meeting reports: enzyme mechanisms: fast reaction and

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65 News February 2009 © 2009 The Biochemical Society Meeting reports Enzyme Mechanisms: Fast Reaction and Computational Approaches Nigel Scrutton and Andrew Munro (Manchester Interdisciplinary Biocentre) A Biochemical Society Focused Meeting held at the Manchester Interdisciplinary Biocentre, 9–10 October 2008 is meeting was a bold venture, bringing together experimentalists and theoreticians with the aim of generating new insight into enzyme mechanisms. e focus was the experimental and theoretical approach, rather than model systems, drawing on recent developments in fast reac- tion methods, computational simulations, electrochemical and related biophysical methods. e impact of new cutting edge approaches win mechanistic e nzymology was discussed, with presentations on magnetic field effects in enzyme systems (Jonny Woodward), light-activated and ultrafast studies (Marloes Groot and Derren Heyes) and internal friction in enzyme systems (András Málnási-Csizmadia). is was peppered with com- putational insights from DFT (Samuel de Visser) and hybrid QM/MM (Adrian Mulholland) simulations. Stefan Weber provided insight into reaction mechanisms of blue-light active proteins using pulsed electron paramagnetic resonance, while Julea Butt and Judy Hirst discussed redox mechanisms explored by electrochemical methods, kinetic simulations and other techniques. Rudolf Allemann and Neil Marsh discussed the use of stable isotopes and rapid reaction studies to discuss H-transfer and tunnelling. e diffusional encounter and reduction in dimensionality in enzyme–nucleic-acid interactions was discussed by Steve Halford, with Mike Jones and Emma Raven presenting their studies of light-activated charge separation in reaction centre complexes and haem-dependent oxi- dation of amino acids, respectively. Arwen Pearson provided a structural focus with her studies on single crystal spectroscopy. e programme was completed by two excellent oral presentations by Ian Greig and Andrew Christofferson selected from poster presentations. e programme was varied and challenging. e hope was to get en- zymologists to ‘think outside the box’. Feedback from delegates indicates this was a successful meeting that had ‘something for everyone’. e organizers thank the Biochemical Society and those involved in contributing to the meeting for delivering an exciting and unique programme. Advances in Nucleic Acid Detection and Quantification Simon Baker (Oxford Brookes University) A Biochemical Society Focused Meeting held at Hinxton Hall, Cambridge, 28–29 October 2008 e quantification and detection of nucleic acid is moving into an exiting phase as new technology becomes accessible to researchers from many disciplines. e end of the lifetime of existing PCR-based technologies will soon be in sight even as we approach the 25th anniversary of PCR’s conception. is meeting gave participants the opportunity to look beyond QPCR and hybridization arrays to what may replace them in the near future. Professor Sir Edwin Southern began the conference by outlining the developments that his company (OGT) have made recently, describ- ing a system for cell lysis and in situ assay of single mRNA molecules by hybridization. is exciting talk set a high standard for subsequent talks, but the remaining speakers were equal to the task. Nucleic acid detection via Raman spectroscopy featured in several talks, but the efficacy of a number of novel systems were discussed, in addition to presentations on the state-of-the-art in forensic and prenatal molecular biology, and in how nucleic acids are detected and quantified in the developing world. e speakers had evidently gone out of their way to focus their presentations on the subject of the meeting, and as a result the participants enjoyed discourse on the philosophy of science as well as the more normal molecular biological talks. is made a welcome change from results-driven presentations we are normally accustomed to at conferences. e meeting concluded with an overview by Professor Roger Lasken of the J Craig Ventner Institute on the latest applications of whole genome amplification. Hinxton Hall in the Sanger Centre Genome Campus provided an excellent venue for the meeting, and the organizers were lucky to able to Papers from this meeting will be published in Biochemical Society Transactions (volume 37, part 2).

