Molecular biology, as does systems biology, relies heavily on the development of novel techniques for the study of biological systems and their subsequent exploitation. Thus, X-ray crystallography (Nobel Prize) for DNA structure determination (Nobel Prize), DNA sequencing (Nobel Prize), soft-ionisation mass spectrometry (Nobel Prize) for proteomics, PCR (Nobel Prize), and the Green Fluorescent Protein (and derivatives) for cell biology (Nobel Prize) have all revolutionized modern biology. In a similar vein, the discovery and use of restriction enzymes for molecular cloning (Lasker Prize) arguably initiated modern biotechnology. A considerable amount of BBSRC support continues to be aimed at basic molecular biology and biotechnology, and just last week we announced candidate swine flu vaccines produced using novel vectors, developed last year and this for rapid molecular engineering in plants, in the laboratory of George Lomonossoff and colleagues from the John Innes Centre. In this case the time from idea to exploitation was very swift, less than 2 years, but 15 years is more common!
Thus, I have long had a personal interest in the role of so-called metabolic channeling in increasing fluxes through metabolic pathways. In metabolic channeling, the product of one reaction is passed straight to the next enzyme in a pathway without becoming free in solution. This was always assumed, and latterly shown, even at constant net flux, to have the benefit of decreasing the size of metabolite pools that could otherwise strain the osmotic capacity of the cell. What was also assumed was that channeling could increase metabolic fluxes by avoiding the dilution of substrates caused by their leaking out into metabolic pools, and this has now been beautifully demonstrated in a metabolic engineering/synthetic biology paper just published by Keasling and colleagues (and Commentary).
A couple of other papers of interest include one in the same issue as Keasling’s on the use of a standardized notation, the Systems Biology Graphical Notation, for the principled and exchangeable description of the layout of biochemical networks (just as electrical engineers have standard formats for describing components and wiring diagrams), and one on the use of a systems biology approach to prion disease, noting (as one would anticipate) the derangement of iron metabolism therein, based on a detailed molecular analysis of the changes relating to the differential development of the disease.
Finally, at home, we successfully incubated and hatched 4 ducklings from eggs produced by our two pet ducks (see one above). Now that is serious biotechnology!
- DeLisa, M. P. & Conrado, R. J. (2009). Synthetic metabolic pipelines. Nat Biotechnol 27, 728-729
- Dueber, J. E., Wu, G. C., Malmirchegini, G. R., Moon, T. S., Petzold, C. J., Ullal, A. V., Prather, K. L. & Keasling, J. D. (2009). Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol. 27, 753-761
- Hwang D, Lee IY, Yoo H, Gehlenborg N, Cho JH, Petritis B, Baxter D, Pitstick R, Young R, Spicer D, Price ND, Hohmann JG, Dearmond SJ, Carlson GA, Hood LE: A systems approach to prion disease. Mol Syst Biol 2009; 5:252. Full free text (PDF)
- Le Novère, N., Hucka, M., Mi, H., Moodie, S., Schreiber, F., Sorokin, A., Demir, E., Wegner, K., Aladjem, M., Wimalaratne, S. M., Bergman, F. T., Gauges, R., Ghazal, P., Hideya, K., Li, L., Matsuoka, Y., Villéger, A., Boyd, S. E., Calzone, L., Courtot, M., Dogrusoz, U., Freeman, T., Funahashi, A., Ghosh, S., Jouraku, A., Kim, S., Kolpakov, F., Luna, A., Sahle, S., Schmidt, E., Watterson, S., Wu, G., Goryanin, I., Kell, D. B., Sander, C., Sauro, H., Snoep, J. L., Kohn, K. & Kitano, H. (2009). The systems biology graphical notation. Nat Biotechnol 27, 735-741
- Mendes, P., Kell, D. B. & Westerhoff, H. V. (1992). Channelling can decrease pool size. Eur. J. Biochem. 204, 257-266. Free full text
- Mendes, P., Kell, D. B. & Westerhoff, H. V. (1996). Why and when channeling can decrease pool size at constant net flux in a simple dynamic channel. Biochim. Biophys. Acta 1289, 175-186
- Sainsbury F, Lomonossoff GP: Extremely high-level and rapid transient protein production in plants without the use of viral replication. Plant Physiol 2008; 148:1212-1218
- Sainsbury F, Thuenemann EC, Lomonossoff GP: pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol J 2009, in press and online