Understanding The Origins Of Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$668,914.00
Summary
Brain cells that control the cardiovascular system are thought to have stopped dividing by adulthood. We recently discovered that this is not the case. Our initial findings suggest that these nascent cells might be important for maintaining normal blood pressure. This work will allow us to elucidate the function of these nascent cells and how they integrate into the circuit that controls the cardiovascular system. Our findings will be fundamental for understanding diseases such as hypertension.
The Brain As A Therapeutic Target For Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$923,432.00
Summary
In heart failure there is a large increase in sympathetic nerve activity to the heart that leads to damage to the heart and sudden death. We have shown that lesion of the area postrema, a brain nucleus that senses hormones in the blood, reduces nerve activity to the heart and, importantly, improves cardiac function. We aim to translate these findings into a treatment that can be used clinically, which our findings compellingly indicate should improve cardiac function in heart failure
Targeting The Sympathetic Nervous System To Reduce The Burden Of Fatty Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$728,152.00
Summary
The metabolic syndrome is characterised by abdominal obesity, high blood pressure and an increased risk of diabetes development. It is clear from our own observations that the sympathetic nervous system (SNS) is important in the generation of obesity-related illness and, through its stimulation of the liver, plays an important role in the development of obesity-related liver disease. We will target the SNS in order to reduce the burden of obesity-related liver disease.
Molecular Targets Of Amino Acid/neurotransmitter Conjugates Of Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$846,390.00
Summary
This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these c ....This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these compounds.Read moreRead less
The Molecular Basis For Target Selection In The Central Nervous System By Sensory Axons
Funder
National Health and Medical Research Council
Funding Amount
$251,325.00
Summary
The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct conne ....The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct connections following injury to the brain or spinal cord. We propose to use a simple model system, the embryo of the fruitfly Drosophila, to find molecules that are involved in this process of neuron target recognition - ' axon targeting' molecules - and to study how they work. Drosophila can be genetically manipulated in ways not possible in higher animals. Furthermore the simplicity of its nervous system means that we can determine the connections of individual nerve cells with a high degree of precision. In the first part of our project, we will examine Drosophila embryos that carry mutations in genes suspected to code for targeting molecules. We will stain individual sensory nerve cells in these embryos with dyes to reveal the anatomy of their axons in the brain. If sensory axons terminate abnormally in the brain of a given mutant, the affected gene is likely to code for an axon targeting molecule. In the second part of the study, we will investigate the functions of candidate axon targeting molecules using two approaches. Firstly, we will seek to determine whether the molecule acts in the sensory axons or in their target cells. Secondly, we will use time-lapse microscopy to study how the homing behaviour of the sensory axons is affected in mutant embryos. The results of these studies will lead us closer to an answer to the question: How do axons recognise their specific target cells in the brain?Read moreRead less
The Role Of Cell Adhesion Molecules In Regulation Of Axon Advance
Funder
National Health and Medical Research Council
Funding Amount
$426,006.00
Summary
All cells contain on their surface a class of molecules, cell adhesion molecules, that enable them to adhere to other cells in tissues. Cell adhesion molecules have long been known to be involved in the guidance of axons to their targets during development. However the molecular mechanisms by which these molecules act are largely unknown. We propose to use the powerful genetic tools available in the fruitfly to dissect the mechanisms by which two cell adhesion molecules promote axon growth.
IDENTIFICATION OF BRAIN NEURONS INVOLVED IN THE CARDIOVASCULAR RESPONSE TO FEAR AND FLIGHT
Funder
National Health and Medical Research Council
Funding Amount
$400,247.00
Summary
The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vess ....The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vessels which restrict the flow of blood to the tissues. These nerves, in turn, are under the control of brain cells or neurons which are located in the brainstem. Blood pressure-controlling neurons, acting upon information they receive from pressure sensors in the major blood vessels in the chest cavity, can alter their activity so that blood pressure is maintained within normal limits. Our laboratory has been examining the properties of these blood pressure-controlling neurons by recording their minute electrical discharges and by studying other brain regions which are able to influence them. In this study, we will use newly-developed procedures which will allow us to identify the precise locations of these neurons in the brain, to study which neurotransmitters (chemicals released by neurons which are used to communicate with other neurons) they use, as well as to identify other regions of the brain they connect with and influence. The major significance of this work will be that new brain circuits which transmit information about the status of the cardiovascular system to other areas of the brain will be identified. Our understanding of, and the development of new treatments for, cardiovascular diseases such as high blood pressure and heart failure are critically dependent on advancing our understanding of the nervous system.Read moreRead less