by Peter Walter, from Altos Labs and the University of California in San Francisco (USA), is one of the four scientists awarded the 2024 BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine for his findings on the physiological mechanisms that control the functioning of proteins, a fundamental discovery to understand the origin of many diseases and develop new treatments. Specifically, together with Kazutoshi Mori, from Kyoto University (Japan), he identifies the response mechanism that is triggered to refold or eliminate proteins when they do not fold properly. When he started researching, did he think that his findings could have implications for diseases like Alzheimer’s, ALS or cancer? No, when we started this work. Our questions were driven by ‘curiosity’. We began our research in the field of unfolded protein response. With one question in mind, we began a genetic screen in yeast to identify the machinery involved in the intracellular signaling pathway that must exist to transmit information across at least one membrane. The screen identified the transmembrane kinase Ire1 as the first molecularly defined player in the unfolded protein response (UPR). With this, the field of unfolded protein response was born. Related News standard No The cell therapy that has revolutionized cancer reaches lupus R. Ibarra standard No Five years of analyzing a patient’s tumor allow us to narrow the gap on the worst breast cancer Esther Armora Can you explain to us how your findings will be used to treat cancer ? ? Cancer cells have an intrinsic problem and that is that they are genomically unstable. They produce many misfolded proteins, proteins that cannot assemble correctly. The response to misfolded proteins provides disproportionate protection to these cells, keeping them alive, even though this response would normally be programmed to self-destruct. Therefore, it is possible to inhibit this response, eliminate this inadequate growth, which would allow acting on cancer cells in a very selective way in the treatment of the disease. Can we talk about a cure for cancer? Cancer is complex and individual cancers are highly variable, so I think it is unlikely that there is a definitive cure for all cancers. However, a common feature is that tumor cells become genomically unstable as they evolve toward increasingly aggressive states. Their evolution is not directed and they accumulate random changes that manifest themselves in a defective proteome. These changes include random mutations in proteins that result in incorrect folding and genes expressed in incorrect ratios that result in incorrectly assembled protein complexes. These defects induce cellular stress pathways that help protect the cancer cell and allow it to survive. Blocking such inappropriate cellular protection promises to become a new and applicable way to fight cancer. How long will it take for all this to develop? It is difficult to predict; We have the basic principles of the system, we understand that inhibiting these components will be beneficial and now we need to develop appropriate drugs and treatments that are not toxic or harmful to the affected people. And this is the task of translating the basic discovery and establishing our principles into applications so that they can help in the clinical setting. Both you and Mori discovered this process simultaneously, but independently, and have never co-written a paper. Did you know that they were investigating in the same direction? Mori’s labs and mine have been working on the same topics for many years, but we have never published together. Our competition has been constructive for the field. Having two labs addressing the same questions independently provided quick validation of our respective perspectives. There is a tendency to portray scientists researching in the same field as rivals, is science a highly competitive environment? Son ‘friends’? Of course, Mori is an exceptional scientist and colleague with whom he enjoys many events.
