Development of efficient CRISPR gene drives in mice. This project aims to generate new tools for vertebrate pest management through development of cutting-edge gene drive technology in mice. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are required to tackle this challenge. Newly developed “gene drives”, which can rapidly spread through populations, have enormous potential for the sustained management and even erad ....Development of efficient CRISPR gene drives in mice. This project aims to generate new tools for vertebrate pest management through development of cutting-edge gene drive technology in mice. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are required to tackle this challenge. Newly developed “gene drives”, which can rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. This project aims to develop gene drive technology in mice as a prototypical vertebrate pest species. The project will potentially deliver valuable tools that directly impact Australia’s Science and Research Priority on Food.Read moreRead less
Understanding the evolution of the alternation of generations in the land plant life cycle. This project will investigate the genetic basis and evolution of the land plant life cycle, in which both haploid and diploid phases consist of complex multicellular bodies. The project's findings, which will be made using two model laboratory plants, will be applicable to all plants and will help understand important processes such as pollen and seed production.
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.
Cell death by self-eating: Autophagy-dependent tissue removal. This project aims to study the mechanisms and regulation of autophagy-dependent cell death. Cell death maintains cell and tissue homeostasis. Although most cell death is mediated by apoptosis, other modes of cell deletion have emerged recently. One form of cell death involves autophagy, the catabolic process of cellular self-digestion through lysosomal enzymes. As autophagy is a default mechanism of cell survival under stress, the id ....Cell death by self-eating: Autophagy-dependent tissue removal. This project aims to study the mechanisms and regulation of autophagy-dependent cell death. Cell death maintains cell and tissue homeostasis. Although most cell death is mediated by apoptosis, other modes of cell deletion have emerged recently. One form of cell death involves autophagy, the catabolic process of cellular self-digestion through lysosomal enzymes. As autophagy is a default mechanism of cell survival under stress, the idea of autophagy-dependent cell death has been controversial. This proposal aims to resolve this question and provide highly topical knowledge of broad biological significance.Read moreRead less
Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precurs ....Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precursors differentiate either along the male or the female pathway. Thus, this project aims to analyse in detail at which stage NEDD4 action is required and what are the crucial target proteins. This project could provide a deeper understanding of how post-translational modifications influence cell fate decisions during embryogenesis.Read moreRead less
Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understandin ....Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understanding of mammalian reproduction. The knowledge gained will have application in captive breeding and conservation of these extraordinary Australian mammals. The project also provides opportunity to train research students in cutting edge molecular biology and informatics.Read moreRead less
Defining The Role Of A Novel Transcriptional Enhancer Element In Regulation Of Prox1 Expression And Endothelial Cell Identity.
Funder
National Health and Medical Research Council
Funding Amount
$706,909.00
Summary
The precise spatial and temporal control of gene expression is regulated by non-coding regions of the genome termed enhancers. Enhancers are crucial to program cell identity and have established roles in development and disease. We have identified a novel enhancer that we hypothesise controls the identity of valve endothelial cells by regulating expression of a master programmer of lymphatic endothelial cell identity, PROX1. Here we will investigate the role of this enhancer during development.
Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 fun ....Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 function in the testes including stem versus progenitor cell activity and genome-wide target gene regulation. These studies will uncover the molecular and cellular mechanism by which SOX3 controls spermatogenesis and provide unique insight into how a single TF controls context-dependent differentiation in sperm versus brain progenitor cells.Read moreRead less
Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control h ....Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control holistic physiological responses is largely unknown. By deciphering how neural networks are formed this project aims to provide broad biological insight to wiring of the entire nervous system which is likely to have significant implications for the formation of synthetic neural networks and for regeneration.Read moreRead less
The transcriptional control of lymphatic vessel development. Lymphatic vessels are a vital, but often overlooked, component of the cardiovascular system. These specialised vessels return tissue fluid to the bloodstream, absorb dietary lipids and transport cells of the immune system throughout the body. Defects in the growth and development of lymphatic vessels result in disorders including lymphedema, obesity, inflammatory diseases and cancer. This project aims to define how transcription factor ....The transcriptional control of lymphatic vessel development. Lymphatic vessels are a vital, but often overlooked, component of the cardiovascular system. These specialised vessels return tissue fluid to the bloodstream, absorb dietary lipids and transport cells of the immune system throughout the body. Defects in the growth and development of lymphatic vessels result in disorders including lymphedema, obesity, inflammatory diseases and cancer. This project aims to define how transcription factors program lymphatic vessel identity and control the development of lymphatic vessel valves. This knowledge will provide new insight into the fundamental mechanisms by which the lymphatic vasculature is constructed during development.Read moreRead less