More generally, the fluxes through some systems are limited mainly by their ‘sources’ (i.e. amounts or rate of inputs), while others – perhaps more commonly – are more limited by the ability to use their inputs and are thus more limited by their ‘sinks’. Quantitatively we can assess all of these using sensitivity analyses; a so-called ‘local’ version of sensitivity analysis in common usage in biology is known via Metabolic Control Analysis, while more ‘global’ ones are also available, see e.g. this paper or this. Of course the relative contributions of ‘source’ and ‘sink’ reactions, even within the same network, are a function of the relative strengths of both.  An interesting analysis of tree growth has looked at this, and concludes that while the sinks may be commonly the more limiting, in many cases the source may contribute significantly. Certainly the known increases in yield that typically follow increased CO₂ levels are most easily interpreted in terms of a significant ‘source’ limitation. At all events, working this kind of analysis through is going to be crucial to deciding where best (plural) to make interventions for biotechnological purposes, as long mooted.

Other papers I enjoyed included an excellent review of modern strategies for effecting biotransformations for industrial biotechnology, focussing on directed evolution and including many examples that lead one to suppose that there is virtually no chemical reaction for which one might find a biocatalyst, and one on different forms of agriculture. A recent paper and commentary shed light on the role of global warming in increasing extreme weather fluctuations via an intensification of the global water cycle (mainly ocean evaporation followed by precipitation). Future agricultural planning will need to take this into account.

• Bornscheuer, U. T., Huisman, G. W., Kazlauskas, R. J., Lutz, S., Moore, J. C. & Robins, K. (2012). Engineering the third wave of biocatalysis. Nature 485, 185-94
• Dikicioglu, D., Dunn, W. B., Kell, D. B., Kırdar, B. & Oliver, S. G. (2012). Short- and long-term dynamic responses of the metabolic network and gene expression in yeast to a transient change in the nutrient environment. Mol Biosyst 8, 1760-1774
• Durack, P. J., Wijffels, S. E. & Matear, R. J. (2012). Ocean salinities reveal strong global water cycle intensification during 1950 to 2000. Science 336, 455-8
• Kell, D. B. & Oliver, S. G. (2004). Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. Bioessays 26, 99-105
• Kell, D. B. & Westerhoff, H. V. (1986). Metabolic control theory: its role in microbiology and biotechnology. FEMS Microbiol. Rev. 39, 305-320
• Kerr, R. A. (2012). The greenhouse is making the water-poor even poorer. Science 336, 405
• Rand, D. A. (2008). Mapping global sensitivity of cellular network dynamics: sensitivity heat maps and a global summation law. J R Soc Interface 5 Suppl 1, S59-69. Full free text
• Seufert, V., Ramankutty, N. & Foley, J. A. (2012). Comparing the yields of organic and conventional agriculture. Nature 485, 229-232
• Wiley, E. & Helliker, B. (2012) A re-evaluation of carbon storage in trees lends greater support for carbon limitation to growth. New Phytol (online)
• Yue, H., Brown, M., He, F., Jia, J. & Kell, D. B. (2008). Sensitivity analysis and robust experimental design of a signal transduction pathway system. Int J Chem Kinet 40, 730-741

Related posts (based on tags and chronology):

• Systems microscopy, Rothamsted, Wales, banking and bioenergy [30 April 2012]
• Institutes, systems and evolution [21 February 2011]
• Cheminformatics, e-science and agroecology [24 January 2011]
• ELIXIR, metabolism, viruses and a conference on systems biology [18 October 2010]
• Chemical biology, biocatalysis, industrial biotechnology, Cheltenham, farming and PhDs [15 June 2010]

In a very interesting plenary, David Glassner from Gevo described some large-scale processes for producing lactate (hence polylactate) and isobutanol in yeast. A 22 million gallon per year facility is being constructed! Many other talks followed a similar pattern, as microbial strain engineering based on systems biology modelling, pathway and enzyme engineering and ’omics were used to create strains with excellent potential and prowess, many of which were progressing to large-scale trials. Examples included 1,4-butanediol from Genomatica (and see the paper), 2,5-furan dicarboxylic acid at Bird Engineering (and paper) and a variety of long-chain alkanes, esters and fatty alcohols from LS9 (and representative paper). What is clear is that substantial progress is being made in developing processes for industrial biotechnology, and that they can only become more economic as the feedstocks for the petrochemical processes that might otherwise be used to make them increase in cost. One speaker pointed out that during one single 3h symposium session the world would use 12 million barrels of oil, or 4 supertankers’ worth!

Novel (and high-throughput) analytical procedures also featured heavily in the presentations, as did genome-scale modelling (not least of algae and cyanobacteria), while I also enjoyed a presentation on computational enzyme design by Andre Zanghellini, first author of this paper and now at Arzeda.

