Approximately 1 in 25 men in the western world are infertile, and while environmental and genetic factors are recognized to contribute to disease, there is currently a poor understanding of the basic mechanisms regulating male fertility. Our long term goal is to identify and study key molecules involved in sperm production. Understanding the role of these molecules will provide insight into the causes of male infertility. Ultimately, these studies will assist to develop new treatments for male r ....Approximately 1 in 25 men in the western world are infertile, and while environmental and genetic factors are recognized to contribute to disease, there is currently a poor understanding of the basic mechanisms regulating male fertility. Our long term goal is to identify and study key molecules involved in sperm production. Understanding the role of these molecules will provide insight into the causes of male infertility. Ultimately, these studies will assist to develop new treatments for male reproductive disorders. Conversely, there is a huge need for additional male based contraceptives. Increased understanding of male fertility and identification of proteins exclusively involved in sperm production provides the opportunity to develop new contraceptive treatments.Read moreRead less
The Balance Of Signals Received By NK Cells Is Modulated By Viruses As A Mean Of Immune Escape.
Funder
National Health and Medical Research Council
Funding Amount
$583,175.00
Summary
Cytomegalovirus (CMV) affects about 60% of the population in Australia. Infection is partially controlled by the immune system but CMV is never eliminated and people remain carriers for the rest of their life. Reactivation of CMV in healthy individuals is usually asymptomatic, but it causes severe diseases in people with immune deficiencies. We seek to discover the mechanisms used by CMV to escape immune surveillance, in order to gain insights into the development of improved antiviral therapies
How Important Is Collagen Destruction In Arthritis? A Study With Collagenase-resistant Knockin Mice
Funder
National Health and Medical Research Council
Funding Amount
$529,723.00
Summary
Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is n ....Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is not known whether inhibiting aggrecanases is sufficient to block cartilage damage long-term. In contrast, other studies suggest that aggrecan is only lost after damage to the collagen scaffold. These studies propose that clipping of the collagen scaffold may initiate aggrecan release; with progressive degeneration and collagen clipping, more aggrecan is lost, until ultimately the scaffold is severely damaged and aggrecan is severely depleted. Cartilage can only withstand a limited degree of collagen degradation and any significant damage to the network is widely considered to be irreparable. It is unclear what role aggrecanases and collagenases have in initiating and perpetuating cartilage damage. We have mice with aggrecan resistant to aggrecanases and mice with inactive aggrecanase. We will also create mice with collagen resistant to collagenase. We will use these mice to determine the contribution of collagenases and aggrecanases to the initiation and progression of cartilage damage, in three models of joint disease. We will identify differences in time of disease onset, rate of disease progression and disease severity. The results will show whether one or both activities is important for the initiation and progression of joint disease. This will reveal whether single or combination therapies are required for the management of arthritis. The research will inform the pharmaceutical industry on directions for the development of new drugs to prevent joint disease.Read moreRead less
Very little is known about mechanisms whereby depression harms the heart. This is especially disturbing as recent evidence indicates that while antidepressants alleviate a depressed persons negative mood, they do not eliminate danger to the heart. We will use an animal model to determine: How depression affects the electrical stability of the heart; The identity of the brain mechanisms that are involved; and which drugs can be used to protect the heart fro the harmful effects of depression.
Functional MRI And MR Spectroscopic Studies Of Penicillin Induced And Kindled Sheep Models Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$311,244.00
Summary
Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new techni ....Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new technique which may improve our ability to localize the seizure focus from which seizures arise, if the brain can be imaged at, or near, the time of a seizure. MR spectroscopy (MRS) enables us to detect metabolic changes in the brain which may persist at the site where seizures have begun for up to 30 minutes after the seizure. The aim of our research is to obtain a greater understanding of the changes detected with these MR modalities so that we can learn to apply these techniques to human sufferers of epilepsy. Ultimately it may help enable previously incurable epilepsy patients to undergo successful surgery and live normal lives.Read moreRead less