How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Identification Of The Molecular Mechanisms By Which Mutations In FHL1 Lead To Protein Misfolding And Skeletal Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,424.00
Summary
Skeletal muscle diseases result in debilitating muscle loss and may result from an error (mutation) within a gene. Mutations in FHL1 were identified as the cause of four different muscle diseases. Using purified FHL1, skeletal muscle cells and animal models we will investigate how FHL1 mutations cause muscle wasting, and loss of muscle strength.
Clarifying Molecular Role Of IGF-1:Ea Isoforms In Skeletal Muscle Hypertrophy And Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$394,718.00
Summary
The growth factor IGF-1 is proposed as a therapeutic agent to increase muscle mass and to reduce muscle wasting resulting from denervation, disuse, ageing and dystrophy. Understanding the precise mechanisms of IGF-1 action is essential for the potential therapeutic use of this factor. This research is focused on the molecular role of IGF-1 in healthy muscle and in the conditions of muscle wasting and degeneration.
Integrated Analysis And Functional Characterisation Of Gene Amplicons In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$453,068.00
Summary
In Australia in 2001 there were ~1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes have multiple copies in ovarian cancer cells and these may be good targets for therapy. We aim to find these genes and determine which ones have a functional effect in the tumour.
The Molecular Mechanisms Of Anabolic Androgen Actions In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in musc ....We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in muscle. We will study the growth of mouse muscle cells in culture, and measure their rate of growth when treated with androgens. All cells contain certain factors that control their growth and replication, and we will test whether androgens activate these factors to increase growth. We will also study the effect of androgens on muscle in mice, to investigate complex effects that only occur in real muscle. We will neuter male mice, which causes muscle wasting. Neutered mice will then be treated with androgens or placebo, and we will compare the muscle growth effect of androgen treatment versus placebo. We will measure muscle strength, size, and the number of muscle cells in treated and placebo mice. We will also see if the effects of androgen require a particular protein, the androgen receptor, which acts as a lock-key mechanism in cells, to allow them to respond to androgens. We will make a strain of mouse with a non-functional version of the androgen receptor only in muscle cells. This will determine if the muscle growth effects of androgens occur through a direct action on muscle, or indirectly through acting on other tissues in the body. This information will ultimately allow us to design more targeted androgen therapies for muscle wasting, that act only on muscle.Read moreRead less
Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less
Dissecting The Role Of Hedgehog Signalling In Chondrogenesis And Skeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,739.00
Summary
There are close to 400 inherited disorders that affect how the skeleton develops, as well as a range of injury and age-related skeletal defects. There is much interest in treating such abnormalities with artificial bone grown outside the body. In order to achieve this aim we must understand all of the processes involved in producing and maintaining bone within the body. We are using both mouse and cell culture models of skeletal development to increase our understanding of these processes.
Restoring Skeletal Muscle In An Experimental Model Of COPD By Targeting The IGF-1-myostatin-macrophage Axis
Funder
National Health and Medical Research Council
Funding Amount
$508,183.00
Summary
Most people think that the serious disabilities of COPD (emphysema) patients follows damage to their lungs but wasted muscles may be even more important. We can not regrow lung but we have found a way that might help regrow muscle. We plan to use stem cells to make one of the body's own cells called 'macrophages' and genetically engineer these cells to help deliver healing proteins directly into the muscle. Making muscle stronger will help COPD patients live longer and improve quality of life.