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Understanding Mitochondrial DNA Segregation And Transmission.
Funder
National Health and Medical Research Council
Funding Amount
$512,449.00
Summary
We inherit our mitochondrial DNA from our mothers. Mutations to mitochondrial DNA can give rise to severely debilitating diseases that can be passed from one generation to the next. The aims of this application are to understand how mutant mitochondrial DNA is selected for; when it affects energy production during development; and to ensure that certain reproductive strategies do not result in the adverse transmission of mitochondrial DNA that will affect subsequent generations.
UNDERSTANDING THE BENEFITS AND LIMITATIONS OF METAPHASE II SPINDLE TRANSFER
Funder
National Health and Medical Research Council
Funding Amount
$1,629,373.00
Summary
Mitochondrial DNA (mtDNA) diseases are transmitted from a mother's eggs to her children. However, the levels of affected mtDNA differ amongst her eggs. Consequently, a carrier would not know if the newborn child were to suffer from these diseases. Mitochondrial Donation offers couples the potential to have an unaffected child. We will undertake the most comprehensive study of mitochondrial donation using one of its associated approaches to determine if it produces healthy embryos and offspring.
Improving Oocyte Mitochondrial DNA Copy Number To Enhance Female Reproductive Capacity.
Funder
National Health and Medical Research Council
Funding Amount
$670,867.00
Summary
Eggs with too few copies of mitochondrial DNA either fail to fertilise or arrest during early development. By supplementing eggs with mitochondrial DNA, we have been able to enhance embryo quality and gene expression profiles. By breeding the offspring derived from eggs given mitochondrial supplementation, we will determine if they and their progeny meet normal developmental milestones, regulate the transmission of mitochondrial DNA appropriately, and are healthy and fertile.
Identifying Mitochondrial Genome Variants Associated With Familial Migraine Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$443,273.00
Summary
New therapeutic targets for migraine are desperately needed. Although studies have identified some migraine genes there remains considerable underlying genetic variation to be characterised. This study aims to identify functional variants in the mitochondrial genome that contribute to migraine susceptibility, utilising the isolated Norfolk Island population. Outcomes will determine the significance of the variants identified, potentially leading to new diagnostics.
Understanding The Pathogenesis Of Mitochondrial Disease Using IPS Cells
Funder
National Health and Medical Research Council
Funding Amount
$640,372.00
Summary
Induced pluripotent stem (iPS) cells are stem cells derived from adult skin cells that can be converted into cell types such as neurons. iPS cells offer great promise in understanding and treating inherited disorders. However, there are concerns that the “epigenetic memory” of iPS cells has not been completely erased, which may limit the utility of iPS cells. We will evaluate and validate the use of iPS technology in mouse and human models of inherited disorders affecting energy generation.
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
Examining The Importance Of DNA Damage Repair For Oocyte Quality, Female Fertility And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
Metabolic And Molecular Basis Of Embryo Signalling
Funder
National Health and Medical Research Council
Funding Amount
$409,836.00
Summary
Cells in the body are powered by mitochondria that essentially generate the energy required for development. This grant will determine how the environment affects the mitochondria in the developing embryo and determine the impacts to the embryo and pregnancy if a mitochondria is partially shut down.
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.