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Gian Gaetano Tartaglia

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Gian Gaetano Tartaglia (born 23 October 1976, Rome), is an Italian biochemist and computational biologists. He is currently a full professor in biochemistry at the Sapienza University of Rome and a Principal Investigator at the Italian Institute of Technology.[1]

Biography

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In 2010 Gian Tartaglia became PI at the Centre for Genomic Regulation (CRG)[2] in Barcelona. He was awarded the prestigious ERC grant[3] in 2013 for his studies on the role of coding and non-coding transcripts in the regulation of amyloid genes ERC 309545[4] In 2014 Tartaglia was tenured in Catalonia as a professor of Life and Medical Sciences .[5] In December 2018, Tartaglia became a full professor of biochemistry in the Department of Biology at University La Sapienza[6] through a procedure of "chiara fama". In 2019 he started to work at the Italian Institute of Technology (IIT)[7] as a PI. In 2020, Tartaglia was awarded an ERC grant[3] for the study on the composition of phase-separated assemblies ERC synergy results.[8]

Research

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The Tartaglia lab observed that the structural content in RNA molecules is correlated to the number of protein interactions. This reveals the existence of a regulation level that directly links RNA to proteins especially for genes that are highly active in cellular processes (Sanchez de Groot et al.)[9]
The lab develop the CROSS method to compute the secondary structure profile of large transcripts1. Positive scores indicate double-stranded regions, while negative values are predicted to be single-stranded. Predictions for murine XIST are shown (repetitive regions are marked with coloured boxes). The area under the ROC curve of 0.75 (inset) indicates high agreement with experimental data (correlations with individual domains are reported; (Vandelli et al.[10])).

Recent discoveries

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Tartaglia's group discovered that RNA plays a central role in protein aggregation, which offers the opportunity to develop methods to combat diseases such as Amyotrophic Lateral Sclerosis. They found that FMR1 mRNA[11] and Xist non-coding RNA[12] are able to trigger the formation of large phase-separated assemblies, while other transcripts such as HSP70 mRNA[13] and aptamers[14] can prevent the aggregation of specific proteins acting as `solubilizers'. These observations strongly indicate that RNA-based molecules may be ideal candidates for the stabilisation of proteins in their native conformation by emulating the natural binding partners.

More specifically, the Tartaglia lab found that messenger RNA is a potent solubilizer blocking the formation of toxic aggregates that are potentially toxic to our organisms.[13]

These results stem from previous computational analyses revealing that interactions of aggregation-prone proteins with messenger RNA have a solubilizing effect.[15] The works lead to important discoveries on the regulation of a gene involved in Parkinson's disease alpha-synuclein. [16]

Early contributions

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In 2019, the Tartaglia lab released the first multi-organism transcriptome-wide database of protein-RNA interactions,[17] which has been incorporated in Uniprot.[18] Earlier n 2014, Gian's lab reported the first large-scale analysis of ribonucleoprotein networks (Genome Biology; [19]). The work, anticipated by a pilot project published in Nucleic Acids Research ,[20] sheds light on the relationship between functional and dysfunctional associations of protein and RNA molecules. In 2019 Gian's lab released the first multi-organism transcriptome-wide database of protein-RNA interactions,[17] which has been incorporated in Uniprot.[18]

Discovering the interactions of long non-coding RNAs

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In 2011, Tartaglia's group introduced a method to perform large-scale predictions of protein-RNA associations (the first paper published by the laboratory was Nature Methods). The algorithm, 'fast predictions of RNA and protein interactions and domains at the Center for Genomic Regulation, Barcelona, Catalonia' (catRAPID [21]), evaluates the interaction propensities of polypeptide and nucleotide chains using their physicochemical properties. The algorithm shows performances comparable to experimental tools, as reported in recent surveys.[22]

The lab developed the catRAPID method (Bellucci et al.,[23] Agostini et al.[24].; Cirillo et al.,[25] ) methods to identify protein partners of non-coding transcripts such as XIST (18000 nt). Top: Predicted binding regions of different proteins, including PTBP1, LBR, SPEN, HNRNPK, HNRNPU and DKC1 (ranked by interaction propensity); Bottom: eCLIP validation of the binding regions. Protein DKC1 is used as a negative control.

