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Partner 2 - Università degli Studi di Milano

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University and research group information

The University of Milan, born in 1924, is one of the most prestigious academic institutions in Italy, with 9 Faculties, 47 Departments and 48 Institutes, counting approximately 2.500 units of teaching and research staff, 2.000 units of non-teaching staff, and 65.000 students, with on average 15.000 new enrollments every year, spread over more than 70 degree programmes. When focusing on the field of scientific research, the University of Milan houses three Centers of Excellence, 16 Interdepartmental and Intradepartmental Centers, participates in seven Interuniversity Centers, and cooperates with several national research institutes, thus proving extremely active in keeping up-to-date with recent technologies.
 
Among the Centers of Excellence housed by the University of Milan, CEND (Center of Excellence on Neurodegenerative Diseases) is directed by Adriana Maggi, group leader of Partner 2. CEND was born as a new platform for the coordinated study of the molecular mechanisms which lead to the onset and progression of neurodegenerative disorders in the elderly. To reach this purpose, about 120 researchers work in a coordinated fashion to develop novel reporter systems suitable to dissect the molecular pathways involved in the aetiology of central nervous system diseases.
 
The strong vocation towards the application of novel multidisciplinary technologies to science has made CEND becoming member of several European Programs (EMIL, DiMI) aimed at the development of innovative research and diagnostic procedures and is now placing its expertise at CASCADE’s disposal for the purposes of the workpackages in which CEND is involved.

Contribution to CASCADE

Partner 2 is leader of Work package 14 – Functional Screening. The main purpose of the work package is to provide novel animal models, which are proving a more and more valuable instrument in the research field devoted to the identification and analysis of environmental contaminants. One of the main advantages in the use of animal models in this research field is the possibility to detect the effects of the exposure to environmental contaminants in time and at low doses, which mostly reproduces what commonly happens in human exposure to pollutants.

 

The work package copes with the problems associated to the generation of transgenic animals, which, to be reliable, must satisfy important requirements, first of all, the ubiquitous expression of the transgene, in order to allow the evaluation of the effects of the pollutant under examination on every district of the organisms. To overcome this limitation, Partner 2 developed a construct to be used for transgenesis which vehicles the gene of interest flanked by the so-called “insulator sequences”, which make the exogenous gene being expressed in a  ubiquitous fashion, independently from the position effects typical of the region of the chromatin were it was integrated. This reporter mouse allows to follow in time and “in vivo” the activity of the estrogen receptors, and therefore to detect estrogenic effects of the substances studied in the frame of the workpackage.

 

The contribution of Partner 2 to CASCADE therefore stems from the pharmacological characterization of the newly generated model to go on with the toxicological evaluation of environmental contaminants in both adult animals and during embryonic development.

Representative scientific articles as relevant to CASCADE

  1. Maggi A and Ciana P. Reporter mice and drug discovery and development. Nat Rev Drug Discovery, 2005;4:249.
  2. Cuzzocrea S, Mazzon E, Dugo L, Genovese T, Di Paola R, Ruggeri Z, Vegeto E, Caputi AP, Van De Loo FA, Puzzolo D, Maggi A. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice. Endocrinology, 2003;144:1098.
  3. Ciana P, Raviscioni M, Mussi P, Vegeto E, Que I, Parker MG, Lowik C, Maggi A. In vivo imaging of transcriptionally active estrogen receptors. Nat Med, 2003;9:82.
  4. Di Lorenzo D, Villa R, Biasiotto G, Belloli S, Ruggeri G, Albertini A, Apostoli P, Raviscioni M, Ciana P, Maggi A. Isomer-specific activity of dychlorodyphenyltrichloroethane with estrogen receptor in adult and suckling estrogen reporter mice. Endocrinology, 2002;143:4544.
  5. Ciana P, Di Luccio G, Belcredito S, Pollio G, Vegeto E, Tatangelo L, Tiveron C, Maggi A. Engineering of a mouse for the in vivo profiling of estrogen receptor activity. Mol Endocrinol, 2001;15:1104.