A particularly interesting session involved a description (and general discussion) of 6 of the major bioenergy centres that have been set up, starting with an excellent presentation of our own BSBEC by Angela Karp. The other centres were the Biomass Technology Research Centre of AIST at Higashi (presented by Kinya Sakanishi), the DOE BioEnergy Science Centre at Oak Ridge National Laboratory (Paul Gilna), the Joint BioEnergy Institute (Blake Simmons), the Great Lakes Bioenergy Research Centre (Tim Donohue) and the Energy Biosciences Institute (Chris Somerville). Overall a very impressive list, and huge advances have been made in a very short time. I was very pleased to see that the UK programme could very much hold its own, despite its comparatively small size. There were far too many highlights to mention, but a couple that I did enjoy were the use of base rather than acid to improve pre-treatment (more interesting and important than it may sound!) and a study of plants for unusual lignin linkages; Angelica sinsensis has some 3% of ester rather than ether linkages, that are considerably easier to hydrolyse and this is under genetic control – so there are some obviously useful consequences. I suspect that a wider survey of the plant kingdom, especially  in terms of understanding the constituents of plants already used in economic botany and thus with at least some useful agronomic performance, would turn up other important and relevant genes.

I also noted the press release on the master plan for the Norwich Research Park, and (given my interests in computational approaches to complex systems) enjoyed a paper from Uri Alon’s group on multiobjective optimisation and trade-offs, an excellent summary of the necessity for (and benefits of) making source code available for validating scientific conclusions, and a blog post on crowd sourcing in bioinformatics.

BBSRC’s Business Interaction Unit has recently been investing some time in attracting industrialists from European companies to serve on its peer review committee Pool of Experts. The aim is to increase industry representation in our grant assessment process and to help with industrial relevance considerations. I encourage industrialists to consider applying for this role through our conventional Appointments Board process. For an informal discussion about the role, the BBSRC contact is Rachel Spencer.

Finally, as Minister for Universities and Science David Willetts said in a speech last week, “If the rest of Britain performed like our research and publishing community, we would have rather fewer economic problems to tackle”.

• Kell, D. B. (2012). Scientific discovery as a combinatorial optimisation problem: how best to navigate the landscape of possible experiments? Bioessays 34, 236-244. Full free text
• Koopman, F., Wierckx, N., de Winde, J. H. & Ruijssenaars, H. J. (2010).n Efficient whole-cell biotransformation of 5-(hydroxymethyl)furfural into FDCA, 2,5-furandicarboxylic acid. Bioresource Technol 101, 6291-6
• Morin, A., Urban, J., Adams, P. D., Foster, I., Sali, A., Baker, D. & Sliz, P. (2012). Shining light into black boxes. Science 336, 159-60
• Schirmer, A., Rude, M. A., Li, X., Popova, E. & del Cardayre, S. B. (2010). Microbial biosynthesis of alkanes. Science 329, 559-62
• Shoval, O., Sheftel, H., Shinar, G., Hart, Y., Ramote, O., Mayo, A., Dekel, E., Kavanagh, K. & Alon, U. (2012). Evolutionary trade-offs, Pareto optimality, and the geometry of phenotype space. Science, online
• Yim, H. et mult al.(2011). Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat Chem Biol 7, 445-452
• Zanghellini, A., Jiang, L., Wollacott, A. M., Cheng, G., Meiler, J., Althoff, E. A., Rothlisberger, D. & Baker, D. (2006). New algorithms and an in silico benchmark for computational enzyme design. Protein Sci 15, 2785-94. Full free text

Related posts (based on tags and chronology):

• Governments, science strategy and industrial biotechnology in the KBBE [29 November 2010]
• Crop World, Industrial Biotechnology and the Knowledge-based BioEconomy [08 November 2010]
• A visit to Taiwan [07 November 2011]
• Cellular systems biology and organisation [01 August 2011]
• Science, society, plant breeding and bioinformatics [23 May 2011]

I attended a very interesting meeting of the Foundation for Science and Technology, on “Reducing the risk of a systemic failure of the banking system” (or ‘yet another’ failure, one might say). The speakers included John Kay, who provided a very thoughtful insight on some aspects that insiders got wrong, and Andy Haldane, whose wonderful paper with Lord May I blogged about before. I would like to conclude that I was reassured, but there is a distance between the perceived remedies (some of which – like requiring banks only to trade at levels that are backed by real assets – seem and are rather obvious) and their application. There was however general agreement about the need to separate investment (‘casino’) banking from retail banking, and the need for simplicity, a loose coupling of subsystems, and proper incentivisation. Certainly we need to get ourselves a financial system (‘responsible capitalism’) that provides for the creation of value and not just the simple transfer of money (real and imaginary) from the majority of taxpayers to others who are seemingly out of the control of the public and the public good.

A follow-up paper to one I published last year on the role of deep roots in carbon sequestration was published, and I note a slightly chilling paper on drought and dust bowls to which it should pertain. I also read an interesting ‘white paper’ on the value of digital archiving in the life sciences (PDF), while my attention was drawn, via a very interesting paper on belief theory, to the Dempster-Schafer theory of evidence.

Finally, I was most honoured to be elected to the Learned Society of Wales, where I am in some very distinguished company (PDF)!