Solubility as an engine of evolution

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In the period 2007–2010, Gian Tartaglia investigated the relationship between expression and solubility of gene. He found a close link between mRNA expression levels and protein aggregation rates. The original observations were published in Trends in Biological Science and received.[26] An experimental follow up was published in Journal of the American Chemical Society.[27] Based on the experimental results, he developed an approach for prediction of heterologous expression in E. coli.[28]

Rationalizing the determinants of protein aggregation

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In the period 2009-2012 Tartaglia studied the toxicity of protein aggregates in the cellular context and determined the fraction of proteome that interacts with insoluble aggregates.[29] He also studied interactions with molecular chaperones[28] and their role in preventing aggregation.[30]

In 2008 Tartaglia developed a method to predict the kinetics of aggregation under a variety of environmental conditions. The method is of the top cited articles in the Journal of Molecular Biology.[31] Importantly, Gian used the algorithm to design protein toxins that were expressed in the central nervous system of D. melanogaster (Biophysical Journal[32] and PLoS Biology[33]).

In 2004–2005, Gian Tartaglia developed the first parameter-free set of equations to predict aggregation rates of proteins using physico-chemical properties. The method reproduces to a remarkable extent the changes of aggregation rates observed in vitro for a large set of peptide and proteins, including those associated with neurological disease. The articles are highly cited.[34][35]

Key publications

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  • Phase separation drives X-chromosome inactivation: a hypothesis – Cerase A, Armaos A, Neumayer C, Avner P, Guttman M, Tartaglia GG. Nat Struct Mol Biol. 2019 May;26(5):331-334
  • RNA structure drives interaction with proteins – Sanchez de Groot N, Armaos A, Graña -Montes R, Alriquet M, Calloni G, Vabulas RM, Tartaglia GG. Nat Commun. 2019 Jul 19;10(1):3246
  • An Integrative Study of Protein-RNA Condensates Identifies Scaffolding RNAs [...] in Fragile X- Associated Tremor/Ataxia Syndrome – Cid-Samper F, Gelabert-Baldrich M, Lang B, [...]., Botta-Orfila T, Tartaglia GG. Cell Rep. 2018 Dec 18;25(12):3422- 3434
  • Quantitative predictions of protein interactions with long noncoding RNAs' – Cirillo D, Blanco M, Armaos A, Buness A, Avner P, Guttman M, Cerase A, Tartaglia GG. Nat Methods. 2017 29;14(1):5-6
  • Predicting protein associations with long noncoding RNAs – Bellucci M, Agostini F, Masin M, Tartaglia GG. Nat Methods. 2011 Jun;8(6):444-5

