We study how ribosome traffic regulates gene expression in the model organism of S. cerevisiae. In order to do that, we use a combined theoretical and experimental approach. We develop mathematical models to predict how the mRNA transcript population is translated by ribosomes into the proteome. The mathematical models are then validated by experiments through our collaboration with the Stansfield lab, which lead to the development of further hypothesis to be incorporated in the models, thereby closing the systems biology reiterative circle.  

We take into account the mRNA sequence, codon composition, tRNA abundances and wobble base-pairing effects to mathematically predict how the current of ribosomes, or translation rate, varies depending on the initiation rate (the rate at which ribosomes bind the mRNA and start translating the Open Reading Frame).  We mainly use approaches from non-equilibrium statistical physics, but also others, such as Max-Plus algebra.

We are interested in both the theoretical analysis of traffic effects in the translation system and the computational genome-wide study of ribosome traffic characteristics, which are then related to Gene Ontology categories.

We also study translation from a more global point of view, considering competition among the mRNAs for translation resources, such as aa-tRNAs and ribosomes, leading to novel predictions. Furthermore, we study the influence of secondary structures on the mRNA on the ribosome traffic.

 

Publications

  • M. C. Romano, M. Thiel, I. Stansfield, and C. Grebogi, “Queueing Phase Transition: Theory of Translation”, Phys. Rev. Lett. 102, 198104 (2009).
  • C. A. Brackley, M. C. Romano, C. Grebogi, and M. Thiel, “Limited Resources in a Driven Diffusion Process”, Phys. Rev. Lett. 105, 078102 (2010).
  • L. Ciandrini, I. Stansfield, and M. C. Romano, “Role of the particle’s stepping cycle in an asymmetric exclusion process: A model of mRNA translation”, Phys. Rev. E 81, 051904 (2010).
  • C. A. Brackley, M. C. Romano, and M. Thiel, “Slow sites in an exclusion process with limited resources”, Phys. Rev. E 82, 051920 (2010).
  • C. A. Brackley, M. C. Romano, and M. Thiel, “The Dynamics of Supply and Demand in mRNA translation”, PLoS Comput. Biol. 7, e1002203 (2011).
  • T. You, I. Stansfield, M. C. Romano, A. J. P. Brown and G. M. Coghill, “Analysing GCN4 Translational Control in Yeast by Stochastic Chemical Kinetics Modelling and Simulation”, BMC Systems Biology 5:131 (2011).
  • C. A. Brackley, D. Broomhead, M.C. Romano, and M. Thiel,  “A Max-Plus Model of Ribosome Dynamics During mRNA Translation”, J. Theor. Biol. 303, 128 (2012).
  • P. Greulich, L. Ciandrini, R. Allen, and M.C. Romano, “A mixed population of competing TASEPs with a shared reservoir of particles”, Phys. Rev. E 85, 011142 (2012).
  • C.A. Brackley, L. Ciandrini and M.C. Romano, “Multiple phase transitions in a system of exclusion processes with limited reservoirs of particles and fuel carriers”, J. Stat. Mech. (2012) P03002 doi:10.1088/1742-5468/2012/03/P03002.
  • L. Ciandrini, I. Stansfield and M.C. Romano, “Ribosome traffic on mRNAs maps to gene ontology: genome-wide quantification of translation initiation rates and polysome size regulation” (submitted).
    • Ø Classification of mRNAs into abrupt and smooth sequences: density versus initiation rate for the entire genome; curves divided into 3 regions. [Download File .tar.gz]
  • F. Turci, A. Parmeggiani, E. Pitard, M. C. Romano and L. Ciandrini, “Exclusion Process on a Lattice with Dynamical Defects” (submitted), arXiv:1207.1804.
  • A. Kemp, R. Betney, L. Ciandrini, A. Schwenger, M. C. Romano and I. Stansfield, “Reduced rates of CAG codon translation in a yeast tRNA mutant cause pseudohyphal growth” (submitted).
  • R. Betney, E. de Silva, C. Mertens, Y. Knox, J. Krishnan and I. Stansfield, “Regulation of release factor expression using a translational negative feedback loop: a systems analysis” (submitted).

 

People (University of Aberdeen)

 

Collaborators (University of Edinburgh)

  • Rosalind Allen
  • Philip Greulich

 

Collaborators (University of Montpellier)

  • Andrea Parmeggiani
  • Estelle Pitard
  • Francesco Turci

 

Funding