Giovanna Musco
Giovanna Musco
affiliation: San Raffaele Scientific Institute
research area(s): Cell Biology, Computational Biology
Course: Cell and Molecular Biology
University/Istitution: Università Vita-Salute San Raffaele
1992 Laurea in Chemistry (University of Milano)
1993-1995 DAAD Fellow at EMBL, Heidelberg
1995-1998 Pre-doctoral Fellow at EMBL, Heidelberg
1998 PhD defense at the Freie Universitaet of Berlin

Professional experiences

1998-2000 Research associate in the NMR laboratory of Dr.A. Pastore,Division of Molecular Structure, National Institute for Medical Research, Mill Hill, London
2000-2001 EMBO fellow at the Biozentrum of the University of Basel in the group of Prof. Stephan Grzesiek
2001-present Head of Biomolecular NMR Laboratory S. Raffaele Scientific Institute
2001-2007 Assistant Telethon Scientist c/o S. Raffaele Scientific Institute
2008-present Associate Telethon Scientist c/o S. Raffaele Scientific Institute
The scientific interest of the group is focused on the structure determination in solution of proteins involved in human diseases by means of Nuclear Magnetic Resonance. This technique is particularly suited to study protein domains (50-200 aminoacids) and their interactions with other ligands (protein, small molecules, other domains). NMR studies of macromolecular complexes can give unique information on the interaction surface, on the strength of the interaction and on the dynamic properties in solution of the complex.

We study the structure and dynamics of biomolecular complexes in solution by nuclear magnetic resonance (NMR) spectroscopy in combination with a wide range of biochemical and biophysical and computational techniques. The laboratory focuses on studying: 1) The interaction of small drugs with extracellular cellular receptors; and 2) Structural and dynamic characterization of novel chromatin-interacting modules. In particular we are studying the protein AIRE (Autoimmune Regulator), which is involved in the genetic disease Autoimmune Polyendocrinopathy Ectodermal distrophy.
We have recently started a new line of research dedicated to NMR based Metabolomics. Metabolomics is a newly emerging field of ‘omics’ research aiming to give an analytical description of the metabolites in complex biological samples and to describe the global, dynamic metabolic response of living systems to biological stimuli or genetic manipulation
Garcia-Manteiga JM, Mari S, Godejohann M, Spraul M, Napoli C, Cenci S, Musco G, Sitia R. (2011) Metabolomics of B to plasma cell differentiation J Proteome Res. In press

Spitaleri A, Ghitti M, Mari S, Alberici L, Traversari C, Rizzardi GP, Musco G. (2011)
Use of metadynamics in the design of isoDGR-based αvβ3 antagonists to fine-tune the conformational ensemble Angew Chem Int Ed Engl. 50(8):1832-6.

.Mollica L, Morra G, Colombo G, Musco G. (2011) HMGB1-carbenoxolone interactions: dynamics insights from combined nuclear magnetic resonance and molecular dynamics
Chem Asian J. May 2;6(5):1171-80.

Chignola F, Mari S, Stevens TJ, Fogh RH, Mannella V, Boucher W, Musco G. (2011)
The CCPN Metabolomics Project: a fast protocol for metabolite identification by 2D-NMR. Bioinformatics.27(6):885-6.

Wodarczyk C, Distefano G, Rowe I, Gaetani M, Bricoli B, Muorah M, Spitaleri A, Mannella V, Ricchiuto P, Pema M, Castelli M, Casanova AE, Mollica L, Banzi M, Boca M, Antignac C, Saunier S, Musco G, Boletta A. (2011) Nephrocystin-1 forms a complex with polycystin-1 via a polyproline motif/SH3 domain interaction and regulates the apoptotic response in mammals. PLoS One. 2010 Sep 14;5(9):e12719.

Mari S, Invernizzi C, Spitaleri A, Alberici L, Ghitti M, Bordignon C, Traversari C, Rizzardi GP, Musco G. (2011) 2D TR-NOESY experiments interrogate and rank ligand-receptor interactions in living human cancer cells. Angew Chem Int Ed Engl. 49(6):1071-

Chignola F, Gaetani M, Rebane A, Org T, Mollica L, Zucchelli C, Spitaleri A, Mannella V, Peterson P, Musco G (2009) The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation. Nucleic Acids Res. 37(9):2951-61.

Musco G, Peterson P (2008) PHD finger of autoimmune regulator: an epigenetic link between the histone modifications and tissue-specific antigen expression in thymus.
Epigenetics. 3(6):310-4.

Spitaleri A, Mari S, Curnis F, Traversari C, Longhi R, Bordignon C, Corti A, Rizzardi GP, Musco G. (2008) Structural basis for the interaction of isoDGR with the RGD-binding site of alphavbeta3 integrin. J Biol Chem. 283(28):19757-68.

Org T, Chignola F, Hetényi C, Gaetani M, Rebane A, Liiv I, Maran U, Mollica L, Bottomley MJ, Musco G, Peterson P (2008) The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. EMBO Rep. 9(4):370-6.
Project Title:
Structural and functional studies of SP140-PHD finger
The plant homeodomain (PHD) finger is a conserved zinc-binding domain found in many
chromatin-remodeling proteins. Mutations in the PHD finger are linked to human diseases,
including cancer, mental retardation, and immunodeficiency (1). Different functions have been
ascribed to the PHD finger module, ranging from "effector" that binds specific epigenetic marks on
histone tail, to E3 ligase in sumoylation reactions (2). PHD fingers work in a combinatorial fashion
with other nuclear interacting domains such as Bromo-domains. The leukocyte-specific protein
Sp140 contains a tandem PHD-Bromo-domain. Sp140 is implicated in immunodeficiency disorders,
and hematological malignancy, however the molecular mechanisms dictating its function are still
unknown (3).
The main goal of this project is to gain insights into the structure function-relationship of SP140
exploring the role of SP140-PHD finger and Bromo-domain as possible epigenetic readers using
both biophysical (NMR, ITC, fluorescence) and biochemical approaches.
(1) Musco G, P Peterson (2008) Epigenetics 3,310-4 PHD finger of autoimmune regulator
(2)Sanchez R, Zhou MM] The PHD finger: a versatile epigenome reader. Trends Biochem Sci.
2011 Apr 20. [Epub ahead of print
(3) Granito A, Yang WH, Muratori L, Lim MJ, Nakajima A, Ferri S, Pappas G, Quarneti C, Bianchi
FB, Bloch DB, Muratori PPML nuclear body component Sp140 is a novel autoantigen in
primary biliary cirrhosis. Am J Gastroenterol. 2010 Jan;105(1):125-31.