• Haldane, A. G. & May, R. M. (2011). Systemic risk in banking ecosystems. Nature 469, 351-5
• Kell, D. B. (2011). Breeding crop plants with deep roots: their role in sustainable carbon, nutrient and water sequestration. Ann Bot 108, 407-418. Online carbon sequestration calculator
• Kell, D. B. (2012). Large-scale sequestration of carbon via plant roots in natural and agricultural ecosystems: why and how. Phil Trans R Soc 367, 1589-1597. Full free text
• Muchmore, S. W., Debe, D. A., Metz, J. T., Brown, S. P., Martin, Y. C. & Hajduk, P. J. (2008). Application of belief theory to similarity data fusion for use in analog searching and lead hopping. J Chem Inf Model 48, 941-8
• Reinhart, C. M. & Rogoff, K. (2009). This time is different: eight centuries of financial folly. Princeton University Press, Princeton
• Romm, J. (2011). The next dust bowl. Nature 478, 450-1

Related posts (based on tags and chronology):

• Sustainability, BSBEC, capital equipment and Newcastle [23 April 2012]
• Celebrations, talks and bioenergy [19 December 2011]
• A visit to Taiwan [07 November 2011]
• Open data, science and celebrations [13 June 2011]
• Science, society, plant breeding and bioinformatics [23 May 2011]

Continuing that theme, I attended part of the very interesting BSBEC grantholders workshop, where excellent progress is being made in this large and wide-ranging programme in sustainable bioenergy.

I had a very interesting visit to Newcastle University, where I visited a number of centres including the Centre for Bacterial Cell Biology, gave a talk about BBSRC strategy and also gave a scientific talk. I then returned south for a meeting by videoconference of the ‘Members’ (part of the new governance arrangements) of the John Innes Centre.

There is a Government survey currently being carried out into future requirements for large capital items.  However, responses from our community have been slow.  I would urge current grant holders and end-users of our research to respond to our call with projected future capital requirements, using the online survey at RCUK. Few responses will make it difficult for us to make the case for capital for our community, since if we do not know what is required we cannot make the strongest possible argument.

BBSRC also welcomed the election of the new Fellows of the Royal Society, 11 of whom were or had been our grantholders – and see Athene Donald’s blog for an insight into the processes involved. Let me also point out the latest issue of BBSRC Business.

I have noted before that while we can certainly design a car quite well, and a protein’s binding site to a reasonable degree, we really do not know enough about the fundamentals of biocatalysis to design an efficient (high-turnover) enzyme very effectively at all. The possessors of such knowledge can expect to make large advances, both intellectually and economically! To this end, I enjoyed reading a paper suggesting that some progress is indeed possible. I also enjoyed Ewan Birney’s latest blog, on epidemiology including the dangers of statistics.

Finally, I was pleased to see the final and Open Access appearance of a detailed paper on the genetic control of growth rate in yeast, and the acceptance of one on the use of semantic annotation of the biomedical literature.

• Broadhurst, D. & Kell, D. B. (2006). Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2, 171-196
• Khare, S. D., Kipnis, Y., Greisen, P., Jr., Takeuchi, R., Ashani, Y., Goldsmith, M., Song, Y., Gallaher, J. L., Silman, I., Leader, H., Sussman, J. L., Stoddard, B. L., Tawfik, D. S. & Baker, D. (2012). Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis. Nat Chem Biol 8, 294-300
• Miwa, M., Thompson, P., McNaught, J., Kell, D. B. & Ananiadou, S. (2012) Extracting semantically enriched events from biomedical literature. BMC Bioinformatics, in press
• Patel, K. (2005) The Master Strategist: Power, Purpose and Principle. Hutchinson, London
• Pir, P., Gutteridge, A., Wu, J., Rash, B., Kell, D. B., Zhang, N. & Oliver, S. G. (2012). The genetic control of growth rate: a systems biology study in yeast. BMC Sys Biol. 6, 4. Full free text as pdf

Related posts (based on tags and chronology):

• Biofuels, sustainability, open access and INRA [05 March 2012]
• Bioeconomy in action and Innovators of the Year [02 April 2012]
• Food, agriculture, text mining, Brazil and manufacturing [19 March 2012]
• Genomics, prizes, DFID and Open Access [27 February 2012]
• Sustainability, media and e-infrastructure [20 February 2012]

As part of this, I also took especial note of the fact that Germany had implemented a Bioeconomy Council, something the UK might wish to consider emulating.

Innovation was the core focus of the finals of our Innovator of the Year 2012 competition, with 9 outstanding finalists and with the winners being presented with their prizes by the Rt Hon Dr Vince Cable, Secretary of State for Business, Innovation and Skills. Many congratulations in particular to Prof George Lomonossoff of the John Innes Centre, the overall Innovator of the Year for his work on the production of vaccines in plants.

It is not 100% clear whether the stagnation of the UK economy is due more to a lack of supply of credit or a lack of demand for goods, but I see that the debtonation blog argues for the latter. Certainly in biology most fluxes are driven by demand, with a more recent paper on sugar accumulation in sugar cane providing an interesting example.

I was pleased to see the potential as a diagnostic, as an immunogenic antigen, and as a TB vaccine target of the Rpf proteins that we discovered in 1998, and I also enjoyed 10 simple rules for starting a company and Athene Donald’s latest blog, on statistics.

Speaking of statistics, my favourite tweet of the week, whose origin (or at least an earlier Web version) is here, went: “A Bayesian is one who, vaguely expecting a horse, and catching a glimpse of a donkey, strongly believes he has seen a mule.” Chasing it down also led me to a very nice site illustrating a variety of graphics for data visualisation in R. Although I have been involved in its use, this is a language I should one day learn!

