Reverse engineering of force integration during mitosis in the Drosophila embryo

Roy Wollman, Gul Civelekoglu-Scholey, Jonathan M. Scholey, Alex Mogilner

Research output: Contribution to journalArticlepeer-review


The mitotic spindle is a complex macromolecular machine that coordinates accurate chromosome segregation. The spindle accomplishes its function using forces generated by microtubules (MTs) and multiple molecular motors, but how these forces are integrated remains unclear, since the temporal activation profiles and the mechanical characteristics of the relevant motors are largely unknown. Here, we developed a computational search algorithm that uses experimental measurements to 'reverse engineer' molecular mechanical machines. Our algorithm uses measurements of length time series for wild-type and experimentally perturbed spindles to identify mechanistic models for coordination of the mitotic force generators in Drosophila embryo spindles. The search eliminated thousands of possible models and identified six distinct strategies for MT-motor integration that agree with available data. Many features of these six predicted strategies are conserved, including a persistent kinesin-5-driven sliding filament mechanism combined with the anaphase B-specific inhibition of a kinesin-13 MT depolymerase on spindle poles. Such conserved features allow predictions of force-velocity characteristics and activation-deactivation profiles of key mitotic motors. Identified differences among the six predicted strategies regarding the mechanisms of prometaphase and anaphase spindle elongation suggest future experiments.

Original languageEnglish (US)
Article number195
JournalMolecular systems biology
StatePublished - 2008


  • Genetic algorithm
  • Mathematical model
  • Mitosis
  • Reverse engineering
  • Spindle

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences
  • Applied Mathematics


Dive into the research topics of 'Reverse engineering of force integration during mitosis in the Drosophila embryo'. Together they form a unique fingerprint.

Cite this