I am interested in the functional roles of two classes of phosphate-rich molecules, inositol pyrophosphates and inorganic polyphosphates. I focus on two new protein post-translational modifications (PTM) mediated by these molecules, pyro- and polyphosphorylation, respectively. Pyrophosphorylation is the transfer of the beta phosphate of IP7 into a pre-phosphorylated serine residue within serine-rich acidic protein domains. I established the functional role of pyrophosphorylation in a mammalian system by demonstrating that pyrophosphorylation of the human AP3B1 negatively regulates the egress of Gag, the major structural protein of HIV-1. Moreover, I discovered and characterized polyphosphorylation, a new PTM in which orthophosphate chains are covalently attached to lysine residues. This modification is mediated by inorganic polyphosphates, linear chains of orthophosphate residues linked by phosphoanhydride bonds that can be 10-100s of phosphate in length and that are present in all kingdoms. I have determined that Topoisomerase is polyphosphorylated and that this modification negatively regulates its function to relax supercoiled DNA. The original studies were performed in budding yeast and at the present I am investigating how abundant this modification is in higher eukaryotes. I am also studying how is this modification regulated and determining its biochemical properties.
PhD, Plant Pathogen Interactions, Sainsbury Laboratory, John Innes Center, Norwich UK
BSc, Agricultural Engineering, Lisbon, Portugal
2015 | Best talk/poster presentation, "Cellular Functions of Phosphoinositides and Inositol Phosphates" meeting, Biochemical Society, University of Cambridge.
2015 | Best talk/poster presentation, "Inorganic polyphosphate (polyP) physiology" meeting, Biochemical Society, Charles Darwin House, London.
Medical Research Council
Light microscopy, Biochemistry