Regulation And Activity Of Fatty Acid Delta-6 Desaturase (D6D)
Funder
National Health and Medical Research Council
Funding Amount
$527,683.00
Summary
Fish and fish oils contain fats known as omega-3 fats. These have health benefits in adult conditions such as rheumatoid arthritis and heart disease, and they are necessary for proper brain and eye development in infants. However, much of the population does not like to eat fish and also, world fish stocks are under stress. Thus, a sustainable alternative source of omega-3 fats needs to be explored. Some vegetable oils such as canola, echium, and flaxseed oils have omega-3 fats. However, these a ....Fish and fish oils contain fats known as omega-3 fats. These have health benefits in adult conditions such as rheumatoid arthritis and heart disease, and they are necessary for proper brain and eye development in infants. However, much of the population does not like to eat fish and also, world fish stocks are under stress. Thus, a sustainable alternative source of omega-3 fats needs to be explored. Some vegetable oils such as canola, echium, and flaxseed oils have omega-3 fats. However, these are not the same as the omega-3s in fish oil. In general, vegetable omega-3s are known as short-chain omega-3s whereas those in fish are long-chain. When the vegetable oil omega-3s are consumed in the diet, the body must convert them to the fish-type, or long-chain, omega-3s in order to gain the health benefits. Currently, human metabolism is poor at doing this conversion. Our studies suggest that the amounts and blends of fats in most diets are well below optimal for conversion to long-chain omega-3s in the body. In particular, our studies show that there may be no point in simply adding more vegetable omega-3 fats to the diet. This project will examine the enzymes that convert the short-chain to the long-chain omega-3 fats. In particular, it will examine how the dietary fats interact with each other in detrimental ways to suppress activity of the conversion enzymes necessary for long-chain omega-3 formation. Evidence for the health benefits of fish-based omega-3 fats is very strong and it is an approach to health that most people can undertake on their own. Our lack of knowledge of the best way to use plant-based omega-3 fats is a large impediment for a more sustainable and broader based use of omega-3 fats. The results from this study will begin to fill in this knowledge gap. The results will be useful across a range of activities that are determinants of the kinds of fat that we eat. These include oil seed breeding, food manufacture, and dietetics.Read moreRead less
Investigating The Action Of Clozapine On The Epidermal Growth Factor System: Implications For Antipsychotic Drug Action
Funder
National Health and Medical Research Council
Funding Amount
$364,535.00
Summary
Current treatments for schizophrenia are ineffective for up to half of sufferers leaving the toxic drug clozapine as the only resort. This project aims to investigate if the unique effectiveness of clozapine is due to a novel action in brain cells that we have identified. The project will delineate this mechanism and from this may lead to the development of a new way of treating schizophrenia and insights into the causes of this disorder.
Molecular Determinants Of Subcellular Localisation And Function Of The Transmembrane 4 Superfamily Protein, PETA-3
Funder
National Health and Medical Research Council
Funding Amount
$322,911.00
Summary
Several years ago we identified the cell membrane protein PETA-3-CD151 based on its ability to cause activation of blood platelets, suggesting a role in thrombosis. More recently we found that the protein is present in a variety of tissues, although its distribution in those tissues is often restricted. It is abundant in a variety of cancer cells, and is present on tissue mast cells that mediate allergic reactions. PETA-3-CD151 forms complexes with molecules (integrins) that are associated with ....Several years ago we identified the cell membrane protein PETA-3-CD151 based on its ability to cause activation of blood platelets, suggesting a role in thrombosis. More recently we found that the protein is present in a variety of tissues, although its distribution in those tissues is often restricted. It is abundant in a variety of cancer cells, and is present on tissue mast cells that mediate allergic reactions. PETA-3-CD151 forms complexes with molecules (integrins) that are associated with cell adhesion and migration, and antibodies to this protein inhibit cell movement. Thus PETA-3-CD151 appears to be involved in cellular interactions that are critical for normal tissue development and function, and may be involved in several disease processes including cancer invasion and metastasis. The molecular basis of PETA-3-CD151 function is not understood and is the focus of this application.Read moreRead less
Inherited Muscle Disorders - Gene Discovery, Pathobiology And Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$1,750,277.00
Summary
The project proposed by Professors Nigel Laing and Kathryn North and Dr Kristen Nowak is based upon the results of their successful identification of disease genes for genetic muscle diseases. The project is divided into three parts. In the first part of the project, the research team will identify further novel disease genes, some of which they are already close to finding. In the second part of the project the team will determine how the mutations they have identified in the disease genes actu ....The project proposed by Professors Nigel Laing and Kathryn North and Dr Kristen Nowak is based upon the results of their successful identification of disease genes for genetic muscle diseases. The project is divided into three parts. In the first part of the project, the research team will identify further novel disease genes, some of which they are already close to finding. In the second part of the project the team will determine how the mutations they have identified in the disease genes actually cause the diseases. The aim of this work is to discover targets that may ultimately lead to new therapies for these muscle diseases. In the third and final part of the project, the team will pursue one possible therapeutic approach, which is based upon the understanding of the diseases the researchers have gained from their previous studies. There are currently no cures for these muscle diseases, though symptoms can be treated. The team will determine whether heart actin can replace muscle actin in skeletal muscle and thus might treat the muscle disease.Read moreRead less
Mechanism Of Flightless I Function In Burn Injury And Scar Formation
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
Extensive scarring is a major clinical problem often resulting from burn injuries. We have previously shown that the cytoskeletal protein, Flightless I (FliI), is an important regulator of wound repair. We now plan to investigate whether FliI is also be the mechanistic link between cytoskeletal remodelling and induction of TGF-betas post-wounding leading to scar formation.
