Move over sequencing - it's a structural future!
Last month the Imperial College Centre for Structural Biology, IC-CSB, was opened by the Rector, Sir Richard Sykes DSc FRS. This day was the culmination of nearly four years work - from the initial idea of setting up the Centre to its housing in the Flowers building. Taslima Khan talks to the Centre's director, Paul Freemont about his plans for structural biology at Imperial.
WHAT IS STRUCTURAL BIOLOGY?
Professor Freemont, over £15 million has already been awarded to the IC-CSB. But what is structural biology and why is it important to me?
 A poster session: visitors and IC staff at the official opening of the new Imperial College Centre for Structural Biology laboratories in the Flowers building |
"It is important," replies Professor Freemont, Director of the IC-CSB and Chair of Protein Crystallography, "by understanding the structure of biological macromolecules you get clues how they function. Imagine a car, how does it work? If you didn't know what it did, you could look at its individual components and take a guess. However, with a full 3D description of the car, you could make a much better guess. If you already knew how it worked, then having the structure would provide you with a more complete understanding of its function. The same is true of macromolecules - by understanding their shape and construction one might understand how they function.
”This information provides molecular insights into the biological systems and processes under study, but it also provides the basis for inhibiting or manipulating their function. This could be directly applicable in the treatment of disease - for example gene therapy or drug design," he adds.
What do you feel about structural biology's future?
 Professor Paul Freemont - Director, Imperial College Centre for Structural Biology |
"I am excited. Structural biology is going through a mini-revolution because of advances in both the techniques that we use to determine structures, and also in our understanding of molecular and cellular biology. We've got full sequences from many prokaryotic organisms including several human pathogens, and information from the human genome project. Structural biology is going to follow on from this because scientists will want to know the functions of all the proteins these DNA sequences encode."
RESEARCH
Formally established on 1 January 2000, the Centre is located in the Flowers building. It will provide a focal point for co-ordinating and promoting interactions between all departments with an interest in structural biology. “There are other structural biology centres in the UK, but what is unique about IC is that we have all the methods and techniques represented on one campus with leading people in those techniques,” says Professor Freemont.
So, where is the research going to originate from?
"What we are going to do is exploit opportunities locally," he continues. "We have excellent molecular microbiologists who are pushing ahead in the area of infectious disease. Then in the medical school, groups are trying to understand what genes either cause predisposition to certain diseases or by mutation result directly in certain diseases. Our role would be to determine the structures of these disease-linked proteins in order to understand how they exert their abnormal effects and also to provide the basis for developing novel therapeutic reagents. It is going to be a highly interactive environment that bridges different disciplines and departments.
 Marin van Heel, Professor of Structural Biology |
"Professor Marin van Heel, Department of Biological Sciences, for example, is a world figure in the emerging field of single particle electron cryo-microscopy. There is also very strong protein crystallography, first established by the eminent Professor David Blow. With Professor Anne Dell amongst the world leaders in mass spectrometry, and the excellent group and facilities led by Dr Stephen Matthews for nuclear magnetic resonance, IC has the potential to be the best in the world for structural biology."
Other College researchers active in the structural biology field share his enthusiasm. Dr Erhard Hohenester, Wellcome Senior Research Fellow, [biophysics section, department of Biological Sciences] writes: "The Centre will represent structural biology to both colleagues at IC and to the outside world. There is a huge reservoir of interesting biomedical projects, which we structural biologists could and should tap. Until now, a clinical scientist would have had to know (of) a structural biologist in order to set up collaborations. The Centre could provide a 'single entry point' and help in setting up pilot projects."
Nick Franks, Professor of Biophysics and Anaesthetics, [Head of biophysics section, department of Biological Sciences] agrees: "I'm delighted that the virtual Centre we have had is now developing into something more tangible. I'm sure it will provide a great opportunity for everyone throughout the College with interests in structural biology to benefit."
BACKGROUND - THE VIRTUAL CSB
It was 1997 when Professors Jim Barber and Nick Franks, both in Biological Sciences, established a steering committee to define what structural biology meant for the College. Professor Marin van Heel, head of the embryonic IC-CSB at this time remembers: "The idea for setting up the Centre for Structural Biology was to give a new impulse to this whole corner of the college. There was not enough contact between the people doing structural biology and there were departmental barriers. We wanted a grouping that would meet once in a while or undertake joint initiatives such as writing grants and seminars - that was the purpose of the exercise."
Spurred on by a Biotechnology and Biological Sciences Research Council initiative to establish centres of excellence in structural biology, members of the IC-CSB steering committee successfully applied for a grant which exceeded £1 million.
With additional money from College, the IC-CSB was able to establish facilities for cryo-electron microscopy and X-ray crystallography, two major methodologies used in the field of structural biology. These facilities added to the existing world-class structural analysis groups already established here.
THE FLOWERS BUILDING
 The Flowers building today |
How will the Flowers building be set up for structural biology analysis?
The Flowers building will provide the opportunity for interaction between scientists from many disciplines. The basement of the new building will house the College cryo-electron microscopes and a custom-made CM300 microscope designed by Phillips. The £2 million CM300 is the first in a new generationof microscopes - the only one in the UK.
 Construction of the Flowers building |
On the ground floor, the IC-CSB laboratory will provide the management for a centralised X-ray crystallography data collection facility to be used by all IC crystallographers. Financing for this part of the Flowers building was achieved by a successful JIF bid totalling some £13 million. It allowed the refurbishment of the Mass Spectrometry Suite; the creation of additional suites for X-ray crystallography and electron microscopy in the Biochemistry building; and NMR and Bioreactor facilities.
THE FUTURE
The Centre's steering committee, with representatives from across College, aims to develop a much higher profile to attract further funding to the Centre and IC, and help in the development of a postgraduate training programme.
For Professor van Heel, College is acknowledging that structural biology is going to be a very important part of education and research in the future. "Whether you are a biology or medical student, you will always sit in front of screens and look at molecules and see why a mutation here or there is so deadly (or beneficial). Structural biology is here to stay. It will only grow. It is everything and will be integrated everywhere."
 Imperial College Centre for Structural Biology plaque unveiled on 7 June 2001 |
What do you hope the Imperial College Centre for Structural Biology will achieve?
Professor Freemont stresses: "We have all the components to be an extremely powerful, world-leading centre in structural biology. The IC-CSB is a vehicle for anyone in College who is interested in developing a structural dimension to their work. It is a great opportunity for interdepartmental science interaction and collaboration in this golden era for structural biology."
Links
Imperial College Centre for Structural Biology
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