Since I had almost no external visits in last week’s Bank Holiday-truncated schedule – although I did have one of my regular 1:1 meetings with Sir Mark Walport of the Wellcome Trust – I shall ruminate a little on the relationships between biochemistry and management. This is partly, of course, because both involve an understanding of systems and how they adapt to external inputs, a rather nice example from this perspective (IMHO) being an analysis that I have just co-authored. As I have remarked before, biological systems have tended to select for robustness over immediate efficiency; one way that this can achieved is via a substantial elasticity of individual biochemical steps to changes in inputs. In the study cited, we looked at the rather extensive changes in gene expression and metabolism consequent upon a pulsed change in nutrient status. Some, such as changes in inosine metabolism, were rather striking and not necessarily expected, which is why it is best not to start with hypotheses for this kind of experiment.
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
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