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SUMMARY:Quantitative comparison of gene expression at cellular resolution 
 in Drosophilids - Angela DePace\, Department of Systems Biology\, Harvard 
 Medical School\, Boston MA
DTSTART:20080909T130000Z
DTEND:20080909T140000Z
UID:TALK13319@talks.cam.ac.uk
CONTACT:Dr Fabien Petitcolas
DESCRIPTION:*Abstract*: Understanding how gene regulatory networks evolve 
 requires us to measure the functional consequences of even small changes i
 n sequence. We have applied high-resolution microscopy and image processin
 g methods to blastoderm embryos of D. melanogaster and D. pseudoobscura to
  determine the expression patterns of key transcriptional regulators and a
  subset of their targets in their native context at cellular resolution in
  3D over the hour prior to gastrulation.  These two species shared their l
 ast common ancestor nearly 30 million years ago\, and comparative sequence
  analysis reveals a wide variety of changes in cis-regulatory elements.  O
 ur imaging techniques allow multiple types of statistically rigorous inter
 -species comparisons to be made\, both between individual embryos and betw
 een composite multi-gene models\, revealing widespread quantitative change
 s in expression patterns. We measure multiple types of gene-specific varia
 tion\, including changes in spatial position\, number of cells comprising 
 a pattern\, and the dynamics of expression.  Our comparative analyses aim 
 to put these differences in the context of complete developing embryos.  W
 hich changes are due to differences in the geometry of the embryos and whi
 ch are due to genetic differences in the transcriptional networks?  Furthe
 rmore\, which are changes initiated by variation in the trans-network\, an
 d which are due to changes in how cis-regulatory sequences interpret that 
 network?  Differentiating these types of variation will allow us to interp
 ret which specific sequence changes have functional consequences for gene 
 expression\, and provide insights into the functional constraints under wh
 ich cis-regulatory elements evolve. \n\n*Biography*: Angela DePace receive
 d her PhD in Biochemistry from the University of California San Francisco 
 in 2002\, where she worked with Jonathan Weissman on the molecular mechani
 sm of yeast prion propagation.  By developing an imaging based approach to
  measure the growth of individual prion fibers\, she was able to show that
  a single protein can misfold into multiple different self-propagating con
 formations with different growth kinetics.  This was powerful evidence for
  the protein-only hypothesis\, which had long been troubled by the existen
 ce of different prion strains\, which would require that a prion protein b
 e able to form not only one pathogenic conformation\, but multiple pathoge
 nic conformations\, each giving rise to different phenotypes.   She contin
 ued her work on quantitative imaging based approaches in a new context whe
 n she began her postdoctoral studies in Michael Eisen's lab at UC Berkeley
 .  There she worked with the Berkeley Drosophila Transcription Network Pro
 ject to apply 2 photon confocal imaging and image processing to characteri
 ze the transcriptional network directing embryonic development of multiple
  species of Drosophila.  She started her own lab in the Department of Syst
 ems Biology at Harvard Medical School in April 2008.\n
LOCATION:Microsoft Research Ltd\, 7 J J Thomson Avenue (Off Madingley Road
 )\, Cambridge
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