Profile of Michael N. Hall, 2017 Albert Lasker Basic Medical Research Awardee: Target of rapamycin, cell growth, and translational control

Abstract

Michael N. Hall (Fig. 1) is the winner of the 2017 Lasker Award “for discoveries concerning the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth.” His seminal and paradigm-shifting discoveries were attained using the yeast Saccharomyces cerevisiae . More recently, he made a number of breakthrough discoveries in mammalian systems wherein he showed that the target of rapamycin (TOR) plays a major role in regulating whole-body metabolism in multicellular organisms. Fig. 1. Michael N. Hall, winner of the 2017 Albert Lasker Basic Medical Research Award, pictured in 2015 for the Gairdner National Program Lecture in Montreal. Image courtesy of University of Basel/Gairdner Foundation. The TOR story began more than 50 years ago, when an expedition was sent by Ayerst Research Laboratories (now Pfizer, located 6 miles from my house) to isolate novel compounds from soil microorganisms. Their quest took them to Easter Island, and ultimately resulted in the isolation of Streptomyces hygroscopicus . In 1975, it was reported that this bacterium produces a compound with antifungal activity (1). The compound rapamycin was named after the indigenous name of the island, Rapa Nui. In the same year, an unrelated important finding was reported by several research groups, the discovery that eukaryotic messenger RNAs (mRNAs) contain the structure m7GpppN (where N is any nucleotide) at their 5′ termini. The structure was termed “cap” (e.g., refs. 2 and 3). Hall was the first to mechanistically link these two discoveries, inferring that TOR controlled growth by effecting the initiation of translation (discussed below). Over 25 years ago, Hall screened for yeast cells that become resistant to rapamycin. This monumental experiment led to the discovery of TOR, and transformed our understanding of cell growth control. TOR, which is a large, atypical serine/threonine kinase, is an evolutionarily conserved key regulator … [↵][1]1Email: nahum.sonenberg{at}mcgill.ca. [1]: #xref-corresp-1-1