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Rohit Pappu on Molecular Grammar of Condensates – Part 1

On July 29, Dewpoint, in partnership with Condensates.com, kicked off a 3-part series of talks featuring condensate pioneer Rohit Pappu. Rohit’s three lectures present the molecular grammar of biomolecular condensates. In this first part, he covered the basic physics of associative polymers, the stickers-and-spacers model, and the insights that emerge from the application of this model to describe the phase behavior of linear multivalent proteins.

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 the first of this fascinating set of lectures below. And Rohit graciously provided written answers to all of attendee’s questions; those are below as well. To watch the full series, you can find part two here and part three here. Rohit’s talks are part of our Kitchen Table Talk series.

Rohit Pappu on Molecular Grammar of Condensates - Part 1


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TRANSCRIPT
Mark Murcko (00:00:00):
Today, we’re kicking off a three part lecture series today from Rohit Pappu. Rohit, who obviously is one of the pioneers of the whole field of condensates. Rohit’s lectures are the latest installments in our series of what we’re calling Kitchen Table Talks, in which we invite prominent researchers in the condensate field to share their thinking about their recent work with the entire global community. And all of those lectures can be found on condensates.com and we’re adding more all the time.

Mark Murcko (00:00:30):
Rohit’s three lectures in that series, he’ll be presenting on the molecular grammar of biomolecular condensates. And today in part one, he’ll cover the basic physics of associated polymers, the stickers and spacers model, and also the insights that are emerging from the application of this model to describe the phase behavior of linear multivalent proteins. And lectures two and three in the series will be next Wednesday, August 5th, and then the following Wednesday, August 12th. And they’ll be at the same time as this lecture, 10 o’clock Eastern time. Lecture two will cover phase transitions of IDRs, Intrinsically Disordered Proteins and domains, while lecture three will cover phase transitions in multi-component systems, which is a fascinating topic in itself.

Mark Murcko (00:01:22):
Just a little bit more background on Rohit. He’s the Edwin H Murti 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 complex cellular processes. Rohit is also a member of Dewpoint’s scientific advisory board. And he’s a wonderful advisor to us at Dewpoint and a great collaborator and a friend. Rohit, we really want to thank you in advance for what all of us know will be a wonderful series of lectures. The floor is yours.

Rohit Pappu (00:02:12):
Thank you very much, Mark. And thank you to Jill and Rebecca for suggesting this idea and for doing all the leg work to make what will, I think, be a seamless operation. I have learned a lot from my conversations with colleagues at Dewpoint and particularly from Mark. I think it’s a wonderful thing to put together, this Kitchen Table Talk series that is also not for profit, which is really, I think, appreciated by the community.

Rohit Pappu (00:02:46):
As Mark pointed out, today what I’m going to do is sort of focus on this general topic of what I refer to as molecular grammar, and really what this refers to is being able to read information that is written into protein and RNA sequences and connect this information to the driving forces for condensate formation, regulation, dissolution, and so on.

Rohit Pappu (00:03:13):
In today’s talk, I’ll focus primarily on what I’ll refer to as linear multivalent proteins, and in the interest of sort of telling you exactly what they are right from the get go, this will be a combination of folded domains and disordered regions. We make sure that we don’t start off with the notion that it’s just about intrinsically disordered proteins or regions…

EXTENDED Q&A

Question from Bede Portz: Rohit, do you mention that Cdense<Cperc<Cdense is where most biology will be, in contrast to Cperc<Cdilute giving rise to system spanning gels. Do you think there are proteins that will form system spanning gels at physiological concentrations? I think of the earlier work on the Laf1 IDR from Elbaum-Garfinkle. In other words, do you think there are exceptions where proteins will gel at low conc?
Rohit’s Response: The reference you are making is to the Nature Chemistry paper Wei et al., (2017). Note that this was a direct collaboration between the Brangwynne and Pappu labs. Your question raises the intriguing possibility that cperc < cdilute for the LAF1 protein and possibly even the LAF1 IDR…

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