The BBVA Foundation Frontiers of Knowledge Award in Biology and Biomedicine has been awarded in its 16th edition to the four scientists who discovered the physiological mechanisms that control the functioning of proteins, a fundamental discovery both for understanding the origin of multiple diseases and for developing new ones. therapeutic strategies, argues the jury. Firstly, professors Ulrich Hartl (Max Planck Institute of Biochemistry, Germany) and Arthur Horwich (Yale University, USA) revealed the cellular machinery on which protein folding depends, an essential process for them to carry out carry out its functions in the body; Subsequently, Kazutoshi Mori (Kyoto University, Japan) and Peter Walter (Altos Labs and University of California in San Francisco, USA) identified the response mechanism that is triggered to refold or eliminate proteins when they do not fold properly.
All the instructions we need to develop, survive and reproduce reside in the DNA of our cells. But the main ones responsible for carrying out these functions are proteins and “to fulfill their function” – as explained in the jury report – “they must adopt certain three-dimensional structures that are achieved in cells with the help of a group of proteins called chaperones. ”.
The four winners made two key discoveries in this field: Hartl and Horwich discovered the first cellular pathway that regulates protein folding, thanks to the discovery of the role played by the so-called chaperone Hsp60, while Mori and Walter identified the mechanism used by cells when protein folding fails, acting on them, either to try to fold them correctly or, if this is not possible, destroy them.
These findings about a biological process so fundamental for life have enormous biomedical implications, since the molecular machinery that controls both protein folding and the response to failures in this mechanism is involved in the origin of multiple diseases, from cancer to neurodegenerative disorders such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS), or the aging process itself. For all this, the jury concludes its minutes by highlighting that the “revolutionary findings” of the four winners have revealed “how cells control the biogenesis and degradation of proteins, something fundamental not only for physiology, but also for understanding the origin and design therapies for many diseases.”
“The two discoveries recognized by the award are fundamental for the health of each cell and therefore of our body. In particular, there are some diseases that are due to the accumulation of proteins that have not folded well and that therefore become toxic,” explains Óscar Marín, professor of Neuroscience and director of the Center for Neurodevelopmental Disorders of the MRC in King’s College London (United Kingdom), who acted as secretary of the jury. “If proteins do not fold properly,” he continues, “this produces loss of cell function, for example, in some degenerative diseases of the nervous system.”
“The findings of the four winners are important not only for our understanding of fundamental biology, but also because they lead to a new way of understanding diseases and treating them better in the future,” highlights Dario Alessi, director of the Unit. of Protein Phosphorylation and Ubiquitination at the MRC at the University of Dundee (United Kingdom) and member of the jury.
“Currently,” he continues, “there is enormous interest, especially in the field of neurodegeneration, to promote therapeutic pathways that can maintain correctly folded proteins in cells, and also to promote the process of eliminating unfolded proteins, because this It is harmful to cells. Furthermore, in the case of cancer, it is thought that if the enzymes that cause protein folding in some types of tumors could be inhibited, this could increase the ability to eliminate cancer cells that grow very quickly and are highly dependent on this process. ”.
The four winners are convinced that their findings on the molecular machinery that regulates both protein folding and failures in this process can drive the development of new effective treatments against multiple diseases and even contribute to understanding and acting on the aging process. .
The BBVA Foundation Frontiers of Knowledge Awards, endowed with 400,000 euros in each of its eight categories, recognize and encourage contributions of singular impact in science, technology, the humanities and music, especially those that significantly expand the scope of knowledge. known in a discipline, they make new fields emerge or build bridges between various disciplinary areas.
