Skip to main content
Explore URMC
menu

Eric M. Phizicky, Ph.D.

Contact Information

Phone Numbers

Office: (585) 275-7268

Fax: (585) 271-2683

Research Labs

Faculty Appointments

Biography

Research

tRNA Biogenesis, Function and Quality Control

One major lab project focuses on understanding the biology of tRNA. tRNA plays a crucial role in translation, and numerous factors participate in its biogenesis, function, intracellular trafficking, and quality control. In the yeast Saccharomyces cerevisiae, cytoplasmic tRNAs have an average of 13 modifications, and there are a total of 25 chemically distinct modifications, many of which are highly conserved in different organisms, and of unknown function. We previously used a biochemical genomics approach to identify the genes encoding a number of different modification enzymes. We are currently focusing on the assignment of other activities to genes, and on two aspects of the biology of modifications: First, we are investigating the roles of modifications. We recently found evidence that lack of certain modifications can lead to rapid degradation of specific mature tRNAs, suggesting the existence of a quality control pathway that monitors the integrity of tRNA. We are currently working to define the components of this rapid tRNA decay pathway, the mechanism by which tRNAs are targeted for turnover, and the conditions under which this pathway is used. Second, we are defining the mechanisms by which modification enzymes recognize and act on their specific tRNA substrates. Since modifications have crucial roles in the cell, incorrect modification of a tRNA is likely to have catastrophic effects. We recently found that recognition of the tRNAHis anticodon is necessary and sufficient for Thg1 to add a guanine nucleotide to the 5' end of the tRNA, a reaction that is essential in wild type cells for proper translation. We are currently examining other modification enzymes to uncover the different mechanisms by which specificity is attained.

Functional Genomics

A second major lab project focuses on the design, construction and implementation of genomic methods to analyze protein structure and function (in collaboration with Elizabeth Grayhack). To facilitate parallel biochemical analysis of the proteome, we previously constructed two genomic libraries of strains in which nearly every yeast gene is expressed as a tagged fusion protein under regulated control. We are currently using these libraries to define new biochemical activities, and to help define cell circuitry by systematic analysis of genetic suppression caused by overexpression of genes. In addition, in collaboration with investigators at the Hauptman-Woodward Institute, we are developing methodology for high throughput expression and purification of protein complexes from yeast, for structural analysis by x-ray crystallography.

Credentials

Education

1976
BS | McGill University
Biochemistry

1983
PhD | Cornell University
Biochemistry

Publications

Journal Articles

4/13/2023
Phizicky EM, Hopper AK. "The Life and Times of a tRNA." RNA.. 2023 Apr 13; Epub 2023 Apr 13.

7/28/2022
Tasak M, Phizicky EM. "Initiator tRNA lacking 1-methyladenosine is targeted by the rapid tRNA decay path way in evolutionarily distant yeast species." PLoS genetics.. 2022 Jul 28; 18(7):e1010215. Epub 2022 Jul 28.

4/26/2022
Funk HM, DiVita DJ, Sizemore HE, Wehrle K, Miller CLW, Fraley ME, Mullins AK, Guy AR, Phizicky EM, Guy MP. "Identification of a Trm732 Motif Required for 2'--methylation of the tRNA Anticodon Loop by Trm7." ACS omega.. 2022 Apr 26; 7(16):13667-13675. Epub 2022 Apr 13.

VIEW ALL PUBLICATIONS