Control Of Organ Size During Development And Disease By The Salvadore-Warts-Hippo Pathway
Funder
National Health and Medical Research Council
Funding Amount
$331,674.00
Summary
Cancer is a disease that results from the generation of too many cells. Many signalling pathways control cell number including the newly identified Salvador-Warts-Hippo pathway. We are studying the mechanisms by which activity of this pathway is controlled, using the vinegar fly as a model. Information obtained from our study will aid understanding of human cancer as cellular processes which go awry in cancer, such as cell proliferation and death, are highly conserved between flies and humans.
Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the ....Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the most fundamental questions in the whole of biology: what is the basis for the primal distinction between sex and soma?Read moreRead less
How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. ....How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. This research will continue Australia's high profile in reproductive biology using one of our iconic native mammals. A greater understanding of marsupial reproduction will also contribute to management of our threatened marsupial populations.Read moreRead less
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
Regulation of DNA replication initiation during Drosophila development. This proposal addresses the fundamental issue of the regulation of DNA
replication during development, using the animal model system, Drosophila melanogaster. This research uses a whole animal genetic and cell biological approach to explore DNA replication regulatory mechanisms that are present in multicellular organisms but not in yeast. The work undertaken here will make a significant contribution to our understanding of ....Regulation of DNA replication initiation during Drosophila development. This proposal addresses the fundamental issue of the regulation of DNA
replication during development, using the animal model system, Drosophila melanogaster. This research uses a whole animal genetic and cell biological approach to explore DNA replication regulatory mechanisms that are present in multicellular organisms but not in yeast. The work undertaken here will make a significant contribution to our understanding of DNA replication regulation within a developing organism that will be relevant to all animals.Read moreRead less
Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctora ....Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctoral researchers in the disciplines of Molecular Genetics, Molecular & Cellular Biology, Developmental Cell Biology, Mass Spectrometry and Proteomics, which will be of immense benefit to their scientific careers and the Australian scientific community.Read moreRead less
Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, ....Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, and timed cultures. The assays will involve maintenance of reprogramming ability and erasure of somatic gene transcription. By subtractive elimination the function of isolated proteins which are involved in reprogramming will be identified for potential recombinant production.Read moreRead less
Head and face development: dissecting tissue-specific gene function. The outcome of our investigation of the early development will inform us of the ways and means for the embryo to assemble the essential building blocks of the body, and insights into the developmental origin of birth defects. This knowledge will benefit the biomedical research community, the education sector and the general public by enabling the formulation of new hypotheses, enriching the curriculum, and providing an evidenc ....Head and face development: dissecting tissue-specific gene function. The outcome of our investigation of the early development will inform us of the ways and means for the embryo to assemble the essential building blocks of the body, and insights into the developmental origin of birth defects. This knowledge will benefit the biomedical research community, the education sector and the general public by enabling the formulation of new hypotheses, enriching the curriculum, and providing an evidence-based understanding of the genetic basis of congenital malformations for delivering informative counselling. The technical expertise gained from this project will enhance the nation's research capability through the sharing of skills and knowledge with other research teams in the academia and the industry. Read moreRead less
The Role Of The Transcriptional Regulator, Taube Nuss, In Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$267,200.00
Summary
Cells are born, mature, age, are eliminated and replaced by new cells in many organ systems throughout life. Stem cells constitute the reserve of cells set aside for this regeneration process and also for the repair of damaged tissue. During embryonic development transient stem cell populations exist for the generation of tissues. Stem cells are capable of self-renewing proliferation and are able to give rise to mature cell types (differentiation). The regenerative capacity of stem cells could p ....Cells are born, mature, age, are eliminated and replaced by new cells in many organ systems throughout life. Stem cells constitute the reserve of cells set aside for this regeneration process and also for the repair of damaged tissue. During embryonic development transient stem cell populations exist for the generation of tissues. Stem cells are capable of self-renewing proliferation and are able to give rise to mature cell types (differentiation). The regenerative capacity of stem cells could potentially be used in the treatment of degenerative diseases like Parkinson s disease and muscular dystrophy, if we knew enough about their function. If stem cell proliferation and differentiation into mature cell types could be influenced in a clinical setting, stem cells could be encouraged to replace diseased or dead cells more efficiently than they do normally. In sharp contrast to the potential medical benefits that could be derived from stem cells, our understanding of the molecular mechanisms controlling self-renewal and maintenance of a wide differentiation potential are very limited. We have isolated a new gene, Taube nuss (- empty nut), which is essential for the survival of the first transient stem cell population in the early embryo. In mice, lack of Taube nuss protein results in the death of these stem cells, whereas the differentiated cells of the same embryos survive. Taube nuss is a member of a protein complex called transcription initiation complex. We plan to investigate if Taube nuss plays a role in other stem cell populations. If this is the case, we will not only be able to identify Taube nuss as a new regulator of stem cell function. We would also be able to demonstrate a new regulatory mechanism, namely the involvement of specific transcription initiation complexes in the control of stem cell function.Read moreRead less
Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulat ....Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulations over the first 5 days of mouse pregnancy on embryonic temporal and spatial organisation.Read moreRead less