Genetic Investigations For Prodromal Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$719,374.00
Summary
The disease process in Alzheimer’s disease (AD) begins decades before a diagnosis is made. We urgently need to investigate this pre-symptomatic stage to learn how the disease process begins, and allow the development of treatments that work before the brain is irreparably damaged. I will use genetic risk factors for AD to predict who is most at risk of developing AD. I will look for early changes and easily accessible markers, including the use of state of the art brain imaging.
Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
Novel Ways Of Utilizing Genome-wide DNA Methylation Data From Peripheral Blood Samples In Genetic Epidemiology
Funder
National Health and Medical Research Council
Funding Amount
$285,186.00
Summary
The aim of this project is to develop statistical methods and paradigms to better leverage the considerable amount of peripheral blood DNA methylation data that has been collected from large scale epidemiological studies. In particular, our focus is on developing and optimizing statistical methods of using DNA methylation profiles to “tag” environmental exposures, so that this information can be better utilized to investigate the genetic and environmental basis of complex traits and diseases.
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
Epigenetic and neurobehavioural changes in a new mouse model of foetal alcohol spectrum disorders. Foetal alcohol syndrome involves changes in growth, skull structure, central nervous system defects and intellectual disabilities. This project will use a mouse model to study the underlying causes of this disorder, focussing on brain structure and function, and aim to identify markers that can be used for early diagnosis and treatment.
The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of pr ....The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of proteins (phasevarions) via variable methylation of the genome. The precise mechanism of action of these regulators is unknown. Characterisation of these systems will provide better understanding of bacterial gene regulation and adaptation, which will inform biotechnology and vaccine development and could contribute to economic and health advancements.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190101078
Funder
Australian Research Council
Funding Amount
$374,433.00
Summary
Functional role of a novel DNA modification in the adult brain. This project aims to understand how neuronal DNA is modified upon learning and how this impacts memory formation. The project will investigate the combination of different genome-wide sequencing approaches and molecular and cell biological assays to provide new insight into the functional role of a novel DNA modification, N6-methyl-2'-deoxyadenosine in the adult brain. This projects expects to have a major impact on many fields, inc ....Functional role of a novel DNA modification in the adult brain. This project aims to understand how neuronal DNA is modified upon learning and how this impacts memory formation. The project will investigate the combination of different genome-wide sequencing approaches and molecular and cell biological assays to provide new insight into the functional role of a novel DNA modification, N6-methyl-2'-deoxyadenosine in the adult brain. This projects expects to have a major impact on many fields, including neuroscience, evolutionary biology, and genetics, by helping to shape a new way of thinking about gene-environment interactionsRead moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100112
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Epitranscriptomic regulation of learning and memory. This project aims to investigate m6A, the most prevalent internal modification in eukaryotic messenger RNA, in the mammalian brain. The adult brain contains a high level of reversible m6A, suggesting that m6A regulates the neuronal transcriptome during synaptic plasticity, the cellular basis of learning and memory. This project will use epitranscriptomics to investigate the more than 100 modifications on RNA, many of which are not yet characte ....Epitranscriptomic regulation of learning and memory. This project aims to investigate m6A, the most prevalent internal modification in eukaryotic messenger RNA, in the mammalian brain. The adult brain contains a high level of reversible m6A, suggesting that m6A regulates the neuronal transcriptome during synaptic plasticity, the cellular basis of learning and memory. This project will use epitranscriptomics to investigate the more than 100 modifications on RNA, many of which are not yet characterised. Through molecular and mouse behavioural assays, the expected outcomes are insights into the post-transcriptional regulation underlying learning and memory, essential for survival in a constantly changing environment.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100976
Funder
Australian Research Council
Funding Amount
$307,058.00
Summary
Identifying parent-of-origin effects and their impact on complex traits. This project aims to systematically identify genetic variants whose effects depend on whether they were inherited from the mother or the father, and to assess their impact on complex human traits. Most gene mapping studies to date assume that the effects of genetic variants are equal regardless of the parent of origin, thus have not explored this source of genetic variation. However, animal studies indicate that parent-of-o ....Identifying parent-of-origin effects and their impact on complex traits. This project aims to systematically identify genetic variants whose effects depend on whether they were inherited from the mother or the father, and to assess their impact on complex human traits. Most gene mapping studies to date assume that the effects of genetic variants are equal regardless of the parent of origin, thus have not explored this source of genetic variation. However, animal studies indicate that parent-of-origin specific effects (POEs) are important contributors to variability of developmental and behavioural traits. Leveraging genetic and epigenetic data from some of the world’s largest cohorts, this project will improve our understanding of POEs on complex human traits related to early development, growth and behaviour.Read moreRead less