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Research Project

Eukaryotic unicellular organism biology – systems biology of the control of cell growth and proliferation

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Path2Models: large-scale generation of computational models from biochemical pathway maps
Publication . Büchel, Finja; Rodriguez, Nicolas; Swainston, Neil; Wrzodek, Clemens; Czauderna, Tobias; Keller, Roland; Mittag, Florian; Schubert, Michael; Glont, Mihai; Golebiewski, Martin; van Iersel, Martijn; Keating, Sarah; Rall, Matthias; Wybrow, Michael; Hermjakob, Henning; Hucka, Michael; Kell, Douglas B; Müller, Wolfgang; Mendes, Pedro; Zell, Andreas; Chaouiya, Claudine; Saez-Rodriguez, Julio; Schreiber, Falk; Laibe, Camille; Dräger, Andreas; Le Novère, Nicolas
Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.
Dynamical Scenarios for Chromosome Bi-orientation
Publication . Zhang, Tongli; Oliveira, Raquel A.; Schmierer, Bernhard; Novák, Béla
Chromosome bi-orientation at the metaphase spindle is essential for precise segregation of the genetic material. The process is error-prone, and error-correction mechanisms exist to switch misaligned chromosomes to the correct, bi-oriented configuration. Here, we analyze several possible dynamical scenarios to explore how cells might achieve correct bi-orientation in an efficient and robust manner. We first illustrate that tension-mediated feedback between the sister kinetochores can give rise to a bistable switch, which allows robust distinction between a loose attachment with low tension and a strong attachment with high tension. However, this mechanism has difficulties in explaining how bi-orientation is initiated starting from unattached kinetochores. We propose four possible mechanisms to overcome this problem (exploiting molecular noise; allowing an efficient attachment of kinetochores already in the absence of tension; a trial-and-error oscillation; and a stochastic bistable switch), and assess their impact on the bi-orientation process. Based on our results and supported by experimental data, we put forward a trial-and-error oscillation and a stochastic bistable switch as two elegant mechanisms with the potential to promote bi-orientation both efficiently and robustly.

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European Commission

Funding programme

FP7

Funding Award Number

201142

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