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Peter Walter

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For the English MP, see Peter Walter (politician).

Peter Walter
Walter in 2021
Born (1954-12-05) December 5, 1954 (age 69)
West Berlin
EducationFree University of Berlin (Vordiplom)
Vanderbilt University (MSc)
Rockefeller University (PhD)[1]
Known forSignal recognition particle
Unfolded protein response
AwardsEli Lilly Award in Biological Chemistry
Wiley Prize in Biomedical Science
Gairdner Foundation International Award
E.B. Wilson Medal
Otto Warburg Medal
Paul Ehrlich and Ludwig Darmstaedter Prize
Ernst Jung Prize
Mendel Lectures
Shaw Prize in Life Science and Medicine
Albert Lasker Award for Basic Medical Research
Breakthrough Prize in Life Sciences
Scientific career
FieldsMolecular biology
Biochemistry
InstitutionsRockefeller University
University of California, San Francisco
Howard Hughes Medical Institute
ThesisPurification and characterization of an 11S protein complex required for the translocation of secretory proteins across the membrane of the endoplasmic reticulum (1981)
Doctoral advisorGünter Blobel

Peter Walter (born December 5, 1954) is a German-American molecular biologist and biochemist. He is currently the Director of the Bay Area Institute of Science at Altos Labs and an emeritus professor at the Department of Biochemistry and Biophysics of the University of California, San Francisco (UCSF).[2][3] He was a Howard Hughes Medical Institute (HHMI) Investigator until 2022.

Early life and education

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Walter was born and raised in West Berlin in 1954. His parents owned a pharmacy, and he was drawn to chemistry at a young age.[4] He entered the Free University of Berlin in 1973 to study chemistry, but the rigid way of teaching science did not engage him. Instead, Walter became interested in biochemistry, which studies the chemistry of cells.[4][5]

In the last year of his Vordiplom (equivalent to a BSc) in 1976, he went on exchange to Vanderbilt University and conducted research under Thomas M. Harris at the Department of Chemistry on the biosynthetic pathway of slaframine, a fungal alkaloid that is toxic to cows.[6] Eventually, Walter completed his MSc in Vanderbilt in 1977.[1]

At the encouragement of Stanford Moore, a biochemistry professor at Rockefeller University and a trustee of Vanderbilt, Walter applied for the PhD programme at Rockefeller.[6] He was placed on the waiting list, but after an accepted student went to Harvard University instead, was offered his place in 1977.[4][5] He took his PhD under Günter Blobel, and obtained the degree in 1981.[1]

Career

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After receiving his PhD, Walter stayed at Rockefeller University as a postdoctoral fellow for a year, then became an assistant professor at the Laboratory of Cell Biology at Rockefeller.[1]

In 1983, he moved to the Department of Biochemistry and Biophysics of the University of California, San Francisco (UCSF) as an assistant professor. Walter was promoted to associate professor in 1986 and then full professor in five years later.[1] He was chair of the Department of Biochemistry and Biophysics of UCSF between 2001 and 2008.[7]

Walter became a Howard Hughes Medical Institute investigator in 1997, and served as the president of the American Society for Cell Biology in 2016.[8]

In 2021, there were reports that he would be joining Altos Labs, a new biotechnology company which reportedly focuses on anti-aging research.[9][10] The next year, he retired from UCSF and the Howard Hughes Medical Institute in 2022,[11][12] and joined Altos Labs as the Director of the Bay Area Institute of Science when the company officially launched.[13][14]

Walter currently sits on the Scientific Advisory Board of the Zentrum für Molekulare Biologie der Universität Heidelberg of Heidelberg University.[15]

Walter is a coauthor of the widely used textbook Molecular Biology of the Cell.[16]

Research

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[1] [2]

During his PhD at Günter Blobel's group, Walter purified a protein complex required for moving proteins out of the endoplasmic reticulum (ER)[17] and showed the complex selectively recognizes newly synthesized secretory proteins.[18] He later confirmed the complex is in fact a nucleoprotein and identified the RNA component essential for the complex's function. He also named the complex signal recognition particle (SRP).[19]

By the time Walter joined the University of California, San Francisco (UCSF), researchers have established a connection between misfolded proteins in the ER and increased expression of a protein called BiP, which is a chaperone protein that helps other proteins fold correctly. This pathway is termed the unfolded protein response (UPR). However, how cells sense misfolded proteins and relays this information to the cell nucleus to increase the production of UPR-target proteins remains unclear.[20]

In 1993, working on baker's yeast, Walter found a gene, IRE1, which encodes a kinase. The IRE1 protein is located across the ER membrane, so a part of it can detect unfolded proteins inside the ER and the other part can phosphorylate proteins outside of the ER.[21] The same year, Kazutoshi Mori, at the time a postdoctoral fellow at the University of Texas Southwestern Medical Center, independently made the same discovery.[22]

Walter and Mori next independently sought the phosphorylation target of the IRE1 protein. Theoretically, upon phosphorylation, this target will enter the cell nucleus and increase the production of UPR-target proteins. Both of them arrived at the same gene, HAC1, in 1996.[23][24] This discovery, however, was unexpected as the HAC1 protein is produced only after IRE1 detects unfolded proteins, meaning the protein is not present to be phosphorylated by IRE1.

