Brunella Franco FTELE.IGM -  Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Fondazione Telethon, Rome, Italy

Institute description
The Telethon Institute of Genetics and Medicine (TIGEM) is part of a science and technology research complex that is also home to the CNR’s Institutes of Genetics and Biophysics (IGB) and of Protein Biochemistry (IBP). The Institute comprises 13 independent research groups with over 170 members including graduate students, post-doc fellows, technicians and administration. Research at TIGEM focuses on the study of rare diseases. Research approaches include cell biology, functional genomics, systems biology and gene therapy. Research activity at TIGEM is supported by several core facilities (AAV vector Core, Microscopy and Imaging Core, Cell Culture and Cytogenetics Core, Behavioural Core, Transgenic and Knock-out Core Facility, Bioinformatics Core) that provide state-of-the art technology as well as “house-keeping” assistance. The Institute is fully equipped to perform molecular and cellular biology experiments. An animal facility (600 sqm) is located on the ground floor of the laboratory building. TIGEM will serve as scientific and administrative coordinator.

Group leader
Brunella Franco, MD, is Associate Professor of Medical Genetics at the Federico II University of Naples and Principal Investigator at TIGEM. Dr Franco has a long-standing interest in the study of the pathophysiology of rare diseases. Her research group identified the gene responsible for OFDI and generated the mouse model for this disorder. The characterization of the mouse model was the key to demonstrate that OFD is due to cilia dysfunction and definitely placed OFDI in the increasing number of genetic disorders associated to primary ciliary dysfunction.

The construct used to generate this mouse model contained the OFD allele flanked by Lox sites, which allow the conditional recombination of the gene by the Cre recombinase, allowing Dr Franco to generate a conditional allele in which OFD is specifically deleted in the genito-urinary tract. This conditional model will allow performing studies on the function of OFD1 and primary cilia in renal cyst development (WP1). Her group has also developed in vitro systems for OFD1 inactivation in cells (unpublished results), which are critical for the development of WP2. In addition, a two-hydrid screen in yeast performed in her laboratory (unpublished results) has led insight into novel OFD1 interactions, shedding light on the role of OFD1 (WP3). Preliminary results in Dr Franco’s lab indicate a possible role of OFD1 in Wnt signalling, sonic hedgehog and mTOR signalling and this will be further addressed in WP4 and WP5. The tools generated in Dr Franco’s laboratory will be important for the evaluation of potential therapeutic agents as described in WP6.

Role in the project
Coordinator for the grant, Workpackage Leader for WP1 and WP7, and Chair of the Plenary Meeting. Her laboratory is involved in all the workpackages (WP1-WP7) of the proposal.

Key personnel

Name	Title	Gender	Role/Expertise
Brunella Franco	Group leader	F	Coordinator, WPL for WP1 and WP7
Michèle Studer	Investigator	F	Generation and characterization of animal models
Diego di Bernardo	Engineer	M	Reverse engineering, modelling gene regulatory networks
Anna D’Angelo	Post-doc Fellow	F	Characterization Ofd1 mouse model
Roberta Tammaro	Technician	F	Project technical aspects
Mara Alfieri	Fellow	F	In vitro system to study role of Ofd1
Graciana Diez Roux	PhD	F	Project Manager
Barbara Zimbardi		F	Secretariat, Administrative Assistant
Luciana Borrelli	PhD	F	Project Administrator, Editor of EUCILIA website
Giampiero Lago	PhD	M	Webmaster

Key publications

Prattichizzo C, Macca M, Novelli V, Giorgio G, Barra A, Franco B (2008). Mutational spectrum of the Oral-facial-digital type I syndrome: a study on a large collection of patients. Hum Mutat 29: 1237-1246.

Giorgio G, Alfieri M, Prattichizzo C, Zullo A, Cairo S, Franco B (2007). Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with subunits of a chromatin remodeling complex. Mol Biol Cell 18: 4397-4404.

Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dolle P, Franco B (2006). Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet 38: 112-117.

Ferrante MI, Barra A, Truong JP, Banfi S, Disteche CM, Franco B (2003). Characterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant. Genomics 81: 560-569.

Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B (2001). Identification of the gene for Oral-facial-digital type I syndrome. Am J Hum Genet 68: 569-576.