The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to ....The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to controlling or modifying their function.Read moreRead less
Beyond linear source-filter theory: how does the vocal tract affect the motion of the vocal folds? The human voice lies at the very core of human culture. Yet the way in which the vocal folds ('vocal cords') vibrate is only partly understood and the way in which sound waves within the vocal tract affect this vibration is almost unknown, beyond the fact that it is sometimes important. Using new and unique non-invasive techniques, we shall conduct acoustic experiments to measure properties of the ....Beyond linear source-filter theory: how does the vocal tract affect the motion of the vocal folds? The human voice lies at the very core of human culture. Yet the way in which the vocal folds ('vocal cords') vibrate is only partly understood and the way in which sound waves within the vocal tract affect this vibration is almost unknown, beyond the fact that it is sometimes important. Using new and unique non-invasive techniques, we shall conduct acoustic experiments to measure properties of the vocal folds and their interaction with the sound they produce in the vocal tract. This knowledge will solve some of the remaining puzzles about the voice. Practical applications will include exercises in voice control (especially for singers and orators) and potential applications in clinical diagnosis techniques.Read moreRead less
The role of intracellular calcium in fibre-type specific gene expression in skeletal muscle. Muscles contain different fibre types whose composition can be changed by activity. The aim of this proposal is to identify the intracellular mechanisms which control fibre type. Our hypothesis is that different patterns of intracellular calcium determine the pattern of gene expression which determines fibre type. Understanding how gene expression is regulated is a central issue in biology.