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Page 1: Meeting reports: Enzyme Mechanisms: Fast Reaction and

65

News

February 2009 © 2009 The Biochemical Society

Meeting reports

Enzyme Mechanisms: Fast Reaction and Computational Approaches

Nigel Scrutton and Andrew Munro (Manchester Interdisciplinary Biocentre)

A Biochemical Society Focused Meeting held at the Manchester Interdisciplinary Biocentre, 9–10 October 2008

This meeting was a bold venture, bringing together experimentalists and theoreticians with the aim of generating new insight into enzyme mechanisms. The focus was the experimental and theoretical approach, rather than model systems, drawing on recent developments in fast reac-tion methods, computational simulations, electrochemical and related biophysical methods.

The impact of new cutting edge approaches win mechanistic e nzymology was discussed, with presentations on magnetic field effects in enzyme systems (Jonny Woodward), light-activated and ultrafast studies (Marloes Groot and Derren Heyes) and internal friction in enzyme systems (András Málnási-Csizmadia). This was peppered with com-putational insights from DFT (Samuel de Visser) and hybrid QM/MM (Adrian Mulholland) simulations. Stefan Weber provided insight into reaction mechanisms of blue-light active proteins using pulsed electron paramagnetic resonance, while Julea Butt and Judy Hirst discussed redox mechanisms explored by electrochemical methods, kinetic simulations and other techniques. Rudolf Allemann and Neil Marsh discussed the use of stable isotopes and rapid reaction studies to discuss H-transfer and tunnelling.

The diffusional encounter and reduction in dimensionality in enzyme–nucleic-acid interactions was discussed by Steve Halford, with Mike Jones and Emma Raven presenting their studies of light-activated charge separation in reaction centre complexes and haem-dependent oxi-dation of amino acids, respectively. Arwen Pearson provided a structural

focus with her studies on single crystal spectroscopy. The programme was completed by two excellent oral presentations by

Ian Greig and Andrew Christofferson selected from poster presentations.The programme was varied and challenging. The hope was to get en-

zymologists to ‘think outside the box’. Feedback from delegates indicates this was a successful meeting that had ‘something for everyone’.

The organizers thank the Biochemical Society and those involved in contributing to the meeting for delivering an exciting and unique programme. ■

Advances in Nucleic Acid Detection and QuantificationSimon Baker (Oxford Brookes University)

A Biochemical Society Focused Meeting held at Hinxton Hall, Cambridge, 28–29 October 2008

The quantification and detection of nucleic acid is moving into an exiting phase as new technology becomes accessible to researchers from many disciplines. The end of the lifetime of existing PCR-based technologies will soon be in sight even as we approach the 25th anniversary of PCR’s conception.

This meeting gave participants the opportunity to look beyond QPCR and hybridization arrays to what may replace them in the near future. Professor Sir Edwin Southern began the conference by outlining the developments that his company (OGT) have made recently, describ-ing a system for cell lysis and in situ assay of single mRNA molecules by hybridization. This exciting talk set a high standard for subsequent talks, but the remaining speakers were equal to the task.

Nucleic acid detection via Raman spectroscopy featured in several

talks, but the efficacy of a number of novel systems were discussed, in addition to presentations on the state-of-the-art in forensic and prenatal molecular biology, and in how nucleic acids are detected and quantified in the developing world. The speakers had evidently gone out of their way to focus their presentations on the subject of the meeting, and as a result the participants enjoyed discourse on the philosophy of science as well as the more normal molecular biological talks. This made a welcome change from results-driven presentations we are normally accustomed to at conferences. The meeting concluded with an overview by Professor Roger Lasken of the J Craig Ventner Institute on the latest applications of whole genome amplification.

Hinxton Hall in the Sanger Centre Genome Campus provided an excellent venue for the meeting, and the organizers were lucky to able to

Papers from this meeting will be published in Biochemical Society Transactions (volume 37, part 2).

Page 2: Meeting reports: Enzyme Mechanisms: Fast Reaction and

66

News

February 2009 © 2009 The Biochemical Society

secure usage of this facility via support from the sponsors — primarily Thermo Fisher Scientific, but also Biochemical Society Transactions, the British Library and the Wellcome Trust. The proximity of the accom-modation to the conference hall meant that all the participants had ample time to talk to the speakers. As the meeting was designed to bring scientists together from many different disciplines (from physical chemistry to environmental microbiology) the intimate atmosphere helped foster new and old collaborations.

