BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:Dynamic response phenotypes as tools for model discrimination in s
 ystems biology
DTSTART:20190606T150000
DTEND:20190606T160000
DTSTAMP:20260407T040351Z
UID:8031c24e284b6ed254e379dfdf789eb2ccafc90a8e925964f29aafa5
CATEGORIES:Conferences - Seminars
DESCRIPTION:Eduardo D. Sontag\, Department of Bioengineering and Departmen
 t of Electrical and Computer Engineering\, Northeastern University\nOne of
  the central questions in systems and synthetic biology is that of underst
 anding the roles of signal transduction pathways and feedback loops\, from
  the elucidation of such pathways in natural systems to the engineering de
 sign of networks that exhibit a desired behavior.  This talk discusses ce
 rtain types of network qualitative information that can be gleaned from 
 “dynamic phenotypes”\, a term that we take as encompassing both the tr
 ansient characteristics of temporal responses and the use of rich classes 
 of probing signals beyond step inputs.  We focus on three examples: fold-
 change detection\, non-monotonic responses\, and subharmonic oscillations.
 \nAn ubiquitous property of sensory systems is "adaptation": a step increa
 se in stimulus triggers an initial change in a biochemical or physiologica
 l response\, followed by a more gradual relaxation toward a basal\, pre-st
 imulus level.  Adaptation helps maintain essential variables within accep
 table bounds and allows organisms to readjust themselves to an optimum and
  non-saturating sensitivity range when faced with a prolonged change in th
 eir environment.  Certain adapting systems\, ranging from bacterial chemo
 taxis pathways to signal transduction mechanisms in eukaryotes\, enjoy a r
 emarkable additional feature: scale invariance or "fold change detection" 
 meaning that the initial\, transient behavior remains approximately the sa
 me even when the background signal level is scaled (“log sensing”).  
 We will review the biological phenomenon\, and formulate a theoretical fra
 mework leading to a general theorem characterizing scale invariant behavio
 r by equivariant actions on sets of vector fields that satisfy appropriate
  Lie-algebraic nondegeneracy conditions.  The theorem allows one to make 
 experimentally testable predictions\, and the presentation will discuss th
 e validation of these predictions using genetically engineered bacteria an
 d microfluidic devices\, as well their use as a "dynamical phenotype" for 
 model invalidation.\nSystems described by order-preserving dynamics are ca
 lled “monotone systems”.  Such systems can be shown to have monotone 
 response properties when starting from steady states: a nondecreasing inpu
 t can never give rise to a biphasic response\, for example.  We briefly r
 eview some of this theory and show as an example how this tool can be used
  to invalidate a published model of M. tuberculosis stress response (hypox
 ic induction pathway). One challenging question in systems biology is that
  of comparing different architectures for perfect adaptation.  For exampl
 e both incoherent feedforward loops (IFFL’s) and integral feedback syste
 ms give rise to perfect adaptation and\, in some configurations\, scale in
 variance.  Recent work with Sahand Jamal Rahi has proposed the use of per
 iodic signals to discriminate between these models.   We review a theore
 tical result showing that feedforward loops and monotone systems both lead
  to entrainment\, but nonlinear feedback architectures (such as nonlinear 
 integral feedback) may lead to period doubling bifurcations and even chaos
 .  This result is illustrated through experimental work with C. elegans A
 IA interneurons\, in which odor-evoked intracellular Ca2+ response signatu
 res\, to periodic on-off pulses of diacetyl\, display subharmonic behavior
  at high forcing frequencies.\nThe talk will also include some speculative
  remarks about the role of the shape of transient responses in immune syst
 em self/other recognition.
LOCATION:BSP 234 https://plan.epfl.ch/?room==BSP%20234
STATUS:CONFIRMED
END:VEVENT
END:VCALENDAR