Dr Charlie Scarff

Profile

I am a British Heart Foundation Jacqueline Murray Coomber Fellow and University Academic Fellow in Structural Biology in the Leeds Institute for Cardiovascular and Metabolic Medicine at the University of Leeds, UK and a member of the Astbury Centre for Structural Molecular Biology.

I obtained a BSc in Computational Biology in 2006 and a PhD in Biological Sciences, in 2010, from the University of Warwick, UK.  In my PhD studies, I explored how structural mass spectrometry-based approaches could be used to study macromolecular complex structure and dynamics. I then moved to the University of Leeds as a postdoctoral researcher, applying structural mass spectrometry to the understanding of amyloid assembly, working with Prof. Alison Ashcroft and Prof. Sheena Radford FRS, and subsequently studying muscle proteins by use of electron microscopy, with Prof. John Trinick. Through this work an interest in muscle, myosin and inherited heart disease grew and I realised how I could contribute to this research area through an integrative structural biology approach. I was awarded a Wellcome Trust Institutional Strategic Support Fund Fellowship in 2017 to explore this avenue of research and this now forms the focus of my current BHF fellowship, awarded in 2020; studying the structural basis of inherited heart disease by mass spectrometry, biochemical analysis and cryo-electron microscopy. In 2022, I was appointed a University Academic Fellow in Structural Biology in the Leeds Institute for Cardiovascular and Metabolic Medicine.

Responsibilities

• Academic Lead for Equity, Diversity & Inclusion in LICAMM

Research interests

My research interests are in understanding structural-functional relationships in muscle, myosin and how defects in myosin and muscle proteins lead to disease. We use an integrative structural biology approach to study this, primarily combining cryo-electron microscopy, mass spectrometry, and mutational analyses with modelling. We are also passionate about the development of integrative structural biology methods as technology drives biomedical research. 

Our current research focus is on understanding the structural mechanisms that underpin inherited heart disease, especially hypertrophic cardiomyopathy. We also have an interest in dilated cardiomyopathy, diabetic cardiomyopathy and the effects of glycation on muscle proteins and structure-based drug design.

In collaboration with Dr Stephen Muench and Prof. Howard White, we use time-resolved cryo electron microscopy to study the mechanochemical cycle of myosin in health and disease and have recently revealed the structural mechanism of myosin force generation (Klebl et al. 2024 BioRxiv https://doi.org/10.1101/2024.01.05.574365)

Qualifications

• PhD

Professional memberships

• Member of the Association of Inherited Cardiac Conditions
• Member of the British Biophysical Society
• Member of the Biochemical Society
• Member of the British Mass Spectrometry Society

Student education

Tutor and Proteins Topic Lead for Introduction to Medical Sciences (MEDI1216)

Lecturer on Advanced Research Topics Module, FBS (BMSC5301M)

Lecturer on Human Disease Module, FBS (BIOL22011)

Research groups and institutes

• Multidisciplinary Cardiovascular Research Centre
• LICAMM - international PhD academy
• Discovery and Translational Science
• Leeds Institute of Cardiovascular and Metabolic Medicine

Projects

<li><a href="//phd.leeds.ac.uk/project/1985-developing-live-cell-crosslinking-mass-spectrometry-methods-to-investigate-cardiac-myosin-folding-and-disease">Developing live cell crosslinking mass spectrometry methods to investigate cardiac myosin folding and disease</a></li>