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SUMMARY:Bacterial LLPS droplets protect mRNA during stress - Mark Leake (U
 niversity of York)
DTSTART:20231009T125000Z
DTEND:20231009T133000Z
UID:TALK206656@talks.cam.ac.uk
DESCRIPTION:Previously\, we reported the discovery of mesoscale membranele
 ss droplets in bacteria called aggresomes which form through liquid-liquid
  phase separation (LLPS) from a plethora of key proteins implicated in cel
 l resuscitation following stress [1\, 2]. Here\, I will discuss new findin
 gs which integrate time-resolved single-molecule live-cell microscopy with
  new biophysical modelling\, that highlight the crucial role aggresomes pl
 ay as an analogue of eukaryotic stress granules (SGs) in safeguarding mRNA
  during stress. We find that upon stress onset\,&nbsp\;mobile mRNA molecul
 es selectively incorporate into individual proteinaceous&nbsp\;SGs&nbsp\;b
 ased on length-dependent enthalpic gain over entropic loss.&nbsp\;As&nbsp\
 ;stress prolongs\,&nbsp\;SGs&nbsp\;undergo compaction facilitated by stron
 ger non-specific RNA-protein interactions\, thereby promoting recruitment 
 of shorter RNA chains. Remarkably\, mRNA ribonucleases are repelled from b
 acterial&nbsp\;SGs\, potentially due to the influence of protein surface c
 harge. This exclusion mechanism ensures the integrity and preservation of 
 mRNA within&nbsp\;SGs&nbsp\;during stress conditions\,&nbsp\;providing val
 uable insights into the intricate processes involved in mRNA storage withi
 n membraneless droplets.&nbsp\;Following stress removal\,&nbsp\;SGs&nbsp\;
 facilitate mRNA translation\, thereby enhancing cell fitness in changing e
 nvironments. These droplets maintain mRNA physiological activity during st
 orage\, making them potentially valuable for mRNA therapeutics manufacturi
 ng.\n1&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp
 \;&nbsp\; Pu\, Y.&nbsp\;et al.&nbsp\;ATP-Dependent Dynamic Protein Aggrega
 tion Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance.
 &nbsp\;Mol Cell&nbsp\;73\, 143-156 e144 (2019).&nbsp\;https://doi.org:10.1
 016/j.molcel.2018.10.022\n2&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp\;&nbsp
 \;&nbsp\;&nbsp\;&nbsp\;&nbsp\; Jin\, X.&nbsp\;et al.&nbsp\;Membraneless or
 ganelles formed by liquid-liquid phase separation increase bacterial fitne
 ss.&nbsp\;Sci Adv&nbsp\;7\, eabh2929 (2021).&nbsp\;https://doi.org:10.1126
 /sciadv.abh2929\n&nbsp\;
LOCATION:Seminar Room 1\, Newton Institute
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