Despite the low number of poster submissions, the organizers were happy to award the poster prize to Rupak Doshi, who despite being only 1 month into his postgraduate studies, gave a mature talk on his undergraduate work on the interactions of molecular oxygen with DNA, revealing that many measurements of OD260 are oxygen-dependent. ■

Papers from this meeting will be published in Biochemical Society Transactions (volume 37, part 2).

Not enough people, not enough moneyFunding University Biosciences in the Post RAE-EraAnnual HUBS (Heads of University Biological Sciences) Meeting, 13 November 2008 (the Institute of Physics, London)

Mark Burgess (Executive editor)

“The last 5 years have been a golden age for funding,” Professor Adrian Smith [Director General, Science and Research, DIUS (Department for Innovation, Universities and Skills)] told an audience of Heads of Departments and other academics. “the next 5 years will not be like that… we will be doing very well to hold what we have.”

The recession gave an urgency to the topic of the meeting: ‘Funding University Biosciences in the Post RAE-Era’. Professor Smith pointed out that the government was expecting 0% growth. And government forecasts tend to be optimistic.

The UK still punches above its weight, he said. The UK has 1% of the world’s population, but accounts for 4.5% of research and 8% of scientific and technical publications (and receives 12% of world citations). It is ranked second in the world for bioscience. However, “the future depends on two things: people and money. …the Government isn’t sure how many [scientists] we need, but is pretty sure that we don’t have enough.”

The problem in counting scientists is that the true state of number of science and engineering graduates is masked by changes in HESA (Higher Education Statistics Agency) classification. For instance, there were 28135 biological science graduates in 2006/07, a growth of 19% from 2005/06. But, of those 28135, only 4670 graduated in biology, a growth rate of just 5%. The number graduating in sports science was 6325 (a growth rate of 69%) and 11655 graduated in psychology, a growth rate of 31%. “Hard core biology is now only 17% of biological science degrees,” he said. In 1994/95, the figure was 31%. In 2002/03, HESA began classifying students taking initial teacher training courses as “half education, half their specialism”. This has created a false impres-sion of an increase in the number of maths degrees, because previously

such degrees had been classified as education.Because of the tighter fiscal environment, scientists need to

demonstrate the value of what they do – both in basic research and in near-to-market innovation – and they need friends. Professor Smith pointed out that scientists need to get industry to tell the Treasury that science makes money – anything from the scientists alone will be dismissed as special pleading.

After that bracing introduction, David Sweeney [Director for Research, Innovation, Skills at HEFCE (Higher Education Funding Council for England)] spoke on ‘The HEFCE perspective on the RAE [Research Assessment Exercise] and the REF [Research Excellence Framework], and the future of the quality-related element of HEFCE

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The fragile pipeline, from Adrian Smith’s presentation. “…the pipeline is broken and the problem has to be addressed. …The impact of subject choices needs to be explained to students.”

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February 2009 © 2009 The Biochemical Society

funding for research’. The HEFCE, he said, undertakes research quality assessment as an assurance mechanism, to provide information and benchmarking for HEIs (higher education institutions), research users and others and as an essential element in the funding allocation process.

He said that the REF aims to build upon the lessons learnt by RAE and that the REF is still a work in progress. It was clear, however, that the focus should be excellence; it will not just be basic research or biometrics. He defined excellence as “significant, original and rigorous.”

“We must be very specific,” he said, “about what sort of behaviour we reward.”

The purpose of quality-related research (QR) he said, was to maintain a research base of world-leading quality across the full range of disciplines, and to create “a sustainable and flexible national baseline capacity which enables the sector to respond strategically to a changing external environment and on which research and other activity funded from other sources can build”. User-valued research, on the other hand, consisted of work that was not basic, applied or published, such as advising government. This is the sort of work that is not dealt with well under RAE.

