Making and breaking myosin filaments: How smooth muscle cells modulate their contractile behaviour.

Smooth muscle is critically important in a range of functions, from maintaining blood pressure, to squeezing food through the gut and many more. Failure of smooth muscle cells to work correctly can lead to acute (aortic aneurysms) or chronic disease. Surprisingly, we have a very limited understanding of the structure and function of the contractile proteins of smooth muscle cells. This project aims to address this major gap in our knowledge by using a combination of approaches.

We will use Cryo-electron tomography to visualise the contractile cytoskeleton in primary smooth muscle cells and tissue and determine its organisation in unprecedented detail. This approach will benefit from and exploit the new Cryo-FIB SEM @Leeds, as well as our access to advanced Cryo microscopes. We will use advanced labelling strategies to determine how the contractile cytoskeleton remodels in response to a range of pharmacological treatments, using advanced live cell imaging approaches.

We will identify novel interacting proteins that help to shape and organise the contractile cytoskeleton using Turbo-ID and mass spectrometry and use super-resolution imaging to identify precisely where they are located.

Taken together, this project will bring new insight into how the contractile cytoskeleton is organised and remodelled in smooth muscle cells and provide excellent training in cutting edge techniques.