Issue 7: Spring 2007
Report from the Centre
This is another exciting year for science at the John Innes Centre and the Sainsbury Laboratory. Several of our latest high-impact publications are described in this issue of Advances. We also highlight two spin-out awards, a potential new use for pea starch, and a new technique that will help search for new anti-cancer and anti-bacterial drugs more quickly and precisely – all examples of the impact and relevance of our science. We report from a ‘Plants for Bioenergy’ workshop, a major challenge, where JIC will be a cornerstone of the national effort. We are also delighted that our scientists are receiving substantial funding from the BBSRC Crop Science Initiative.
A top plant pathologist in the USA, Sophien Kamoun, has joined the Sainsbury Laboratory. We welcome him and his team to the Centre this year, together with Volker Lipka, from the Eberhard-Karls-Universität, Tübingen in Germany. As some arrive, others leave. JIC’s Nick Harberd has been elected to the Sibthorpian Chair of Plant Science in the University of Oxford and a professorial fellowship at St. John's College. Tracey Palmer will also be leaving us this summer, to help establish a mulit-investigator division in molecular microbiology at the University of Dundee. These are prestigious appointments and we wish them continued success in their new roles.
I am delighted that the contribution not only to plant biology, but also to science in society, and particularly education by JIC Emeritus, Keith Roberts, has been recognised by the award of OBE in the New Year Honours.
Caroline Dean will give the Genetics Society’s 2007 Medal Lecture ‘The need for winter in the switch to flowering’ at their Spring meeting in Edinburgh. The award recognises her outstanding research contribution to genetics. Caroline was present at a quite different event recently - a reception for representatives of the British scientific community, held at Buckingham Palace and hosted by HM The Queen and HRH The Duke of Edinburgh.
At
the Centre the status of mathematical biology, and the focus we are attaching
to it, is reflected in the naming of a full Department of Computational
and Systems Biology. Recruitment of a senior appointment to head the new
Department is under way. A major co-investment is in progress with the
Institute of Food Research and the University of East Anglia which aims
to make Norwich a leading centre for biomathematics, underpinning science
for sustainability.
Visitors to the Centre will see the start of ‘new-build’, an extension to the Biffen building primarily for Cell and Developmental Biology Department, which is scheduled for completion by end-2007. This new building, designed by architects Fielden & Mawson with engineering by Robert Somerville and Associates, combined with modifications to th Biffen building itself, are an energy-efficient solution to address our needs for state-of-the-art bioimaging facilities and dry bench space for increasing computational work.
Last but not least, I was pleased to welcome Jonathon Porritt to JIC recently.
The former Director of Friends of the Earth, now Chairman of the UK Sustainable
Development Commission, asked a capacity audience at the fourth Friends
of JIC Annual Lecture if "Living in an Oil Scarce World would be Misery
or Sustainability". He was challenging and provocative about what
the future may hold, and the audience reactions to his predictions were
equally challenging with lively discussions continuing long after the Lecture
had finished.
Chris Lamb
Director, John Innes Centre
Science highlights
Old enzyme learns new tricks
Norwich Research Park scientists, led by Anne Osbourn at JIC, have discovered an antibiotic-producing enzyme in oats that could be used in the future to protect cereal crops from fungal diseases such as “take-all”. Take-all is a devastating disease of wheat and barley world-wide and there is currently no resistance to it. In collaboration with IGER Aberystwyth and the Institute of Plant Molecular Biology, Université Louis Pasteur, Strasbourg, they found that an enzyme from oats, called Sad2, helps produce a chemical that makes the plant resistant to infections. Their research shows that Sad2 has evolved from an ancient family of enzymes that have remained unchanged over millions of years and are almost identical across the plant, fungi and animal kingdoms. All the other enzymes in this family are involved in producing essential fats called sterols, such as cholesterol in humans, and include targets for cholesterol-lowering drugs, antifungals and herbicides. The discovery of a new member of this enzyme family with a completely different function was therefore surprising.
If we could transfer this gene cluster from oats into other plants, it might be possible to breed cereals that are resistant to devastating crop diseases such as take-all. The findings also have broad significance for understanding how new metabolic pathways arise in plants, and this is an area that we are now investigating in other plant species such as rice and Arabidopsis.
The team are currently working with PBL (Plant Bioscience Ltd) to patent the technology and develop commercial applications together with the company Dupont and other potential licensees in the AgBiotech sector.
