Calcium uptake and heart relaxation

Understanding the calcium uptake in cardiac sarcoplasmic reticulum: toward new routes to combat human dilated cardiomyopathy

Alfonso De Simone (lead researcher)

Imperial College London

Start date: 01 March 2015 (Duration 3 years)

Calcium uptake in part of the heart muscle cell called the sarcoplasmic reticulum (SR) is crucial for the heart to relax, and is controlled by a protein called SERCA. In dilated cardiomyopathy, a cause of heart failure, SERCA either does not work or is not controlled properly. As well as SERCA, a protein called phospholamban (PLN) is important for calcium uptake, and regulates SERCA activity. Currently, we don’t really understand how SERCA and PLN interact.

The BHF has awarded a grant to Dr Alfonso De Simone from Imperial College London to examine this interaction in detail using state-of-the-art techniques called solid-state nuclear magnetic resonance (ssNMR) spectroscopy and biomolecular computations. They will also work out how gene alterations in PLN have an effect on the interaction with SERCA, which may reveal new ways to design gene therapies for heart failure.

This project will reveal how heart relaxation is controlled at the molecular level and may uncover the cause of dilated cardiomyopathy. Their work may also reveal ways to design new drugs and molecules to combat heart failure by targeting the SERCA/PLN proteins.

Project details

Grant amount £198,531
Grant type Project Grant
Start Date 01 March 2015
Duration 3 years
Reference PG/14/93/31237
Status Complete

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