And on that note, the blog is having a week off and will reappear after Easter.

• Chegou, N. N. et al. (2012) Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting. BMC Infect Dis 12. DOI: 10.1186/1471-2334-12-10. Full, free text. 
• Fletcher, A.C. & Bourne, P.E. (2012) Ten Simple Rules for Starting a Company. PLoS Comput Biol 8, e1002439. doi:10.1371/journal.pcbi.1002439. Full, free text.  
• Hofmeyr, J. S. & Cornish-Bowden, A. (2000). Regulating the cellular economy of supply and demand. FEBS Lett 476, 47-51.
• Li, P., Castrillo, J. I., Velarde, G., Wassink, I., Soiland-Reyes, S., Owen, S., Withers, D., Oinn, T., Pocock, M. R., Goble, C. A., Oliver, S. G. & Kell, D. B. (2008). Performing statistical analyses on quantitative data in Taverna workflows: an example using R and maxdBrowse to identify differentially expressed genes from microarray data. BMC Bioinformatics 9, 334. Full, free text.
• McCormick, A. J., Watt, D.A. & Cramer, M. D. (2009) Supply and demand: sink regulation of sugar accumulation in sugarcane. J Exp Bot 60, 357-364. Full, free text.
• Mukamolova, G. V., Kaprelyants, A. S., Young, D. I., Young, M. & Kell, D. B. (1998). A bacterial cytokine. Proc. Natl. Acad. Sci. 95, 8916-8921. Full, free text.
• Riaño, F. et al. (2012) T cell responses to DosR and Rpf proteins in actively and latently infected individuals from Colombia. Tuberculosis 92, 148–159.
• Romano, M. et al. (2012) Potential of Mycobacterium tuberculosis resuscitation-promoting factors as antigens in novel tuberculosis sub-unit vaccines. Microbes and Infection 14, 86-95.

Related posts (based on tags and chronology):

• Sustainability, BSBEC, capital equipment and Newcastle [23 April 2012]
• Prions, development, accreditation, sci foo and climate change [26 March 2012]
• Rothamsted, Council, ELC and the bioeconomy [12 March 2012]
• Biofuels, sustainability, open access and INRA [05 March 2012]
• Sustainability, media and e-infrastructure [20 February 2012]

The next major event was a meeting of the Board of the UK Collaborative for Development Sciences, (UK-CDS) of which we are a founding member. Part of this meeting involved a review of the activities and effectiveness of the first 5 years of the Collaborative. The UK-CDS provides a very useful forum for the exchange of ideas and the co-funding of activities in this important space.

Much of the UK’s strength in biology comes from the rigorous quality control measures that we apply to our research activities, and the Society of Biology recognised that this should also apply to teaching activities. To this end, they have organised a scheme (whose development we sponsored) for the accreditation of appropriate courses, and I was pleased to attend the announcement by David Willetts in the Palace of Westminster of the first set of winners.

I also enjoyed an informal meeting of various Sci Foo alumni, where I was particularly pleased to exchange some thoughts with Tim Hubbard from the Wellcome Trust Sanger Institute.

I also attended a useful meeting held at Defra and led by Minsters Lord Taylor and Jim Paice on the (substantial) risks and (possibly more limited) opportunities arising from climate change, based in part on the UK Climate Change Risk Assessment. A good number of these risk pertain to agriculture, where there was widespread recognition that research had a very major part to play, both in food and non-food crops, and where the existing threats from the arrival of ‘novel’ diseases of crops and livestock have already been manifest.

When this blog appears, I shall be attending a high-level meeting on the Bioeconomy in Europe, under the auspices of the Danish presidency of the EU. It promises to be a very useful forum for articulating the importance of the BioEconomy in Europe, and the role of scientific research in developing it further.

Finally, I enjoyed reading a short piece on the use of RNA aptamers as fluorogenic metabolite sensors, and another on the surveillance of animal influenza for preparedness against pandemics, while I was pleased to see the online version of a paper based on fluorescence-activated cell sorting assessing a number of important contributions to cellular longevity in baker’s yeast.

• Davey, H. M. & Kell, D. B. (1996). Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analysis. Microbiol. Rev. 60, 641-696. Full free text
• Davey HM, Cross EJM, Davey CL, Gkargkas K, Delneri D, Hoyle DC, Oliver SG, Kell DB, Griffith GW (2012) Genome-wide analysis of longevity in nutrient-deprived Saccharomyces cerevisiae reveals the importance of recycling in maintaining cell viability. Env Microbiol:in press
• Kell, D. B. (2009). A systems biologist ponders how disparate ideas can sometimes come together beautifully. Nature 460, 669
• Paige JS, Nguyen-Duc T, Song W, Jaffrey SR: Fluorescence imaging of cellular metabolites with RNA. Science 2012; 335:1194
• Peiris JS, Poon LL, Guan Y: Surveillance of animal influenza for pandemic preparedness. Science 2012; 335:1173-1174
• Singh, A., Isaac, A. O., Luo, X., Mohan, M. L., Cohen, M. L., Chen, F., Kong, Q., Bartz, J. & Singh, N. (2009). Abnormal brain iron homeostasis in human and animal prion disorders. PLoS Pathog 5, e1000336. Full free text
• Singh, A., Qing, L., Kong, Q. & Singh, N. (2012). Change in the characteristics of ferritin induces iron imbalance in prion disease affected brains. Neurobiol Dis 45, 930-8