It was not HEFCE’s job to micromanage the system through targeted allocations or detailed incentives, but neither was it to take too broad an approach and create undesired incentives, or fail to support important activity. HEFCE’s funding is allocated as a block grant which the receiving institutions may spend in ways that they consider will best meet QR, and is distributed selectively by reference to robust indicators of research quality

He stressed that the REF must carry the confidence of the scientific sector and the government. David Sweeney was followed by Douglas Kell, Chief Executive of the BBSRC (Biotechnology and Biological Sciences Research Council), who gave ‘A research council perspective’. He stressed that it was excellence with impact that should be rewarded and this means supporting industry and engaging with the public. The BBSRC’s budget will rise from £386m to £471m by 2010/11. It will be investing £115m in systems/predictive biology, increasing responsive mode funding by 3% a year, and provide £80m for FECs (further educa-tion colleges). It will increase interactions with business by redirecting £50m to research directly relevant to industry; providing at least £34m for complementary and collaborative activities with the Technology Strategy Board and operating at least four Research and Technology Clubs by 2011, in partnership with over 40 companies.

It hopes to increase the number of PhD students from 2000 to 2400 by 2010/11 and double its funding for Fellowships to £10m. Professor Kell was keen that the BBSRC continued to support ‘systems approach-es’ that harnessed the power of mathematics, physics and engineering to generate new understanding of biological processes. The need for data management is shown by the challenge of ‘big data’; 1000 papers are published every 2 hours.

There are other problems, including the greatly lowered knowledge displayed by undergraduates and grade inflation, which meant that universities were often doing remedial education.

He said that the development of ‘good’ science has to be commu-nicated to the public – it is important that everybody understands, not just those who fund it.

Nicola Perrin, Senior Policy Advisor for the Wellcome Trust, gave

‘A charity perspective’. Charities fund 15% of research, most of it (75%) in the life and medical sciences. This amounts to about £800m, of which the Wellcome Trust contributes £520m and will spend £4bn between 2008 and 2012. The Trust’s priorities include genetics, neuroscience and mental health, emerging infectious diseases, health innovation and the UK Centre for Medical Research and Innovation, which is due to open in 2013.

They are pleased that there is support for the dual-support system as it allows diversity of funders and means that universities can plan strategically. On FECs, it funds the full directly incurred costs, but expects general running costs to be provided by Government. However, the Trust will fund additional costs where in line with its mission; these include such things as the cost of animal research, open access, equip-ment and infrastructure such as clinical research facilities.

Charity Research Support Fund, a Partnership between Govern-ment and charities had a ‘pot size’ of £180m in 2007/08, but, she said, there needs to be a better assessment of demands on it. She argued that the REF should be transparent in assessment and allocation and must reward excellence. It should also consider publication, career develop-ment and long-term sustainability.

Nigel Brown gave a presentation on ‘Costing the Biosciences’: this was report on the HUBS-funded exercise to assess the true cost of teaching biosciences in UK Higher Education. Undergraduate teaching income per FTE (full-time education) student shows a very similar pattern with variation around a mean of £5600 in 2004/05 [FC (funding council) grant plus tuition fees] and research grant and contract income per FTE member of academic staff shows similar variations between £25000 and £150000. Of course, the FC QR grant is dependent on RAE score. The survey suggested that the research-intensive institutions more or less break even on teaching and any deficits were driven by research costs exceeding income.

The outlook, however, was grim: undergraduate tuition fees are unlikely to rise again before 2013 and perhaps even longer, the cost of paying an increased contribution to project overheads seems to be lead-ing to further concentration of grants from research councils on a few departments and it is difficult to get a significantly increased contribu-tion to overheads from other sources of research funding. ■

Total: £519.8m

BIOMEDICAL SCIENCE£327.1 M

TECHNOLOGY TRANSFER£20.1 M

MEDICINE, SOCIETY AND HISTORY1

£12.0 M

WELLCOME TRUST SANGER INSTITUTE£72.9 M

DIRECT ACTIVITIES£40.6 M

SUPPORT COSTS£47.1 M

GRANTS AWARDED

OTHER EXPENDITURE

1 History of medicine, biomedical ethics and public engagement with science funding.

Where the money goes: recipients of Wellcome’s funding, from Nicola Perrin’s presentation