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SUMMARY:Hard numbers—physicochemical models of a mitotic signalling orga
 nelle​ - Kevin A. Janes\, Ph.D.​ Departments of Biomedical Engineering
  and Biochemistry &amp\; Molecular Genetics\, University of Virginia​
DTSTART:20251202T160000Z
DTEND:20251202T170000Z
UID:TALK241249@talks.cam.ac.uk
CONTACT:Simona Valeviciute
DESCRIPTION:Abstract:  Cancer is a complex disease that is best tackled by
  iterations of quantitative experiments and mathematical models at the sys
 tems level. Biochemically\, obtaining protein copy numbers and binding aff
 inities is laborious\, but absolute quantities are powerful to test and re
 fine hypotheses. We have built fully parameterized models that combine phy
 sics and chemistry to abstract a key biochemical reaction network that is 
 essential for ensuring the fidelity of mitosis. Disruptions of the network
  in cancer do not occur by mutation but instead by alterations in protein 
 abundances that change its emergent switch-like detection of proper chromo
 somal alignment on the metaphase plate. By integrating kinase enzymology w
 ith protein-protein interactions and biomolecular condensation on chromati
 n\, we identify surprising stoichiometric constraints and flexibilities fo
 r network function. The models support a working hypothesis that a membran
 eless organelle formed by the chromosomal passenger complex buffers abunda
 nce changes to a point that is exceeded periodically by stoichiometrically
  imbalanced cancers and precancers.
LOCATION:CRUK CI Lecture Theatre
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