This difference was mitigated by the finding of Mori and Walter that after IRE1 senses unfolded proteins, it splices the HAC1 precursor mRNA, which is transcribed from the HAC1 gene, resulting in a mature mRNA that is translated into the HAC1 protein.[25][26] Walter also discovered the phosphorylation target of IRE1, which turned out to be another IRE1 molecule, a process known as trans-autophosphorylation,[27] and also the enzyme stitching the spliced precursor HAC1 mRNA together.[28]

In 2013, Walter's group identified a molecule that inhibits the integrated stress response (ISR). The ISR is the cell's response to stresses such as viral infection, ultraviolet light and the accumulation of unfolded and misfolded proteins. ISR activates the EIF2α protein, reducing most protein synthesis and increasing the production of some regulatory molecules.[29] His group found the inhibitor reversed EIF2α activation, and named it ISRIB for "integrated stress response inhibitor". Remarkably, they found mice injected with ISRIB had improved memory.[30] ISRIB was licensed to Alphabet subsidiary Calico in 2015.[31]

Awards and honors

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Personal life

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Walter is married to Patricia Caldera-Muñoz,[53] whom he met in New York City during his PhD years at Rockefeller University and when Caldera-Muñoz was a chemistry PhD student at New York University.[5] Before retiring, Caldera-Muñoz worked at the University of California, San Francisco (UCSF) Science and Health Education Partnership, where she coordinated outreach to local science teachers.[54][55]

Walter was diagnosed with neck cancer in 2009.[56]