Related posts (based on tags and chronology):

• Food, agriculture, text mining, Brazil and manufacturing [19 March 2012]
• Rothamsted, Council, ELC and the bioeconomy [12 March 2012]
• Genomics data, the media and Harper Adams [16 January 2012]
• Oxford Farming, synthetic biology and our hi-tech future [09 January 2012]
• Rothamsted Research, the Office for Life Sciences and the Campaign for Science and Engineering [17 January 2011]

Food and agriculture, as well as Industrial Biotechnology, also figured largely in a meeting I had with Mary Creagh, Shadow Secretary of State for Environment Food and Rural Affairs. Brazil is, of course, an agricultural superpower, and we had a very useful meeting with Professors Glaucius Oliva (Head of the CNPq funding agency) and João Carlos Teatini (Head of the CAPES agency, that mainly looks after graduate education). We already have many excellent links with Brazil, including a LabEx (laboratory exchange) scheme with the Agricultural Research agency Embrapa (and whose Head I also saw at the GFFF meeting); we now anticipate strengthening these further.

Readers will be aware that I am very keen on the opportunities offered by text mining, especially when we solve the problems of Open Access to the literature, and I attended and spoke at the launch of a JISC study on the Value and benefits of data and text mining to UK further and higher education (pdf). The report had used one of my own papers as a case study, not least because of its slightly voluminous reference list – 2469 papers, of which comparatively few had cited each other, such is the balkanisation of the literature. Speakers were unanimous (and see blog) in the view that Governments need to implement the recommendation of Hargreaves that there should be an exception in copyright law for access to the outputs of scholarly activity, especially for the adding of value.

Finally I had a couple of very interesting visits in Cambridge, the first to Cambridge Temperature Concepts, a company that has developed a device for high-precision, ambulatory monitoring of temperature, for use in the prediction of human fertility – an approach that is substantially cheaper than say in vitro fertilisation. As the world becomes ever more wired, I foresee a lot more science being done by collecting lifestyle data ‘on the fly’ (whether via smartphone apps or more specialised hardware) and relating them to medical and other outcomes. It is already easy to make estimates of things like calories burned, steps walked and height ascended using simple motion and altitude sensors; physiological self-monitoring may well become the norm, and with tens or hundreds of thousands of participants the statistics can become very reliable.

My other visit in Cambridge was to the Institute for Manufacturing, a well known and high powered set of Centres at the western site of the University of Cambridge, led by Professor Sir Mike Gregory. The IfM have had comparatively little activity in biomanufacturing to date, and are keen to turn their sophisticated methods towards helping the bioeconomy. We of course are always keen to encourage more engineering types to join the bioeconomy, and I foresee some exciting opportunities here.

I have blogged before about the potential of 3D printing in manufacturing, and my attention was drawn to a truly astonishing video on Youtube that shows how far things have already progressed. Regarding the integration of design and manufacturing, I also read an interesting review (Form and Fortune) at The New Republic of a biography of Steve Jobs, while another paper with my coauthorship, analysing the dynamics and control of an NFkappaB signalling pathway, was published.

I have also blogged before about the importance of ecological models in terms of understanding stability, dynamics and risk in complex systems more generally, including financial ones. A new paper describes analytical solutions for these kinds of system, that should be of important utiity in determining how best to regulate them if stability is the main desired criterion.

As the costs of genomics move mainly from the sequencing to the analysis, the focus moves inevitably towards useful and usable tools for doing such analyses; one I noticed is designed for secure personal genomics, and many others can be accessed via crowdsourcing. The availability of such genomic data then allows personal omics analyses over time.

• Allesina, S. & Tang, Y. (2012) Stability criteria for complex ecosystems. Nature 483, 205-8
• Broadhurst, D. & Kell, D. B. (2006). Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2, 171-196
• Chen, R. et mult al. (2012) Personal omics profiling reveals dynamic molecular and medical phenotypes . Cell 148, 1293-1307
• Foresight. (2011). The Future of Food and Farming: final project report. Government Office for Science, London
• Haldane, A. G. & May, R. M. (2011) Systemic risk in banking ecosystems. Nature 469, 351-5
• Karczewski, K. J., Tirrell, R. P., Cordero, P., Tatonetti, N. P., Dudley, J. T., Salari, K., Snyder, M., Altman, R. B. & Kim, S. K. (2012). Interpretome: a freely available, modular, and secure personal genome interpretation engine. Pac Symp Biocomput, 339-50
• Kell, D. B. (2009). Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Medical Genomics 2, 2. Full free text
• Isaacson, W. (2012) Steve Jobs. Simon and Schuster, New York
• Li, J. W., Schmieder, R., Ward, R. M., Delenick, J., Olivares, E. C. & Mittelman, D. (2012). SEQanswers: An open access community for collaboratively decoding genomes. Bioinformatics. Weblink
• Wang, Y., Paszek, P., Horton, C. A., Yue, H., H.White, M. R., Kell, D. B., Muldoon, M. R. & Broomhead, D. S. (2012). A systematic survey of the response of a model NF-kappaB signalling pathway to TNF alpha stimulation. J Theoret Biol 297, 137-147

