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Robert P. Perry
File:Biologist Robert P. Perry (cropped).jpg
Born	(1931-01-10)January 10, 1931 Chicago, U.S.
Died	July 15, 2013(2013-07-15) (aged 82) Elkins Park, Pennsylvania, U.S.
Nationality	United States
Alma mater	Northwestern University and University of Chicago
Known for	Xx
Awards	Genetics Society of America Medal (1981) Ernst Jung Gold Medal for Medicine (1990) Pearl Meister Greengard Prize (2007) March of Dimes Prize in Developmental Biology Szent-Györgyi Prize for Progress in Cancer Research
Scientific career
Fields	Embryology, Developmental biology
Institutions	University of Chicago Fox Chase Cancer Center
Doctoral advisor	Raymond E. Zirkle

Robert P. Perry (January 10, 1931 – July 15, 2013) was an American biologist who contributed xx

Early life and career

Robert P. Perry was born in Chicago in 1931, to Robert Perry and Gertrude Hyman. He received a B.A. from Northwestern University in 1951 and then attended the University of Chicago, where he received his Ph.D. in biophysics in 1956, studying xx

Perry began his career as a research associate and then an associate member (equivalent of assistant professor) at Fox Chase Cancer Center in 1960. Since 1969 he was a senior member (equivalent of full professor) at the same center. Also Robert served as an associate director at Fox Chase Cancer Center from 1971 to 1974. In addition, in 1973 he was appointed an adjunct professor of biophysics at the University of Pennsylvania and held it for twenty-two years.

He worked as a visiting professor at the University of Belgrade in 1965 and at the University of Paris in 1974. Perry served in the United States Army Reserves as an Italian interpreter and translator. He held the position of a president of the UNESCO-based International Cell Research Organization.

From 1994 Robert was a Stanley P. Reimann Endowed Chair in Research at Fox Chase Cancer Center. International Cell Research Organization (president, 1983-1986) and European Molecular Biology Organization.

Dr. Perry's contributions were recognized early, leading to his election to the National Academy of Sciences in 1977. He served on the organization's Committee on Human Rights and was part of a 1978 fact-finding mission to Argentina and Uruguay.

As an Academy member, he also took part in a 1987 scholar-exchange program with the Academy of Sciences of the former Soviet Union.

Research

In 1962, Perry reported in a single author PNAS paper that ribosomal RNA was made in the nucleolus. This important discovery was based on his finding that low doses of the drug actinomycin D specifically inhibited incorporation of [3H] labeled cytidine into nucleolar and ribosomal RNA, as revealed by autoradiography and sucrose gradient centrifugation, respectively. Further RNA-labeling and size fractionation experiments performed by the groups of Perry, James E. Darnell, and Sheldon Penman suggested that both ribosomal RNA and mRNA are processed from large precursors.

In 1974, Perry made another groundbreaking discovery, namely that mRNA molecules contain methylated bases and sugar residues. This discovery resulted in the identification of the 5′-terminal m7GpppNp CAP structure and internal m6A residues. In a short article appearing a few months later in Cell, Bob Perry, Fritz Rottman at Michigan State University, and Aaron Shatkin at the Roche Institute of Molecular Biology, speculated on the chemical structure of the 5'-terminal methylated oligonucleotide sequences of mRNA. Based on simple experiments conducted in the three laboratories, the authors proposed a 5′ to 5′ pyrophosphate linkage between an m7G residue and the first transcribed nucleotide. Furthermore, they predicted that the first, and sometimes the second transcribed nucleotides carry methyl groups at the 2′ positions of their ribose moieties. They almost got it right, except that three rather than two phosphates bridge the m7G to the first transcribed nucleotide. Perhaps they did not take into account that m7G is positively charged at neutral pH and therefore compensated for the negative charge contributed by the third phosphate during DEAE Sepharose ion exchange chromatography.

Perry’s last important contribution in the BC era was his demonstration that large nuclear RNA molecules, known as heterogeneous nuclear RNA (hnRNA), harbor the same CAP structures as mRNA. This finding was taken as further support for the precursor-product relationship between hnRNA and mRNA. However, this view was not entirely satisfactory at the time, because hnRNA and mRNA also shared 3-terminal poly(A) sequences. So the question as to whether mRNAs were derived from 5-terminal or 3-terminal hnRNA sequences remained open. The enigma was finally demystified in 1977 with the discovery of pre-mRNA splicing by Richard Roberts and Philip Sharp. Using adenovirus as a model system—in the BC era viral genes were the only protein encoding genes amenable to experimental dissection in mammalian cells—Roberts and Sharp independently came to the conclusion that mRNA was processed by the removal of internal rather than external sequences. One of us (U.S.) was in the laboratory when Bob Perry breathlessly stormed through the door to tell us about his exciting phone call with Phil Sharp.

When molecular cloning techniques became available, Bob soon realized that his mRNA turnover work had to switch from global to specific analysis. In other words, to make progress he needed model systems permitting the analysis of individual gene products. To this end Oscar Valbuena, a graduate student, and Kenneth Marcu, a postdoctoral fellow, initiated work on a plasmacytoma cell line producing light and heavy chain immunoglobulin mRNAs in large quantities. With the mission to clone cDNA copies for these mRNAs enriched in the size-fractionated RNA samples prepared by Oscar and Ken, one of us (U.S.) was sent to the Carnegie Institution of Embryology in Baltimore, headed by Donald D. Brown, another icon in eukaryotic gene transcription. With a lot of help by Yasumi Ohshima and Yoshiaki Suzuki this was eventually accomplished, and we could now use these DNA probes to follow the fates of specific immunoglobulin pre-mRNAs. The consecutive studies on immunoglobulin gene transcription and mRNA processing resulted in a series of high-impact articles published in Cell, Nature, and PNAS.

