Consequences Of Disulfide Exchange In CD4 For Function
Funder
National Health and Medical Research Council
Funding Amount
$332,580.00
Summary
CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells res ....CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells respond to infection and how the HIV virus infects immune cells. Moreover, we have designed a small synthetic compound that blocks the redox chemistry in CD4 and prevents HIV infection in the test tube. We propose to investigate how the redox chemistry in CD4 controls the function of immune cells and infection by HIV.Read moreRead less
Regulation Of Nuclear Calcium Concentration In The Life Or Death Of Cells
Funder
National Health and Medical Research Council
Funding Amount
$195,047.00
Summary
The nucleus is the most prominent of all cell organelles and contains the primary genetic material for cellular development and growth. It performs some of the most important functions in the life and death of all living cells. However, little is known about many of the regulatory signals and events that control nuclear function. We will use new genetically-encoded sensor molecules that a living cell can be instructed to produce at various internal locations to explore important features of cell ....The nucleus is the most prominent of all cell organelles and contains the primary genetic material for cellular development and growth. It performs some of the most important functions in the life and death of all living cells. However, little is known about many of the regulatory signals and events that control nuclear function. We will use new genetically-encoded sensor molecules that a living cell can be instructed to produce at various internal locations to explore important features of cell control. This study will look specifically at how changes in the concentration of ionised Ca2+ in the nucleus control the switching on of genes and the initiation of programmed cell death pathways. This information is of significance to our understanding of normal cell growth and development, as well as abnormal growth (e.g. cancer).Read moreRead less
Visualisation Of Functionally Activated Circuitry In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
We are seeking to develop a method to precisely determine which parts of the brain are involved in the carrying out of different brain functions. The main advantage of our new method will be that we will be able to directly visualise the circuitry involved in a specified brain function. The brain is like a vast computer, with literally billions of connections between different parts, and it is these connections which are used to form functional circuits, which ultimately result in the brain cont ....We are seeking to develop a method to precisely determine which parts of the brain are involved in the carrying out of different brain functions. The main advantage of our new method will be that we will be able to directly visualise the circuitry involved in a specified brain function. The brain is like a vast computer, with literally billions of connections between different parts, and it is these connections which are used to form functional circuits, which ultimately result in the brain control of bodily function. Up until now, there has been no direct way of being able to directly visualise which of those billions of connections are involved in the formation of a circuit for any particular brain function. We plan to use a genetic approach to help to visualise functionally activated brain circuits. We know that some genes are turned on in the nerve cells which are activated during a brain function. We will use this knowledge to generate a new line of genetically engineered mice. In these mice, the genes which are turned on during brain activation will in turn be used to turn on special markers which will light up the activated circuits. This will be of great signficance in our understanding of brain function. It should also help us to understand what happens to these circuits in different diseases of the brain, such as following stroke, in senility, and Alzheimer's disease.Read moreRead less
Spatial And Temporal Aspects Of Epigenetic Remodelling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$626,707.00
Summary
Epigenetic deregulation occurs commonly in cancer, and can affect not only single genes but can encompass large chromosomal domains, leading to altered expression of oncogenes and tumour suppressor genes, and genomic instability. We will investigate the role of epigenetic remodeling, how spacial reorganisation of the genome, nuclear architecture, chromatin looping and replication timing may affect long range epigenetic deregulation, and ultimately contribute to cancer formation and progression.
How Does Basal Chromatic Structure Predict Cytokine Gene Responses?
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
To recognise foreign pathogens and eradicate them from the body, immune cells need to quickly switch on genes encoding factors which communicate between cells and drive the immune response. Incorrect expression of these genes contributes to immune diseases such as asthma, arthritis and leukaemia. The aim of this project is to study how the DNA environment of immune genes controls their ability to be switched on and off, and how altering this environment leads to incorrect gene expression.
An Alternate Function Of The MicroRNA Biogenesis Machinery
Funder
National Health and Medical Research Council
Funding Amount
$302,981.00
Summary
Controlling the activity of genes is crucial. Too much or too little can result in a cell not functioning properly. We have discovered a new way genes are controlled. We have found that an enzyme called Drosha can prevent too much activation of some genes by chopping up the products of these genes. This way of controlling genes appears to be especially important for developmental processes, such as occurs in the embryo. Our goal is to understand this mechanism precisely at the molecular level.