Experience-dependent Maturation And Plasticity Of The Cerebral Cortex Mediating Schizophrenia-like Endophenotypes
Funder
National Health and Medical Research Council
Funding Amount
$384,199.00
Summary
We will use genetic mouse models of schizophrenia to understand how specific abnormal behaviours are caused, focusing on cells and molecules within the brain. We will investigate how the gene mutations disrupts communication between, and production of, brain cells (neurons), and the role of mental and physical activity. The results of this project will not only have implications for understanding schizophrenia, but also for other brain disorders involving cognitive problems, such as dementia.
An Investigation Of The Aetiology Of Eating Disorders: Interactions Between Genes And Environmental Risk Factors.
Funder
National Health and Medical Research Council
Funding Amount
$225,000.00
Summary
Eating disorders, along with substance abuse, carry the highest risk of premature death, from both natural and unnatural causes, out of 27 mental disorder categories. Eating disorders, including anorexia nervosa, bulimia nervosa, and binge-eating disorder, affect about 6% of Australian women. Despite increased levels of research into the aetiology of eating disorders over the last 20 years, little knowledge exists as to which risk factors cause women to attempt weight loss to the point of increa ....Eating disorders, along with substance abuse, carry the highest risk of premature death, from both natural and unnatural causes, out of 27 mental disorder categories. Eating disorders, including anorexia nervosa, bulimia nervosa, and binge-eating disorder, affect about 6% of Australian women. Despite increased levels of research into the aetiology of eating disorders over the last 20 years, little knowledge exists as to which risk factors cause women to attempt weight loss to the point of increasing their risk of premature mortality. A review of twin studies in eating disorders concludes that there is increasing evidence to suggest that genetic factors play a role in the development of eating disorders. In addition, a recent series of studies, examining risk factors before the age of eating disorder onset, have found the following events to specifically predict the development of an eating disorder as opposed to another psychiatric condition: negative self-evaluation, parental alcoholism, low parental contact and high parental expectations, critical comments about weight, shape or eating during childhood, and childhood obesity. To date, no studies have attempted to integrate the findings from twin studies with the findings from early risk factor studies. Specifically, the ways in which genes interact with the environment to increase the chances of genetic vulnerability to an eating disorder being expressed have not been examined. The proposed project seeks to investigate precisely these interactions between genes and the environment, by examining a large number of female twins, aged 29-37. An enhanced understanding of how genes interact with the environment to either increase the chances that a woman will develop an eating disorder, or alternatively to protect a woman from developing an eating disorder, will benefit our understanding of how to target prevention and treatment strategies.Read moreRead less
Environmental Influences On Allergic Airways Disease From Birth To 8yrs: Long-term Outcomes Of A Randomised Trial (CAPS)
Funder
National Health and Medical Research Council
Funding Amount
$530,000.00
Summary
The prevalence of asthma in Australia is among the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the ....The prevalence of asthma in Australia is among the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the Childhood Asthma Prevention Study (CAPS) which has been underway since mid-1997. CAPS is a randomised controlled trial in which 616 infants at high risk of developing asthma because of a family history have been enrolled. The interventions include allergen reduction and dietary supplementation with omega-3 fatty acids. The interventions are designed to have maximum effect but be simple to implement by parents. Objective and subjective measurements of exposures, atopy, diet and asthmatic symptoms are being collected at 3 month intervals and at medical assessments when the children are 18 months, 3 and 5 years old. The interventions are stopped at age 5 years. The continued follow up of the cohort to age 8 will enable us to test conclusively if the interventions have had a positive effect. If so, CAPS will form the basis for a nationwide public health campaign which will have the potential to reduce the incidence of childhood asthma in Australia.Read moreRead less
KConFaB - A CONSORTIUM FOR RESEARCH ON FAMILIAL BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$1,624,711.00
Summary
Breast cancer is the most common disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australia-wide study is to collect clinical, epidemiological and genetic data on approximately 700 of these severely-affected families. This national resource will be of great value for researchers who want to identify and characterize the genetic and life-style factors that affect the onset and progression of t ....Breast cancer is the most common disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australia-wide study is to collect clinical, epidemiological and genetic data on approximately 700 of these severely-affected families. This national resource will be of great value for researchers who want to identify and characterize the genetic and life-style factors that affect the onset and progression of the disease. The data emerging from the study will lead to more accurate genetic counselling, better surveillance and, ultimately, better methods to prevent and treat the disease in families who inherit a predisposition to the disease.Read moreRead less
Molecular Mechanisms Mediating Experience-dependent Cellular Plasticity And Cognitive Deficits In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$550,387.00
Summary
We will use a genetic mouse model of Huntington's disease (HD), to understand how cognitive disorders (dementia) are caused, focusing on cells and molecules within the brain. We will investigate how the HD gene mutation disrupts communication between brain cells (neurons), as well as disrupting production of new cells (via adult neural stem cells). The results of this project will not only have implications for treating HD but also for other diseases involving dementia, such as Alzheimer's.
Melanoma is one of Australia?s major cancer problems, but we still do not completely understand why certain people are at higher risk than others. This study is focussed on people who have developed melanoma at an early age (under 40yrs) and will compare their family history of cancer, skin features, genetic characteristics and various aspects of their previous sun exposure with people who don?t have melanoma. The large number of people involved and the fact that they will be selected at random ....Melanoma is one of Australia?s major cancer problems, but we still do not completely understand why certain people are at higher risk than others. This study is focussed on people who have developed melanoma at an early age (under 40yrs) and will compare their family history of cancer, skin features, genetic characteristics and various aspects of their previous sun exposure with people who don?t have melanoma. The large number of people involved and the fact that they will be selected at random from the population of Melbourne, Sydney and Brisbane which have very different melanoma rates, means that the study will be able to clarify what roles genes and environment play in the disease. It is intended to be an international benchmark in this regard, and Australia is the only country in which a study of this scope could be mounted. Potential benefits from this research will be a better understanding of the way sun exposure affects people differently, depending on their genetic makeup, the place of genetic testing in assessing people?s risk of melanoma, particularly if they have relatives with the disease, and way in which skin features like moles should be taken into account in that assessment. Finally, it is likely that better information about the types of genetic susceptibility to melanoma in the population will translate to more effective programs for the prevention of melanoma and for detection of melanomas efficiently at the earliest possible stage.Read moreRead less
It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of ....It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of depression. If true, this could have important practical implications for preventative mental health, in identifying those at greatest risk if depression and counselling them to avoid stressful situations. However, success in replicating this finding has been mixed, and this is possibly because another important risk factor, social support, has not been taken into account. We have DNA samples from over 5000 twins who have been assessed for depression and risk factors including SLE and SS. This will give us unprecedented power to estimate the importance of the genotype x environment interaction. We shall also type other genes that have been implicated in depression and check for interactions with life events and social support. Our results will inform preventative strategies in mental health practice.Read moreRead less
Transport And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$592,023.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins and how the virus escapes from nerves to infect skin and cause disease. Such information on viral transport will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities. Finally this data will assist in understanding similar mechanisms for other viruses transported in nerve cells such as those causing shingles and rabies.Read moreRead less
Characterization Of The Chloroquine Resistance Transporter Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$400,527.00
Summary
The malaria parasite is a single-celled organism which invades the red blood cells of its host. The aim of this project is to characterise the mechanism by which parasites have become resistant to the antimalarial drug chloroquine. Resistance is conferred by small changes in a single protein, but the underlying mechanism is not known. The results of this project will constitute a major advance in our understanding of the increasingly widespread phenomenon of antimalarial drug resistance.