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MASTERS BY RESEARCH PROJECT: Cryo-EM and High-resolution structural studies of cardiac thin filaments


Project Description

Start 23 September 2019

This MSc by Research is a laboratory-based project which offers the exciting opportunity to spend 1 year in one of our State-of-the-Art laboratories (plus 1 year thesis writing) at the University of Bristol and experience life as a researcher. You will be working with one of our cutting-edge research groups where you will learn new skills and techniques, including experimental design and implementation, data analysis and scientific writing.

To understand how mutations in the thin filament regulatory protein troponin cause familial hypertrophic cardiomyopathy (HCM) it is important to know the structure of the cardiac thin filament. Techniques for the genetic manipulation of the zebrafish are well established and it has become a major model for the study of human cardiac disease. Our lab isolates zebrafish thin filaments from adult fish and are working to create a zebrafish model with mutations which cause HCM in humans. We study the 3D structure using Cryo-Electron Microscopy (EM), where the thin filaments are preserved in a frozen hydrated state. Using transmission EM and single particle analysis we can reconstruct a 3D map of the filament.

We now want to study the structure of these filaments in situ and our goal for this project is to look at frozen hydrated cardiomyocytes from zebrafish. After freezing the myocytes, we will perform cryo-sectioning and tomography of the to elucidate the ultrastructure. Some of the techniques that will be learnt in this project include; microdissection, EM and Cryo-EM sample preparation, EM and Cryo-EM imaging, image processing and 3D molecular fitting.

Please visit the UOB/faculty of Life Sciences/ School of Physiology, Pharmacology and Neuroscience/ postgraduate studies website for the complete list of available MSc by Research projects.

Funding Notes

This is a one-year, self-funded Masters (MSc) by research. Fees are £4300 (UK/EU Fee) and bench costs are £5000. Applicants should have (or expect to receive) the equivalent of a First or Upper second-class honours degree in a biomedical discipline.

When applying please select the Faculty of Life Sciences, MSc by Research, School of Physiology, Pharmacology and Neuroscience

References

González-Solá M, Al-Khayat HA, Behra M, Kensler RW: Zebrafish cardiac muscle thick filaments: isolation technique and three-dimensional structure. Biophys J. 2014 Apr 15;106(8):1671-80
Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism.
Paul DM, Squire JM, Morris EP. J Struct Biol. 2017 Mar;197(3):365-371.
Becker JR, Deo R C, Werdlich AA, Panakova D, Coy S and MacRae C A: Human Cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenisis in zebrafish. Disease Models & Mechanisms. 2011 4, 400-410

Related Subjects

How good is research at University of Bristol in Biological Sciences?

FTE Category A staff submitted: 64.60

Research output data provided by the Research Excellence Framework (REF)

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