Related posts (based on tags and chronology):

• Sustainability, media and e-infrastructure [20 February 2012]
• Food security, open access and mobile computing [20 June 2011]
• Science, society, plant breeding and bioinformatics [23 May 2011]
• Rothamsted Research, the Office for Life Sciences and the Campaign for Science and Engineering [17 January 2011]
• Agriculture, botany and plant diversity [06 September 2010]

We had a lengthy meeting of Council, the first day of which involved some major decisions regarding the funding of the Institutes that receive strategic support from BBSRC. Subject to some further work, these outcomes are likely to be announced in the next week or two.

I attended a superb talk by Sir Greg Winter, run by the Foundation for Science and Technology,  that covered the history of his production and commercialisation (via Cambridge Antibody Technology, now MedImmune) of humanised monoclonal antibodies. It was notable that 6 of the top ten selling drugs (generating $5-10Bn per year) are humanised antibodies – a huge success for a British technology.

e-infrastructure is a regular feature of this blog (and a very important topic), and I attended the first meeting of the e-infrastructure leadership Council, co-chaired by David Willetts. There was broad consensus that software and skills were going to be very important not only for science but for their contribution to the bioeconomy, that multiple architectures were required, and that these should be both distributed and determined by the needs of users rather than the capabilities and wishes of providers. One interesting distributed computation system is represented by the kind that involves some kind of crowd-sourcing, especially for so-called NP-hard problems. An interesting addition to the menagerie is represented by a system for attacking problems of multiple sequence alignment.

The Bioeconomy was the theme for a reception in the Palace of Westminster hosted by MP for mid-Norfolk George Freeman, who gave a resounding endorsement of the ever greater contributions that are to be expected from the existing and emerging bioeconomy.

I also attended the launch (Sir Steve Redgrave gave an excellent and predictably inspirational talk) of In the zone, a package of activities that will be made available in every single school in the UK, plus a touring show, based in this Olympic year on understanding human physiology and athleticism. Tip: if you try the hand-cycling test, don’t go off too fast or you’ll hit the wall!

Readers of this blog may well have come via the BBSRC website. The site was recently refreshed to ensure we are providing the best possible ‘user experience’ while clearly presenting examples of the impact of the research we fund. We are now seeking your comments on how you use the site. Continuing last week’s Open Access (OA) theme, I noted a useful and interesting paper rehearsing some of the issues. Other benefits of OA include the ability to assess the interest in and utility of articles by a variety of novel metrics, though despite the accessibility of biomedical abstracts it remains early days.

Evolution is of course largely based on re-inventing (i.e. evolving) the wheel – but how much so is revealed in a very nice paper indicating that 71% of all known (natural) enzyme activities are based on just 276 protein superfamilies. (This of course excludes those enzymes for which data are not yet public.) Such findings probably underpin the ligand and drug promiscuity widely observed, and may be exploited for useful drug repurposing.

• Furnham N, Sillitoe I, Holliday GL, Cuff AL, Laskowski RA, Orengo CA, Thornton JM: Exploring the evolution of novel enzyme functions within structurally defined protein superfamilies. PLoS Comput Biol 2012; 8:e1002403. Full free text
• Kawrykow A, Roumanis G, Kam A, Kwak D, Leung C, Wu C, Zarour E, Phylo players, Sarmenta L, Blanchette M, Waldispühl J: Phylo: a citizen science approach for improving multiple sequence alignment. PLoSone 2012; 7:e31362. Full free text
• Van Noorden R: Trouble at the text mine. Nature 2012; 483:134-135
• Xie L, Li J, Xie L, Bourne PE: Drug discovery using chemical systems biology: identification of the protein-ligand binding network to explain the side effects of CETP inhibitors. PLoS Comput Biol 2009; 5:e1000387. Full free text
• Xie L, Xie L, Kinnings SL, Bourne PE: Novel computational approaches to polypharmacology as a means to define responses to individual drugs. Annu Rev Pharmacol Toxicol 2012; 52:361-379

Related posts (based on tags and chronology):

• Warwick, BioIndustry, JISC and outreach [30 January 2012]
• Non-food crops, industrial biotechnology and IAH [05 December 2011]
• Biofuels, sustainability, open access and INRA [05 March 2012]
• Finance, assurance, policy and DSTL [13 February 2012]
• Unilever, Institutes, TSB and Foo [06 February 2012]

We had a useful meeting with all the Governing Body Chairs and Directors of the Institutes to whom we provide strategic support, including a catch-up on organisational details following recent governance changes. This week Council meets to decide funding allocations to them. We also had a very useful catch-up and planning meeting with Marion Guillou and colleagues from INRA, with whom we lead on the Joint Programming Initiative in Food Security, Agriculture and Climate Change.

Last week’s blog elicited some further comments on Open Access (OA), to which I have responded. I also note a new summary to the effect that OA articles are more cited than those not openly available.

