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Glauco Tocchini-Valentini

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Glauco P. Tocchini-Valentini is an Italian molecular biologist. As of 2009, he was elected as a foreign associate of the National Academy of Sciences, affiliated with the National Research Council of Italy (CNR).[1] In his forty plus years in molecular biology, he has published over 140 papers on topics like mutagenesis, RNA molecules, structure, function and evolution, disease models, neurodegenerative diseases, and cognitive disorders.[1] He currently resides in Rome, Italy as director at the Institute of Cell Biology. He is also the coordinator for European Mouse Mutant Archive, also known as EMMA.[2] Currently, he is actively advocating advancement in infrastructure for science buildings across Europe.

Early life and education

Tocchini-Valentini graduated the University Rome La Sapienza in 1959, interested in producing special phosphates in order to synthesize RNA. He pursued his interests at the Karlsruhe Institute of Technology in Karlsruhe, Germany, where he became a radiobiologist in their Institute of Radiology.[3] At the end of his fellowship, Tocchini-Valentini went on teach at the University of Chicago, where he published numerous papers on asymmetrical transcription in collaboration with Franco Graziosi, Peter Geiduschek, Robert Haselkorn, and Samuel Weiss. After leaving University of Chicago in 1996, he returned to Italy, where he is currently affiliated with the National Research Council of Italy.

Research interests

Glauco Tocchini-Valentini's early research focused on demonstrating genetic transcription as an asymmetric process.[4] His publication on findings of asymmetric synthesis of RNA in vitro concluded that the synthesis of mRNA and rRNA is asymmetric whereas DNA yielded symmetric synthesis.[5] From there, he aided in isolating, characterizing, and discovering several enzymes involved in the transcription process, such as DNA and RNA polymerases, rDNA cistrons, and Typell DNA topoisomerase.[6][7][8] Much of his work was characterized using various Xenopus laevis cell types, including oocytes, unfertilized eggs, and kidney cells; the characteristics of these amphibian cells and their enzymes were related to mammalian cells and their respective enzymes.[6]

Tocchini-Valentini has also contributed to current understanding of enzyme-substrate rules, stemming from his publication on RNase P and endonuclease from Xenopus laevis cell types.[9][10] He characterized the tRNA endonucleases of Archaea, finding three forms of tRNA endonuclease.[11] His current research focus is using an archaeal endonuclease (MJ-EndA) to control splicing in both live mice and mice lines.[12] This emergent technology, which can perform both cis- and trans-splicing, allows perturbations to be introduced at the RNA level, thus allowing more specific targeting in mRNA as well as other RNAs.[12] More recently, his research focuses on improving phenotyping data by using "soft windowing." which use adaptive windows of time to include certain controls to result in better analysis across small variations in experiments.[13] He is also involved in the Deep Genome Project, a project which focuses on sequencing all analogous genes in mice as humans in order to better understand disease models and mechanisms.[14] Through phenotyping screens of these mice, genetic components of metabolism and auditory dysfunction has been identified.[15][16]

Patents

Tocchini-Valentini has filed several patents pertaining to RNA cleavage and recombination.[17] The following two have been approved by the United States Patent and Trademark Office (USPTO): method of RNA cleavage and method of RNA cleavage and recombination.

In 2003, the RNA cleavage method[18] first exposes the target molecule (not containing a tRNA structure[19]) to a eukaryotic tRNA splicing endonuclease. This puts the molecule in the bulge-helix-bulge conformation,[20] and cleavage occurs in this formation, resulting in cleavage products. The cleavage reaction can occur both in vitro and in vivo, and it is mainly used to demonstrate the presence of specific RNAs in samples. Using fluorescence resonance energy transfer (FRET), the target molecule can be labeled and fluorescence would be measured upon cleavage of the oligonucleotide.

In continuation of this previous patent, he filed a follow up patent in 2004, which was approved on August 20, 2013.[21] As described previously, the RNA molecule is cleaved within the bulge-helix-bulge. As the target RNA molecule and the exogenous RNA molecule are treated with the correct ligase, RNA chimeras form.[22][23] This results in the recombination of the target RNA and the exogenous RNA across the bulge-helix-bulge structure, thus this method can also be used for recombining RNA molecules in order to alter RNA function and hence gene expression.[24]

Awards and honors

Tocchini-Valentini was awarded the San Giacomo Della Marca Prize in 2007. The San Giacomo della Marca prize is awarded to an esteemed person originating from the Marche area.[25]