References

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  1. ^ "Gian Gaetano Tartaglia". www.iit.it. Retrieved 4 August 2024.
  2. ^ "Centre for Genomic Regulation Website". www.crg.eu.
  3. ^ a b "Homepage". ERC.
  4. ^ "The Role of Non-coding RNA in Protein Networks and Neurodegenerative Diseases | RIBOMYLOME Project | Fact Sheet | FP7". CORDIS | European Commission.
  5. ^ "ICREA". www.icrea.cat.
  6. ^ https://www.uniroma1.it/en/pagina-strutturale/home
  7. ^ "Istituto Italiano di Tecnologia - IIT". www.iit.it.
  8. ^ https://erc.europa.eu/sites/default/files/document/file/erc-2019-syg-results.pdf
  9. ^ Sanchez De Groot, Natalia (2019). "RNA Structure Drives Interaction With Proteins". Nature Communications. 10 (1): 3246. Bibcode:2019NatCo..10.3246S. doi:10.1038/s41467-019-10923-5. PMC 6642211. PMID 31324771.
  10. ^ Vandelli, andrea (2020). "CROSSalive: A Web Server for Predicting the in Vivo Structure of RNA Molecules". Bioinformatics (Oxford, England). 36 (3): 940–941. doi:10.1093/bioinformatics/btz666. PMC 9883674. PMID 31504168.
  11. ^ Cid-Samper, Fernando; Gelabert-Baldrich, Mariona; Lang, Benjamin; Lorenzo-Gotor, Nieves; Ponti, Riccardo Delli; Severijnen, Lies-Anne W.F.M.; Bolognesi, Benedetta; Gelpi, Ellen; Hukema, Renate K.; Botta-Orfila, Teresa; Tartaglia, Gian Gaetano (December 18, 2018). "An Integrative Study of Protein-RNA Condensates Identifies Scaffolding RNAs and Reveals Players in Fragile X-Associated Tremor/Ataxia Syndrome". Cell Reports. 25 (12): 3422–3434.e7. doi:10.1016/j.celrep.2018.11.076. PMC 6315285. PMID 30566867.
  12. ^ Cerase, Andrea; Armaos, Alexandros; Neumayer, Christoph; Avner, Philip; Guttman, Mitchell; Tartaglia, Gian Gaetano (May 4, 2019). "Phase separation drives X-chromosome inactivation: a hypothesis". Nature Structural & Molecular Biology. 26 (5): 331–334. doi:10.1038/s41594-019-0223-0. PMID 31061525 – via PubMed.
  13. ^ a b Sanchez de Groot, Natalia; Armaos, Alexandros; Graña-Montes, Ricardo; Alriquet, Marion; Calloni, Giulia; Vabulas, R. Martin; Tartaglia, Gian Gaetano (July 19, 2019). "RNA structure drives interaction with proteins". Nature Communications. 10 (1): 3246. Bibcode:2019NatCo..10.3246S. doi:10.1038/s41467-019-10923-5. PMC 6642211. PMID 31324771.
  14. ^ E, Zacco; R, Graña-Montes; Sr, Martin; Ns, de Groot; C, Alfano; Gg, Tartaglia; A, Pastore (April 5, 2019). "RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43". Journal of Molecular Biology. 431 (8): 1671–1688. doi:10.1016/j.jmb.2019.01.028. hdl:11573/1254422. PMC 6461199. PMID 30742796.
  15. ^ Zanzoni, Andreas; Marchese, Domenica; Agostini, Federico; Bolognesi, Benedetta; Cirillo, Davide; Botta-Orfila, Maria; Livi, Carmen Maria; Rodriguez-Mulero, Silvia; Tartaglia, Gian Gaetano (December 4, 2013). "Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein". Nucleic Acids Research. 41 (22): 9987–9998. doi:10.1093/nar/gkt794. PMC 3905859. PMID 24003031.
  16. ^ D, Marchese; T, Botta-Orfila; D, Cirillo; Ja, Rodriguez; Cm, Livi; R, Fernández-Santiago; M, Ezquerra; Mj, Martí; E, Bechara; Gg, Tartaglia (December 15, 2017). "Discovering the 3' UTR-mediated regulation of alpha-synuclein". Nucleic Acids Research. 45 (22): 12888–12903. doi:10.1093/nar/gkx1048. hdl:10230/34993. PMC 5728410. PMID 29149290.
  17. ^ a b https://rnact.crg.eu/
  18. ^ a b "UniProt". www.uniprot.org.
  19. ^ D, Cirillo; D, Marchese; F, Agostini; Cm, Livi; T, Botta-Orfila; Gg, Tartaglia (January 2, 2014). "Constitutive patterns of gene expression regulated by RNA-binding proteins". Genome Biology. 15 (1): R13. doi:10.1186/gb-2014-15-1-r13. PMC 4054784. PMID 24401680.
  20. ^ A, Zanzoni; D, Marchese; F, Agostini; B, Bolognesi; D, Cirillo; M, Botta-Orfila; Cm, Livi; S, Rodriguez-Mulero; Gg, Tartaglia (December 4, 2013). "Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein". Nucleic Acids Research. 41 (22): 9987–9998. doi:10.1093/nar/gkt794. hdl:10230/22555. PMC 3905859. PMID 24003031.
  21. ^ Bellucci, Matteo; Agostini, Federico; Masin, Marianela; Tartaglia, Gian Gaetano (June 4, 2011). "Predicting protein associations with long noncoding RNAs". Nature Methods. 8 (6): 444–445. doi:10.1038/nmeth.1611. PMID 21623348 – via PubMed.
  22. ^ "Probe Noncoding RNA Biology with Protein-lncRNA Interaction Tools | Biocompare: The Buyer's Guide for Life Scientists".