Single-chain Antibodies For Directed Stem Cell Homing And Targeting Of Effector Cells In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$596,677.00
Summary
Regenerative cellular therapy e.g. with adult stem cells is a promising novel medical therapy. However, until now there is no reliable method to direct cells to areas where they are needed. We aim to develop a biotechnological approach based on genetically tailored antibody molecules that will allow cell targeting. As a pilot project we will test whether this approach improves lipid deposition and hardening of arteries.
The Role Of The ABCA12 Transporter In Epidermal Lipid Homeostasis And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$516,401.00
Summary
We have shown that a protein called Abca12 can control the transport of lipids in our bodies. If the function of this gene is attenuated both human and mice develop severe skin disease. Our preliminary results indicate the Abca12 protein regulates cholesterol transport in particular, and this grant will investigate how this might affect normal skin function and contribute to the heart disease atherosclerosis, one of the most common causes of death in the western world.
Childhood Cognitive Antecedents Of Adult Psychopathology: Follow-up Of The Port Pirie Lead Cohort Into Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$587,263.00
Summary
The role of childhood factors in the development of adult psychiatric disorder is an important public health concern. Indvividuals identified before birth and followed across the life course offer the most powerful means of establishing predictors for particular types of psychiatric disorder. Not only do these studies enable researchers to more clearly determine the exact age of onset of disorder but they also give us insight into the background and hence possible risk factors that may have lead ....The role of childhood factors in the development of adult psychiatric disorder is an important public health concern. Indvividuals identified before birth and followed across the life course offer the most powerful means of establishing predictors for particular types of psychiatric disorder. Not only do these studies enable researchers to more clearly determine the exact age of onset of disorder but they also give us insight into the background and hence possible risk factors that may have lead to the development of that disorder. Early identification of disorder can significantly reduce public health cost and reduce the burden on the community by enabling individuals to get help before their symptoms become too severe and unmanageable. Few long-term studies have investigated the combined role of pre-natal, developmental, parental characteristics, biological and childhood cognitive risk factors in the development of adult psychiatric dysfunction. Even fewer studies have examinined this interrelationship in a group of individuals who have been exposed to an environmental toxin such as lead. This study will follow-up 723 adults from the lead smelting city of Port Pirie who were originally recruited between 1979 and 1982. All adults were exposed to lead to some degree in childhood and have been followed over various time points over the course their lives. This project will be conducted 27 years since they were first involved, and will hence be one of the longest studies to be conducted in this field. The extensive information already collected on this group of individuals will enable us to create a very comprehensive picture of risk and protective factors for various types of adult disorder.Read moreRead less
In Vivo Role Of LMO4 And Isolation Of An LMO4-containing Proteosome In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understandi ....Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes thought to contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. Nuclear regulatory proteins have been implicated in many different types of cancers and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their structural properties and biological roles, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific regulatory molecule which we recently demonstrated to be overexpressed in 56% of human primary breast cancers and in 38% of pre-invasive ductal carcinoma in situ. These studies will include defining its normal biologic function and identification of the proteins that this regulator associates with in breast cancer cells.Read moreRead less
Immunopathogenesis Of Human And Murine Herpes Simplex Infections
Funder
National Health and Medical Research Council
Funding Amount
$315,000.00
Summary
Herpes Simplex virus causes genital herpes, brain infections, eye infections and if passed by a mother to her infant during delivery can cause a highly damaging and sometimes lethal disease in the newborn. The virus has developed a number of strategies to overcome our immune system. The aim of this grant is to define some of these strategies in human tissue and in mice and in order to reverse them we are also defining the viral proteins which stimulate the critical immune cells . In addition we ....Herpes Simplex virus causes genital herpes, brain infections, eye infections and if passed by a mother to her infant during delivery can cause a highly damaging and sometimes lethal disease in the newborn. The virus has developed a number of strategies to overcome our immune system. The aim of this grant is to define some of these strategies in human tissue and in mice and in order to reverse them we are also defining the viral proteins which stimulate the critical immune cells . In addition we wish to understand the reasons why newborn babies have severe herpes disease compared to adults . What we learn from our experiments will assist us in developing a more effective vaccine against herpes and find new ways to treat this virus in the very young.Read moreRead less