Acquiring a chemo-mechanical understanding of myosin dysregulation

Julien Ochala (primary)
School of Basic and Medical Biosciences
King's College London
Arianna Fornili (secondary)
School of Biological and Chemical Sciences
Queen Mary University London

Abstract

Myosin is one of the most abundant proteins in the human body. After decades of intense research using a wide range of structural and biological approaches, its functions in muscles begin to be elucidated. Despite this knowledge, the field is still at the tip of an iceberg. What remains remarkably unknown is how mutations in this particular protein induce muscle pathologies in horses. In the present proposal, the student will aim to uncover how myosin mutants alter the molecular structure and mechanics. This is a unique multi-disciplinary project combining molecular dynamics simulations and physiological assessments of the mutants.


References

A missense mutation in MYH1 is associated with susceptibility to immune-mediated myositis in Quarter Horses.
https://www.ncbi.nlm.nih.gov/pubmed/29510741

Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil.
https://www.ncbi.nlm.nih.gov/pubmed/29108014

The fraction of strongly bound cross-bridges is increased in mice that carry the myopathy-linked myosin heavy chain mutation MYH4L342Q.
https://www.ncbi.nlm.nih.gov/pubmed/23335206

Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function.
https://www.ncbi.nlm.nih.gov/pubmed/27112274

Ensemble force changes that result from human cardiac myosin mutations and a small-molecule effector.
https://www.ncbi.nlm.nih.gov/pubmed/25937279


BBSRC Area
Animal disease, health and welfare
Area of Biology
Chemical BiologyPhysiology
Techniques & Approaches
BiochemistryBiophysicsMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling