Translational Research Project Grant (PhD studentship)
Dr Tom Van Agtmael, University of Glasgow
Summary: A better understanding of how heart function is controlled and what goes wrong in heart disease will help in the development of new and better treatments. Tissues in our body including the heart are made up of cells which are surrounded by a material called the extracellular matrix. Within this matrix there is a structure called the basement membrane which forms a sheet-like structure that surrounds the muscle cells of the heart. However, the role of the basement membrane in the function of the heart and heart disease is unclear.
One of the major components of the basement membrane is a protein called collagen and Dr Van Agtmael’s team has previously shown that small changes in this protein, called mutations, cause eye, kidney and blood vessel defects. They have now shown that mutations in collagen also lead to defects in the structure and function of the heart. New data suggest these mutations cause the mutant protein to accumulate within cells leading to defects in the matrix including the formation of scar tissue in the heart, a process called fibrosis which is linked with heart failure.
The aim of this project is to understand more about the role of the basement membrane in heart biology and the development of heart defects due to these mutations. Recent work by the team suggests that treatment with a drug can reduce the accumulation of abnormal collagen. They now plan to exploit this exciting result by testing whether they can prevent or reduce the severity of heart defects due to collagen mutations. Since the drug is already approved for other clinical uses, if successful, the project could lead to a more rapid development of new treatments for heart conditions such as cardiomyopathy, heart failure and damage following heart attack.