References

  1. ^ a b "Member Directory". National Academy of Sciences. Retrieved 4 April 2020.
  2. ^ Tocchini-Valentini, Glauco (11–13 November 2014). "EMMA - INFRAFRONTIER - IMPC Monterotondo Mouse Clinic (MMC)". IMPC Annual Meeting, Barcelona. POSTER.
  3. ^ Tocchini-Valentini, Glauco. Personal Letter. https://www.lucacavallisforza.com/wp-content/uploads/2019/09/Memory-Glauco-Tocchini-Valentini.pdf
  4. ^ Geiduschek, E. Peter; Tocchini-Valentini, Glauco P.; Sarnat, Marlene T. (August 1964). "Asymmetric Synthesis of RNA in Vitro: Dependence of DNA Continuity and Conformation". Proceedings of the National Academy of Sciences of the United States of America. 52 (2): 486–493. Bibcode:1964PNAS...52..486G. doi:10.1073/pnas.52.2.486. ISSN 0027-8424. PMC 300303. PMID 14206614.
  5. ^ Colvill, A. J.; Kanner, L. C.; Tocchini-Valentini, G. P.; Sarnat, M. T.; Geiduschek, E. P. (May 1965). "Asymmetric RNA synthesis in vitro: heterologous DNA-enzyme systems; E. coli RNA polymerase". Proceedings of the National Academy of Sciences of the United States of America. 53 (5): 1140–1147. Bibcode:1965PNAS...53.1140C. doi:10.1073/pnas.53.5.1140. ISSN 0027-8424. PMC 301385. PMID 4958034.
  6. ^ a b Tatò, F.; Gandini, D. A.; Tocchini-Valentini, G. P. (September 1974). "Major DNA polymerases common to different Xenopus laevis cell types". Proceedings of the National Academy of Sciences of the United States of America. 71 (9): 3706–3710. Bibcode:1974PNAS...71.3706T. doi:10.1073/pnas.71.9.3706. ISSN 0027-8424. PMC 433845. PMID 4530330.
  7. ^ Mattoccia, E.; Baldi, M. I.; Carrara, G.; Fruscoloni, P.; Benedetti, P.; Tocchini-Valentini, G. P. (November 1979). "Separation of RNA transcription and processing activities from X. laevis germinal vesicles". Cell. 18 (3): 643–648. doi:10.1016/0092-8674(79)90119-3. ISSN 0092-8674. PMID 519751. S2CID 42075603.
  8. ^ Crippa, M.; Tocchini-Valentini, G. P. (1970-06-27). "Performance of a bacterial RNA polymerase factor in an amphibian oocyte". Nature. 226 (5252): 1243–1244. Bibcode:1970Natur.226.1243C. doi:10.1038/2261243a0. ISSN 0028-0836. PMID 4912321. S2CID 4251098.
  9. ^ Carrara, G.; Calandra, P.; Fruscoloni, P.; Tocchini-Valentini, G. P. (1995-03-28). "Two helices plus a linker: a small model substrate for eukaryotic RNase P". Proceedings of the National Academy of Sciences of the United States of America. 92 (7): 2627–2631. Bibcode:1995PNAS...92.2627C. doi:10.1073/pnas.92.7.2627. ISSN 0027-8424. PMC 42271. PMID 7708695.
  10. ^ Doria, M.; Carrara, G.; Calandra, P.; Tocchini-Valentini, G. P. (1991-05-11). "An RNA molecule copurifies with RNase P activity from Xenopus laevis oocytes". Nucleic Acids Research. 19 (9): 2315–2320. doi:10.1093/nar/19.9.2315. ISSN 0305-1048. PMC 329436. PMID 1710353.
  11. ^ Tocchini-Valentini, Giuseppe D.; Fruscoloni, Paolo; Tocchini-Valentini, Glauco P. (2005-06-21). "Structure, function, and evolution of the tRNA endonucleases of Archaea: an example of subfunctionalization". Proceedings of the National Academy of Sciences of the United States of America. 102 (25): 8933–8938. Bibcode:2005PNAS..102.8933T. doi:10.1073/pnas.0502350102. ISSN 0027-8424. PMC 1157037. PMID 15937113.
  12. ^ a b Putti, Sabrina; Calandra, Patrizia; Rossi, Nicoletta; Scarabino, Daniela; Deidda, Giancarlo; Tocchini-Valentini, Glauco P. (September 2013). "Highly efficient, in vivo optimized, archaeal endonuclease for controlled RNA splicing in mammalian cells". FASEB Journal. 27 (9): 3466–3477. doi:10.1096/fj.13-231993. ISSN 1530-6860. PMID 23682120. S2CID 6486064.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ Haselimashhadi, Hamed; Mason, Jeremy C.; Munoz-Fuentes, Violeta; López-Gómez, Federico; Babalola, Kolawole; Acar, Elif F.; Kumar, Vivek; White, Jacqui; Flenniken, Ann M.; King, Ruairidh; Straiton, Ewan (2020-03-01). "Soft windowing application to improve analysis of high-throughput phenotyping data". Bioinformatics. 36 (5): 1492–1500. doi:10.1093/bioinformatics/btz744. ISSN 1367-4811. PMC 7115897. PMID 31591642.
