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UID:20260806T155636EDT-6908zwGIwk@132.216.98.100
DTSTAMP:20260806T195636Z
DESCRIPTION:Discussion of two problems in computational circadian biology: 
 1. Stochastic phase oscillators and circadian bioluminescence recordings c
 ultured circadian oscillators from peripheral tissues were recently shown 
 to be both cell autonomous and self-sustained. Therefore the dominant caus
 e for amplitude reduction observed in bioluminescence recordings of cultur
 ed fibroblasts is desynchronization rather than the damping of individual 
 oscillators. We propose a generic model for quantifying luminescence signa
 ls from biochemical oscillators\, based on noisy phase oscillators. Our mo
 del incorporates 3 essential features of circadian clocks: stability of th
 e limit cycle\, fluctuations and inter-cellular coupling. The model is the
 n used to analyze bioluminescence recording from immortalized and primary 
 fibroblasts. Fits to population recordings allow simultaneous estimation o
 f the stability of the limit cycle (or equivalently the stiffness of indiv
 idual frequencies)\, the period dispersion and the interaction strength be
 tween cells. Consistently with other work\, coupling is found to be weak a
 nd insufficient to synchronize cells. Interestingly\, we find frequency fl
 uctuations remain correlated for longer than one clock cycle\, which is co
 nfirmed from individual cell recordings. We discuss how to link the generi
 c model with more microscopic models\, which suggests mechanisms by which 
 circadian oscillators resist fluctuations and maintain accurate timing in 
 the periphery. 2. Modeling an evolutionary conserved circadian cis-element
  Circadian oscillator networks rely on a transcriptional activator called 
 CLOCK. Identifying the targets of this heterodimeric bHLH transcription fa
 ctor poses challenges and it has been difficult to decipher its specific s
 equence affinity beyond a canonical E-box motif\, except perhaps for some 
 flanking bases contributing weakly to the binding energy. Here we use a co
 mparative genomics approach and first study of the conservation properties
  of the best-known circadian enhancer in the Drosophila melanogaster perio
 d gene. This shows a signal involving the presence of two closely spaced s
 equence motifs\, a configuration we can also detect in the other 4 promine
 nt CLOCK targets genes in flies: timeless\, vrille\, Pdp1 and cwo. The exa
 mples allow training a probabilistic model that we can test using function
 al genomics datasets. We find the sequences predicted from our model are o
 verrepresented in promoters of genes induced in a recent study by a glucoc
 orticoid receptor-CLOCK fusion protein. We then scanned the mouse genome w
 ith the fly model and found that many known CLOCK/BMAL1 targets harbour se
 quences matching our consensus. The phase of predicted cyclers in liver ag
 reed with known CLOCK/BMAL1 regulation. Felix Naef studied theoretical phy
 sics at ETHZ and obtained his PhD from EPFL in 2000\, then pursued postdoc
  training at the Center for Studies in Physics and Biology\, Rockefeller U
 niversity\, NYC. His research focuses on modeling and interpretation of hi
 gh-throughput functional data and study of biomolecular oscillators. He jo
 ined ISREC as associate scientist in the NCCR Molecular Oncology program i
 n 2004 and was nominated Tenure Track Assistant Professor in the School of
  Life Sciences\, EPFL\, in 2005.\n
DTSTART:20070926T183000Z
DTEND:20070926T193000Z
LOCATION:Duff Medical Building\, CA\, QC\, Montreal\, H3A 2B4\, 3775 rue Un
 iversity
SUMMARY:Modeling an evolutionary conserved circadian cis-element using func
 tional and comparative genomics
URL:/channels/event/modeling-evolutionary-conserved-ci
 rcadian-cis-element-using-functional-and-comparative-genomics-27169
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