Dr. Eric Phizicky

Written by: Isha Verma, PhD.

Dr. Eric Phizicky is a Professor in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry in the USA. He has studied his favorite RNA (tRNA obviously) for 40 years, focusing on tRNA processing and biology in the yeast Saccharomyces cerevisiae and more recently, in the evolutionarily distant yeast Schizosaccharomyces pombe. Dr. Phizicky began his research career by doing his Ph.D. work in the lab of Jeff Roberts at Cornell in Ithaca, NY, where he used phage λ and lambdoid phages to study the bacterial SOS response.  He studied how DNA damage activated the RecA protein to mediate cleavage of the phage repressor to propel the phage from the dormant lysogenic phase to the lytic phase of its life cycle. He completed his postdoctoral training with John Abelson at the California Institute of Technology (CalTech) in Pasadena, CA, where he worked on tRNA processing in S. cerevisiae by purifying the tRNA ligase involved in tRNA splicing, analyzing its activity, cloning its gene, and analyzing conditional mutants.

After finishing his postdoc, Dr. Phizicky started his lab at the University of Rochester over 35 years ago because it had outstanding basic scientists in both the Medical School and the College of Arts and Sciences. His early colleagues included both Dr. Fred Sherman in Biochemistry and Dr. Marty Gorovsky in Biology. He also chose the Rochester, New York area because it was an ideal place to live and raise a family, with high-quality schools, affordable housing, and a great living environment. Dr. Phizicky's favorite RNA is tRNA – in his opinion, “the greatest ncRNA of them all.” As mentioned above, his lab focuses on tRNA biogenesis, function, and quality control mechanisms in both budding and fission yeast. tRNA biogenesis is crucial in all organisms and involves multiple steps including: end processing, splicing, the addition or formation of numerous post-transcriptional modifications, and precisely controlled intracellular trafficking. Errors in tRNA biogenesis often have profound consequences, and can lead to cell death, growth defects, and translational defects in yeast, while contributing to several neurological and mitochondrial disorders in humans including pontocerebellar hypoplasia, familial dysautonomia, intellectual disability, microcephaly, and mitochondrial encephalomyopathies. The Phizicky lab studies the mechanisms by which tRNA quality is maintained during and after tRNA biogenesis in S. cerevisiae and the conservation and evolution of these quality control pathways in S. pombe. Major current research topics in his lab include the evolution and biology of the two major tRNA decay pathways that target hypomodified tRNAs, plus studies to characterize the mechanism and specificity of a newly described tRNA decay pathway. His team is also working to understand the connections between modification defects and signaling pathways such as the general amino acid control pathway and the regulation of initiator tRNA.

"My mentors taught me the value of question-directed science and the careful construction and interpretation of results. One mentor often said that: If you ask interesting questions, you will get interesting answers. I also learned the value of using new technology … to ask and answer new important questions in the field."

Dr. Phizicky has a strong and continuing interest in teaching and training students. Since opening his lab, he has trained several dozen postdoctoral fellows, graduate students, undergraduate students, and summer students. He urges starting graduate students to find a lab in which science is exciting and the PI and lab personnel are committed to high-quality work. Dr. Phizicky states, "Both my Ph.D. advisor, Jeff Roberts, and my postdoctoral advisor, John Abelson, were fantastic role models, albeit with different personalities and styles. Both of them had exciting research programs at the forefront of their fields, and it was really exciting to work in their labs. From Jeff, I learned the value of question-directed science and the careful construction and interpretation of results. Jeff often said- If you ask interesting questions, you will get interesting answers. From John, I learned the value of using new technology to address scientific questions, with his quick ability to see the use and the applications of new methods to ask and answer new important questions in the field."

Dr. Phizicky is currently most excited about his lab's journey into modern genetics and the use of whole genome suppressor sequencing as a means for studying the biology of tRNA modifications in both S. pombe and  S. cerevisiae. "While visiting Emory for a seminar in 2016, I had a conversation with my friend Danny Reines in which he described his recent use of whole genome sequencing of suppressor strains to identify the relevant mutations responsible for suppressing a conditional mutant. This was amazing to me because it was easy to extract the relevant mutations. Moreover, the method was rapid and affordable, particularly when compared to the time and effort required to clone by plasmid complementation", he states. He further added, "At the time, we had started to compare the biology of tRNA modifications in S. pombe with that known in S. cerevisiae because of the great potential for new evolutionary insights from the study of the same problem in two organisms that diverged 600 million years ago (Mya), which pre-dates the Cambrian explosion of 540 Mya during which the major animal phyla diverged. We have been applying this whole genome sequencing approach ever since to identify suppressor mutations, and it has been great. With initial help from Jeff Pleiss at Cornell and now from Justin Fay at the University of Rochester, we have substantially reduced costs and improved the analysis so we can easily sequence and analyze dozens of suppressor strains at once. This approach has led us to identify several unexpected pathways of suppression, which in turn has led to re-examining both the biology and of body modifications in S. cerevisiae, with intriguing results.”

In addition to his research, Dr. Phizicky has been a key contributor to RNA, the RNA Society’s journal, for the past eight years. He first worked with Dr. Tim Nilsen as the Associate Editor (2015-  2017) and then as Deputy Editor until Tim retired in December 2022, when he and Dr. Javier Caceres both became the journal’s Senior Editors. His goal is to make RNA the journal of choice to publish significant results in all fields of RNA science. RNA has always had an excellent reputation, built up during Tim's stewardship from 1995-2022, with an unusually high percentage of highly cited papers. The journal has recently focused on three initiatives to continue that success in the face of the dramatically increased competition from new journals. First, RNA has been driving engagement by actively promoting newly-published papers (and their authors) using social media posts in addition to the “Meet the First Authors” features, and the RNA Journal Prize. Second, RNA has published Special Issues with review/opinion pieces focused on important current topics, including RNA in Biological Condensates (2022) and RNA Therapeutics (2023). Thirdly, the journal has been working with its great cast of Associate Editors, prominent RNA scientists with wide-ranging expertise in their own right, to promote timely reviews of manuscripts, with informed manuscript decisions that focus only on critical experimental revisions needed for publication, resulting in a relatively fast average time from manuscript submission until acceptance.

As a Senior Editor for RNA, Dr. Phizicky can’t just pick one ‘favorite’ research article in RNA. That being said, he cites this paper from 2005 by Anders Byström and colleagues as one of his many. That work was the first to link all six components of the elongator (Elp) complex and three killer toxin-insensitive (Kti) gene products to the formation of the crucial modification 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U)m found at the wobble U34 nucleotide of tRNAs. That manuscript is a great example of using initial results in S. pombe to leverage a seminal discovery in the better-studied S. cerevisiae. In this case, it opened an entire branch of study in the field of tRNA modifications. His other favorite paper in RNA is this paper from 2002 by Christian Marck and Henri Grosjean on tRNomics.  The authors compared the common sequence characteristics of tRNAs from fifty genomes among eukaryotes, archaea, and bacteria. This bioinformatics paper is a tour-de-force because it contains such a large volume of useful information but is presented in a clear easy to access manner. Even today after over two decades, it remains an excellent resource for those studying tRNA.