References

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  1. ^ a b c d e "PETER WALTER Ph.D." Vanderbilt University School of Medicine. Archived from the original (PDF) on August 28, 2023. Retrieved August 28, 2023.
  2. ^ "Peter Walter". Altos Labs. Archived from the original on August 22, 2023. Retrieved August 22, 2023.
  3. ^ "Peter Walter, PhD". University of California, San Francisco. Archived from the original on August 21, 2023. Retrieved August 21, 2023.
  4. ^ a b c Dreifus, Claudia (June 15, 2015). "Peter Walter's Voyage Into a Microscopic World". The New York Times. Archived from the original on August 23, 2023. Retrieved August 23, 2023.
  5. ^ a b c "Autobiography of Peter Walter". Shaw Prize. September 24, 2014. Archived from the original on August 23, 2023. Retrieved August 23, 2023.
  6. ^ a b Davis, Tinsley H. (2006). "Profile of Peter Walter". Proceedings of the National Academy of Sciences. 103 (14): 5259–5261. Bibcode:2006PNAS..103.5259D. doi:10.1073/pnas.0600257103. PMC 1459343. PMID 16567626.
  7. ^ "Prof. Peter Walter". International Institute of Molecular Mechanisms and Machines, Polish Academy of Sciences. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  8. ^ "ASCB Presidents". American Society for Cell Biology. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  9. ^ Regalado, Antonio (September 4, 2021). "Meet Altos Labs, Silicon Valley's latest wild bet on living forever". MIT Technology Review. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  10. ^ Ansede, Manuel (September 8, 2021). "Silicon Valley start-up funded by billionaires hires top 'anti-aging' experts". El País. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  11. ^ "Peter Walter, PhD". Howard Hughes Medical Institute. Archived from the original on August 21, 2023. Retrieved August 21, 2023.
  12. ^ "Peter Walter". LinkedIn. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  13. ^ "Altos Labs Launches with $3B and a Focus on Reversing Disease, Aging". Genetic Engineering & Biotechnology News. January 19, 2022. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  14. ^ Otmani, Malin (January 25, 2022). "Altos Labs launches with the goal to restore cell health". Nordic Life Science. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  15. ^ "ZMBH – Scientific Advisory Board". Heidelberg University. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  16. ^ Alberts, Bruce; Heald, Rebecca; Johnson, Alexander; Morgan, David; Raff, Martin; Roberts, Keith; Walter, Peter; Wilson, John; Hunt, Tim (2022). Molecular Biology of the Cell (7 ed.). W. W. Norton & Company. ISBN 978-0-393-88482-1. Archived from the original on August 28, 2023. Retrieved August 28, 2023.
  17. ^ Walter, Peter; Blobel, Günter (1980). "Purification of a membrane-associated protein complex required for protein translocation across the endoplasmic reticulum". Proceedings of the National Academy of Sciences. 77 (12): 7112–7116. Bibcode:1980PNAS...77.7112W. doi:10.1073/pnas.77.12.7112. PMC 350451. PMID 6938958.
  18. ^ Walter, Peter; Ibrahimi, Ibrahim; Blobel, Günter (1981). "Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein" (PDF). Journal of Cell Biology. 91 (2): 545–550. doi:10.1083/jcb.91.2.545. PMC 2111968. PMID 7309795. Archived from the original (PDF) on August 31, 2023. Retrieved August 31, 2023.
  19. ^ Walter, Peter; Blobel, Günter (1982). "Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum". Nature. 299 (5885): 691–698. Bibcode:1982Natur.299..691W. doi:10.1038/299691a0. PMID 6181418. S2CID 4237513.
  20. ^ Mori, Kazutoshi (2015). "The unfolded protein response: the dawn of a new field". Proceedings of the Japan Academy, Series B Physical and Biological Sciences. 91 (9): 469–480. Bibcode:2015PJAB...91..469M. doi:10.2183/pjab.91.469. PMC 4754504. PMID 26560836. Archived from the original on September 5, 2023. Retrieved September 5, 2023.
  21. ^ Cox, Jeffrey S.; Shamu, Caroline E.; Walter, Peter (1993). "Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase". Cell. 73 (6): 1197–1206. doi:10.1016/0092-8674(93)90648-A. PMID 8513503. S2CID 16065404.
  22. ^ Mori, Kazutoshi; Ma, Wenzhen; Gething, Mary–Jane; Sambrook, Joseph (1993). "A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus". Cell. 74 (4): 743–756. doi:10.1016/0092-8674(93)90521-q. PMID 8358794. S2CID 20732881. Retrieved September 5, 2023.
  23. ^ Cox, Jeffey S.; Walter, Peter (1996). "A Novel Mechanism for Regulating Activity of a Transcription Factor That Controls the Unfolded Protein Response". Cell. 87 (3): 391–404. doi:10.1016/s0092-8674(00)81360-4. PMID 8898193.
  24. ^ Mori, Kazutoshi; Kawahara, Tetsushi; Yoshida, Hiderou; Yanagi, Hideki; Yura, Takashi (1996). "Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway". Genes to Cells. 1 (9): 803–817. doi:10.1046/j.1365-2443.1996.d01-274.x. PMID 9077435.
  25. ^ Sidrauski, Carmela; Walter, Peter (1997). "The Transmembrane Kinase Ire1p Is a Site-Specific Endonuclease That Initiates mRNA Splicing in the Unfolded Protein Response". Cell. 90 (6): 1031–1039. doi:10.1016/s0092-8674(00)80369-4. PMID 9323131.
  26. ^ Kawahara, Tetsushi; Yanagi, Hideki; Yura, Takashi; Mori, Kazutoshi (1997). "Endoplasmic Reticulum Stress-induced mRNA Splicing Permits Synthesis of Transcription Factor Hac1p/Ern4p That Activates the Unfolded Protein Response". Molecular Biology of the Cell. 8 (10): 1845–1862. doi:10.1091/mbc.8.10.1845. PMC 25627. PMID 9348528.
