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SUMMARY:A Framework study of the NF-kB signalling pathway - Adaoha Ihekwab
 a\, CoSBi
DTSTART:20090325T110000Z
DTEND:20090325T120000Z
UID:TALK14745@talks.cam.ac.uk
CONTACT:Dr Fabien Petitcolas
DESCRIPTION:*Abstract*: The study of complex biological systems requires a
 n interplay between theory\, experimentation\, modelling and simulation.  
 Hypotheses are tested by experimental observations which are integrated in
 to theoretical models that are then amenable to simulations for predicting
  the responses to perturbations made to a biological model. Thus\, detaile
 d understanding of these systems cannot be achieved by modelling or experi
 ments alone but requires a tight integration between the two.  This type o
 f scientific approach is required for investigating the dynamic relationsh
 ips between components\, their organisation and regulation in cellular sig
 nal transduction networks. Mathematical modelling can further facilitate t
 he understanding of these networks by enabling quantified relationships be
 tween components to be studied. \nThe nuclear factor-kB (NF-kB) signalling
  pathway is an example of a complex signal transduction network.  NF-kB is
  a transcription factor which has crucial roles in inflammation\, immunity
 \, cell proliferation and apoptosis.  Proteins involved in the NF-kB signa
 lling pathway undergo phosphorylation which ultimately leads to the activa
 tion of the transcription factor and expression of genes involved in vario
 us cellular processes. \nThis work investigates how NF-kB oscillations dep
 end on the kinetics of phosphorylation by IKK\; and describes a “trial
 ” to analyze temporal behaviour of NF-kB signalling pathway in a frame w
 ork of combined experimental and in silico approach. We show that in the p
 opulation average one finds damped oscillations upon IL1-alpha treatment. 
 We then characterise the kinetics of IkB-alpha phosphorylation by IKK and 
 use the measured values to refine the insilico model. Finally\, we use an 
 inhibitor of IKK to show the effect of decreased phosphorylation by IKK on
  NF-kB oscillations experimentally and subsequently compared them to simul
 ation. Results of which were used to explain the contribution of IKK2 to t
 he control of frequency and amplitude of the observed NF-kB oscillations.\
 n\n*Biography*: Adaoha Ihekwaba graduated with a BSc. in Pharmaceutical Sc
 iences from the University of Greenwich\, London\, 2001 (thesis title - Sy
 mmetric & Asymmetric Synthesis of 4-Aryl-1\,4-dihydro-2\,6-dimethyl-3\,5-p
 yridine dicarboxylate and their conversion to pyridine by the process of O
 xidation ) and a Ph.D degree in 2006 from The University of Manchester (th
 esis title - Modelling of Cellular Signal Transduction Process (NF-kB sign
 alling pathway) using Numerical Simulation Techniques) under the supervisi
 on of Prof. DB Kell and Dr. Neil Benson (Pfizer). One of the main focus of
  the research was to explore the effectiveness of numerical simulation tec
 hniques to better understand the implications of complex and kinetics of c
 ellular signal transduction events – with the intension to use existing 
 data\, state-of the art Cellular Fluorescence reader technology and standa
 rd inhibitors to generate data sets that would then be used to build and t
 est computer models. For her postdoctoral research\, a Wain International 
 Fellowship was awarded to Adaoha Ihekwaba through obtained support from th
 e BBSRC in 2006 (which was carried out at the Virginia Bioinformatics Inst
 itute under the guidance of Prof. Pedro Mendes) to establish a methodology
  for developing computational models of cellular biochemistry based on gen
 ome-wide molecular profiling data. The methods were applied to existing ti
 me course data sets of metabolite\, protein and transcript profiles of the
  forage crop Medicago truncatula after elicitation with the hormone methyl
 -jasmonic acid.
LOCATION:Small public lecture room\, Microsoft Research Ltd\, 7 J J Thomso
 n Avenue (Off Madingley Road)\, Cambridge
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