I have long been interested in what happens ‘between the bud and the rose (PDF)’; now at least we have a much better idea of what happens between a bud and a leaf, thanks to some superb (and experimentally tested) new modelling work, also featured in a video. Finding a protein with desirable properties is a combinatorial optimisation problem, and I enjoyed a paper that took a mix-and-match approach to protein design. I also enjoyed a useful summary of tools for (transcriptome-based) pathway analysis, and noted the potential Babel surrounding the use of the same name for multiple genes, as well as enjoying a summary of the design of narrative visualisations.

Given the number of interesting things available online, it can be hard to find the nuggets, so lists of ‘100 best <anything>’ can be useful and thus I liked the one for infographic tools. Without OA many would not of course functionally be available.

• Bennani-Baiti B, Bennani-Baiti IM: Gene symbol precision. Gene 2012; 491:103-109
• Eisenbeis S, Proffitt W, Coles M, Truffault V, Shanmugaratnam S, Meiler J, Höcker B: potential of fragment recombination for rational design of proteins. J Am Chem Soc 2012
• Kell DB: Scientific discovery as a combinatorial optimisation problem: how best to navigate the landscape of possible experiments? Bioessays 2012; 34:236-244
• Khatri P, Sirota M, Butte AJ: Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol 2012; 8:e1002375. Full free text
• Kuchen, E.K. et al. (2012) generation of leaf shape through early patterns of growth and tissue polarity. Science 335: 1092-1096
• Segel E, Heer J: narrative visualization: telling stories with data. IEEE Transactions on Visualization and Computer Graphics 2010; 16:1139-1148
• Xia J, Nakanishi K: Self-selection and the citation advantage of open access articles. Online Inf Rev 2012; 36:40-51

Related posts (based on tags and chronology):

• Sustainability, BSBEC, capital equipment and Newcastle [23 April 2012]
• Babraham, TGAC, Schrödinger and economic growth [28 November 2011]
• Rothamsted, Council, ELC and the bioeconomy [12 March 2012]
• Genomics, prizes, DFID and Open Access [27 February 2012]
• Sustainability, media and e-infrastructure [20 February 2012]

Stephen Curry in his recent comments on Open Access (OA) raised some important points relating to OA and the Research Councils, quoting BBSRC as an example (in his opinion) of things not working as well as they should. Anyone who knows me will know that I am a very strong supporter of Open Access and of text and data mining. Indeed, I have blogged quite often about Open Access (and have been known to write scholarly articles such as this and this) on the subject. There is no doubt that significant aspects of my own scientific work would be made much easier if all papers were freely available, and it is straightforward to give examples in areas such as genome-based metabolic network reconstruction, text mining for systems biology, and pulling together disparate literatures and synthesising inductive knowledge in pharmacokinetics, medicine and toxicology.

And it will all happen (note my use of the future tense). So, it is, put simply, coming in the future, but the future is not always easy to get to and this is a case in point. In BBSRC we are very conscious of the need to do more to make OA publication as straightforward as possible for our research community and we are working with the other Research Councils to help make this happen. In doing that it is worth bearing in mind some of the constraints that we face:

• There is genuine pressure – not least from academic institutions – for all the Research Councils to run the same systems, which means having to cater for different and equally strongly held views across the academic community, be they historians, bioscientists or particle physicists (physicists being of course well catered for by arXiv).
• Funding is limited, particularly at the moment, and we must be very clear about how and why public money is spent.  It is a zero-sum game, so if more money is channelled into publishing costs then this means that there will be fewer grants.
• Establishing more clearly which published outputs relate to which individual grant or funder is not without its difficulties, as is sorting out which side of dual support has the lead responsibility for meeting OA costs and where the boundary lies

Running a parallel system in which libraries continue to pay subscriptions for ‘closed access’ while funders are also asked to contribute to Gold Open Access publication is not intellectually defensible, and we have to recognise the difficulties of the period of transition to an era of fully Open Access under sensible business models that respect the legitimate aspirations of stakeholders including researchers, public and charity funders, publishers and learned societies. All that said, BBSRC is fully committed to moving ahead as quickly as we can on open access, and things that will help are indeed happening, not least as a result of Hargreaves.

Working cross- Council

• We are closely involved via our ESRC colleagues in Dame Janet Finch’s group on expanding access, which is tackling several of the barriers to access and has good representation from interested parties
• The RCs are rewriting the joint statement and each Council is aiming to tighten up compliance with existing policy where clearly more needs to be done
• Within this we aim to have comparable mandates and comparable sanctions, for example withholding the final payment on an award, withdrawing the eligibility to apply for further Research Council funding from individuals who fail to comply, and accepting only open access publications as part of the track record of delivery of Research Council-funded research
• All Councils have established and introduced systems for comprehensive reporting on publications (among other outputs), through which it will be possible to check compliance levels routinely.  The most recent system (the Research Outcomes System, ROS, used by AHRC, BBSRC, EPSRC and ESRC, and shortly to be adopted by NERC) has only recently been made available to grant holders, with the first full round of  data collection currently underway.  By early in the next financial year the Councils already using ROS should be in a position to check compliance levels systematically.
• As well as checking compliance levels, we will continue to work with our communities to ensure the OA policy remains known and understood by our grant holders.  This will involve further specific and targeted communications, to remind grant holders of their obligations, and to reiterate why we consider this to be important.

