Process Model for JAK-STAT signal transduction pathway using Stochastic Pi Machine (SPiM) and...

Process    Model  for  JAK-­‐STAT  signal  transduc8on  pathway  using  Stochas8c  Pi  Machine(SPiM)  and  COmplex  PAthway  SImulator  (COPASI)    

Students:  Vishakha  Sharma(CS),  Yifei  Bao(CS)  Advisors:  Prof.  Adriana    Compagnoni(CS)  

IntroducAon  The JAK(Janus kinase)-STAT(Signal transducer and activator of transcription) signal transduction pathway is a cascade of downstream cellular events initiated from outside the cell through cell surface to the DNA in the nucleus, causing transcription.

Since dysregulation in the functionality of JAK-STAT pathway results in immune deficiency syndrome and cancers, like lymphomas, leukemia and breast cancer, we believe that models like this have the potential to contribute to cancer research.

Results    •  Time  course  of  mRNA  in  cytoplasm    

     a.  COPASI                                                                                            b.  SPiM    •  Time  course  of  SOCS1  

       a.  COPASI                                                                                            b.  SPiM    

•  Time  course  of  STAT1n*-­‐STAT1n*  

                                         a.  COPASI                                                                                                                  b.  SPiM  

•  Overview  of  different  species  in  JAK-­‐STAT  signal  transducAon  pathway  

Experiment    SPiM  –  StochasAc  Pi  Machine  

•  The Stochastic Pi Machine, SPiM is an implementation of stochastic pi calculus and it is used to build computational models for biological processes.

COPASI  –  Complex  Pathway  Simulator  

•  COmplex  Pathway  SImulator  produces  determinisA  simulaAon  results.  COPASI  automaAcally  converts  the  reacAon  equaAons  to  ODEs  using  ODEPACK  .  

SPiM  Model  for  JAK-­‐STAT    pathway  •   The  computaAonal  model    consists  of  

46  reacAons  Conclusion  •  In  our  model  we  scale  the  iniAal  concentraAons  

to   formulate   the   fact   that   solving   ordinary  differenAal   equaAons   is   faster   than  execuAng  a  concurrent  model.  

•  The  behavioral  expressivity  of   the  stochasAc  pi-­‐calculus   out   stands   the   analyAcal   behavior   of  the  ODEs  systems.    

•  The  simulaAon  results  of  JAK/STAT  pathway  can  be   tested   in   the  wet   labs  and  contribute   in   the  area  of  biological  research  as  how  specific  drugs  affect   a   parAcular   reacAon   in   the   biological  system.    

Graduate Student Research Conference

2011

Time, s

nM/L

JAK-STAT Signal trabsduction pathway