  23. ^ Bellucci, Matteo (2011). "Predicting Protein Associations With Long Noncoding RNAs". Nature Methods. 8 (6): 444–445. doi:10.1038/nmeth.1611. PMID 21623348.
  24. ^ Agostini, Federico (2013). "X-inactivation: Quantitative Predictions of Protein Interactions in the Xist Network". Nucleic Acids Research. 41 (1): e31. doi:10.1093/nar/gks968. PMC 3592426. PMID 23093590.
  25. ^ Cirillo, Davive (2017). "Quantitative Predictions of Protein Interactions With Long Noncoding RNAs". Nature Methods. 14 (1): 5–6. doi:10.1038/nmeth.4100. PMID 28032625.
  26. ^ Tartaglia, Gian Gaetano; Pechmann, Sebastian; Dobson, Christopher M.; Vendruscolo, Michele (May 4, 2007). "Life on the edge: a link between gene expression levels and aggregation rates of human proteins". Trends in Biochemical Sciences. 32 (5): 204–206. doi:10.1016/j.tibs.2007.03.005. PMID 17419062 – via PubMed.
  27. ^ Baldwin, Andrew J.; Knowles, Tuomas P. J.; Tartaglia, Gian Gaetano; Fitzpatrick, Anthony W.; Devlin, Glyn L.; Shammas, Sarah Lucy; Waudby, Christopher A.; Mossuto, Maria F.; Meehan, Sarah; Gras, Sally L.; Christodoulou, John; Anthony-Cahill, Spencer J.; Barker, Paul D.; Vendruscolo, Michele; Dobson, Christopher M. (September 14, 2011). "Metastability of native proteins and the phenomenon of amyloid formation". Journal of the American Chemical Society. 133 (36): 14160–14163. doi:10.1021/ja2017703. hdl:11573/1451766. PMID 21650202 – via PubMed.
  28. ^ a b Tartaglia, Gian Gaetano; Pechmann, Sebastian; Dobson, Christopher M.; Vendruscolo, Michele (May 1, 2009). "A relationship between mRNA expression levels and protein solubility in E. coli". Journal of Molecular Biology. 388 (2): 381–389. doi:10.1016/j.jmb.2009.03.002. PMID 19281824 – via PubMed.
  29. ^ Olzscha, Heidi; Schermann, Sonya M.; Woerner, Andreas C.; Pinkert, Stefan; Hecht, Michael H.; Tartaglia, Gian G.; Vendruscolo, Michele; Hayer-Hartl, Manajit; Hartl, F. Ulrich; Vabulas, R. Martin (January 7, 2011). "Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions". Cell. 144 (1): 67–78. doi:10.1016/j.cell.2010.11.050. hdl:11573/1287804. PMID 21215370 – via PubMed.
  30. ^ Calloni, Giulia; Chen, Taotao; Schermann, Sonya M.; Chang, Hung-Chun; Genevaux, Pierre; Agostini, Federico; Tartaglia, Gian Gaetano; Hayer-Hartl, Manajit; Hartl, F. Ulrich (March 29, 2012). "DnaK functions as a central hub in the E. coli chaperone network". Cell Reports. 1 (3): 251–264. doi:10.1016/j.celrep.2011.12.007. hdl:10230/24950. PMID 22832197 – via PubMed.
  31. ^ Tartaglia, Gian Gaetano; Pawar, Amol P.; Campioni, Silvia; Dobson, Christopher M.; Chiti, Fabrizio; Vendruscolo, Michele (July 4, 2008). "Prediction of aggregation-prone regions in structured proteins". Journal of Molecular Biology. 380 (2): 425–436. doi:10.1016/j.jmb.2008.05.013. PMID 18514226 – via PubMed.
  32. ^ Ac, Brorsson; B, Bolognesi; Gg, Tartaglia; Sl, Shammas; G, Favrin; I, Watson; Da, Lomas; F, Chiti; M, Vendruscolo; Cm, Dobson; Dc, Crowther; Lm, Luheshi (April 21, 2010). "Intrinsic determinants of neurotoxic aggregate formation by the amyloid beta peptide". Biophysical Journal. 98 (8): 1677–1684. Bibcode:2010BpJ....98.1677B. doi:10.1016/j.bpj.2009.12.4320. hdl:11573/1451802. PMC 2856165. PMID 20409489.
  33. ^ Luheshi, Leila M.; Tartaglia, Gian Gaetano; Brorsson, Ann-Christin; Pawar, Amol P.; Watson, Ian E.; Chiti, Fabrizio; Vendruscolo, Michele; Lomas, David A.; Dobson, Christopher M.; Crowther, Damian C. (October 30, 2007). "Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity". PLOS Biology. 5 (11): e290. doi:10.1371/journal.pbio.0050290. PMC 2043051. PMID 17973577.
  34. ^ Tartaglia, Gian Gaetano; Cavalli, Andrea; Pellarin, Riccardo; Caflisch, Amedeo (July 4, 2004). "The role of aromaticity, exposed surface, and dipole moment in determining protein aggregation rates". Protein Science. 13 (7): 1939–1941. doi:10.1110/ps.04663504. PMC 2279921. PMID 15169952.
  35. ^ Tartaglia, Gian Gaetano; Cavalli, Andrea; Pellarin, Riccardo; Caflisch, Amedeo (October 4, 2005). "Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences". Protein Science. 14 (10): 2723–2734. doi:10.1110/ps.051471205. PMC 2253302. PMID 16195556.
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