Reference: X. Qi et al. (2006) A new function for a member of an ancient and highly conserved cytochrome P450 family – from essential sterols to plant defence. Proceedings of the National Academy of Sciences 103 18848-18853 - http://intl.pnas.org/cgi/content/short/103/49/18848
Funding: Biotechnology & Biological Sciences Research Council and Gatsby Foundation
Weblink: PBL - www.pbltechnology.com
Fit for Climate Change
Whilst
most of us would prefer to avoid the cold winter months, many plants growing
in a temperate climate need to experience a period of cold to trigger flowering
when temperatures rise in the spring. This cold-induced acceleration of
flowering is called vernalization, and plants growing in different regions
have considerable variation in vernalization responses and flowering times.
Caroline Dean’s group at JIC has been studying the molecular
basis of this variation in Arabidopsis plants collected from sites
across Europe, in collaboration with the University of Southern California.
They measured levels of a gene called FLC that delays flowering over the winter and found that the variation in vernalization response is due to differences in the epigenetic silencing mechanism underpinning vernalization. This mechanism acts like a memory, enabling the plant to “remember” cold exposure; Arabidopsis collected from the Arctic Circle needed longer cold exposure, to silence the FLC gene.
Their research, recently published in the journal Genes and Development, could give clues as to how plants could be bred to extend their geographical range and cope with possible future changes in global climate.
Reference: Shindo et al. (2006) Variation in the epigenetic silencing of FLC contributes to natural variation in Arabidopsis vernalization response. Genes and Development 20 (22) 3079-3083 - http://www.genesdev.org/cgi/content/abstract/20/22/3079
Funding: BBSRC & Natural Environment Research Council
Exploring bacterial nanomachines
Many bacteria produce toxins that can threaten human health, however new research into how bacteria secrete these substances is giving clues as to how scientists could harness these processes to produce biopharmaceuticals.
Tracy Palmer’s group are studying a nanomachine in soil bacteria called the Tat system, which the bacteria use to secrete a range of proteins that help them digest food and compete with other microorganisms in the soil. Their latest work has identified which proteins are exported via the Tat system, revealing that this system is used by more proteins than previously thought. The biotechnology industry already uses bacteria to make proteins to use in products such as biological washing powder or pharmaceuticals, but some are difficult to produce using current methods. By harnessing the Tat system, she hopes that it will be easier to make these proteins for biotechnological and biomedical purposes.
Her group have joined forces with the “Tat Machine Project”, an EU-funded consortium of researchers from across Europe studying the Tat system. The consortium is studying the system in several different types of bacteria, including pathogenic species such as E. coli O157 and Pseudomonas aeruginosa to explore Tat as a potential target for new antibiotics.
Reference: Widdick et al. (2006) The twin-arginine translocation pathway is a major route of protein export in Streptomyces coelicolor. Proceedings of the National Academy of Sciences 103 (47) 17927-17932 - http://intl.pnas.org/cgi/content/abstract/103/47/17927
Funding: BBSRC Exploiting Genomics Initiative & European Commission
Weblink: www.tatmachine.net
Another piece of the membrane protein puzzle solved
 |
| By establishing the structure of a protein complex we come closer to understanding how it works. The trimeric AmtB protein is shown in surface view and the smaller trimeric GlnK protein is shown in ribbon view. A specific loop of each GlnK subunit inserts into the ammonia conduction channel thereby blocking ammonia entry into the cell |
Nitrogen uptake and metabolism is essential for living cells. The uptake mainly occurs through the most reduced form of nitrogen, ammonia. When nitrogen is limited, ammonia uptake in bacteria, fungi and plants is facilitated by a family of membrane proteins known as the ammonium transport (Amt) family. Work on this ubiquitous protein family has been pioneered by Mike Merrick’s team at JIC, using the bacterium Escherichia coli as a simple model system.
In collaboration with researchers at the University of Sheffield and the Paul Scherrer Institute in Switzerland, they have elucidated how bacteria control the entry of ammonia into cells. They have determined the crystal structure of a complex between the ammonia channel AmtB and its regulatory protein GlnK. This marks a significant advance in understanding of the process of nitrogen regulation in prokaryotic cells. (Prokaryotes are organisms without a cell nucleus).
