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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

10/16/2019
Payea MJ, Hauke AC, De Zoysa T, Phizicky EM. "Mutations in the anticodon stem of tRNA cause accumulation and Met22-dependent decay of pre-tRNA in yeast." RNA.. 2019 Oct 16; Epub 2019 Oct 16.

10/1/2019
Ramos J, Han L, Li Y, Hagelskamp F, Kellner SM, Alkuraya FS, Phizicky EM, Fu D. "Formation of tRNA Wobble Inosine in Humans Is Disrupted by a Millennia-Old Mutation Causing Intellectual Disability." Molecular and cellular biology.. 2019 Oct 1; 39(19)Epub 2019 Sep 11.

2/18/2019
Shaheen R, Tasak M, Maddirevula S, Abdel-Salam GMH, Sayed ISM, Alazami AM, Al-Sheddi T, Alobeid E, Phizicky EM, Alkuraya FS. "PUS7 mutations impair pseudouridylation in humans and cause intellectual disability and microcephaly." Human genetics.. 2019 Feb 18; Epub 2019 Feb 18.

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