The Role Of Dopamine And Other Neuromodulators As Light Signals In The Inner Retina: A Link To Night Blindness Disorders
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-ligh ....Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.Read moreRead less
How Does Sudden Cardiac Death Occur In Familial Hypertrophic Cardiomyopathy?
Funder
National Health and Medical Research Council
Funding Amount
$1,312,606.00
Summary
Familial hypertrophic cardiomyopathy is a leading cause of sudden cardiac death but the mechanisms for the induction of arrhythmia are unknown. This proposal has the potential to impact sudden death in the young and enable significant expansion of Australia’s research capacity into the treatment of familial hypertrophic heart disease in humans.
The primary aim of my research has been to understand how biological ion channels work. All electrical activities in the nervous system, including communication between cells and influences of hormones and drugs on cell function, are regulated by the opening and closing of ion channels. Thus, understanding how these ion channels operate will ultimately help us find the causes of, and possibly cures for, many neurological, muscular and cardiac disorders.
The L-type Calcium Channel In Cardiovascular Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Calcium influx into cardiac muscle cells occurs via the L-type calcium channel. The channel is essential to life but when function is altered it can contribute to the development of sudden death and heart failure. I have made significant discoveries in understanding the role of the channel in disease and I have exploited this knowledge to design therapy including a novel class of calcium channel antagonists to prevent the development of heart failure.
Investigating CRAC Channel Assembly And Interactions Important In Immunity
Funder
National Health and Medical Research Council
Funding Amount
$398,247.00
Summary
#ERROR: -Transmission and amplification of signals between subcellular compartments underpins cell function. Calcium ions are cellular messengers that can cross Membranes using specialised pores. CRAC Calcium channels in particular are critical for immune system function,and partner Proteins switch them on and off in a feedback response to compartmental Calcium levels. the objective of my research is to investigate how opening and closing of the CRAC pore is triggered at a molecular level.
Role Of Calcium Channels And Small-conductance Potassium Channels In Myenteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$131,717.00
Summary
This proposal will investigate the electrical properties of neurons in the wall of the intestine that control movements of the bowel. These neurons form an extensive network that runs the length of the gastrointestinal tract and control mixing and propulsion of food along the intestine. We will determine the basic electrical properties of these neurons and investigate why some of them transmit signals in a continuous manner while others transmit signals intermittently and how these patterns of a ....This proposal will investigate the electrical properties of neurons in the wall of the intestine that control movements of the bowel. These neurons form an extensive network that runs the length of the gastrointestinal tract and control mixing and propulsion of food along the intestine. We will determine the basic electrical properties of these neurons and investigate why some of them transmit signals in a continuous manner while others transmit signals intermittently and how these patterns of activity fit into the overall activity of the gut. This study will build on a large body of data obtained from our laboratory that has shown that some of these neurons act as sensors of the presence-absence of food in the intestine while others send signals to the muscle in the wall of the intestine to either relax or contract it so that the food can be processed properly. By knowing what makes these neurons different from each other we will be able to understand what goes wrong in functional bowel disorders where motility is affected, resulting in pain and discomfort.Read moreRead less
Despite dramatic improvements in diagnosis, prevention and treatment of heart disease, cardiovascular disease remains the commonest cause of death in Australia. The continuing decline in mortality from ischaemic heart disease has been offset by an increase in the incidence of sudden cardiac death due to abnormal heart rhythms. By understanding the basic mechanisms underlying cardiac arrhythmias we are seeking to develop more effective therapies to treat and/or prevent sudden cardiac death.
Understanding Uterine Contractility: What Can We Learn From Obesity?
Funder
National Health and Medical Research Council
Funding Amount
$600,792.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified five dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems, particularly those mechanisms in common.