Must Read

VIDEO: Broder Schmidt on Targeting Intrinsically Disordered Proteins (IDPs): In the Pack vs. the Lone Wolf

On September 15, we were beyond thrilled to welcome Broder Schmidt, from Stanford University School of Medicine, for a lively Kitchen Table Talk—finally broadcast in part from Dewpoint’s actual (and new) kitchen table!

Broder has been interested in phase transitions throughout his training. He did his PhD studies with Dirk Görlich at Max Planck Institute for Biophysical Chemistry, where he helped shape our current understanding of the nuclear pore’s selectivity and permeability. He is currently a postdoc studying functional consequences of aberrant TDP43 condensates with Rajat Rohatgi, where they have published several elegant studies including the effects of phase separation on splicing.

Broder delivered a phenomenal lecture that spanned many of the main concepts currently emerging from the condensates field: from thermodynamics and reentrant behavior to partitioning of small molecules into condensates. I’m happy to share it with you below. And make sure to check out Broder’s recent bioRxiv preprint because it shows that condensates not only can be drugged, but that we have been doing so unknowingly.

Broder Schmidt on Targeting Intrinsically Disordered Proteins (IDPs): In the Pack vs. the Lone Wolf

Create an Account or Sign In to view the video.


Bede Portz (00:01):
So it’s a real thrill to introduce Broder. Having had countless conversations with him about science, I find him to be one of the deeper and more rigorous thinkers in our field. And Broder’s been interested in phase transitions throughout his training, dating back to his time as a Ph.D. candidate with Dirk Gorlich. He had an excellent paper where he reconstituted via phase separation the nuclear pore in vitro, and really elucidated rules about its selectivity and permeability, and that paper’s been cited nearly 200 times.

Bede Portz (00:36):
He then went on to Raj Rohatgi’s lab at Stanford, where he currently is, and he continued working on phase transitions there despite it not really being a phase separation lab. And there Broder had a series of papers that were really elegant on TDP43. The first was really prescient. It sort of helped to usher in this current interest in condensates with multi-layered topologies. And then the follow-up paper was really a careful dissection of the molecular grammar of TDP43’s self assembly, and how that relates to function. I note that second paper in Nature Communications also involved this ingenious splicing reporter assay that’s now been used by other groups.

Bede Portz (01:24):
More recently, he has turned his attention to cancer, where he’s studying the partitioning of chemo-therapeutic agents into condensates, and this paper really highlights some of the things that make Broder unique. So Broder reads essentially every paper, and his most recent work on cancer really is a synthesis of everything that’s happening in our field right now, from thermodynamics to reentrant behavior, to the partitioning of small molecules into condensates with specificity. I think that really reflects who Broder is as a scientist.

Bede Portz (02:01):
I finally want to add that Broder’s also a leader. He’s one of the founders of the intrinsically disordered special interest group at Stanford and the Carnegie Institute. And that organization exploded during COVID and provided an opportunity for scientists from diverse backgrounds and across the globe to present their work in an environment that was otherwise devoid of in-person meetings. I owe Broder a debt of gratitude for that organization because I gave a talk there, and that helped put me on Dewpoint’s radar, for which I’m obviously very grateful.

Bede Portz (02:39):
I want to highlight that although Broder has only been in the cancer game for a short period of time, he recently won a Forbeck scholarship for his work in that arena. And without further adieu, I’m going to turn it over to Broder.

Broder Schmidt (02:53):
Well, thank you Bede for this very kind introduction. And thank you for Dewpoint for inviting me today to discuss approaches to target disordered proteins. But I wanted to actually start out our discussions by acknowledging one of the most powerful concepts in biochemistry, and that is the idea that structure is function. The idea that the three dimensional folding of a protein is intimately linked to its function. For example, this kinase that I show here that adds phosphate groups to proteins. In fact, we now know that cells rely so heavily on correctly folded proteins that they employ a sophisticated network of chaperones and spend vast amounts of energy to ensure the proper folding of proteins…

Join the conversation

Create an Account or Sign In to comment.