The Role Of The NPY System In The Regulation Of Appetite And Satiety
Funder
National Health and Medical Research Council
Funding Amount
$1,088,384.00
Summary
Eating disorders that have a causative role in the development of obesity and anorexia present massive health care problems for which current preventive methods and therapies are unsatisfactory. The studies proposed here combine sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses. By utilising a panel of unique mouse models (many of which are only available to us), missing or overproducing key factors in the regulation of appetite and satiety this rese ....Eating disorders that have a causative role in the development of obesity and anorexia present massive health care problems for which current preventive methods and therapies are unsatisfactory. The studies proposed here combine sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses. By utilising a panel of unique mouse models (many of which are only available to us), missing or overproducing key factors in the regulation of appetite and satiety this research will make highly original and internationally competitive contributions to the understanding of these disorders. The results will have a significant impact on the development of novel diagnostics and potential treatments for obesity and anorexia. In addition, funding provided through this grant would not only help to find answers to these important questions but will also provide the basis for the generation of several novel mouse models. These animal models will also be beneficial tools for the wider scientific community here in Australia and worldwide. We have a proven record in the generation and comprehensive analysis of transgenic and knockout mice models making this proposal not only feasible but also highly likely to succeed and provide great new insight into extremely important health problems.Read moreRead less
Obesity is an every increasing problem worldwide, with major risks for the development of associated cardivasular and type II diabetes related disorders. This research project will determine the underlying mechanisms of how specific receptors in the brain control energy metabolism, appetite and body fat accumulation. It will also determine how peripheral factors can influence this process. The outcome of this research should identify new targets and approaches to prevent and treat obesity and th ....Obesity is an every increasing problem worldwide, with major risks for the development of associated cardivasular and type II diabetes related disorders. This research project will determine the underlying mechanisms of how specific receptors in the brain control energy metabolism, appetite and body fat accumulation. It will also determine how peripheral factors can influence this process. The outcome of this research should identify new targets and approaches to prevent and treat obesity and the associated, type 2 diabetes and cardiovascular disorders.Read moreRead less
This study combines sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses to determine how gut hormones regulate satiety. By utilising unique conditional and germline KO mice , this research will make highly original and internationally competitive contributions to the understanding of the regulation of satiety and energy expenditure. Knowledge as to the causes of lack of satiety will be of great benefit in the search for novel treatments for obesity.
Molecular Definition Of Neural Pathways In The Embryo And Adult Mouse
Funder
National Health and Medical Research Council
Funding Amount
$401,000.00
Summary
It is our objective to gain insight into the role of the Stem Cell leukaemia (SCL) gene in the central nervous system (CNS). SCL is known to play a crucial role in blood cell development and if aberrantly expressed can lead to T-cell leukemia. Although we do know that SCL is expressed in the brain, its role in the CNS has not been addressed so far and it is of great interest to us to study its potential function in neural development. We have designed a series of experiment in mice to elucidate ....It is our objective to gain insight into the role of the Stem Cell leukaemia (SCL) gene in the central nervous system (CNS). SCL is known to play a crucial role in blood cell development and if aberrantly expressed can lead to T-cell leukemia. Although we do know that SCL is expressed in the brain, its role in the CNS has not been addressed so far and it is of great interest to us to study its potential function in neural development. We have designed a series of experiment in mice to elucidate the expression pattern of SCL in the CNS, to identify the phenotype of neural cells that express SCL in different regions of the mouse brain, and to ablate the SCL gene at different time points during life (during embryonic development, just after birth and during adulthood). These experiments will be performed in conditional transgenic mice that have unique and precisely defined genetic alteration and are generated by us specifically for our research on the SCL-gene. This genetic approach is used to define the neuroanatomical and molecular bases of SCL-function in the brain.Read moreRead less
The Role Of Platelet Derived Growth Factor Receptor Alpha (Pdgfra) In Coronary Vascular Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$666,840.00
Summary
The coronary vessels supply blood to heart muscle. Blockage of coronary vessels causes heart attacks which are the leading cause of death in the Western world. A recent focus for heart attack researchers is to re-establish the blood supply to the injured area by creating new blood vessels. We have found a new gene involved in creating coronary blood vessels. We will characterize how this gene is involved in this process. Knowledge about this gene may foster new treatments for heart attack.
Epilepsy is a serious condition having a massive impact on individuals and the community at large. Our understanding of the genetic causes of epilepsy is growing rapidly. We have created new animal models based on human mutations. We have shown that mutations can change the wiring of the brain during development so that the adult brain is more likely to become epileptic. Projects in this grant test if we can stop this developmental impact- allowing us to treat epilepsy before seizures occur.
Epilepsy is an important human disease because it causes physical trauma and sudden death in addition to immense social and economic hardship. The genetic basis of a number of epilepsy syndromes has been identified but the precise mechanism whereby mutations produce seizures is unknown. Several mutations in the alpha4 neuronal nicotinic receptor (a4 nAChR) gene have been identified in Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). This is a rare form of inherited epilepsy character ....Epilepsy is an important human disease because it causes physical trauma and sudden death in addition to immense social and economic hardship. The genetic basis of a number of epilepsy syndromes has been identified but the precise mechanism whereby mutations produce seizures is unknown. Several mutations in the alpha4 neuronal nicotinic receptor (a4 nAChR) gene have been identified in Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE). This is a rare form of inherited epilepsy characterized by the presence of seizures during light sleep. In vitro studies using the human mutated DNA (i.e. DNA containing the genetic defect) have suggested that this mutation results in reduced activity of the receptor. Therefore a mouse in which this gene is destroyed would be relevant in understanding the human disease. We have generated an a4 nAChR knockout (KO) mouse and plan to use the mouse to test the idea that loss of function of the a4 nAChR in vivo is associated with enhanced seizure activity. The KO mice do not have unprovoked seizures but appear to have an increased number of major motor seizures in response to pentylenetetrazole, an agent which is known to cause seizures by blocking the effects of the brain inhibitory molecule GABA. Interestingly, a4 nAChRs are known to control the release of GABA. We therefore propose that our knockout mice have seizures because they tend to under produce GABA. We will also make and analyse a mouse line with the same genetic mutation as patients with ADNFLE. The experiments are aimed at understanding the way that seizures are generated and spread in the brain in these rare forms of epilepsy. The hope is that understanding these mechanisms will help us better understand and therefore treat common forms of epilepsy.Read moreRead less