Gian Gaetano Tartaglia

Gian Gaetano Tartaglia (born 23 October 1976, Rome) is an Italian biophysicist and computational biologist. He is currently a Principal Investigator at the Italian Institute of Technology.

Biography

After a PhD in biochemistry at the University of Zurich and a postdoc at the University of Cambridge in the chemistry department, in 2010 Gian Tartaglia became PI at the Centre for Genomic Regulation (CRG) in Barcelona. He was awarded a European Research Council grant in 2013 for his studies on the role of coding and non-coding transcripts in the regulation of amyloid genes (ERC 309545). In 2014 Tartaglia was tenured in Catalonia as a professor of Life and Medical Sciences . In December 2018, Tartaglia became a full professor of biochemistry in the Department of Biology at University La Sapienza through a procedure of "chiara fama". In 2019 he started working at the Italian Institute of Technology (IIT) as a PI. In 2020, Tartaglia was awarded another ERC grant for the study on the composition of phase-separated assemblies.

Research

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.

Recent discoveries

Since 2020, the group has worked on developing RNA aptamers. The lab discovered that these molecules can be used to detect aggregates and have the potential to inhibit progressive accumulation of TDP-43. There is potential for two major applications: diagnostics (i.e., identification of aggregates at the early stages) and therapeutics (i.e., intervention on aggregate development) in the context of Amyotrophic Lateral Sclerosis.

Early contributions

In 2019, Tartaglia's group discovered that RNA plays a central role in protein assembly. They found that FMR1 mRNA are able to trigger the formation of large phase-separated assemblies, while other transcripts such as HSP70 mRNA can prevent the aggregation of specific proteins acting as 'solubilizers'. evaluates the interaction propensities of polypeptide and nucleotide chains using their physicochemical properties. The algorithm shows performances comparable to experimental tools.

The lab developed the catRAPID method 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

During 2007–2010, Tartaglia investigated the relationship between expression and solubility of genes. He found a close link between mRNA expression levels and protein aggregation rates. The original observations were published in Trends in Biological Science Solubility as an engine of evolution. An experimental follow up was published in Journal of the American Chemical Society. Based on the experimental results, he developed an approach for prediction of heterologous expression in E. coli.

Rationalizing the determinants of protein aggregation

Between 2009 and 2012, Tartaglia studied the toxicity of protein aggregates in the cellular context and determined the fraction of the proteome that interacts with insoluble aggregates. He also studied interactions with molecular chaperones

In 2008, Tartaglia developed a method to predict the kinetics of aggregation under a variety of environmental conditions. For several years, the method was one of the top cited articles in the Journal of Molecular Biology. Importantly, Tartaglia used the algorithm to design protein toxins that were expressed in the central nervous system of D. melanogaster.

In 2004–2005, Tartaglia developed the first parameter-free set of equations to predict aggregation rates of proteins using physicochemical properties. The method reproduces the changes of aggregation rates observed in vitro for a large set of peptides and proteins, including those associated with neurological disease.

Key publications May 2019 Phase separation drives X-chromosome inactivation: a hypothesis – Cerase, Armaos, Neumayer, Avner, Guttman, Tartaglia July 2019 RNA structure drives interaction with proteins – Sanchez de Groot, Armaos, Graña -Montes, Alriquet, Calloni, Vabulas, Tartaglia Dec 2018 An Integrative Study of Protein-RNA Condensates Identifies Scaffolding RNAs and Reveals Players in Fragile X- Associated Tremor/Ataxia Syndrome – Cid-Samper, Gelabert-Baldrich, Lang, Lorenzo-Gotor, Ponti, Severijnen, Bolognesi, Gelpi, Hukema, Botta-Orfila, Tartaglia Dec 2016 Quantitative predictions of protein interactions with long noncoding RNAs''' – Cirillo, Blanco, Armaos, Buness, Avner, Guttman, Cerase, Tartaglia May 2011 Predicting protein associations with long noncoding RNAs'' – Bellucci, Agostini, Masin, Tartaglia