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VIDEO: Alex Holehouse on A Computational Ecosystem for Exploring Disordered Proteins and Condensates

On September 28, the Dewpoint scientists welcomed brilliant scientist and my long-time friend Alex Holehouse for a Kitchen Table Talk. Alex started his academic career in the UK, where he got biochemistry and computer science degrees from Oxford University and Imperial College, respectively. This unique set of skills primed him for his PhD and postdoc work in Rohit Pappu’s lab, where he moved from systems biology to modeling disordered proteins and emergent properties of condensates. Alex is now an assistant professor in the Department of Biochemistry and Molecular Biophysics at Washington University School of Medicine in St. Louis. He and his lab work to solve the complex questions surrounding how function is encoded in proteins, specifically disordered regions (a recent example can be found here).

In the video, Alex describes how answering these questions has required a suite of novel bioinformatics and molecular simulation tools. He details his motivation behind creating each tool and explains how they can interrogate and connect questions ranging from proteome-wide bioinformatics to complex condensate dynamics. Further, Alex provides a guide for how scientists outside of his lab can use the tools to approach their own research questions. Through his many collaborations—and I feel fortunate to be one of them—Alex has contributed to much of the seminal research that has shaped the biomolecular condensate field. Enjoy the video below and check out the tools section of the Holehouse lab website for more information about the methods he discusses (among others).  

Alex Holehouse on A Computational Ecosystem for Exploring Disordered Proteins and Condensates

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Erik Martin (00:00:00):
Hello. It’s my pleasure to introduce Alex Holehouse today. To give a brief background, Alex started his academic career in the UK where he collected a series of master’s degrees–first in biochemistry at Oxford University and second in computer science at Imperial College, which, frankly, I always assumed was to work on whatever the 2010 version of Animal Crossing was. But yes, it actually turned out it was modeling cell system biology.

Erik Martin (00:00:34):
I think from there, if anyone’s paying attention, this gave him the perfect background to move on and do his PhD in Rohit Pappu’s lab, where he moved from systems biology to modeling disorder proteins and emergent properties of disorder proteins in condensates. And we kind of like to joke for a long time that you’d go to a conference in the disorder protein or condensate field and literally every talk would mention either Rohit or Alex at some point in time or another.

Erik Martin (00:01:03):
On a personal note, I would, I guess, like to say that not only are Alex and I wearing nearly the same shirt today, but we’ve known each other for quite a long time. I was going through a series of talks to try and figure out when it was exactly I met Alex. Best I can figure it was winter of 2014. And from there we started a series of very fruitful collaborations, which not only was scientifically interesting but was personally very rewarding for me. So it’s my pleasure to introduce Alex, who’s now an assistant professor of biophysics at Washington University in St. Louis.

Alex Holehouse (00:01:44):
Erik, thanks very much for the kind introduction. Yes, it was winter of 2014, many moons ago. So thank you to Dewpoint firstly for inviting me to speak in this series. I was saying to Jill before, I think the value of having these recorded interactive talks on this topic is really valuable for the whole community regardless of a pandemic or not.

Alex Holehouse (00:02:06):
Today I’m going to give a slightly different talk to the talks I normally give. I’m going to talk more about our tools and our methodologies. And typically when I give a talk, I like to tell a story. I like to explain a biological observation and think about what that means and how we think about that. I’m not going to do that as much today. I’m going to talk instead more about the practical components of how and why we built certain tools, what they do and our goals in doing that…

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