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Rohit Pappu on Molecular Grammar of Condensates – Part 2

On August 5, Dewpoint, in partnership with Condensates.com, welcomed back Rohit Pappu, one of the leaders in the condensates field, for the second installment in his 3-part series on the molecular grammar of biomolecular condensates. In this second part, he delved into the relationship between intrinsically disordered proteins and phase behavior. He showed how theory predicts the sequence-encoded conformational heterogeneity of IDPs and demonstrated how these sequence-ensemble relationships are relevant for describing phase behavior by applying the stickers-and-spacers model.

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 made seminal contributions to the field of biomolecular condensates, 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.

See Rohit’s second excellent lecture below. Rohit also kindly provided written answers for all of attendees’ questions; those are below as well. Or see part one here and see part three here. Rohit’s talks are part of our Kitchen Table Talk series.

Rohit Pappu on Molecular Grammar of Condensates - Part 2


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TRANSCRIPT

Mark Murcko (00:00:00):
Good morning, good afternoon everybody. Greetings from Dewpoint it’s good to see everybody back again, and also some new names and faces. This is the second of a three-part lecture series from Rohit. And I think as everyone knows, Rohit is one of the leaders and pioneers in the field of condensates. And this is an ongoing series of lectures that’s part of our Kitchen Table Talk series, which is all available online on the website, condensates.com. It’s intended to be really an opportunity for prominent researchers like Rohit to share their work and their knowledge with the whole community to help all of us to go faster, which is important in such a complex and interesting field as cellular condensates.

Mark Murcko (00:00:45):
So Rohit, today, will be getting more into intrinsically disordered proteins and their relationship to phase behavior. It’ll be a very interesting lecture, of course, as Rohit’s lectures always are. And although I did mention this last time, I’ll just for those of you who are new, I’ll mention that Rohit is the Edwin H. Murty professor of engineering and the director of the Center for Science and Engineering at Wash U in St. Louis and really has been a key leader. And also, he is a member of Dewpoint’s Scientific Advisory Board and has been a great collaborator, mentor, friend and all of that.

Mark Murcko (00:01:26):
And one last point I’d like to make before handing it off to Rohit is since Rohit’s lecture last week, I’ve received interesting intelligence from several sources about the fact that Rohit at the intrinsically disordered proteins Gordon Conference has been known to lead dancing events. And so, I’m hoping that someone in the audience has video of this, that they could share with the community, that would be a great thing, Rohit off to you.

Rohit Pappu (00:01:57):
Well, on that very important note, let’s get started. Thank you, Jill, thank you, Mark. And I should add that Jill has been very kind in recording the transcripts of the various questions that were posted on the chat because, of course, it’s difficult to get to all of the questions. I have been a little tied down, but my plan is to over the next 24 hours, respond to the questions from lecture one, as well as the questions from today’s lecture. So please feel free to either email me or post your questions on chat.

Rohit Pappu (00:02:34):
So as Mark mentioned, today, we are going to get into the contribution of intrinsically disordered proteins. And I’m going to refer to these as multivalent IDPs. As we discussed last time, the stickers and spacers formalism gives us a very good anchor point. But before we launch in, it’s useful to ask something of a rhetorical question at this juncture, what are intrinsically disordered proteins/regions–they go by the name of IDPs and IDRs…

EXTENDED Q&A

Question from Achuthan Raja Venkatesh: Professor Pappu, I have the following question with regards to discussions from the previous session: To what degree can condensates function as entropy reservoirs, that help compensate for unfavourable biomolecular reactions?
Rohit’s Response: The question, if I understand it correctly, appears to be about being able to enhance the efficiencies of biochemical reactions can be enhanced…

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