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SUMMARY:Evolution of cellular networks: from interactions to phenotypes - 
 Pedro Beltrao (EMBL-EBI)
DTSTART:20130204T160000Z
DTEND:20130204T170000Z
UID:TALK41682@talks.cam.ac.uk
CONTACT:Florian Markowetz
DESCRIPTION:Understanding how changes in DNA are propagated through biomol
 ecules and interactions to give rise to phenotypic diversity is an importa
 nt objective for evolutionary biology. To contribute to this goal we used 
 a comparative approach to study the evolution of post-translational and ch
 emical-genetic networks.\n\nProtein function is highly regulated by post-t
 ranslational modifications (PTMs) but little is known about the evolution 
 of these regulatory networks. Using mass-spectrometry we characterized the
  in-vivo phosphoproteomes of three fungal species. We observed that kinase
  networks diverge at a fast rate although the average phosphorylation leve
 l of functional modules (i.e. complexes and pathways) is well conserved.  
 To study the importance of the observed variation we curated over 200.000 
 published PTMs for 11 species and developed approaches to predict their fu
 nction. Our analysis suggests that there are a significant number of non-f
 unctional modifications as well as potential routes for neutral variation 
 of these regulatory interactions.  \n\nIn parallel we performed a chemical
  genetic screen to measure the functional interactions between genes and s
 mall-molecules in S. cerevisiae and S. pombe. In analogy to the observatio
 ns made for the PTM networks\, drug-module interactions were found to dive
 rge slower than drug-gene interactions. Importantly\, data from both speci
 es could be combined to improve the prediction of the mode-of-action of th
 e tested compounds. \n\nThese interaction networks offer us a glimpse into
  how genotypes are translated to phenotypes and we envision that they will
  increasingly be used in interpreting the consequences of genetic variatio
 n occurring within populations as well as in the rational design of combin
 atorial therapeutics.\n
LOCATION:Cancer Research UK Cambridge Institute\, Lecture Theatre
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