Cryo-Electron Microscopy Facility – funding target achieved
The Cryo-EM consortium has been awarded by the University the final tranche of funding needed to deliver phase two of the project which will allow the consortium to complete the purchase of a second, high resolution 300kV FEI Krios microscope, complementing the 200kV instrument acquired at the end of 2016. The combination of these two complementary instruments establishes a comprehensive core Cryo-EM Facility, for use primarily (but not exclusively) by investigators across the Schools of the Biological Sciences and Clinical Medicine.
The development of new methods to determine the structures and assemblies of biological molecules and macromolecular complexes has underpinned major conceptual advances in our understanding of life, from the basis of genetic heredity to the origins of complex diseases. For more than half a century, X-ray crystallography and NMR spectroscopy have been the principal tools for elucidating the detailed structures of biological molecules at the atomic level. The challenge for the future is to understand how biological molecules interact to form larger, and often transient, macromolecular assemblies in the cell and how aberrant assembly processes lead to disease. Large, dynamic assemblies are very challenging to study by X-ray crystallography or NMR. However, advances in electron microscopy over the past few years have made it the method of choice for elucidating the structures of complex assemblies at near atomic resolution. The new Cryo-EM Facility therefore provides a revolutionary new tool for researchers in the University that, together with cutting-edge computational approaches to processing Cryo-EM data, will allow determination the structures of diverse biological complexes and machines in normal physiology and disease. The beneficial effects of a Cryo-EM Facility will be far-reaching across the University, the wider Cambridge research community and beyond by enabling a diverse range of investigations, including on-going studies of: membrane transporters involved in multi-drug efflux; assemblies that govern RNA metabolism; the large-scale structure of chromatin; the complex and dynamic assemblies that mediate gene transcription, DNA replication and DNA repair; mitochondrial complex I and its roles in various human pathologies; ribosome assembly and defects in bone marrow failure; structural analysis of presenilin complexes and other assemblies implicated in neurodegenerative disease; and the general development of Cryo-EM based technologies.
The Department of Biochemistry was the catalyst for the creation of the consortium to deliver Cryo-EM and was the University lead to seek funding. However, many other institutions contributed and support from them and the University was integral for this project to achieve its objective. Ben Luisi was the lead investigator for funding requests to the Wellcome Trust, supported within the department by Luca Pellegrini, Dima Chirgadze, Tom Blundell, Simone Weyand and Nick Smith. Within the cryo-EM consortium, thanks must go to Prof. Alan Warren, Prof. Peter St George Hyslop, Prof. Randy Read and Prof. David Owen of CIMR, Dr Judy Hirst and Prof. Sir John Walker of the MRC Mitochondrial Biology Unit, and Prof. Melinda Duer from Chemistry, all of whom not only contributed to the applications but were instrumental in raising finance as well. We should also thank the Wellcome Trust for its generous support across the two phases, amounting to £4m, and the University through its central funding, amounting to just under £1.4m. We also gratefully acknowledge Prof. Sir Mark Welland, of the Dept. of Engineering, who was instrumental in gaining initial access for the consortium to the commercial 300kV instrument located in the Nanoscience centre, and for his support and advice throughout. Thanks also to Prof. Gillian Griffiths, Director of CIMR, and to the two Heads of School – Prof. Abby Fowden at SBS and Prof. Patrick Maxwell, Regius Professor of Physic at the Clinical School.
The Cryo-EM Facility will be located in the Sanger Building, where we have made available two dedicated rooms in the second basement to house the two instruments. Work has commenced and will shortly be available for installation and commissioning of the 200kV instrument. The 300kV instrument has now been ordered and delivery is scheduled for December 2017. We are indebted to the Department’s NMR facility for their support in developing plans to accommodate the cryo-EM facility in the basement. Use of the new cryo-EM facility will be provided through a transparent access plan and backed by highly trained technical and scientific support.
More information regarding the Cryo-Electron Microscopy Facility can be found here.