Developing new methods to retrieve and analyse preserved genetic information. This project will position Australia at the leading edge of research into preserved DNA, and will use innovative molecular biology approaches to develop a range of new forensic, archaeological and medical applications. It will build Australian knowledge and scientific capacity by developing core expertise and training personnel in areas important for biosecurity, customs and quarantine, forensics/counter-terrorism, and ....Developing new methods to retrieve and analyse preserved genetic information. This project will position Australia at the leading edge of research into preserved DNA, and will use innovative molecular biology approaches to develop a range of new forensic, archaeological and medical applications. It will build Australian knowledge and scientific capacity by developing core expertise and training personnel in areas important for biosecurity, customs and quarantine, forensics/counter-terrorism, and studies of climate change. It will also create and foster research innovation in molecular biology with spin-offs for evolution, archaeology, medical and conservation biology research, and will also encourage involvement with the rapidly expanding field of genomics and bioinformatics.Read moreRead less
Control of Wolbachia replication: maintaining a stable symbiosis. This project will use a comparative genomics approach to better understand how Wolbachia infections of insects are able to maintain themselves in insects without causing pathology. The results will allow us to better understand a distinguishing characteristic of an intracellular symbiont, namely replication control. The results also have the potential to lead to new approaches to insect pest control through a better understanding ....Control of Wolbachia replication: maintaining a stable symbiosis. This project will use a comparative genomics approach to better understand how Wolbachia infections of insects are able to maintain themselves in insects without causing pathology. The results will allow us to better understand a distinguishing characteristic of an intracellular symbiont, namely replication control. The results also have the potential to lead to new approaches to insect pest control through a better understanding of how Wolbachia might be used to skew insect population age structure.Read moreRead less
The genomics of adaptation in Wolbachia pipientis, an emerging biocontrol agent. Australians are increasingly exposed to insect-transmitted diseases such as dengue fever. Novel biocontrol methods using the bacterium Wolbachia aim to control insect populations to reduce disease transmission. Our research will be the first to investigate genomic variation and the process of adaptation to new insect hosts in Wolbachia. The novel data and understanding of evolutionary processes we generate will be c ....The genomics of adaptation in Wolbachia pipientis, an emerging biocontrol agent. Australians are increasingly exposed to insect-transmitted diseases such as dengue fever. Novel biocontrol methods using the bacterium Wolbachia aim to control insect populations to reduce disease transmission. Our research will be the first to investigate genomic variation and the process of adaptation to new insect hosts in Wolbachia. The novel data and understanding of evolutionary processes we generate will be critical for screening bacterial biocontrol candidates and designing biocontrol release strategies. It will also strengthen the position of Australian research as a world-leader in the fusion of post-genomics and applied microbiology. Read moreRead less
A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect p ....A comparative genomics approach to understanding host-endosymbiont interactions. Australia's unique ecosystems are vulnerable to invasion by exotic pests that threaten agriculture and human health. The bacterial symbiont Wolbachia is found in many major pests of agricultural and medical importance. Our results will give insights into how Wolbachia spreads into host populations and improve its use as a tool to impair insect transmission of disease, e.g. as an agent to carry genes into an insect population that limit disease transmission. Our results will also make fundamental contributions to understanding host-parasite evolution, host-parasite communication, and insect developmental processes, and will be of interest to a large international community of researchers in this field. Read moreRead less
Functions Of A Novel Conserved DNA Damage Response Protein Family In Telomere Stability
Funder
National Health and Medical Research Council
Funding Amount
$282,825.00
Summary
The free DNA ends of chromosomes, termed telomeres, generally resemble broken DNA. Because broken DNA is a major contributing factor to the onset of cancer, cells try to fix broken ends. However, in case of telomeres, such repair processes have to be prevented because otherwise different chromosomes would fuse with each other. Fused chromosomes are very fragile and cannot be evenly distributed between dividing cells, and are therefore another important trigger of cancer development. Therefore, c ....The free DNA ends of chromosomes, termed telomeres, generally resemble broken DNA. Because broken DNA is a major contributing factor to the onset of cancer, cells try to fix broken ends. However, in case of telomeres, such repair processes have to be prevented because otherwise different chromosomes would fuse with each other. Fused chromosomes are very fragile and cannot be evenly distributed between dividing cells, and are therefore another important trigger of cancer development. Therefore, chromosome ends are covered by a cap, which hides them from the DNA damage response machinery. From these considerations it is clear that there are close connections between the cellular DNA damage response and chromosome ends. Moreover, recently it has become clear that DNA damage proteins are also required to stop normal cells from growing, a process termed senescence. Senescence is a consequence of shortened chromosome ends, and does not occur in cancer cells. Altogether, it is clear that DNA breaks and senescence are two of the major questions for our understanding of cancer development. We have identified a novel conserved protein family that is involved in the response to DNA damage in yeast and humans. In addition, the yeast Mdt1 protein is a very sensitive indicator of changes in the telomere cap. Absence of proteins that organise the cap leads to the addition of several phosphate groups to the Mdt1 protein. We propose that phosphate-coupled Mdt1 prevents chromosome ends from fusion with each other, or from fusing with broken DNA ends after widespread damage. As a consequence, cells that have mild cap defects die at an >1000-fold increased rate in response to DNA damage when they also lack Mdt1. As part of this application we want to find out the precise mechanism by which Mdt1 stabilises chromosome ends, and test our hypothesis that the corresponding human protein termed ASCIZ also has similar functions in protecting chromosome ends.Read moreRead less
The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general ....Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general population.Read moreRead less
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