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VIDEO: Dorothee Dormann on Aberrant Phase Transitions of Neurodegeneration-Linked RNA-Binding Proteins: control mechanisms and functional consequences

The Dewpoint scientists welcomed Dorothee Dormann for a Kitchen Table Talk on February 15. Dorothee received her PhD from Rockefeller University, and pursued her postdoc at the LMU in Munich with Christian Haass, where she then advanced to an independent Emmy Noether group leader position with Michael Kiebler. She is now an adjunct Director at the IMB in Mainz, Germany and Professor of Molecular Cell Biology at the University of Mainz. Her research is focused on the dysregulation of phase separation, aggregation, and transport of RNA-binding proteins such as TDP-43 and FUS in neurodegenerative diseases.

In 2018, I was blown away by her landmark study published in Cell showing that arginine methylation and the chaperone-like activity of the import receptor TNPO1 were able to counteract phase separation and aggregation of the ALS-associated protein FUS, which I was also working on at the time. Her lab continues to impress with research into how post-translational modifications modulate these processes and might be leveraged to suppress aberrant mechanisms, which she shares in the video below. I hope you enjoy the stimulating discussion.

VIDEO: Dorothee Dormann on Aberrant Phase Transitions of Neurodegeneration-Linked RNA-Binding Proteins


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TRANSCRIPT

Edgar Boczek (00:00:00):
Hi, good morning and good afternoon everyone. So we are pleased today to welcome Dorothee Dormann at the Dewpoint Kitchen Table. And so I’m just going to introduce her a little bit. Dorothee received her PhD from Rockefeller after pursuing her postdoc at the LMU in Munich with Christian Haass. She became an independent Emmy Noether group leader with Michael Kiebler.

Edgar Boczek (00:00:23):
Since 2021 Dorothee, is now an adjunct Director at the IMB in Mainz, Germany and Professor of Molecular Cell Biology at the university there. Her research is focused on the dysregulation of phase separation, aggregation, and transport of RNA-binding proteins, such as TDP-43 and FUS, in neuro degenerative diseases. More specifically, Dorothee is interested in how post-translational modifications modulate these processes and might be leveraged to suppress aberrant mechanisms.

Edgar Boczek (00:00:55):
I first met Dorothee at the MPI-CBG here in Dresden when she gave a talk invited by my former supervisors, Simon Alberti and Tony Hyman. I was actually blown away by her landmark study at that time she just published in Cell. She and her group had found that arginine methylation and the chaperone-like activity of the import receptor TNPO1 were able to counteract phase separation aggregation of the ALS-associated condensate protein FUS, that I was also working on at the time.

Edgar Boczek (00:01:24):
And yes, and now I’m super interested to hear what she will present today. Today, Dorothee will talk about aberrant phase transitions of neurodegeneration-linked RNA-binding proteins: control mechanisms and functional consequences. Dorothee, the floor is yours.

Dorothee Dormann (00:01:40):
Thanks very much, Edgar, and also to Jill for inviting me to this Kitchen Table talk. I’m really excited to present here and also have a nice discussion with the Condensation community at the end. So feel free to ask a lot of questions or as Jill said, also interrupt in between if you want to.

Dorothee Dormann (00:01:58):
So yeah, I’ll start introducing a little bit the proteins and questions that we are interested in. Yeah, try to give you a broad overview of the questions we are asking in the lab. So as was already mentioned, we are particularly interested in RNA-binding proteins that aggregate in neurodegenerative disorders. And this was discovered about 15 years ago that in ALS and frontotemporal dementia, the major deposited proteins are RNA-binding proteins. And so the most prominent RBPs that we find deposited in these brain regions that degenerate are TDP-43 and FUS. So yeah, as indicated here in ALS, TDP is by far the major deposited protein, and in rarer cases where you have genetic mutations in the FUS gene then the FUS protein is affected…

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