In BBSRC

• BBSRC is one of the funders of UKPMC, which includes a system for authors to deposit their publications, as well as having automatic deposit by some publishers.  And we are working through the Funders Group and through other routes to engage publishers in revising their business models.  We are not yet in a position, as MRC does, to mandate deposit in UKPMC because our remit is broader than biomedicine.  But we do recommend UKPMC as a first choice.
• On the detailed funding side we are aware of the complexity of the system and, as part of the RCUK review of current practices this too will be reviewed.  In the meantime we are also very happy to work with individual institutions on how they might build an institutional OA fund, drawing sums per grant from indirect costs as a number of universities have already done.

So I’d say both that we are moving in the right direction and that we know that we have more to do, but it is good to know the interest and support that there is for us to progress more on OA and indeed with the data and text mining that become possible when the data and text themselves become fully and openly available. But it is authors, not Research Councils, who choose where to submit their manuscripts…and some are committing publicly to publish only in OA journals…albeit ironically some Open Access is more Open than others…

Meanwhile, I enjoyed reading a variety of papers, including an excellent one (including some first class data visualisation) on how metagenomics projects can reconstruct full genomes from previously unknown clades, one on channelrhodopsin structure, and one on cellular control exerted more by the dynamics than the structure of RNA. As seen also in the work of Tom McLeish with whom I chatted last week, I think the study of enzyme dynamics will have much to teach us for industrial biotechnology. And for a splendidly whimsical piece of writing, look no further than a judgement of Lord Denning on a cricketing dispute.

• Ananiadou, S., Kell, D. B. & Tsujii, J.-i. (2006). Text Mining and its potential applications in Systems Biology. Trends Biotechnol 24, 571-579
• Ananiadou, S., Pyysalo, S., Tsujii, J.-i. & Kell, D. B. (2010). Event extraction for systems biology by text mining the literature. Trends Biotechnol 28, 381-390
• Attwood, T. K., Kell, D. B., McDermott, P., Marsh, J., Pettifer, S. R. & Thorne, D. (2009). Calling International Rescue: knowledge lost in literature and data landslide! Biochem J. 424, 317-333. Full free text as pdf
• Dethoff, E. A., Chugh, J., Mustoe, A. M. & Al-Hashimi, H. M. (2012). Functional complexity and regulation through RNA dynamics. Nature 482, 322-30
• Dobson, P. D. & Kell, D. B. (2008). Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nat Rev Drug Discov 7, 205-220
• Herrgård, M. J., Swainston, N., Dobson, P., Dunn, W. B., Arga, K. Y., Arvas, M., Blüthgen, N., Borger, S., Costenoble, R., Heinemann, M., Hucka, M., Le Novère, N., Li, P., Liebermeister, W., Mo, M. L., Oliveira, A. P., Petranovic, D., Pettifer, S., Simeonidis, E., Smallbone, K., Spasić, I., Weichart, D., Brent, R., Broomhead, D. S., Westerhoff, H. V., Kırdar, B., Penttilä, M., Klipp, E., Palsson, B. Ø., Sauer, U., Oliver, S. G., Mendes, P., Nielsen, J. & Kell, D. B. (2008). A consensus yeast metabolic network obtained from a community approach to systems biology. Nature Biotechnol. 26, 1155-1160
• Hull, D., Pettifer, S. R. & Kell, D. B. (2008). Defrosting the digital library: bibliographic tools for the next generation web. PLoS Comput Biol 4, e1000204. Full free text
• Iverson, V., Morris, R. M., Frazar, C. D., Berthiaume, C. T., Morales, R. L. & Armbrust, E. V. (2012). Untangling genomes from metagenomes: revealing an uncultured class of marine Euryarchaeota. Science 335, 587-90
• Kato, H. E., Zhang, F., Yizhar, O., Ramakrishnan, C., Nishizawa, T., Hirata, K., Ito, J., Aita, Y., Tsukazaki, T., Hayashi, S., Hegemann, P., Maturana, A. D., Ishitani, R., Deisseroth, K. & Nureki, O. (2012). Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482, 369-74
• Kell, D. B. & Oliver, S. G. (2004). Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. Bioessays 26, 99-105
• Kell, D. B. (2009). Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Medical Genomics 2, 2. Full free text
• Kell, D. B. (2010). Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 577, 825-889. Full free text
• Toncrova, H. & McLeish, T. C. B. (2010). Substrate-modulated thermal fluctuations affect long-range allosteric signaling in protein homodimers: exemplified in CAP. Biophys J 98, 2317-26. Full free text

Related posts (based on tags and chronology):

• Sustainability, BSBEC, capital equipment and Newcastle [23 April 2012]
• Food security, open access and mobile computing [20 June 2011]
• Industrial biotechnology, e-infrastructure and systems biology [12 August 2010]
• UKPubMedCentral – an Open Access digital library of biomedical science [18 January 2010]
• Universities, synthetic biology, digital publishing and translational medicine [30 November 2009]