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SUMMARY:Lineage as a conception of space in compartmental stochastic proce
 sses across cellular populations - Christian Ray (University of Kansas)
DTSTART:20160408T100000Z
DTEND:20160408T104500Z
UID:TALK65378@talks.cam.ac.uk
CONTACT:INI IT
DESCRIPTION:Co-author: Arnab Bandyopadhyay (University of  Kansas)<span><b
 r><br>Cytoplasmic regulatory networks often approximate well-mixed reactio
 n  kinetics in single cells\, but with variability from cell to cell. As a
  result\,  inheritance dynamics and kin correlations have been implicated 
 in effects on  cell cycle\, regulatory networks\, and modulation of popula
 tion growth rate. Based  on an experimental result in our lab suggesting l
 ineage correlations in  bacterial growth arrest\, we developed a cellular 
 stochastic simulation framework  to analyse the role of lineage in bacteri
 al cells regulating growth rate by  means of an intracellular molecular ne
 twork. The simulation framework thus  models both intrinsic and inherited 
 noise sources while maintaining lineage data  between cell agents assigned
  individual unique identifiers. <br> <br>Our initial application of the fr
 amework demonstrates the role of lineage in  the probability of bacterial 
 growth arrest controlled by an endogenous toxin  from a toxin-antitoxin sy
 stem. These systems have tight binding between toxin  and antitoxin\, so t
 hat there is a discrete critical threshold in the  toxin:antitoxin ratio b
 elow which a cell is essentially toxin-free and growth is  unrestricted\, 
 and above which toxin rapidly slows the growth rate. The subset of  high-t
 oxin cells crossing into the growth arrested state are associated with  an
 tibiotic persistence. Our implementation of a simple toxin-antitoxin syste
 m in  the simulation framework revealed the statistical dependence of grow
 th arrest on  cellular lineage: after several generations of growth\, the 
 probability of  cellular growth arrest began to depend on lineage distance
 . Clusters of closely  related cell agents had a high probability of trans
 itioning into growth arrest\,  while the rest of the lineage continued to 
 grow withou t restriction. <br> <span><br>We consider various quantities o
 f interest in multiscale lineage simulations\,  and conclude that growth t
 ransitions in a cellular colony cannot be fully  understood without quanti
 tative knowledge of its lineage.</span></span>
LOCATION:Seminar Room 1\, Newton Institute
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