Role Of Chromatin Structure In The Regulation Of Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
The aim of this project is to understand more about the nature of stem cells. Stem cells are cells which have the capacity to proliferate indefinitely but, at the same time, retain the capacity to differentiate into one or more cell types. Lower animals, such as amphibians, have a much greater capacity than humans to regenerate body parts. For example, axolotls can regenerate an entire limb if one limb is injured. This is because they retain undifferentiated stem cells in their limbs which can b ....The aim of this project is to understand more about the nature of stem cells. Stem cells are cells which have the capacity to proliferate indefinitely but, at the same time, retain the capacity to differentiate into one or more cell types. Lower animals, such as amphibians, have a much greater capacity than humans to regenerate body parts. For example, axolotls can regenerate an entire limb if one limb is injured. This is because they retain undifferentiated stem cells in their limbs which can be reactivated in the event of injury. Interestingly the adult human brain contains a small population of stem cells. The aim of this project is to find out more about how these cells remain undifferentiated and what is it about them which allows them to form different cell types. If more is known about these cells maybe in the future it will be possible to stimulate them to repair damaged parts of the nervous system. It may also be possible to treat people suffering from diseases like Alzheimer's disease, Parkinson's disease or spinal injuries.Read moreRead less
State Dependent Drug Binding To The Human Ether-à-go-go Related Gene Channel
Funder
National Health and Medical Research Council
Funding Amount
$33,193.00
Summary
Heart rhythm disturbance is a common cause of death in our community. In a subset of patients the heart rhythm disturbance is caused by mutations in genes that encode for special proteins called ion channels. However, even in patients without a mutation certain drugs can cause the same problem. Such drugs need to be identified early in their development but current methods to do this are inaccurate. An understanding of how these drugs disturb the heart rhythm will allow more accurate testing.
Genetic Analysis Of De Novo And Inherited Exome Variation In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$1,351,522.00
Summary
Schizophrenia (SCZ) is a severe mental disorder affecting ~1% of the world’s population. The majority of risk is explained by genetic factors, and thus identifying susceptibility genes may lead to the development of novel therapeutics and personalised treatments. We will join forces with international collaborators to perform the largest DNA sequencing analysis of de novo and inherited protein-coding sequence variation in SCZ to date. We aim to identify key risk genes and genetic pathways.
Genetic Analysis Of The Relationship Between Parental Age And Risk Of Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$301,012.00
Summary
Age-related de novo mutations are widely assumed to explain the association between advanced paternal age and risk of psychiatric illness, but this mechanism cannot explain the known risk to offspring of teenaged parents. We will investigate an alternative hypothesis for risk to children due to parental age, which is that elevated liability to mental illness, arising from shared genetic factors between parents and offspring, leads to delayed, or conversely teenage, parenthood.
Understanding The Etiology Of Psychiatric Disorders Through Whole Genome Analyses
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Psychiatric disorders exert a huge social and economic burden on society. In recent years, large genetic studies have led to important new insights into these disorders. Major new human genomics resources will soon become available. My research will take advantage of these datasets to investigate the genetic basis of key epidemiological features of psychiatric disorders, including risk due to parental age and sex-biased prevalence, and to identify novel risk genes for schizophrenia and autism.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
The Role Of The EphA1 In The Normal Epithelial Organs And In Epithelial Tumour Progression.
Funder
National Health and Medical Research Council
Funding Amount
$564,500.00
Summary
The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in ....The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in the cells which form the skin, liver, kidneys, breast and prostate. These cells also form the lining of the mouth, stomach, bowel and lungs. Understanding how the EphA1 protein and other members of this family cooperate to control the development and maintenance of these organs will allow us to determine whether this protein might be involved in congenital defects and diseases in these organs (such as kidney failure, cirrhosis of the liver and skin diseases). A second main aim of this project is to explore further the observation that Eph proteins are abnormally highly expressed in a wide rangre of human cancers. This abnormal expression is directly correlated with the tumours spreading throughout the body. EphA1 is abnormally highly expressed in cancers of the bowel, lung, breast and prostate. These are the commonest cancers in man and some of the most difficult to treat. The work proposed asks how EphA1 contributes to the development and progression of these cancers. These results will have very direct implications for the development of therapies which target the EphA1 protein.Read moreRead less
The Nutritional Geometry Of Ageing In A Rodent Model
Funder
National Health and Medical Research Council
Funding Amount
$979,269.00
Summary
A central belief in ageing research is that eating fewer calories prolongs life, and that the source of calories (carbohydrate, fat or protein) is irrelevant. However, a critical assessment indicates that this conclusion is premature. We will use recent techniques in nutrition to define for the first time in mammals the relationship between diet and ageing in a normal and a prematurely ageing strain of mice. The project will provide a novel nutritional approach for promoting healthy ageing.