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NOTCH SIGNALING IN DEVELOPMENT AND PATHOLOGY

Final Report Summary - NOTCHIT (NOTCH SIGNALING IN DEVELOPMENT AND PATHOLOGY)

Executive Summary:

NotchIT - Notch signalling in development and pathology

Summary description of the objectives of NotchIT

Eight partners from six different EU countries converged in NotchIT, a multi-site Initial Training Network, from January 2009 to December 2012. The overarching aim of NotchIT is to increase the knowledge of a key signalling mechanism, Notch, which is critical for normal development and, when deregulated, leads to a range of diseases.

NotchIT integrated the research and training activities of eight partners, who are leaders in Notch signalling and related fields, to specifically address three strategic issues, which are central to European science and health economy:

• To gain a deep understanding of the Notch signalling mechanism, to develop a state-of-the-art molecular tool box for Notch signalling and to disseminate this knowledge and reagents at a pan-European level in order to accelerate Notch research in Europe.
• To unravel the role of Notch signalling in differentiation and pathology, with the long-term aim to improve our capacity to steer stem cell differentiation and to correct aberrant Notch signalling in pathologies, ranging from leukemia to breast cancer and vascular disease.
• To explore new ways of controlling Notch signalling through pharmacological approaches with the aim to break new ground and to ultimately design new diagnostic and therapeutic protocols.

The training component in NotchIT has been deeply integrated within the research programme. The recruited researchers have worked in operationally diverse environments: Hospitals, universities, research institutes and industry. These experiences, combined with an integrated set of courses, workshops, meetings and cross-laboratory visits, provided excellent training opportunities, preparing them for professional positions in academia and industry.

Description of the work performed and main results achieved

The work performed during the four years of activity of NotchIT resulted in the following tangible outcomes:

Recruitment

14 Early-Stage Researchers (ESR), 4 Experienced Researcher (ER) and 1 Visiting Scientist have been recruited during the four years of the project. 11 of them were from 6 different European Countries, while 8 from 5 different extra-European countries (Australia, India, Serbia, Tunisia, USA). All recruited Researchers were involved in specific research projects and most of them were performing their research under close day-to-day supervision of staff scientists working in the different labs. All of them attended periodic lab and journal club meetings organized in the respective labs; all of them could participate in seminars and NotchIT training organized by the various NotchIT Partner Institutions. Most of them participated in different International scientific meetings, outside of NotchIT. Finally, many of the recruited ESR have been enrolled in PhD programs of NotchIT Partner Institutions and got or will get soon PhD degrees.

Training courses

15 training courses have been held and the fellows of the NotchIT network benefited greatly from the training program and from inter-laboratory visits. The training network allowed them to enhance old and establish new contacts across Europe. While directly working on NotchIT project, the recruited researchers have had the opportunity to follow seminars and lab meetings related to many other research projects carried out in the host Institutions.

Theoretical and practical courses have been organized, focusing on different theoretical, practical and ethical aspects in the area covered by the NotchIT project. Significant attention was paid to translational aspects related to possible applications of experimental results obtained on different experimental models to understanding of mechanisms underlying human diseases and possible therapy approaches. Courses centered on intellectual property aspects and routes for commercialization of basic research findings have also been organized in the consortium.

Scientific results and their potential impact and use

Notch signaling is a signalling mechanism critical for normal development and frequently deregulated in disease. In NotchIT, several very important scientific results have been obtained that shed new light on the role of Notch in various contexts and have been published in leading scientific journals and presented at international meetings. During the four years of the project, NotchIT partners, together with the recruited researchers, identified novel Notch-related molecular and cellular mechanisms involved in hematopoiesis, normal development of brain, hearth and muscle. NotchIT provided novel insights into the role of deregulated Notch signalling in human diseases, including familial stroke, breast cancer and leukemias. Novel therapeutic approaches, targeting deregulated Notch signaling, have been studied in different experimental models. The results in the project will increase the understanding of pathophysiology of several diseases and potentially will lead to developing new therapeutic approaches.

The possibility for NotchIT fellows to be trained in leading laboratories in Notch research in the beginning of their careers, combined with the cross-laboratory interactions, has provided them with excellent opportunities to head start their career paths and to contribute to further advancing academic and industrial research in Europe.

Project Web site

A project website has been created (www.notchit.eu) illustrating and promoting the NotchIT project. It contains informations about NotchIT partners and research fellows, including individual profiles (e.g. research interests, possible previous research experience, photo, email address, host organisation and the duration of fellowship). The site, which is frequently updated, gives visibility to the NotchIT project itself and to the fellows, allowing them to share their professional profiles with potential future employers. The website also contains a calendar of the training courses and general information on the project.

Project Logo

The project website is introduced by the original logo specifically created for NotchIT project (see the attached file)

Contact details

Scientific Coordinator, Prof. Isabella Screpanti
Department of Molecular Medicine
Sapienza University of Rome
Viale Regina Elena, 291
00161 Roma, Italy
Tel. +39-06 44 70 08 16
e-mail: isabella.screpanti@uniroma1.it