Sidney Altman is molecular biologist, who is the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. In 1989 he shared the Nobel Prize in Chemistry with Thomas R. Cech for their work on the catalytic properties of RNA.
After graduation he went to the United States to study physics at the Massachusetts Institute of Technology. While at MIT, he was a member of the ice hockey team. After achieving his bachelor’s degree from MIT in 1960, Altman spent 18 months as a graduate student in physics at Columbia University. Due to personal concerns and the lack of opportunity for beginning graduate students to participate in laboratory work, he left the program without completing the degree. Some months later, he enrolled as a graduate student in biophysics at the University of Colorado Medical Center. His project was a study of the effects of acridines on the replication of bacteriophage T4 DNA. He received his Ph.D. in biophysics from the University of Colorado in1967.
After receiving his Ph.D., Altman embarked upon the first of two research fellowships. He joined Matthew Meselson’s laboratory at Harvard University to study a DNA endonuclease involved in the replication and recombination of T4 DNA. Later, at the MRC Laboratory of Molecular Biology in Cambridge, England, Altman started the work that led to the discovery of RNase P and the enzymatic properties of the RNA subunit of that enzyme. John D. Smith, as well as several post-doctoral colleagues, provided Altman with very good advice that enabled him to test his ideas. “The discovery of the first radiochemically pure precursor to a tRNA molecule enabled me to get a job as an assistant professor at Yale University in1971, a difficult time to get any job at all.”
Altman’s career at Yale followed a standard academic pattern with promotion through the ranks until he became Professor in 1980. He was Chairman of his department from 1983–1985 and in 1985 became the Dean of Yale College for four years. On July1, 1989 he returned to the post of Professor on a full-time basis.
While at Yale, Altman’s Nobel Prize work came with the analysis of the catalytic properties of the ribozyme RNase P. RNase P is a ribonucleoprotein particle consisting of both a structural RNA molecule and one (in prokaryotes) or more (in eukaryotes) proteins. Originally, it was believed that, in the bacterial RNase P complex, the protein subunit was responsible for the catalytic activity of the complex, which is involved in the maturation of tRNAs. During experiments in which the complex was reconstituted in test tubes, Altman and his group discovered that the RNA component, in isolation, was sufficient for the observed catalytic activity of the enzyme, indicating that the RNA itself had catalytic properties, which was the discovery that earned him the Nobel prize. Although the RNase P complex also exists in eukaryotic organisms, his later work revealed that in those organisms, the protein subunits of the complex are essential to the catalytic activity, in contrast to the bacterial RNase P.
- (2017). Microfluidic droplet platform for ultrahigh-throughput single-cell screening of biodiversity. Proc. Natl. Acad. Sci. U.S.A. 114 (10), 2550–2555 [+]
Ultrahigh-throughput screening (uHTS) techniques can identify unique functionality from millions of variants. To mimic the natural selection mechanisms that occur by compartmentalization in vivo, we developed a technique based on single-cell encapsulation in droplets of a monodisperse microfluidic double water-in-oil-in-water emulsion (MDE). Biocompatible MDE enables in-droplet cultivation of different living species. The combination of droplet-generating machinery with FACS followed by next-generation sequencing and liquid chromatography-mass spectrometry analysis of the secretomes of encapsulated organisms yielded detailed genotype/phenotype descriptions. This platform was probed with uHTS for biocatalysts anchored to yeast with enrichment close to the theoretically calculated limit and cell-to-cell interactions. MDE-FACS allowed the identification of human butyrylcholinesterase mutants that undergo self-reactivation after inhibition by the organophosphorus agent paraoxon. The versatility of the platform allowed the identification of bacteria, including slow-growing oral microbiota species that suppress the growth of a common pathogen, Staphylococcus aureus, and predicted which genera were associated with inhibitory activity.ID:1962