Biology is the nanotechnology par excellence – 4 Gigayears of evolution have seen to that – and recent work has highlighted the ability of DNA to fold itself into unusual shapes (held together mainly by H-bonds) with interesting machine-like properties – see e.g. recent papers from the laboratories of Ned Seeman and Milan Stojanovic. DNA aptamers also have interesting and complex binding properties, and I have recently published on a first complete landscape thereof. But it is proteins, with a choice of 20 rather than just 4 building blocks, that give the evolutionary tinkerer or design engineer the greater scope for protein engineering. Nowadays this means not only the engineering of proteins – important in industrial biotechnology – but engineering with proteins, to make interesting and potentially useful structures (with or without catalytic properties) by molecular self-assembly.
One issue in particular in the engineering of structures from parts is how to join their components, and noting the strength of metal-ligand interactions, a series of three papers highlights the utlility of using metals to staple together suitably engineered proteins. I have long felt that proteins are truly wonderful things – suitable ones can survive boiling yet are at once both flexible and practically incompressible – but we have generally rather neglected their physical properties over their catalytic ones. I was alerted by a tweet to Apple’s licensing of a strong and mouldable ‘liquid metal’ technology that has a useful combination of material properties. Because of the regularity of protein structures one can anticipate that they too might well contribute to novel materials. Needless to say this is not at all a new idea, as a couple of recent reviews from a themed issue of Chem Soc Rev on peptide and protein-based materials demonstrate!
In 2012, the UK is hosting the quadrennial summer Olympic Games, of course, but in fact there is another series of Olympiads that takes place annually for secondary school students, in mathematics and various sciences. BBSRC is pleased to suport the British Biology Olympiad and to sponsor the UK team’s attendance at the International Biology Olympiad, which this year took place in Korea. I am delighted to report that our team of three each returned with medals – many congratulations to all! (I might also record the International Physics Olympiad, which this year took place in Croatia, as I have a filial interest!)
Much of science involves looking for regularities, and clustering objects on the basis of their properties (as in taxonomy) can help us make sense of biological complexity. Comparing a new or unknown thing with what we do know can also give clues to the role of the new thing (‘guilt by association’), and this was an early tool of expression profiling for functional genomics. Of course any clustering algorithm will give some result, but there are now very good means of testing such results for validity. Equally, what we mean by ‘similar’ can have more than one meaning, albeit that we can nowadays explore these simultaneously. As Shakespeare wrote (in Hamlet), “when sorrows come they come not single spies but in battalions”, and a correlation between two variables can mean either that one causes the other or that they both share a separate cause or causes. It is becoming increasingly evident that the greater the likelihood of developing a particular disease, the greater the likelihood of being more susceptible to a different one (e.g. see here). Biological systems, as systems, fail in ways that reflect their construction, and determining how systems fail can tell one much about their organization. To this end, I have been re-reading The Spirit Level, a wonderful book containing some striking correlations together with evidence for causation. Economists take note!
Finally, I enjoyed a metabolomics paper that lit up at least one of the ‘natural’ roles of the rather non-specific organic cation transporter, and as a fan of modeling for understanding complex systems, my attention was drawn by a tweet to another very useful online resource – the Stanford Encyclopedia of Philosophy, on this and other matters.
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- Gu H, Chao J, Xiao SJ, Seeman NC: A proximity-based programmable DNA nanoscale assembly line. Nature; 465:202-205.
- Handl J, Knowles J, Kell DB: Computational cluster validation in post-genomic data analysis. Bioinformatics 2005; 21:3201-3212. Free full text.
- Handl J, Kell DB, Knowles J: Multiobjective optimization in bioinformatics and computational biology. IEEE Trans Comput Biol Bioinformatics 2007; 4:279-292.
- Kato Y, Kubo Y, Iwata D, Kato S, Sudo T, Sugiura T, Kagaya T, Wakayama T, Hirayama A, Sugimoto M, Sugihara K, Kaneko S, Soga T, Asano M, Tomita M, Matsui T, Wada M, Tsuji A. Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res. 2010, 27:832-40.
- Kell DB 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 2009; 2:2
- Lund K, Manzo AJ, Dabby N, Michelotti N, Johnson-Buck A, Nangreave J, Taylor S, Pei R, Stojanovic MN, Walter NG, Winfree E, Yan H: Molecular robots guided by prescriptive landscapes. Nature; 465:206-210.
- Rowe W, Platt M, Wedge D, Day PJ, Kell DB, Knowles J: Analysis of a complete DNA-protein affinity landscape. J R Soc Interface 2010; 7:397-408.
- Salgado EN, Ambroggio XI, Brodin JD, Lewis RA, Kuhlman B, Tezcan FA: Metal templated design of protein interfaces. Proc Natl Acad Sci U S A 2010; 107:1827-1832. Free full text.
- Salgado EN, Radford RJ, Tezcan FA: Metal-directed protein self-assembly. Accounts of Chemical Research 2010; 43:661-672.
- Ulijn RV, Woolfson DN: Peptide and protein based materials in 2010: from design and structure to function and application. Chem Soc Rev 2010.
- Wilkinson R, Pickett, K. The Spirit Level. Penguin Books, London, 2009.
- Zelzer M, Ulijn RV: Next-generation peptide nanomaterials: molecular networks, interfaces and supramolecular functionality. Chem Soc Rev 2010.
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