Friday, 19 September 2014

Mathematical Modelling and Patient Stratification - Monday 22 September

FMS BIOINFORMATICS & SYSTEMS BIOLOGY SEMINAR SERIES 2014

 

Monday 22 September @ 3.30 pm

Room 2.21 Research Beehive

 

Professor Walter Kolch

Director of Systems Biology Ireland & Conway Institute

University College Dublin

 

Walter Kolch is Director of Systems Biology Ireland and the Conway Institute at University College Dublin (Ireland). Trained as an MD he worked in experimental clinical research, the pharmaceutical industry, and basic biological research. He is best known for his work in oncogene signal transduction, proteomics and systems biology. His current research interest focuses on understanding how biochemical networks specify biological decisions, and how systems biology approaches can help clinical advances.  Prof Kolch will introduce a select number of projects aimed at a general (non-specialist) audience and therefore I strongly encourage attendance to what promises to be a really exciting seminar.

 

"Using mathematical pathway modelling for patient stratification"

 

Signalling pathways exert finely tuned control over cell fate decisions that ultimately determine the behaviour of cancer cells. It could therefore be expected that the dynamics of key pathway activation may contain prognostically relevant information over and above that which is contained in the static expression levels of individual biomarkers. To investigate this hypothesis we have characterised the network architecture that regulates JNK stress signalling in neuroblastoma cells and applied a modelling approach to extract prognostic information from neuroblastoma patient-specific simulations of JNK activation. Our experimental analysis identified a stress induced, ultrasensitive mode of JNK activation facilitated by positive feedback from JNK to its upstream kinase MKK7, which was constrained by inhibitory crosstalk from Akt and further regulated through scaffolding by the MAP3K ZAK. We then utilised an experimentally calibrated and validated mathematical model of this network structure to simulate patient-specific JNK network responses for 369 neuroblastoma patients. Survival analysis based upon the dynamics of these responses revealed that an inability to initiate switch-like JNK signalling in silico was significantly associated with decreased survival for both MYCN amplified and non-amplified neuroblastoma patients.

 

Faculty contacts: 

Mauro Santibanez-Koref (mauro.santibanez-koref@newcastle.ac.uk)

Diego Miranda-Saavedra (diego.miranda-saavedra@ncl.ac.uk)

Sponsored by: Scientific Laboratory Supplies

 

 

 

 

 

 

 

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