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SUMMARY:Measuring the liquid structure of condensates in live cells - Josh
  Riback (Baylor College of Medicine)
DTSTART:20231012T103000Z
DTEND:20231012T112000Z
UID:TALK204907@talks.cam.ac.uk
DESCRIPTION:Biomolecular condensates are liquid-like membrane-less organel
 les where essential biochemistry occurs\, including ribosome and spliceoso
 me biogenesis. Many studies posit that to carry out biochemical processes\
 , the condensate preferentially enriches or excludes specific molecules. U
 nlike gases\, condensates are liquid-like phases and thus can have locally
  correlated structure. Such liquid structure may facilitate long-range con
 formational changes (i.e.\, allostery) between biomolecules\, spatiotempor
 ally coordinating interactions that direct binding\, processing\, and fold
 ing of biomolecules. Measurement of structure is classically obtained thro
 ugh diffraction-based methods\, which is not conducive to condensates in c
 ells. We instead turned to a different approach using live cell fluorescen
 t microscopy to extract the strength driving molecules into condensates\, 
 quantified by their partitioning (i.e.\, free energy of transfer). To acco
 mplish this\, we employed a construct with two domains separated by a vari
 able-sized linker. We surmised that its partitioning would depend on the e
 xact length of the linker. For example\, if the linker is too short or too
  long the transfer free energy would weaken as the domains are infrequentl
 y capable of &ldquo\;reaching&rdquo\; their preferred interaction partners
  within the condensate. Based on this intuition and other thermodynamic co
 nsiderations\, we converted these free energies into a measure of the degr
 ee of correlation between the two domains\, known as the pair correlation 
 function. Employing this scheme on a common condensate driver protein\, NP
 M1\, allowed us to elucidate general principles underlying preferred molec
 ular arrangements within the nucleolus. Furthermore\, by perturbing nucleo
 lar composition and identifying how the degree of its structure is impacte
 d\, we gain insights into the connection between nucleolar form and riboso
 me biogenesis. Overall\, this novel methodology opens the door to understa
 nding the liquid structure of condensates\, how they mechanistically facil
 itate function\, and how they may change during development\, aging\, and 
 disease.
LOCATION:Seminar Room 1\, Newton Institute
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