Research Fellow

Vacancy Reference Number

MHLCM1316

Organisation:

University of Leeds

Closing Date

31 Jan 2023

Salary

35,333

Address

University of Leeds

Duration

2 years

Investigating the structural basis of inherited heart disease with mass spectrometry and cryoEM https://jobs.leeds.ac.uk/Vacancy.aspx?ref=MHLCM1316

Further Information

We are looking for a highly motivated postdoctoral research fellow to join a team of researchers investigating the structural basis of hypertrophic cardiomyopathy, an inherited heart disease that affects more than 1 in 500 people. Most mutations resulting in disease are found in either β-cardiac myosin heavy chain or cardiac myosin-binding protein-C (cMyBP-C) yet the link between mutation and disease outcome is poorly characterised. By use of an integrative structural biology approach this research project will unravel structural-functional relationships between β-cardiac myosin and cMyBP-C and the impact of disease mutation on those relationships. The project will use a combination of electron microscopy (negative-stain and cryo), structural mass spectrometry, biochemistry, biophysics, molecular modelling and cell biology methods to achieve this.We are looking for a highly motivated postdoctoral research fellow to join a team of researchers investigating the structural basis of hypertrophic cardiomyopathy, an inherited heart disease that affects more than 1 in 500 people. Most mutations resulting in disease are found in either β-cardiac myosin heavy chain or cardiac myosin-binding protein-C (cMyBP-C) yet the link between mutation and disease outcome is poorly characterised. By use of an integrative structural biology approach this research project will unravel structural-functional relationships between β-cardiac myosin and cMyBP-C and the impact of disease mutation on those relationships. The project will use a combination of electron microscopy (negative-stain and cryo), structural mass spectrometry, biochemistry, biophysics, molecular modelling and cell biology methods to achieve this.

You should have a PhD (or be close to completion) in Structural Biology, Biochemistry, Biophysics or a related discipline. You should have experience in the analysis of macromolecular structure using either structural mass spectrometry methods (e.g. native mass spectrometry, chemical crosslinking, covalent footprinting and/or hydrogen-deuterium exchange), and/or cryo-electron microscopy, and complementary biophysical methods (e.g. circular dichroism, SDSPAGE). You should also have experience in protein production.

You will be based in the laboratory of Dr Charlie Scarff (BHF Intermediate Fellow) and will work closely with collaborators at Leeds (Dr James Ault, Dr Sarah Harris and Prof. Michelle Peckham), across the UK and internationally (Prof. Howard White, EVMS and Prof. Donald Winkelmann, Rutgers). You will join the vibrant LICAMM and Astbury Centre communities and benefit from the world-leading facilities we have in the Astbury Biostructure Laboratory (two Titan Krios microscopes) and Mass Spectrometry Facility (dedicated HDX-MS system, UHMR Q-Exactive and Orbitrap Exploris).

Contact Details

Charlie Scarff
c.a.scarff@leeds.ac.uk