PROTEIN CHEMISTRY STRUCTURAL BIOLOGY YEARS OF ‘DESIGNING’ BRAND AT THE UK’S LARGEST BIOCHEMICAL NEW PROTEINS PARTICLE ACCELERATOR 50 BREAKTHROUGHS : A BIOCHEMISTRY SPECIAL THE MAGAZINE OF THE ROYAL SOCIETY OF BIOLOGY ⁄www.rsb.org.uk Vol 62 No 5 supplement • Oct/Nov 2015 FLUORO SCIENCE Nobel Prize winner Roger Tsien on the discovery and development of the green fluorescent protein Foreword About David Baulcombe Contents this issue Volume 62 No 5 Oct/Nov 2015 Produced in partnership with the Biochemical Society, this mini special issue aims to showcase the fascinating and important work that biochemists do. Biochemistry has created the tools, techniques and knowledge on which modern bioscience depends. It is at the very core of how all life on Earth works Welcome and its output underpins many other areas of the life sciences ROYAL SOCIETY OF BIOLOGY Charles Darwin House, including medicine, pharmaceuticals, agriscience and 12 Roger Street, London WC1N 2JU biotechnology. Our content here is focused towards the iochemistry is sometimes compared to cookery. Tel: 020 7685 2550 exciting chemistry of proteins, just one of many different types Chefs and biochemists both mix ingredients and Fax: 020 3514 3204 of macromolecule studied by biochemists. We can never do wait with excited expectation for the result – either a [email protected] justice to such a remarkable field in just 16 pages, but we delicious new dish or an experimental outcome. They www.rsb.org.uk hope this one-off biochemistry special whets your both follow recipes, although biochemists refer appetite to find out more. to theirs as ‘experimental protocols’. Continuing this Managing editor Tom Ireland MRSB metaphor, I am reminded of the famous recipe for @Tom_J_Ireland Bjugged hare that is said to [email protected] start with “first catch Tom Ireland, managing editor, your hare”. Royal Society of Biology Biochemists do not normally race around the countryside chasing furry BIOCHEMICAL SOCIETY animals, but until recently Charles Darwin House, there was a parallel 12 Roger Street, London WC1N 2JU preliminary step in our Tel: 020 7685 2400 protocols. We had to process Fax: 020 7685 2467 litres of culture or extract [email protected] www.biochemistry.org kilograms of tissue before we could start work with Science editor, The Biochemist milligrams of the molecule Frederica Theodoulou of interest. freddie.theodoulou@ We now operate on a micro rothamsted.ac.uk scale way beyond the tiniest We are ‘bio’ chemists Community and press editor, amuse bouche in a nouvelle Biochemical Society cuisine restaurant. We can and our ultimate goal Helen Albert start with tiny amounts of [email protected] The Biochemist tissue and get information is to understand how This is an exciting time to be a biochemist as new tools and technologies are about thousands of living systems are offering unprecedented insights into the molecular workings of life. It has been a molecules, rather than just one as in the past. more than the sum of The Biologist and its supplements pleasure to help to develop this special issue for The Biologist and share a small are produced on behalf of With genomics and their parts, for the the Royal Society of Biology by sample of what biochemistry has to offer with a wider audience. If you like what molecular biology, we can Think Publishing Ltd you see in this taster issue, please do take a look atThe Biochemist, to explore isolate genes affecting benefit of humankind Capital House processes that were the wonderful world of molecular biosciences. 25 Chapel Street Roger Tsien on the previously inaccessible to the London NW1 5DH Professor Frederica Theodoulou, science editor, The Biochemist development of the biochemist. From the genes www.thinkpublishing.co.uk 020 3771 7200 green fluorescent protein we see the proteins, and from the proteins we find other Art director Matthew Ball PAGE 6 Designer Dominic Scott components of the Production editor Sian Campbell Breakthroughs in biochemical circuitry in the Professor David Baulcombe, Sub editor Kirsty Fortune IN THIS SUPPLEMENT biochemistry at the cell or organism. president of the Biochemical Society Publisher John Innes Diamond Light Source Metaphors normally break [email protected] 02 50 YEARS OF INNOVATION chemistry will help us down under close inspection and this one is no exception. Few people Views expressed in this magazine are not PAGE 12 necessarily those of the Biochemical Society Seven biochemists make hardier crops would compare modern molecular genetics to mere cookery (and or the Royal Society of Biology. pick their favourite 12 DIAMOND LIGHT biochemists certainly do not ‘cook’ their results…). There is, however, © 2015 Royal Society of Biology breakthroughs Lessons in structural one element of the cookery metaphor that still applies: slow food. (Registered charity no. 277981) 06 INTERVIEW biology from Slow food enthusiasts would relish catching the hare, and they may The Society permits single copying of Roger Tsien on his most the UK’s largest embrace new technology, but they do not wish to lose sight of the whole individual articles for private study or research, irrespective of where the copying is famous work, the green particle accelerator food chain. Biochemists need to remember this slow food movement as done. Multiple copying of individual articles fluorescent protein 14 DESIGNER PROTEINS we bury ourselves in the enormous amounts of data pouring out of our for teaching purposes is also permitted without specific permission. For copying or 10 PLANT POWER How biochemists are mass spectrometers, imaging devices and next generation sequencers. reproduction for any other purpose, written Joseph Jez on why making new proteins for permission must be sought from the Society. We are ‘bio’ chemists and our ultimate goal is to understand how Exceptions to the above are those institutions understanding plant medicine and research living systems are more than the sum of their parts, for the benefit and non-publishing organisations that have an agreement or licence with the UK of humankind. We should not lose sight of the biological hare that Copyright Licensing Agency or the US Facebook “f” Logo RGB / .ai Facebook “f” Logo RGB / .ai is our raison d’être. Are we succeeding? I believe we are. Readers Copyright Clearance Center. Access to the TWITTER FACEBOOK WEBSITE magazine is available online; please see the twitter.com/ www.facebook.com/ www.biochemistry.org of The Biologist can judge for themselves by reading this special Society’s website for further details. BiochemSoc biochemicalsociety issue on the field. Biochemistry Supplement / The Biologist / 1 History History Seminal discoveries Seminal discoveries The cell cycle Multiple checkpoints in the eukaryotic cell cycle ensure that cells only divide after sufficient growth and faithful DNA replication – a process essential to preventing cell division going awry. Of the many proteins involved in cell cycle control, cyclin-dependent kinases (CDKs) are among the most important, modifying other chemicals involved in the cell’s progression towards division. I remember as a PhD student back in the intricate and exquisite details of how 1980s making a brief visit to Jim Maller’s the cell cycle is regulated: cyclin- laboratory in Denver, en route to a dependent protein kinase (CDK1), meeting in Colorado. Maller’s group had encoded by the cdc2 gene in yeast, and discovered a protein from Xenopus together with cyclin B, forms a protein oocytes that had a key role in controlling kinase complex known as MPF – the very cell division. At the time, this seemed a one that had previously been isolated in million miles away from my own project – Xenopus oocytes. working on a protein involved in Tim Hunt and Paul Nurse, together with regulating lipid metabolism in rat liver – Lee Hartwell, shared the Nobel Prize in but the significance of the work was not Physiology or Medicine in 2001 for their lost on me. discovery. Hindsight is a wonderful thing, 50 Shortly afterwards, I heard about work and looking back it is easy to see how all from Tim Hunt’s group at the Imperial the pieces slotted together, but at the Cancer Research Fund’s Clare Hall time this was far from the reality. This laboratories. A small family of proteins simply reflects the nature of most had been detected in sea urchin eggs scientific discoveries – very rarely are YEARS whose levels went up and down things crystal clear in the heat of the synchronously with each cell cycle – moment, and cut and dried results tend OF BIOCHEMISTRY proteins that would later be called cyclins. to be the exception rather than the rule. Sometime later, as a postdoc in Nonetheless, the discovery of the Seven leading biochemists pick the most important Dundee, I heard a talk from Paul Nurse in fundamental mechanisms regulating the which he described the identification of a cell cycle is a beautiful example of the European breakthroughs of the past five decades* protein from yeast that was regulated by elegance of nature itself. binding to cyclins, and which was DNA sequencing amazing thing about the Sanger required for cell division. Of course, 25 Professor David Carling, method is that it was so elegant, so years on, we now know many of the Imperial College London, UK In this method of DNA sequencing, robust and so simple to use. Of course, chemically altered nucleotides in time it became automated, which LIBRARY PHOTO ISM/SCIENCE DELARUE, MICHEL terminate newly synthesised DNA led to the human genome project. fragments at specific bases – Sanger’s method remained the understanding of membrane protein either A, C, G or T. These universally adopted and undisputed The chemiosmotic theory structure was still more than 20 years away fragments are then ranked by best way to sequence DNA for nearly Peter Mitchell’s chemiosmotic theory illustrated how the movement of ions through – they were known to associate with lipid size, and the DNA sequence 25 years, and it’s only in the past biological membranes could provide useful energy to catalyse biological processes.