Reference: Conroy, J.M. , Durand, A., Lupo, D., Li, X-D., Bullough,
P.A., Winkler, F.K. & Merrick, M. (2007) The crystal structure of
the Escherichia coli AmtB-GlnK complex reveals how GlnK regulates
the ammonia channel. Proceedings of the National Academy of Sciences 104 12131218
http://intl.pnas.org/cgi/content/abstract/104/4/1213
Funding: BBSRC Responsive Mode Grant
Extraordinary
insights, in Nature
Jonathon Jones from the Sainsbury Laboratory, and Jeffrey Dangl of the
University of North Carolina have co-authored a major review on the plant
immune system (Nature 444, 323-329 [16 November 2006]).
www.nature.com/nature/journal/v444/n7117/abs/nature05286.html - a
fast-developing area of research of huge significance and potential for
food security, reducing the environmental impact of agriculture and development
of sustainable bioenergy crops.
Many plant-associated microbes are pathogens that impair plant growth and reproduction. Plants respond to infection using a two-branched innate immune system. The first branch recognises and responds to molecules common to many classes of microbes, including non-pathogens. The second responds to pathogen virulence factors, either directly or through their effects on host targets. These plant immune systems, and the pathogen molecules to which they respond, provide extraordinary insights into molecular recognition, cell biology and evolution across biological kingdoms. A detailed understanding of plant immune function will underpin crop improvement for food, fibre and biofuels production.
NOTE: Subcriptions may be required to access some of these articles electronically.
FOCUS ON AMINOCOUMARINS
Despite the success of antibiotics in the 20th century, bacterial disease
is still a major health concern worldwide.
JIC’s biological chemists are making a key contribution to our understanding of antibiotics produced by the soil bacterium Streptomyces. The compounds may also hold a key to the treatment of some non-bacterial diseases.
Designer drugs for Superbugs?
The EU-funded consortium ‘CombiGyrase’ has been looking at the possibility of new ‘designer drugs’ to combat bacterial disease. The key is to find a good target; something in bacteria that can be used to kill the ‘bug’ without affecting the human host. The researchers chose the bacterial enzyme DNA gyrase, a well-validated drug target that is not present in humans. Their starting point was aminocoumarins (novobiocin and clorobiocin) from Streptomyces; excellent inhibitors of DNA gyrase, but poor drugs in the clinic. Could they be re-designed to become clinically useful?
The principal output from CombiGyrase has been large numbers of totally new aminocoumarin compounds (dubbed ‘novclobiocins’), which have been tested against the target, DNA gyrase, and compared with the parent compounds.
Several novclobiocins show comparable activity to the parent compounds but with improved properties. These drugs are being investigated further.
Perhaps the most exciting output has been the finding that simocyclinone, another aminocoumarin, also targets DNA gyrase, but with an entirely new mode of action. The hope is that this discovery can be exploited to design completely new drugs to combat drug-resistant bacteria.
Funding: An EU-funded specific targeted research project
Collaboration: CombiGyrase is a 7-lab European consortium involving research groups from 5 countries: Germany, Switzerland, Italy, Spain and the UK, headed by Prof. Lutz Heide from the University of Tübingen (Germany).
Two of the labs are in companies and the others are academic partners, including Tony Maxwell’s Group at JIC.
Designer drugs for cancer?
The biological chemists have also been collaborating with a team led by the University of Kansas, aiming to transform novobiocin into an anti-cancer compound. Novobiocin inhibits Hsp90, a protein necessary for all human cells and particularly important for the growth of cancer cells. Two new compounds have been found that no longer work like an antibiotic but instead target Hsp90, blocking the protein that cancer cells need to proliferate. In effect, the antibiotic has been transformed into an anti-cancer compound that researchers say may hold promise for the treatment of many types of cancers. The next steps are to determine what is needed in the molecule, what is important, what is not, and what can be changed so the compounds specifically kill the cancer cells and leave the normal ones alone.
Publication: Burlison et al. (2006) Novobiocin: Redesigning a DNA gyrase inhibitor for selective inhibition of Hsp90. Journal of the American Chemical Society 128 15529-15536 - http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/2006/128/i48/abs/ja065793p.html
Cliff Hedley and colleagues from JIC have developed a process for producing
a range of novel film materials from pea starch that may be suitable for
use in wound dressing applications. PBL (to whom international patent rights
have been assigned) have signed an Evaluation Licence Agreement to enable
a company, Polymer Health Technology, to evaluate the feasibility of using
their manufacturing process for producing the starch films on a commercial
scale. 
Wendy @ Westminster
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