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SUMMARY:Disentangling Polydispersity in Biological Systems by SAXS - Pau B
 ernadó\, Centre de Biochimie Structurale (CBS)
DTSTART:20170222T103000Z
DTEND:20170222T113000Z
UID:TALK71220@talks.cam.ac.uk
CONTACT:Priyanka Joshi
DESCRIPTION:Many biological systems are inherently polydisperse. In other 
 words\, they present multiple co-existing species with relative population
 s that are governed by thermodynamic and kinetic laws. Conformational fluc
 tuations\, transient biomolecular interactions\, or irreversible aggregati
 on processes are examples of biological polydisperse systems. The structur
 al characterization of these phenomena is arduous as traditional approache
 s are not adapted to study complex equilibriums.\nSmall-Angle X-ray Scatte
 ring (SAXS)\, which probe the overall size and shape of particles in solut
 ion\, is in principle a very well adapted technique to structurally descri
 be polydisperse systems. Experimental SAXS profiles correspond to averaged
  values from all co-existing species of the sample. Two strategies to dise
 ntangle complex polydisperse biological systems developed in our group wil
 l be presented. The first approach uses previous structural information an
 d integrative strategies to build atomistic models of the (supposedly) exi
 sting species. These models are subsequently used to describe experimental
  SAXS data in terms of ensembles of multiple species in equilibrium. The s
 econd strategy aims at disentangling complex systems for which no structur
 al information is available. Concretely\, the formation of insulin and α-
 synuclein E46K familial mutant amyloids have been monitored by SAXS in a t
 ime-dependent manner. These large SAXS datasets are decomposed using speci
 fically modified chemometric routines to yield the species-pure SAXS profi
 les and their relative populations linked to the fibrillation kinetics. In
  both cases an oligomeric species has been detected and characterized. The
  perspectives and limitations of the approaches used to disentangle comple
 x mixtures will be discussed.\n
LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre
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