  27. ^ Shamu, Caroline E.; Walter, Peter (1996). "Oligomerization and phosphorylation of the Irelp kinase during intracellular signaling from the endoplasmic reticulum to the nucleus". The EMBO Journal. 15 (12): 3028–3039. doi:10.1002/j.1460-2075.1996.tb00666.x. PMC 450244. PMID 8670804.
  28. ^ Gonzalez, Tania N.; Sidrauski, Carmela; Dörfler, Silke; Walter, Peter (1999). "Mechanism of non-spliceosomal mRNA splicing in the unfolded protein response pathway". The EMBO Journal. 18 (11): 3119–3132. doi:10.1093/emboj/18.11.3119. PMC 1171393. PMID 10357823. Archived from the original on September 7, 2023. Retrieved September 7, 2023.
  29. ^ Pakos-Zebrucka, Karolina; Koryga, Izabela; Mnich, Katarzyna; Ljujic, Mila; Samali, Afshin; Gorman, Adrienne M. (2016). "The integrated stress response". EMBO Reports. 17 (10): 1374–1395. doi:10.15252/embr.201642195. PMC 5048378. PMID 27629041.
  30. ^ Sidrauski, Carmela; Acosta-Alvear, Diego; Khoutorsky, Arkady; Vedantham, Punitha; Hearn, Brian R.; Li, Han; Gamache, Karine; Gallagher, Ciara M.; Ang, Kenny K.-H.; Wilson, Chris; Okreglak, Voytek; Ashkenazi, Avi; Hann, Byron; Nader, Karim; Arkin, Michelle R.; Renslo, Adam R.; Sonenberg, Nahum; Walter, Peter (2013). "Pharmacological brake-release of mRNA translation enhances cognitive memory". eLife. 2: e00498. doi:10.7554/eLife.00498. PMC 3667625. PMID 23741617.
  31. ^ Piore, Adam (August 25, 2021). "The miracle molecule that could treat brain injuries and boost your fading memory". MIT Technology Review. Archived from the original on September 2, 2023. Retrieved September 2, 2023.
  32. ^ Fambroug, Douglas M. (2006). "Searle Scholars Program: Selection and Evaluation of Searle Scholars National Academies of Sciences, Engineering, and Medicine". Enhancing Philanthropy's Support of Biomedical Scientists: Proceedings of a Workshop on Evaluation National Academies of Sciences, Engineering, and Medicine. National Academies Press. pp. 43–51. ISBN 9780309100977. Archived from the original on September 8, 2023. Retrieved September 8, 2023.
  33. ^ "Eli Lilly Award in Biological Chemistry" (PDF). Division of Biological Chemistry, American Chemical Society. Archived from the original (PDF) on August 29, 2023. Retrieved August 29, 2023.
  34. ^ "Fellows Database". Alfred P. Sloan Foundation. Archived from the original on August 26, 2023. Retrieved August 26, 2023.
  35. ^ "Peter Walter". American Academy of Arts and Sciences. Archived from the original on August 26, 2023. Retrieved August 26, 2023.
  36. ^ "Peter Walter". National Academy of Sciences. Archived from the original on August 26, 2023. Retrieved August 26, 2023.
  37. ^ "Peter Walter". European Molecular Biology Organization. Archived from the original on May 31, 2023. Retrieved May 31, 2023.
  38. ^ "The Wiley Prize in Biomedical Sciences". Wiley Foundation. Retrieved August 29, 2023.
  39. ^ "Peter Walter". German National Academy of Sciences Leopoldina. Archived from the original on April 19, 2023. Retrieved April 19, 2023.
  40. ^ "Peter Walter". Gairdner Foundation. Archived from the original on August 29, 2023. Retrieved August 29, 2023.
  41. ^ "E.B. Wilson Medal". American Society for Cell Biology. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
  42. ^ "Otto-Warburg-Medaille". German Society for Biochemistry and Molecular Biology. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
  43. ^ "Prize Winner of the Paul Ehrlich and Ludwig Darmstaedter Prize 2012". Goethe University Frankfurt. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
  44. ^ "Laureates 1976 to 2022". Ernst Jung Foundation. Archived from the original on August 14, 2023. Retrieved August 14, 2023.
  45. ^ "The unfolded protein response in health and disease". Mendel Lectures. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
  46. ^ "The 2014 Prize in Life Science & Medicine". Shaw Prize. Archived from the original on August 23, 2023. Retrieved August 23, 2023.
  47. ^ "2014 Albert Lasker Basic Medical Research Award". Lasker Award. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
  48. ^ "Peter Walter". Vilcek Foundation. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
  49. ^ "Fellows List". National Academy of Inventors. Archived from the original on August 26, 2023. Retrieved August 26, 2023.
  50. ^ "Dr. Peter Walter". National Academy of Medicine. Archived from the original on August 26, 2023. Retrieved August 26, 2023.
  51. ^ "Peter Walter". Breakthrough Prize. Archived from the original on August 22, 2023. Retrieved August 22, 2023.
  52. ^ BBVA Foundation Frontiers of Knowledge Award 2023
  53. ^ Kim, Leland (September 19, 2014). "Peter Walter: 'This Honor Really Belongs to All of Us'". University of California, San Francisco. Archived from the original on August 25, 2023. Retrieved August 25, 2023.
  54. ^ Landhuis, Esther (2015). "Harnessing Serendipity". HHMI Bulletin. Vol. 28, no. 3. pp. 18–23. Archived from the original on August 25, 2023. Retrieved August 25, 2023.
  55. ^ Kaarlela, Corinna (May 31, 2006). "New council promotes partnerships between UCSF and community". University of California, San Francisco. Archived from the original on August 25, 2023. Retrieved August 25, 2023.
  56. ^ McFarling, Usha Lee (September 28, 2016). "Peter Walter just won the Breakthrough Prize. His work? Trying to heal human brains". Stat. Archived from the original on September 1, 2023. Retrieved September 1, 2023.
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