Molecular Mechanisms And Pharmacology Of The Dynamins
Funder
National Health and Medical Research Council
Funding Amount
$883,375.00
Summary
His research focuses on the molecular mechanisms of synaptic transmission in the nervous system to: a) understand the basic science of nerve communication and b) develop drugs to control diseases of nerve terminals like epilepsy. The main focus is on proteins called the dynamins, which are self-assembling molecular machines acting in many intracellular functions. There are three dynamin genes: dynI, II and III with diverse functions in the different parts of the body.
A Novel Mechanism For The Maintenance Of Catecholamine Synthesis
Funder
National Health and Medical Research Council
Funding Amount
$356,250.00
Summary
Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the dru ....Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the drugs all affect the catecholamine systems. Tyrosine hydroxylase controls catecholamine synthesis and it is activated in both the acute and adaptive phases of the stress response in order to replace catecholamines that have been secreted. Tyrosine hydroxylase is activated by protein phosphorylation in the acute phase and by the synthesis of new tyrosine hydroxylase in the adaptive phase. We have now discovered an additional and novel phase that we refer to as sustained tyrosine hydroxylase activation. This phase spans at least the period between the acute (mins) and adaptive phases (days). It involves the sustained phosphorylation of tyrosine hydroxylase and its mechanism appears to differ from the other two phases. In this project we will answer three questions. Does sustained tyrosine hydroxylase activation: 1 Occur in response to many stimuli and in many catecholamine cell types? 2 Occur by a single mechanism, different to the other phases, in all circumstances? 3 Play a role in the control of blood pressure and depression? This project will provide fundamental data about the mechanisms and consequences of sustained tyrosine hydroxylase activation, which is a part of the stress response not previously discovered. The data may impact on the way we design drugs to control stress responses, including antidepressants and antihypertensives.Read moreRead less