Istituto di Cristallografia - CNR
Ricercatore

Paoletti Francesca

Trieste

Education and training

04/04/2006 Awarded the PhD in Structural and Functional Genomics from SISSA (Scuola Internazionale Superiore di Studi Avanzati – Trieste). The PhD is equivalent to the Italian “Dottorato di ricerca in Biologia” according to the Statute of SISSA, Art.18, comma 3 (G.U. no. 62, 15.03.2001).

Thesis Title: Structural and functional insights into the biological function of mouse proNGF

Supervisors: prof. A.Cattaneo (SISSA), dr. Doriano Lamba (CNR).

External examiner: prof. M.Chao (New York University).

November 2001 Italian “State Exam” for the professional habilitation in Chemistry (official Chemist).

Università degli Studi di TRIESTE

13/07/2001 Laurea” degree (110 on 110 cum laude) in Chemistry at the University of Trieste

Thesis Title: “Fluorescence molecular probes for the imaging of local protein synthesis in living cells”,

Supervisors: professors G.Manzini (Univ. Trieste) and A.Cattaneo (SISSA).

Professional Experience

01/12/2022 – present

Researcher (Ricercatore III livello) Institute of Crystallography, CNR

Secondary Unit of Trieste

01/11/2017 – 30/11/2022

Research Assistant Professor (znanstvena sodelavka) at the National Institute of Chemistry, Ljubljana (Slovenia). Department D01 – Laboratory for molecular structural dynamics, Group of Prof. Dr. Simona Golič Grdadolnik

Main Research topic: Investigation of the interactions between proteins and small ligands of pharmaceutical interests by mean of biophysical techniques (NMR, SPR, FT-IR, MD)

January 2012 – November 2022 Guest scientist at U.O.S. Trieste, IC-CNR, group of Dr. Doriano Lamba.
13/03/2017 – 19/08/2017

Maternity leave

17/11/2016 – 16/06/2017

Teacher (Science, chemistry, biology) at the High School (Liceo Scientifico) “Galileo Galilei”, Trieste, Italy

01/09/2014 – 31/08/2016

Research Fellow (Assegno di Ricerca) at Scuola Normale Superiore (Pisa) on the European Project PAINCAGE (UE14PAIN FP7-HEALTH-2013-INNOVATION-1 PAINCAGE “The NGF system and its interplay with endocannabinoid signalling, from peripheral sensory terminals to the brain: new targets for the development of next generation drugs for neuropathic pain”).

16/01/2014 – 21/06/2014

Maternity leave

23/05/2008 – 31/07/2014

Research Fellow at Fondazione EBRI – Rita Levi-Montalcini, Roma. Research group: Neurotrophic Factors and neurodegenerative Diseases. Group Leader: Prof. Antonino Cattaneo

01/06/2011 – 31/10/2011

Guest scientist at National Institute for Medical Research (NIMR) – London, UK (Research group of Prof. Annalisa Pastore) with a Royal Society – Accademia Nazionale dei Lincei Fellowship

29/08/2011 – 29/09/2011

Guest Scientist at the University of Helsinki, Institute of Biotechnology, in the Group of Dr. Hideo Iwai (Biomolecular NMR & Protein Engineering)

20/12/2009 – 28/02/2010

Guest scientist at National Institute for Medical Research (NIMR) – London, UK (Research group of Prof. Annalisa Pastore) with EMBO Short term fellowship

13/11/2006 – 16/05/2008

Post-doctoral fellow at Fondazione EBRI – Rita Levi-Montalcini, Roma. Research group: Neurotrophic Factors and neurodegenerative Diseases. Group Leader: Prof. Antonino Cattaneo

15/02/2006 – 31/10/2006

Post-doctoral fellow at SISSA (Scuola Internazionale Superiore di Studi Avanzati), Trieste – Neurobiology Sector

09/11/2005 – 09/01/2006

Fellow at SISSA (Scuola Internazionale Superiore di Studi Avanzati), Trieste – Neurobiology Sector

01/11/2001 – 31/10/2005

Doctoral fellow at the PhD program in structural and functional genomics at SISSA, Trieste – Neurobiology Sector.

01/10/2004 – 15/03/2005

Visiting graduate student at the Institute for Protein Biotechnology of the Martin Luther University, Halle-Wittenberg – Halle (Saale), Germany, with EMBO Short term fellowship. Research group: Prof. Dr. Elisabeth Schwarz

22/05/2001 – 30/09/2001

Undergraduate fellow at SISSA (Trieste) – Biophysics Sector

The main research interest is related to the biophysics and structural biology of the proteins of the neurotrophin family. In particular, the focus of the work is on the structure/function relationship between the neurotrophins, their receptors and other interacting partners. Among these, a set of specific antibodies and their possible applications in neurodegeneration, as well as a set of small ligand interactors, which might be explored as potential pharmaceutical agents.

The main goal is achieved through complementary techniques: NMR, solution x-ray scattering (SAXS), protein crystallography, surface plasmon resonance (SPR) and molecular modelling.

One central topic has been on the structural study of proNGF, the natural precursor of NGF, the prototype of the neurotrophin family. proNGF was described to have a complementary and somewhat opposite biological role in comparison to mature NGF. We have been able to describe the first structural information on this protein, which is characterized by an Intrinsically Unstructured Domain (IUD). Its nature of intrinsically unstructured protein makes it interesting in its biological context, but at the same time complicates its in vitro characterization. For these reasons I concentrated more on the structural techniques in solution, and on NMR in particular.

As a complement to the structural studies, I perform protein-protein interactions investigations, with traditional immunoassays as well as using SPR. These are needed for a complete description of the molecular basis of the biological role of proNGF, especially in neurodegeneration and in the functional equilibrium between the precursor and the mature form of the protein. Moreover, SPR technique is applied to the development of novel immunoassays with diagnostic interest.

Recent work concentrated also on molecular aspects of neurotrophins, with a more direct interest to diagnostic/therapeutic aspects.

Most recently I focused more on dynamical aspects of the interactions of proteins and small ligands of potential pharmaceutical interest. The research goal is achieved using complementary techniques, namely solution NMR, vibrational spectroscopies, molecular dynamics, as well as protein-protein interaction studies via Surface Plasmon Resonance and Isothermal Titration Calorimetry.

Prof. Simona Golic Grdadolnik (Laboratory for molecular structural dynamics – Theory Department, National Institute of Chemistry, Ljubljana, Slovenia)

Prof. Franci Merzel (Laboratory for molecular structural dynamics – Theory Department, National Institute of Chemistry, Ljubljana, Slovenia)

Prof. Joze Grdadolnik (Laboratory for molecular structural dynamics – Theory Department, National Institute of Chemistry, Ljubljana, Slovenia)

Prof. Antonino Cattaneo (Scuola Normale Superiore, Pisa, Italy)

Dr. Francesca Malerba (Fondazione EBRI, Roma, Italy)

Dr. Anton Calabrese (School of Molecular and Cellular Biology, Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK)

Dr. Petr Konarev (A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre, Russian Academy of Sciences, Moscow, Russia)

Distinct conformational changes occur within the intrinsically unstructured pro-domain of pro-Nerve Growth Factor in the presence of ATP and Mg2+

Paoletti, Francesca; Covaceuszach, Sonia; Cassetta, Alberto; Calabrese, Antonio N. N.; Novak, Urban; Konarev, Petr; Grdadolnik, Joze; Lamba, Doriano; Grdadolnik, Simona Golic

Protein science (Print) (2023) [IF=6.993]