  14. ^ Lloyd, K. & Adams, David & Baynam, Gareth & Beaudet, Arthur & Bosch, Fatima & Boycott, Kym & Braun, Robert & Caulfield, Mark & Cohn, Ronald & Dickinson, Mary & Dobbie, Michael & Flenniken, Ann & Flicek, Paul & Galande, Sanjeev & Gao, Xiang & Grobler, Anne & Heaney, Jason & Herault, Yann & Angelis, Martin & Brown, Steve. (2020). The Deep Genome Project. Genome Biology. 21. 18. 10.1186/s13059-020-1931-9.
  15. ^ Bowl, Michael R.; Simon, Michelle M.; Ingham, Neil J.; Greenaway, Simon; Santos, Luis; Cater, Heather; Taylor, Sarah; Mason, Jeremy; Kurbatova, Natalja; Pearson, Selina; Bower, Lynette R. (12 October 2017). "A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction". Nature Communications. 8 (1): 886. Bibcode:2017NatCo...8..886B. doi:10.1038/s41467-017-00595-4. ISSN 2041-1723. PMC 5638796. PMID 29026089.
  16. ^ Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A.; Schütt, Christine; Ravindranath, Aakash Chavan; Leuchtenberger, Stefanie; Sharma, Sapna; Kistler, Martin; Willershäuser, Monja; Brommage, Robert; Meehan, Terrence F. (18 January 2018). "Identification of genetic elements in metabolism by high-throughput mouse phenotyping". Nature Communications. 9 (1): 288. Bibcode:2018NatCo...9..288R. doi:10.1038/s41467-017-01995-2. ISSN 2041-1723. PMC 5773596. PMID 29348434.
  17. ^ "Patents by Inventor Glauco P. Tocchini-Valentini". JUSTIA. August 20, 2013. Retrieved 18 April 2020.
  18. ^ Publication number: 20040023239 Type: Application Filed: Jan 7, 2003 Publication Date: Feb 5, 2004 Inventors: Glauco P. Tocchini-Valentini (Rome), Giancarlo Deidda (Rome), Nicoletta Rossi (Rome), Maria Irene Baldi (Rome), Paolo Fruscoloni (Rome) Application Number: 10296574
  19. ^ Bufardeci, E., Fabbri, S., Baldi, M. I., Mattoccia, E. and Tocchini-Valentini, G. P., “in vitro genetic analysis of the structural features of the pre-tRNA required for determination of the 3′ splice site in the intron excision reaction,” EMBO J. 12:46974704 (1993).
  20. ^ Gandini-Attardi, D., Margarit, I. and Tocchini-Valentini, G. P., “Structural alteration in mutant precursors of the yeast tRNALeu3 gene which behave as defective substrates for a highly purified splicing endoribonuclease,” EMBO J. 4:3289-3297 (1985).
  21. ^ "US Patent for Method of RNA cleavage and recombination Patent (Patent # 8,512,945 issued August 20, 2013) - Justia Patents Search". patents.justia.com. Retrieved 2020-04-19.
  22. ^ Perkins, K. K., Furneaux, H. and Hurwitz, J., “Isolation and characterization of an RNA ligase from HeLa cells,” Proc. Natl. Acad. Sci. USA 82:684-688 (1985).
  23. ^ Mattoccia, E., Baldi, M. I., Gandini-Attardi, D., Ciafrè, S. and Tocchini-Valentini, G. P., “Site selection by the tRNA splicing endonuclease of Xenopus laevis,” Cell 55:731-738 (1988)
  24. ^ Patent number: 8512945 Type: Grant Filed: Apr 9, 2004 Date of Patent: Aug 20, 2013 Patent Publication Number: 20050043259 Inventors: Glauco P. Tocchini-Valentini (Rome), Giancarlo Deidda (Rome), Nicoletta Rossi (Rome) Primary Examiner: Dana Shin Application Number: 10/821,777
  25. ^ Ferrazzoli, Marco (November 11, 2001). "Sarnano: a Glauco Tocchini Valentini il Premio San Giacomo della Marca". Vivere Marche. Retrieved March 8, 2020.
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