Last week I managed to attend a scientific conference on the topic of how cells are organised, mainly from a systems biology point of view. There is an emerging trend that recognises that cellular proteins are organised in a much more coherent manner than the ‘bag of enzymes’ view of (e.g.) the cytoplasm might suggest. As there is not space to mention everything, and conference rules disallow communicating unpublished data presented, I shall comment on just a few areas. One was a reminder of the fascinating work on cell stratification (recently reprised) showing the essential absence of ‘soluble’ proteins in living cytoplasm (and see also a classic review), while another gave an update on the role of supercomplexes in oxidative phosphorylation. A third focussed on protein unfolding in vivo (quite different from in vitro…), and another on the increasingly widely recognised role of intrinsically disordered proteins.
This meeting series always has quite a significant technology or methodological strand, and I was very impressed by the single cell enzyme assay work presented by Nancy Allbritton, the use of Qconcats for quantitative proteomics and the present status of electron cryomicroscopy for intracellular imaging.
Needless to say in a meeting of this type, there was plenty of network biology and modelling. Since I blog more regularly on this topic, I shan’t include much of this here save for noting work from Dupont on the use of the methods of systems biology for improving a variety of fermentations for industrial biotechnology such as that for propane 1,3-diol, an interesting computational strategy combing metabolic network biology with gene expression data for inferring useful drug targets, and some excellent studies of transcription, hedgehog signalling and NFkappaB.
Overall, this was an excellent opportunity to get some first-hand exposure to some world-class research across our space. I shall repeat the process in a couple of years since, due to an unexpected drop-out, I have been elected co-chair of the next meeting in this series.
Finally, I also enjoyed reading about a neat approach that served to identify the main transporter type used for getting the large, Streptomyces-derived natural product tunicamycin into cells. The method would seem to have more general applicability.
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- Brownridge P, Holman SW, Gaskell SJ, Grant CM, Harman VM, Hubbard SJ, Lanthaler K, Lawless C, O’cualain R, Sims P, Watkins R, Beynon RJ. Global absolute quantification of a proteome: Challenges in the deployment of a QconCAT strategy (2011). Proteomics. 11, 2957-70
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- Hong J, Gierasch LM. Macromolecular crowding remodels the energy landscape of a protein by favoring a more compact unfolded state. (2010) J Am Chem Soc. 132, 10445-52
- Kempner,E.S. & Miller, J. H.(2003) The molecular biology of Euglena gracilis. XV. Recovery from centrifugation-induced stratification. Cell BiolCytoskel 56, 219-224
- Korinek A, Beck F, Baumeister W, Nickell S, Plitzko JM. (2011) Computer controlled cryo-electron microscopy – TOM(2) a software package for high-throughput applications. J Struct Biol. Epub
- Kovarik ML, Allbritton NL. (2011) Measuring enzyme activity in single cells. Trends Biotechnol. 29, 222-30
- Parker DS, White MA, Ramos AI, Cohen BA, Barolo S. (2011) The cis-regulatory logic of Hedgehog gradient responses: key roles for gli binding affinity, competition, and cooperativity. Sci Signal. 4, ra38
- Reiling JH, Clish CB, Carette JE, Varadarajan M, Brummelkamp TR, Sabatini DM. (2011) A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin. Proc Natl Acad Sci 108, 11756-65
- Seelert H, Dani DN, Dante S, Hauss T, Krause F, Schäfer E, Frenzel M, Poetsch A, Rexroth S, Schwassmann HJ, Suhai T, Vonck J, Dencher NA. From protons to OXPHOS supercomplexes and Alzheimer’s disease: structure-dynamics-function relationships of energy-transducing membranes (2009) BBA 1787, 657-71
- Tompa, P. (2011) Unstructural biology coming of age. Curr Opin Struct Biol. 21, 419-25
- Turner DA, Paszek P, Woodcock DJ, Nelson DE, Horton CA, Wang Y, Spiller DG, Rand DA, White MR, Harper CV. (2010) Physiological levels of TNFalpha stimulation induce stochastic dynamics of NF-kappaB responses in single living cells. J Cell Sci. 123, 2834-43. Full free text
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