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]
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]
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]
By the time Walter joined the University of California, San Francisco (UCSF), researchers have established a connection between misfoldedproteins 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]
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 HAC1gene, 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 misfoldedproteins. 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]
^"E.B. Wilson Medal". American Society for Cell Biology. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
^"Otto-Warburg-Medaille". German Society for Biochemistry and Molecular Biology. Archived from the original on August 30, 2023. Retrieved August 30, 2023.
^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.
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