Dan Nicholson at the Biological Interest Group – Monday, 29th January, 2018, 2-3pm, Byrne House

For the first meeting of BIG of the spring semester, Dan Nicholson (University of Exeter) discussed a paper entitled “Is the Cell Really a Machine?” Dan explained that this paper has been a long time in the making, and that different versions of it have been presented at conferences over the past few years. It presents a systematic attempt to bring together a large amount of scientific literature in order to argue that molecular biology is currently undergoing a fundamental shift in its ontological conceptualisation of the cell.

In order to make his case, Dan looks at recent research in four areas: (i) cellular architecture, which has often been conceptualised as a static and highly ordered structure; (ii) protein complexes, which have often been characterised as highly specific and exquisitely designed molecular machines; (iii) intracellular transport, which has tended to be described in terms of miniaturised engines propelled by mechanical forces; and (iv) cellular behaviour in which it has been frequently assumed that a deterministic program encoded in the genome governs its actions.

Synthesising a vast range of studies and findings from molecular biology, Dan addresses a number of philosophical questions at the end of each of these four areas. According to his view: cellular architecture is regarded as a fluid self-organising process (regarding the mitotic spindle, cf. Duncan & Wakefield, 2011, p. 330); protein complexes are comprehended as transient, pleomorphic ensembles (regarding intrinsically disordered proteins, cf. Dunker et al., 2008); intracellular transport is understood to result from the harnessing of Brownian motion (see the Brownian ratchet model of intracellular transport, cf. Astumian, 1997; Ait-Haddou & Herzog; Hänggi et al., 2005); and cellular behaviour is viewed as an inherently probabilistic affair subject to stochastic fluctuations (see the stochastic model of gene expression, cf. Walters, et al., 1995; McAdams & Arkin, 1997; Elowitz, et al., 2002). Dan’s claim is that the traditional mechanical, reductionistic, and deterministic view is gradually giving way to a conception of the cell that stresses the fluidity and plasticity of its constitution, and the stochasticity and nonlinearity of its behaviour.

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Ait-Haddou, R., & W. Herzog, ‘Brownian ratchet models of molecular motors’, Cell Biochemistry and Biophysics, 38 (2003) 191-212

Astumian, R.D., ‘Thermodynamics and kinetics of a Brownian motor’, Science, 276 (1997) 917-922

Duncan, T. & J.G. Wakefield, ’50 ways to build a spindle: The complexity of microtubule generation during mitosis’, Chromosome Research, 19 (2011) 321-333

Dunker, A.K., I. Silman, V.N. Uversky, & J.L. Sussmann, ‘Function and structure of inherently disordered proteins’, Current Opinion in Structural Biology, 18 (2008) 756-764

Elowitz, M.B., A.J. Levine, E.D. Siggia, & P.S. Swain, ‘ Stochastic gene expression in a single cell’, Science, 297 (2002) 1183-1186

Hänggi, P., F. Marchesoni, & F. Nori, ‘Brownian motors’, Annalen der Physik, 14 (2005) 51-70

McAdams, H.H., & A. Arkin, ‘Stochastic mechanisms in gene expression’, Proceedings of the Natural Academy of Sciences of the United States of America, 94 (1997) 814-819

Walters, M.C., S. Fiering, J. Eidemiller, W. Magis, M. Groudine, & D.I. Martin, ‘Enhancers increase the probability but not the level of gene expression’, Proceedings of the Natural Academy of Sciences of the United States of America, 92 (1995) 7125-7129

 

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