Elucidating Genetic Mechanisms Responsible For Familial Hyperaldosteronism Type II
Funder
National Health and Medical Research Council
Funding Amount
$424,812.00
Summary
Primary aldosteronism (PAL) is the commonest specifically treatable and potentially curable form of hypertension (high blood pressure), a common disease, expensive to treat, with serious morbidity and mortality. This project will use cutting edge technology to gain new knowledge concerning how genes regulate the body's production of aldosterone (salt hormone), which will help us understand how PAL develops and how common it is, and could lead to better approaches to diagnosis and treatment.
Identification Of A Genetic Defect Characterized By Radiosensitivity And Defective P53 Stabilization
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identifica ....Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identification of new syndromes with radiosensitivity assists in delineating the overall response to radiation and the connection with cancer. This project is designed to identify the molecular basis of what appears to be a novel defect. It has some of the characteristics of a well described syndrome ataxia-telangiectasia (A-T), namely signs of neurodegeneration and sensitivity to radiation but the protein defective in A-T appears to have normal function in this case. A comprehensive investigation of a number of pathways of radiation signaling is planned to identify the nature of the defect.Read moreRead less
Hypothalamic Regulation Of Appetite And Energy Homeostasis In Prader-Willi Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$39,987.00
Summary
Prader-Willi syndrome (PWS) is a genetic disease affecting 1/~15 000 people. It causes insatiable appetite and often morbid obesity, as well as other developmental problems. It is thought that there is a defect in the way that the brain regulates eating behaviour in PWS, but the exact mechanism is still unknown. This study proposes to explore metabolic and genetic factors contributing to the appetite disorder in PWS. It will also explore new ways of treating excessive appetite.
Leveraging Record Linkage For Single-indication Medications To Boost Recruitment In Psychiatric And Pharmaco- Genetics
Funder
National Health and Medical Research Council
Funding Amount
$1,840,595.00
Summary
Genome-wide association studies (GWAS) have shown that psychiatric disorders are highly polygenic and that increasing the power of these analyses by increasing the number of participants does lead to the identification of new treatment targets and biomarkers. We seek funding to greatly boost the power of GWAS for Schizophrenia and Bipolar Disorder by using prescription records to recruit individuals who have been prescribed medications that are only used to treat these conditions.
AusGDB-Depression: An Australian Genetic Database Study Of Functional Genetic Variants And Environmental Factors In Major Depression
Funder
National Health and Medical Research Council
Funding Amount
$620,486.00
Summary
Major depression is the leading cause of disability in Australia, but its causes are unknown. Despite a significant role of genes in this disorder and many genetic studies, researchers have not been able to identify the genes that increase the risk for this disorder. In this project, we will identify, characterize and use genetic functional variants and environmental factors to create a way to predict diagnosis of this disorder.
Functional Analysis Of The P160 Myb-binding Protein - A Regulator Of Multiple Transcription Factors?
Funder
National Health and Medical Research Council
Funding Amount
$376,697.00
Summary
The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is like ....The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is likely to be responsible for regulating Myb. However, it has recently become apparent that p160 interacts with a number of other transcription factors in addition Myb. The primary aim of this project is to elucidate precisely how p160 interacts with Myb and what the consequences of this interaction are. A range of experimental approaches, which range from in vitro to genetic studies, will be employed to do this. We will test a specific role of p160 suggested by our preliminary studies - that of a transporter of transcription factors between the nucleus and the cytoplasm of the cell. Because of the wide range of transcription factors that p160 interacts with, its effects on the function of the cell are likely to be profound. For this same reason, it is difficult to specifically predict the possible medical-health implications of this work However, what we know to date is consistent with a role for p160 as a tumour suppressor gene. Moreover, parts of this project aim to generate genetic information and tools which will help in determining whether p160 does play such a role and generally, in identifying any other associations of p160 with particular diseases.Read moreRead less
Noradrenaline Transporter Dysfunction In Neural Circulatory Disorders: Clinical, Molecular And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$510,870.00
Summary
We will investigate the clinical relevance of noradrenaline transporter (NET) dysfunction and its molecular and genetic regulation in (1) essential hypertension, (2) postural tachycardia syndrome where the heart rate increases abnormally when the patient assumes an upright position and (3) syncope where subjects experience recurrent blackouts. In a therapeutic approach, we will explore whether NET inhibition can reduce the number of episodes and alleviate the symptoms associated with syncope.
Genetic Influences On The Comorbidity Between Attention Deficit Hyperactivity Disorder And Substance Use
Funder
National Health and Medical Research Council
Funding Amount
$244,852.00
Summary
Substance use (SU) problems are more common among individuals with a history of ADHD. However, the reasons for this relationship are unclear. Our study will examine the extent to which this relationship is due to shared genetic influences using data collected during interviews about ADHD and SU in a large sample of young adult twins, their siblings and their parents. The results will aid in developing treatments targeting the symptoms of ADHD and SU concurrently.
Unravelling The Genetic Causes Of Bipolar Disorder: Lessons From Rare But Highly Penetrant Variants In Very Heritable Forms Of Illness
Funder
National Health and Medical Research Council
Funding Amount
$705,834.00
Summary
Bipolar disorder is a severe mood disorder affecting over 350,000 Australians, for which the causes remain largely unknown. This project will apply a powerful new technology, exome sequencing, to rare families with highly heritable forms of bipolar disorder to identify specific genetic factors which increase disease risk. A greater understanding of the genetic causes of this illness may eventually lead to improvements in diagnosis, treatment and quality of life of people suffering with this debi ....Bipolar disorder is a severe mood disorder affecting over 350,000 Australians, for which the causes remain largely unknown. This project will apply a powerful new technology, exome sequencing, to rare families with highly heritable forms of bipolar disorder to identify specific genetic factors which increase disease risk. A greater understanding of the genetic causes of this illness may eventually lead to improvements in diagnosis, treatment and quality of life of people suffering with this debilitating mental illness.Read moreRead less