultural populations and will inform us with respect to past evolutionary events.Read moreRead less
Genetic Basis of Variable Expression of Glycan Xeno-Autoantigens by Cattle. Meat and dairy products from cattle contain sugar structures (glycans) that are not made by humans. These structures can be recognised by the immune system and lead to allergic reactions, inflammation and potentially cancer. These non-human structures are called xeno-autoantigens or XAs. We have discovered individual cattle that do not produce one of these XAs. We will study the gene required to make XA in the XA-free ca ....Genetic Basis of Variable Expression of Glycan Xeno-Autoantigens by Cattle. Meat and dairy products from cattle contain sugar structures (glycans) that are not made by humans. These structures can be recognised by the immune system and lead to allergic reactions, inflammation and potentially cancer. These non-human structures are called xeno-autoantigens or XAs. We have discovered individual cattle that do not produce one of these XAs. We will study the gene required to make XA in the XA-free cattle to find the underlying mutation. The same approach will be used to look for natural XA-free individuals in other food species. This knowledge may enable us to create a test to facilitate the natural breeding of non-GMO, XA-free livestock to benefit Australian primary producers and provide safer food for consumers.Read moreRead less
Structural and functional alteration of red blood cells by Babesia parasites. Cattle Tick Fever caused by Babesia parasites causes significant economic loss to the Australian livestock industry. New approaches to prevent this disease are urgently needed but this requires greater knowledge of how the parasites cause disease in cattle. By identifying novel proteins involved in the disease process we will be able to make better vaccines and drugs and save the Australian livestock industry millions ....Structural and functional alteration of red blood cells by Babesia parasites. Cattle Tick Fever caused by Babesia parasites causes significant economic loss to the Australian livestock industry. New approaches to prevent this disease are urgently needed but this requires greater knowledge of how the parasites cause disease in cattle. By identifying novel proteins involved in the disease process we will be able to make better vaccines and drugs and save the Australian livestock industry millions of dollars each year.Read moreRead less
Evolutionary genetics of bovid genomes over 60,000 years. This project will provide data critical for understanding the genetic background of modern cattle and bison, and how humans have shaped factors such as milk yield, growth rates and muscle mass. It will also reveal genes and genomic regions that were favoured in the domestication process, including those potentially linked to genes of commercial interest for future research. This pioneering ancient DNA approach will also be applicable to a ....Evolutionary genetics of bovid genomes over 60,000 years. This project will provide data critical for understanding the genetic background of modern cattle and bison, and how humans have shaped factors such as milk yield, growth rates and muscle mass. It will also reveal genes and genomic regions that were favoured in the domestication process, including those potentially linked to genes of commercial interest for future research. This pioneering ancient DNA approach will also be applicable to a variety of other domestic crops and animals. The unique temporal analysis of microevolution will provide crucial data for genetic research, and groundproof our attempts to analyse the timing and nature of human evolutionary history, major domestication events and inform conservation management.Read moreRead less
Proteomic and genetic analysis of subfertile bull spermatozoa. This project aims to identify protein changes on spermatozoa that are highly correlated with the fertility status of bulls. Bull fertility has approached an all-time low as breeding practice has focused predominately on milk production and beef tenderness. This project aims to understand the genetic causes that underpin bull and cattle infertility, and investigate better methods to predict the fertility status of bulls. This project ....Proteomic and genetic analysis of subfertile bull spermatozoa. This project aims to identify protein changes on spermatozoa that are highly correlated with the fertility status of bulls. Bull fertility has approached an all-time low as breeding practice has focused predominately on milk production and beef tenderness. This project aims to understand the genetic causes that underpin bull and cattle infertility, and investigate better methods to predict the fertility status of bulls. This project expects to contribute to better clinical management of cattle. This information can then be used for the development of a better diagnostic assay for both the dairy and beef industry.Read moreRead less
Epigenetic and biomarker approaches to improving dairy cow fertility. The dairy industry will not deliver sustainable higher productivity unless the reproductive performance of dairy cows is significantly improved. This expected outcome will be achieved via the identification of epigenetic and protein biomarkers of improved fertility that will be used to develop superior breeding stock. Caruncular and intercaruncular tissues and blood have been obtained from both fertile (New Zealand Holstein-Fr ....Epigenetic and biomarker approaches to improving dairy cow fertility. The dairy industry will not deliver sustainable higher productivity unless the reproductive performance of dairy cows is significantly improved. This expected outcome will be achieved via the identification of epigenetic and protein biomarkers of improved fertility that will be used to develop superior breeding stock. Caruncular and intercaruncular tissues and blood have been obtained from both fertile (New Zealand Holstein-Friesian) and sub-fertile (North American Holstein-Friesian) cows within pasture-based dairying systems that include seasonal calving and subclinical uterine inflammation (associated with poor reproductive performance). Determinations will be conducted using deep parallel (next generation) sequencing and mass spectrometry.Read moreRead less
The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increa ....The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increasing the profitability and ensuring the sustainability of both the dairy and meat industries. Better understanding of the mechanisms controlling mammary epithelial cell differentiation should enable augmentation of lactation such as increasing milk protein content, using marker assisted selection (of targets such as Runx2) in cattle.Read moreRead less
Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statis ....Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statistical methods provide the opportunity to close this gap. The outcome will be identification of many genomic variants causing variation in complex traits. This will benefit scientific understanding of complex traits and the ability to predict traits for individuals from their genome sequence.Read moreRead less
Subcellular co-localisation of interacting proteins that control maturation in mammalian eggs. The final maturation of mammalian eggs (oocytes) before fertilisation involves a cascade of interactions between protein kinases and phosphatases, the shuttling of these proteins between cytoplasm and nucleus, and microtubule assembly and disassembly. In this project we have proposed that interacting proteins involved in oocyte maturation are co-localised at subcellular sites in oocytes, in a strict t ....Subcellular co-localisation of interacting proteins that control maturation in mammalian eggs. The final maturation of mammalian eggs (oocytes) before fertilisation involves a cascade of interactions between protein kinases and phosphatases, the shuttling of these proteins between cytoplasm and nucleus, and microtubule assembly and disassembly. In this project we have proposed that interacting proteins involved in oocyte maturation are co-localised at subcellular sites in oocytes, in a strict temporal and spatial manner. The co-localisation of proteins in oocytes is considered a fundamental mechanism that ensures coordination of time-bound cellular events and proper preparation of oocytes for fertilisation and early embryo development. There are important implications for IVF and cloning by nuclear transfer.Read moreRead less
Identification of at-risk transition cows: Use of exosomal biomarkers. This project aims to improve the early diagnosis of cows at risk of infectious disease and debilitating metabolic syndromes. Animal health and longevity are pillars of the dairy industry. The risk of death is up to 6 times greater during the transition from pregnancy to lactation, making this ‘transition period’ the time for detection and intervention. If successful, this project will permit the focus of resources on high ris ....Identification of at-risk transition cows: Use of exosomal biomarkers. This project aims to improve the early diagnosis of cows at risk of infectious disease and debilitating metabolic syndromes. Animal health and longevity are pillars of the dairy industry. The risk of death is up to 6 times greater during the transition from pregnancy to lactation, making this ‘transition period’ the time for detection and intervention. If successful, this project will permit the focus of resources on high risk cows and reduce poor outcomes: lower milk production, involuntary culling and increased cow maintenance costs. Within this overall objective, a cost-effective project design will leverage partner facilities and existing networks to translate findings to farm use, thereby clearly delivering economic value.Read moreRead less