EPFL BioE Talks SERIES "Harnessing Evolutionarily Optimized Signaling Pathways for Therapeutic Benefits"
Event details
| Date | 08.03.2021 |
| Hour | 16:00 › 16:30 |
| Speaker | Prof. Anne Bertolotti, MRC Laboratory of Molecular Biology, Cambridge (UK) |
| Location | Online |
| Category | Conferences - Seminars |
WEEKLY EPFL BIOE TALKS SERIES
(note that this talk is number one of a double-feature seminar - see details of the second talk here)
Abstract:
During optimal conditions, a majority of the cellular resources is dedicated to protein synthesis. To survive under challenging conditions, cells adapt by phosphorylating the translation initiation factor, eiF2 to reduce protein synthesis, thereby sparing their resources to neutralize the challenges. We have exploited this pathway pharmacologically and showed its benefits in diverse models of neurodegenerative diseases. eIF2 phosphorylation is believed to cause a global reduction in protein synthesis whilst enabling translation of few transcripts. A global reduction of protein synthesis comes with the life-threatening risk of depleting essential proteins. We found that translation attenuation following eIF2a phosphorylation is not as uniform as anticipated but preferentially targets long-lived proteins. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.
Phosphorylation of the translation initiation factor eIF2a is a rapid and vital response to many forms of stress, including protein-misfolding stress in the endoplasmic reticulum (ER stress). It is believed to cause a general reduction in protein synthesis while enabling translation of few transcripts. Such a reduction of protein synthesis comes with the threat of depleting essential proteins, a risk thought to be mitigated by its transient nature. Here, we find that translation attenuation is not uniform, with cytosolic and mitochondrial ribosomal sub- units being prominently downregulated. Translation attenuation of these targets persists after translation recovery. Surprisingly, this occurs without a measurable decrease in ribosomal proteins. Explaining this conundrum, translation attenuation preferentially targets long-lived proteins, a finding not only demonstrated by ribosomal proteins but also observed at a global level. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.
Bio:
Since 2006: Group leader at MRC Laboratory of Molecular Biology, Cambridge, UK
2014: Hooke medal
2013: EMBO member
2004: EMBO Young Investigator
2001-2006: Associate professor,
Ecole Normale Supérieure, Paris, France
1998-2000: Post-doctoral training with Prof. David Ron,
The Skirball Institute of Biomolecular Medicine, NYU Medical Center, New York, USA
EMBO long term fellowship
HFSP long term fellowship
1999: INSERM Position
1993-1998: PhD training with Dr. Laszlo Tora and Prof. Pierre Chambon,
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 pandemic, this seminar can be followed via Zoom web-streaming only, (following prior one-time registration through the link above).
(note that this talk is number one of a double-feature seminar - see details of the second talk here)
Abstract:
During optimal conditions, a majority of the cellular resources is dedicated to protein synthesis. To survive under challenging conditions, cells adapt by phosphorylating the translation initiation factor, eiF2 to reduce protein synthesis, thereby sparing their resources to neutralize the challenges. We have exploited this pathway pharmacologically and showed its benefits in diverse models of neurodegenerative diseases. eIF2 phosphorylation is believed to cause a global reduction in protein synthesis whilst enabling translation of few transcripts. A global reduction of protein synthesis comes with the life-threatening risk of depleting essential proteins. We found that translation attenuation following eIF2a phosphorylation is not as uniform as anticipated but preferentially targets long-lived proteins. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.
Phosphorylation of the translation initiation factor eIF2a is a rapid and vital response to many forms of stress, including protein-misfolding stress in the endoplasmic reticulum (ER stress). It is believed to cause a general reduction in protein synthesis while enabling translation of few transcripts. Such a reduction of protein synthesis comes with the threat of depleting essential proteins, a risk thought to be mitigated by its transient nature. Here, we find that translation attenuation is not uniform, with cytosolic and mitochondrial ribosomal sub- units being prominently downregulated. Translation attenuation of these targets persists after translation recovery. Surprisingly, this occurs without a measurable decrease in ribosomal proteins. Explaining this conundrum, translation attenuation preferentially targets long-lived proteins, a finding not only demonstrated by ribosomal proteins but also observed at a global level. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.
Bio:
Since 2006: Group leader at MRC Laboratory of Molecular Biology, Cambridge, UK
2014: Hooke medal
2013: EMBO member
2004: EMBO Young Investigator
2001-2006: Associate professor,
Ecole Normale Supérieure, Paris, France
1998-2000: Post-doctoral training with Prof. David Ron,
The Skirball Institute of Biomolecular Medicine, NYU Medical Center, New York, USA
EMBO long term fellowship
HFSP long term fellowship
1999: INSERM Position
1993-1998: PhD training with Dr. Laszlo Tora and Prof. Pierre Chambon,
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 pandemic, this seminar can be followed via Zoom web-streaming only, (following prior one-time registration through the link above).
Practical information
- Informed public
- Registration required
Organizer
- Prof. David Suter, EPFL
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD