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SUMMARY:Disruptions on the Highways of Cell Communication - Dario Alessi\,
  MRC Protein Phosphorylation Unit\, University of Dundee
DTSTART:20120306T161500Z
DTEND:20120306T180000Z
UID:TALK35557@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The formation of aggregates by misfolded proteins is thought t
 o be inherently toxic\, affecting thus cell fitness. This observation has 
 lead to the suggestion that selection against protein aggregation might be
  a\nmajor constraint on protein evolution. The precise fitness cost associ
 ated to protein aggregation has been traditionally difficult to evaluate.\
 nMoreover\, it is not known if the deleterious effect of aggregates in cel
 l physiology is generic or depends on the specific structural features of 
 the protein deposit. In bacteria\, the accumulation of intracellular\nprot
 ein aggregates reduces cell reproductive ability\, promoting therefore cel
 lular aging. Here we exploit the cell division defects promoted by the int
 racellular aggregation of the Alzheimer’s A&#946\; peptide in bacteria t
 o demonstrate that the fitness cost associated to protein misfolding and a
 ggregation are connected to the protein sequence\, which controls both the
  in vivo aggregation rates and the conformational properties of the aggreg
 ates. We also show that the deleterious impact of protein aggregation in b
 acterial division can be buffered by molecular chaperones\, likely broaden
 ing the sequential space on which natural selection can act.\nOverall\, th
 e results in the present work have potential implications for the evolutio
 n of proteins and provide a robust system in which to experimentally model
  and quantify the impact of protein aggregation on cell fitness.
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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