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Rohit Pappu on Molecular Grammar of Condensates – Part 3

On August 12, Dewpoint and Condensates.com welcomed back Rohit Pappu for the last segment of his three-part series on the molecular grammar of biomolecular condensates. After introducing the stickers and spacers model and describing phase transitions of linear multivalent and intrinsically disordered proteins in Part 1 and Part 2, in his third lecture Rohit expanded this model to multicomponent systems–in effect, showing how to treat real world examples of intracellular liquid-liquid phase separation by incorporating protein-RNA interactions and ligand effects.

Along with being an excellent dancer and an avid fan of cricket, Rohit is the Edwin H. Murty Professor of Engineering and the Director of the Center for Science and Engineering of Living Systems at Washington University in St. Louis. Rohit has been a key player in the field of biomolecular condensates since its beginning–in particular the drivers of phase transitions that lead to the formation of protein and RNA condensates, and the role that disordered regions play in these cellular processes. Rohit is also a member of Dewpoint’s Scientific Advisory Board and a wonderful advisor, collaborator, and friend.  

We hope you enjoy the final lecture in Rohit’s 3-part series, below. Rohit was also kind enough to provide written answers for all of attendees’ questions; those are below as well. If you want to watch his full series you can find part one here and part two here. And to hear more from the likes of Amy Gladfelter, Magnus Kjærgaard, Dominique Weil, and many other leading researchers, check out our ongoing series of Kitchen Table Talks.

Rohit Pappu on Molecular Grammar of Condensates - Part 3


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TRANSCRIPT

Mark Murcko (00:00:00):
Today is the third and final lecture in this wonderful series from Rohit Pappu, who I think all of you know by now. Rohit really is one of the pioneers in the field of molecular condensates. His lectures are part of this larger Kitchen Table Talks series in which we’re inviting prominent researchers in the field of condensate research to share their thinking to help the whole community to go a little bit faster by learning together. And all of these lectures are on the website, condensates.com. So you can look for them there. In the last two lectures, Rohit walked through the basics of molecular grammar, the stickers and spacers model, phase transitions of IDRs, intrinsically disordered regions in proteins.

Mark Murcko (00:00:47):
And now this lecture will cover phase transitions in multi-component systems as Rohit would say, trying to make this more real, looking at real world situations in which phase separation is occurring. And Rohit, as I’m sure many of you know, is the Edwin H. Murty Professor of Engineering and the director of the Center for Science and Engineering of Living Systems at Wash. U in St. Louis, has been a key player in the condensate field since its beginning. Last week I shared a little bit of information about Rohit that was given to me by several people that Rohit is an excellent dancer and has been known to lead dancing sessions at Gordon Conferences. I have since then learned that he is also an avid fan of cricket. And so if you have questions about that, you could also check with Rohit and he’d, I’m sure be happy to answer those questions as well as any you might have about condensates.

Mark Murcko (00:01:44):
Rohit, the floor is yours.

Rohit Pappu (00:01:47):
Thank you, Mark. Setting dancing and cricket aside, so we’ll jump in today to discuss the phase transitions in multi-component systems and this builds on the foundations that we’ve set forth in the first two lectures. So the program for today is to first talk about protein-RNA interactions and phase transitions, because as many of you will acknowledge, RNA is a key component of many of these condensates. And so an RNA is just not some random polymer. We have to think a bit harder about the specifics that RNA brings to these condensates. I will then segue to thinking about or articulating ways to think about ligand effects on phase separation for multivalent macromolecules and then basically point the way forward for the way we’ve been thinking about complexities of multicomponent phase diagrams and what the broader implications are going to be…

EXTENDED Q&A

Question from Bede Portz: Can you understand from the modeling if longer DPRs would require more heat/energy to transition from the dynamically arrested state to spherical state?
Rohit’s Response: For a fixed RNA length, the conjecture would be that a significant increase in the DPR length would probably help alleviate the dynamical arrest caused by secondary structures adopted by RNA…

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