Does Mobile DNA Activity Contribute To Reproductive Failure?
Funder
National Health and Medical Research Council
Funding Amount
$389,076.00
Summary
One in four pregnancies in Australia will end in miscarriage. Infertility affects about 15% of Australian couples and is highly correlated with increasing maternal age. In this study, we will use cutting edge single-cell genomic approaches to investigate the activity of mobile DNA elements or “jumping genes” as a previously unexplored cause of reproductive failure, including spontaneous miscarriage and age-related female infertility.
Schizophrenia affects 1 in 100 people, and yet its causes remain largely unclear. To improve understanding, treatment and management of the disease, the team performing this research will evaluate whether mobile DNA elements found in our genome are activated by stress and thereby alter how brain cells work in individuals affected by schizophrenia. They will also test whether mobile DNA can be blocked by drugs, perhaps revealing new strategies to treat the disease.
The cross-disciplinary team performing this research will examine how mobile DNA elements found in brain cells move in response to learning and memory exercises in mice, and whether these changes generate an address system for parts of the brain to be turned on by specific experiences. This work has major implications for our fundamental understanding of how the brain works in healthy individuals, as well as people affected by neurodevelopmental and neurodegenerative conditions.
A Three-tiered Strategy To Prevent Destabilisation Of The Induced Pluripotent Stem Cell Genome By L1 Retrotransposition
Funder
National Health and Medical Research Council
Funding Amount
$708,707.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In recent publications in Cell and Nature, we found that retrotransposons move in mature human cells. In the current study, we will determine whether the same activity occurs when these cells are reprogrammed to become stem cells, possibly impacting stem cell based therapies.
Epigenetic Regulation Of L1 Retrotransposition In Mouse Models Of Abnormal Human Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$417,812.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves to spread in DNA. Until very recently, they were thought to only be active in sperm and egg. In our recent work, we demonstrated that they also move in the brain. In the current study, we will use cutting-edge technologies to determine how retrotransposons change the genetic makeup of neurons in neurodevelopmentally impaired mice to predict whether these mutations would also be present in human brain disorders.
Harnessing Endogenous L1-mediated Mutagenesis To Elucidate New Candidate Genes For Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$632,656.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver canc ....Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver cancer.Read moreRead less
Multiple Antibiotic Resistance In An Acinetobacter Baumannii Global Clone
Funder
National Health and Medical Research Council
Funding Amount
$606,580.00
Summary
Antibiotic resistant bacteria that cause infections in hospitals can originate anywhere, then spread world wide. They start off resistant to a few antibiotics, then become resistant to new antibiotics that are introduced to treat them. This project will investigate how resistance to antibiotics was acquired by Acinetobacter baumannii which is now resistant to most antibiotics, and why the old resistance genes are not being lost. This will help track these bacteria moving into and around Australi ....Antibiotic resistant bacteria that cause infections in hospitals can originate anywhere, then spread world wide. They start off resistant to a few antibiotics, then become resistant to new antibiotics that are introduced to treat them. This project will investigate how resistance to antibiotics was acquired by Acinetobacter baumannii which is now resistant to most antibiotics, and why the old resistance genes are not being lost. This will help track these bacteria moving into and around Australia.Read moreRead less
A New Mechanism For Transposition Of Antibiotic Resistance Genes
Funder
National Health and Medical Research Council
Funding Amount
$501,839.00
Summary
Understanding how antibiotic resistance genes are acquired by bacteria is important if we are to understand how bacteria become resistant in so many antibiotics, limiting treatment options. This project will investigate the way a family of insertion sequences captures and then moves resistance genes. This mechanism contributes to resistance in many bacterial pathogens including ones that are resistant to many different antibiotics.
How Insertion Sequences Mobilize Antibiotic Resistance Genes
Funder
National Health and Medical Research Council
Funding Amount
$675,086.00
Summary
Resistance to all antibiotics available for treatment of bacterial infections is a cause for global concern (Word Health Organization, US Centres for Disease Control) as it also compromises therapies relying on antibiotics such as transplantation and cancer chemotherapy. This project will seek to understand how resistance genes are recruited and disseminated into different types of bacteria that repeatedly spread around the world.
Transposon Mutagenesis For Discovery Of Disease Causing Genes And Their Cooperative Interactions In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$659,302.00
Summary
The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help dev ....The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help develop new cancer therapies.Read moreRead less