The Saiardi lab is interested in the intersection between signalling and basic metabolism. Specifically, we study the role played by inositol pyrophosphates in maintaining cell homeostasis.
Inositol pyrophosphates are present in all eukaryotic cells and belong to the inositol phosphate family of soluble signaling molecules. Both inositol phosphates and inositol pyrophosphates are obtained by the combinatorial attachment of phosphate groups to inositol. However, the inositol pyrophosphates are distinguished by their one or more high-energy phosphoanhydride bonds (pyro-moieties). The energy stored in these bonds provides the inositol pyrophosphates with the potential to take part in new and not yet fully understood molecular actions.
The structure of these molecules and their conservation in eukaryotic biology suggests a fundamental signalling role, acting through a unique mechanism. Alteration of inositol pyrophosphate levels has been associated with a wide collection of phenotypes as well as important human pathology such as obesity, diabetes and cancer. These pleiotropic effects suggest an ability to control a central cellular function.
Our finding that inositol pyrophosphates regulate intracellular levels of ATP places these molecules at the interface between signalling and basic metabolism. Research in our lab focuses on understanding how inositol pyrophosphates regulate basic metabolism.
Azevedo C & Saiardi A (2016). Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective. Trends Biochem Sci. doi:10.1016/j.tibs.2016.10.008Azevedo C, et al (2015). Protein Polyphosphorylation of Lysine Residues by Inorganic Polyphosphate. MOLECULAR CELL, 58 (1), 71-82. CELL PRESS. doi:10.1016/j.molcel.2015.02.010Wilson MSC, et al (2015). A novel method for the purification of inositol phosphates from biological samples reveals that no phytate is present in human plasma or urine. OPEN BIOLOGY, 5 (3), UNSP 150014. doi:10.1098/rsob.150014Wilson MS, et al (2013). Inositol pyrophosphates: between signalling and metabolism. Biochem J, 452 (3), 369-379. doi:10.1042/BJ20130118Szijgyarto Z, et al (2011). Influence of inositol pyrophosphates on cellular energy dynamics. Science, 334 (6057), 802-805. doi:10.1126/science.1211908Lonetti A, et al (2011). Identification of an evolutionarily conserved family of inorganic polyphosphate endopolyphosphatases. J Biol Chem, 286 (37), 31966-31974. doi:10.1074/jbc.M111.266320
Medical Research Council
Filipy Borghi (Research Associate)
Xue (Bessie) Su (Research Associate)
Jonathan Chubb (LMCB, UK)Antonella Riccio (LMCB, UK)Chris Stefan (LMCB, UK)Bojan Djordjevic (University of Sydney, Australia)Henning J. Jessen (Albert-Ludwigs-University, Germany)Pina Rose (University of Calabria, Cosenza, Italy)Steve B. Shears (NIEHS, USA)Marco Gaspari (University of Catanzaro, Italy)Gabriel Schaaf (University Tübingen, Germany)