Role Of Sirtuins In The Regulation Of The Carcinogen Metabolising Arylamine N-acetyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$327,324.00
Summary
This project will investigate critical biochemical pathways that regulate metabolic differences in normal and cancer cells. By understanding how these processes differ, novel approaches for detecting and managing cancer cell proliferation in humans may be achievable.
Role Of The Drug Metabolising Enzyme Arylamine N-acetyltransferase 1 In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,196.00
Summary
The current project will identify the molecular mechanism(s) that underpins the significant changes in phenotype seen in a range of human cancer cells. The expected outcomes will be to demonstrate that NAT1 is critical for the clearance of pABG in cancer cells. The results will be important in the context of understanding this family of intracellular enzymes and will change the current thinking on the function of the arylamine N-acetyltransferase in normal and cancer cells.
The Role Of GAPDH Acetylation And HDAC6 In Liver Metabolism And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$635,428.00
Summary
Type 2 diabetes (T2D) is characterised by persistent elevated blood glucose levels. Altered liver metabolism is a key contributor to elevated blood glucose levels in T2D, through uncontrolled synthesis and release of glucose. This project will examine whether regulation of a metabolic enzyme called GAPDH by a process termed acetylation, contributes to normal liver glucose metabolism. This project will also assess whether altered GAPDH acetylation contributes to hyperglycaemia in T2D.
Essential Roles Of RNA Polymerase II Transcription And DNA Damage Response Pathway In The Maintenance Of Centromere Chromatin Assembly
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growt ....A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growth and cancer development.Read moreRead less
Epigenetic Regulation Of Telomere Chromatin And Genome Stability
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
Telomeres are structures at the end of the chromosomes that impact cell replication. 15% of cancers, called ALT cancers, show telomere instability, increased DNA damage and are frequently mutated for the ATRX gene. ALT cancers have poor prognosis, due to the limited understanding of ALT cancer activation. This study aims to create a model of ALT activation to uncover the mechanisms that control ALT tumourigenesis. This could lead to potential ALT-specific diagnostic and therapeutic tools.
Function Of ATRX, H3.3 And PML Nuclear Bodies In The Regulation Of Telomere Chromatin Integrity
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
The telomere is required for protecting chromosome ends. During cell division and development, telomeres lose their repeats, exposing the chromosome ends to damage. The consequences of this damage are disease, cancer, and aging. By contrast, embryonic stem cells (ES) continually renew their telomeres and do not stop growing. ES cells thereby provide a means to unravel the molecular mechanisms of indefinite telomere renewal. Here we propose a novel mechanism that operates to control continual tel ....The telomere is required for protecting chromosome ends. During cell division and development, telomeres lose their repeats, exposing the chromosome ends to damage. The consequences of this damage are disease, cancer, and aging. By contrast, embryonic stem cells (ES) continually renew their telomeres and do not stop growing. ES cells thereby provide a means to unravel the molecular mechanisms of indefinite telomere renewal. Here we propose a novel mechanism that operates to control continual telomere renewal in ES cells.Read moreRead less
Epigenetic Regulation Of Core Centromere CENP-A Chromatin Integrity
Funder
National Health and Medical Research Council
Funding Amount
$318,284.00
Summary
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growt ....A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growth and cancer development.Read moreRead less
Human Arylamine N-acetyltransferase Regulation And Function - Effect Of Genetic Poymorphisms.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase ....How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase that has been implicated as a risk factor in diseases such as cancer, asthma, liver cirrhossis and adverse drug reactions. We plan to look at the enzyme in cells and determine what environmental factors contribute to its variation between individuals, and how this impacts on the genetic mutations that have been found in its gene. From these studies, we will have a much better undersanding of how different people metabolise foreign chemicals, and should be able to predict those most at risk of certain diseases.Read moreRead less
The Special Role Of Histone Variants In Regulating The Inheritance And 3-dimensional Organisation Of The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$962,716.00
Summary
It has been more than a decade since the human genome has been completely sequenced but how this genomic information is selectively utilized to direct gene expression that is unique to each of the 200 different cell types of the human body remains to be elucidated. We have new data to suggest that it is how our genome is packaged into a variety of different and dynamic 3-dimensional structures in a cell that determines cell type specific programs of gene expression