Bio-bibliography

Switzerland/USA

Michael N. Hall

2024 Balzan Prize for Biological Mechanisms of Ageing

For groundbreaking contributions to our understanding of the molecular mechanisms regulating cell growth. Michael Hall discovered two proteins, TOR1 and TOR2, that regulate cell growth and metabolism in response to nutrients. These play a central role in the ageing process and in the development of ageing-related diseases such as cancer, diabetes and cardiovascular disease.

Michael N. Hall, born on 12 June 1953, San Juan, Puerto Rico, is a Swiss citizen.

Since 1987 Professor at the Biozentrum of the University of Basel, Switzerland, where he was Vice-Director and Chairman of the Division of Biochemistry; since 2023 Distinguished Scientist at the Institute of Human Biology F. Hoffmann-La Roche Ltd, Basel.

BS with Honors, 1976, University of North Carolina, Chapel Hill, and PhD, 1981, Harvard University; Postdoctoral Fellow, 1981-1984 at the University of California, San Francisco.

Among his numerous memberships: US National Academy of Sciences, European Molecular Biology Organization, American Association for the Advancement of Science; Genetics Society of America; Swiss Biochemical Society; American Society for Cell Biology; European Association for Cancer Research; Louis-Jeantet Foundation, Geneva; Marcel Benoist Foundation, Bern; American Association for Cancer Research (AACR); Swiss Institute for Basic Cancer Research (ISREC) Foundation; American Society for Biochemistry and Molecular Biology (ASBMB); Clare Hall, Cambridge University, UK; Institute of Oncology Research (IOR) Board, Bellinzona, Switzerland; Center for Genomic Regulation Board, Barcelona.

Member of awards selection Committees and of many Editorial Boards: Breakthrough Prize in Life Sciences Committee; Albert Lasker Awards Jury; Louis Jeantet Prize Committee; Shaw Prize Selection Committee; Dr. Paul Janssen Award Committee; Szent-Györgyi Prize Committee; EMBO Journal; Current Opinions in Cell Biology.

Among his mainpublications:

Heitman, J., N. R. Movva, and M. N. Hall. 1991. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253, 905-909. Discovery of TOR. Isolation of rapamycin resistant mutants.

Kunz, J., R. Henriquez, U. Schneider, M. Deuter-Reinhard, N. R. Movva, and M. N. Hall. 1993. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73, 585-596. Discovery of TOR. Cloning and characterization of TOR2 gene (for cloning and characterization of TOR1 gene, see Helliwell et al. 1994 MBC 5, 105-118).

Barbet, N. C., U. Schneider, S. B. Helliwell, I. Stansfield, M. F. Tuite, and M. N. Hall. 1996. TOR controls translation initiation and early G1 progression in yeast. Mol. Biol. Cell. 7, 25-42. First evidence that TOR controls cell growth and does so in response to nutrients.

Schmidt, A., M. Bickle, T. Beck, and M. N. Hall. 1997. The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell 88, 531-542. TOR controls the actin cytoskeleton, thus demonstrating that TOR mediates spatial control of cell growth in addition to temporal control.

Beck, T. and M. N. Hall. 1999. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402, 689-692. First demonstration that TOR signals into the nucleus and thus constitutes a bona fide signaling pathway that controls transcription.

Loewith, R., E. Jacinto, S. Wullschleger, A. Lorberg, J. L. Crespo, D. Bonenfant, W. Oppliger, P. Jenoe, and M. N. Hall. 2002. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10, 457-468. Discovery of the two TOR complexes TORC1 and TORC2. Also shows that TORC1 is conserved from yeast to human (mTORC1 in mammals).

Jacinto, E., R. Loewith, A. Schmidt, S. Lin, M. A. Rüegg, A. Hall, and M. N. Hall. 2004. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nature Cell Biol. 6, 1122-1128. Discovery of mTORC2, thus demonstrating that the entire TOR signaling machinery is conserved from yeast to human.

Martin, D. E., A. Soulard, and M. N. Hall. 2004. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119, 969-979. Defines mechanism by which TOR controls ribosome biogenesis, the major determinant of cell growth.

Polak, P., N. Cybulski, J. N. Feige, J. Auwerx, M. A. Rüegg, and M. N. Hall. 2008. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 8, 399-410. First conditional knockout of mTORC1. Shows that tissue-specific mTOR controls whole body metabolism.

Zinzalla, V., D. Stracka, W. Oppliger, and M. N. Hall. 2011. Activation of mTORC2 by association with the ribosome. Cell 144, 757-768. Mechanism of mTORC2 activation.

Robitaille, A. M., S. Christen, M. Shimobayashi, L. L. Fava, M. Cornu, S. Moes, C. Prescianotto-Baschong, U. Sauer, P. Jenoe, and M. N. Hall. 2013. Quantitative phosphoproteomics reveal mTORC1 phosphorylates CAD and activates de novo pyrimidine synthesis. Science 339, 1320-1323. Demonstrates that mTOR controls nucleotide synthesis (in addition to protein and lipid synthesis), thus establishing that TOR controls all major anabolic processes.

Aylett, C. H. S., E. Sauer, S. Imseng, D. Boehringer, M. N. Hall*, N. Ban*, and T. Maier*. 2016. Architecture of human mTOR Complex 1. Science 351, 48-52. *Corresponding authors. First high resolution structure of a PIKK family member (for structure of mTORC2, see Stuttfeld et al. 2018 eLife doi.org/10.7554/eLife.33101.001 and Scaiola et al. 2020 Science Advances doi: 10.1126/sciadv.abc1251).

Guri, Y., M. Colombi, E. Dazert, S. K. Hindupur, J. Roszik, S. Moes, P. Jenoe, M. H. Heim, I. Riezman, H. Riezman, and M. N. Hall. 2017. mTORC2 promotes tumorigenesis via lipid synthesis. Cancer Cell 32, 807-823. Elucidates mechanism by which dysregulated mTORC2 promotes cancer development.

Böhm, R., S. Imseng, R. P. Jakob, M. N. Hall*, T. Maier*, S. Hiller*. 2021. The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1. Mol. Cell 81, 2403-2416. *Corresponding authors. Atomic level resolution of mechanism by which mTORC1 hierarchically phosphorylates a substrate.

Mossmann, D., C. Müller, S. Park, B. Ryback, M. Colombi, N. Ritter, D. Weissenberger, E. Dazert, M. Coto-Llerena, S. Nuciforo, L. Blukacz, C. Ercan, V. J. Cenzano, S. Piscuoglio, F. Bosch, L. M. Terracciano, U. Sauer, M. H. Heim, M. N. Hall. 2023. Arginine reprograms metabolism in liver cancer via RBM39. Cell 186, 5068-5083. Arginine is a second messenger-like molecule that reprograms metabolism in cancer.