In parallel one of us (O.M.), who joined the laboratory in the late 70s, reanimated work on ribosome biogenesis in Bob’s group. He cloned cDNAs for several ribosomal proteins and used them to study the structure and expression of the corresponding genes. Again, these studies culminated in several high-profile research papers published in Cell and other prestigious journals. In the early 1990s, Bob fortuitously discovered a mammalian cDNA specifying a polypeptide, dubbed “CHD-1,” with homology to yeast and Drosophila chromatin remodeling proteins. This was one of the first chromatin remodelers to be discovered in mammalian cells, and, remarkably, Bob found that it was distinct from the original remodelers by having a chromodomain in addition to the SWI/SNF ATPase domain. Although Bob immediately recognized that the chromodomain provided a link to chromatin compaction states, it took another decade until others appreciated that the chromodomain allows recruitment of the remodeler to sites of core histone methylation. CHD proteins now constitute a family in diverse complexes that regulate chromatin structure and gene expression in all eukaryotes. Curiously, both the first and the last paper Bob published as an investigator at the Fox Chase Cancer Center deal with ribosome biogenesis, and both he signed as the sole author. While the first focuses on the RNA moieties of these tiny protein-production factories, the last reviews the possible mechanisms accounting for the balanced production of the 79 ribosomal proteins.

Through most of his rich research career, Bob was assisted by Dawn Kelley, a very talented and exceedingly meticulous research associate who taught pre-and postdocs proper working habits. Considering that some of the RNA-labeling experiments conducted in Bob’s lab during the 70s required hundreds of millicuries of [32P]orthophosphate, the close surveillance of the sometimes too impatient rookies by a severe (but beloved) “laboratory mother” was an absolute necessity.

Robert P. Perry, Reimann Professor of Oncology Research, emeritus, at the Fox Chase Cancer Center and the University of Pennsylvania, known to all as “Bob,” died on July 15, 2013, at the age of 82.

Bob grew up in Chicago and received his undergraduate training in mathematics at Northwestern University before earning a PhD in biophysics at the University of Chicago in 1956. After independent fellowships at the Oak Ridge National Laboratory and the Université Libre de Bruxelles, Bob took a position at the Fox Chase Cancer Center, to which he devoted the remainder of his scientific life, not only with rigorous science but also as a key advisor to administration and a beloved mentor to students.

Bob was one of the pioneers of RNA research, and he advanced our understanding of RNA Biology in many ways during his long career. In the late 1950s, Bob began to study the effects of UV microbeam irradiation of the nucleolus of HeLa cells. He concluded that two-thirds of the cytoplasmic RNA is derived from the nucleolus. Finding that low concentrations of Actinomycin D blocked ribosome synthesis, he could show that the nucleolus was the source of the cell's ribosomal RNA. He independently found that RNA labeled with a short pulse of radioactivity was larger than steady-state RNA, and he went on to help delineate the pathway from the large 45S pre-rRNA transcript through several intermediates to the mature cytoplasmic ribosomal RNAs. Some of his observations also presaged our current understanding of the large number of protein components that contribute to ribosome assembly.

Bob was a major player in the long struggle to determine how the small cytoplasmic mRNA was derived from the large heterogeneous nuclear RNA (hnRNA). A key observation was his demonstration of a methylated, blocked 5′ end of mRNA, which he, with Rottman and Shatkin, tentatively identified as a 5′-5′ di-phospho-dinucleotuide linkage, close to what Shatkin and Moss showed to be the CAP structure that we know today. An important contribution was Perry's demonstration that hnRNA had CAPs. With both hnRNA and mRNA having the same capped 5′ end and polyadenylated 3′ end, it was inevitable, but not foreseen, that sequences would be spliced from the middle, as shown only three long years later by the Sharp and Roberts labs.

Over the next three decades, Bob continued to contribute to our understanding of mRNA formation and turnover, to the modes of transcription and the regulated alternative splicing/termination of the immunoglobulin mRNA, and to his enduring passion, the ribosome. Many of his later papers, including his last (which was published well after his “retirement”), concern the mechanisms of transcription of ribosomal protein genes as well as the coupled control of ribosomal protein synthesis.

Bob Perry's contributions to RNA Biology were recognized by his election to the National Academy of Sciences in 1977, as well as by his receipt of the Stanley P. Reimann Honor Award, the highest honor from the Fox Chase Cancer Center.

Bob was a stimulating, inspiring, and warm mentor to his graduate students and post-docs, many of whom have gone on to make important marks in RNA Biology. His enthusiasm, rigor, and clear-sightedness, which have been an inspiration to his colleagues, will be sorely missed. He is survived by his wife of 56 years, the sculptor Zoila Perry; his children, Adele, Monique, and Rocco; and seven grandchildren.

Honors

Awards

He was a member of the National Academy of Sciences,

Personal life and death

Perry died on July 15, 2013. He left behind his wife Zoila Figueroa Perry, a well-known sculptor, his two daughters Adele and Monique, his son Rocco, and seven grandchildren.

References

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https://www.researchgate.net/scientific-contributions/Robert-P-Perry-38273855 https://cancerhistoryproject.com/people/robert-bob-perry-a-scientist-ahead-of-his-time/ https://rnajournal.cshlp.org/content/19/11/vii.full https://www.inquirer.com/philly/obituaries/20130721_Robert_P__Perry__82__early_leader_in_DNA_research.html https://www.cell.com/fulltext/S0092-8674(13)01013-1

External links

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Category:1931 births Category:2013 deaths Category:Members of the United States National Academy of Sciences

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