High resolution structural studies of cardiac thin filaments; heart disease at the molecular level (Mr. Marston Bradshaw)
Proteins that make up heart muscle are arranged into structures called filaments. There are two types of filament: thick and thin. A protein called troponin is one of the main components of the thin filament and acts like a switch that turns the muscle on. When the heart receives a signal to contract, calcium binds to troponin and causes the proteins in the thin filament to move. This process is the start of muscle contraction. It is generally well understood, but a lot of valuable information about the proteins that make up the thin filament is unknown. For example, structural information such as how the proteins change shape when calcium binds to troponin, and what goes wrong with them in heart disease. In this project, researchers will study the structure of the thin filament proteins using cryogenic electron microscopy (cryo-EM). This technique can preserve proteins in their natural state and visualise them at extremely high resolution. The researchers aim to obtain images of the thin filaments when troponin is switched on and off (by calcium), and create 3D models that show how the proteins change shape and position during contraction. They will first study thin filaments from zebrafish hearts, then develop their techniques to study thin filaments from pig and human heart muscle. This research will help inform us how we can improve the function of abnormal or diseased heart muscle e.g. by using the structural information to guide drug design.
Project details
| Grant amount | £120,154 |
|---|---|
| Grant type | Fellowships |
| Application type | PhD Studentship |
| Start Date | 01 January 1900 |
| Duration | 3 years |
| Reference | FS/20/5/34973 |
| Status | In Progress |
