Analysis of human myosin with cardiomyopathy linked mutations
Research type
Research Study
Full title
Analysis of human myosins carrying mutations linked to hypertrophic and dilated cardiomyopathies
IRAS ID
254142
Contact name
Michael Geeves
Contact email
Sponsor organisation
University of Kent
Duration of Study in the UK
2 years, 3 months, 30 days
Research summary
The work forms one part of a 10 centre, EU funded, Horizon 2020 grant to establish computer software system to aid the diagnosis and treatment of inherited heart disease. The Kent part of program is to provide expertise and experimental data on molecular aspects of the disease to help guide the software development and then to help validate the software as it is produced. The software would eventually be made available to clinicians across Europe.
Inherited heart disease affects one in 500 of the population and remains the biggest killer of young adults. 40% of the inherited mutations linked to heart disease are in the protein myosin - the major muscle protein involved in heart muscle contraction. Since the mutations are the trigger for the disease and the mutations are present in the heart from birth we need to understand how the mutations alter the behaviour of the protein that then leads to the disease over a period of 20 or more years.We will extract myosin from 100 mg samples of patient heart tissue and use a range of sophisticated analysis methods define the behavioural differences between the normal myosin and the myosin carrying the mutations of interest. The tissue will be provided by a tissue bank within the European consortium.
Synthesis of human myosin remains extremely difficult with only one or two labs worldwide having this capacity. Thus extracting samples for human tissue remains essential.
We have previous used human cardiac myosin recombinantly expressed in mouse cells in tissue culture. We need to know if the protein in patient hearts is the same. Have there been modifications during the disease progression or changes in the isoforms expressed. Finally if pour analysis provides any diagnostic information on this highly variable disease.REC name
London - Fulham Research Ethics Committee
REC reference
19/LO/1178
Date of REC Opinion
1 Aug 2019
REC opinion
Favourable Opinion