News & Articles

NEWS RELEASE
Brussels May 2005

On 21-24 April 2005, Dr Isabella Screpanti, partner in Euro-Thymaide project, co-organised the first EMBO Workshop on Notch signalling in development and cancer.

This meeting gathered several scientists who study this pathway in cell differentiation and cancer.

The workshop focused on the biology of Notch signalling. Notch receptors are among the critical integrators of cell fate that control differentiation decisions during embryonic development, during cell maturation processes in post-natal animals and during carcinogenesis. The processes regulated by Notch receptors regulate phenomena as disparate as neurogenesis, T-cell activation and the survival of numerous types of neoplastic cells.

The investigators working on Notch worldwide have never had the opportunity to participate in a common meeting and share insights. This is largely due to the fact that the field includes scientists with different interests, from invertebrate embryologists to cancer biologists.
The main objective of this workshop was to bring together scientists who have been working on this crucial regulatory network from different perspectives.

Dr Isabella Screpanti, co-organiser of the event is Full Professor of General Pathology and Head of the Laboratory of Molecular Pathology at the Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.

As partner in the Euro-Thymaide project, Dr Isabella Screpanti commented the workshop:  

“The main aim of the EMBO workshop on Notch signalling in development and cancer was exactly to bring together investigators with diverse interests in order to share insights and possibly establish new collaborations. More that 100 scientists, many of them being young PhD students and post-docs, coming from different European and non European (U.S. and Asian) countries met in this workshop in a friendly and relaxed ambience and everybody had the opportunity to talk with the most important Researchers on the Notch field.

The different topics related to the Notch signalling pathway were treated in the Lecture Sessions and many interesting results were discussed during the Poster Session.”  

What is Notch signalling and what is the importance in autoimmune diseases ?

Notch is a cell surface receptor that was first identified in the fruit fly, where it plays an important role in determining the developmental fates of dividing cells. In the early 1990s, the human equivalents to the fruit fly Notch and Notch Binding Proteins were discovered. The Notch receptors are also present on the surface of T-cells, the cell type that is central to coordinating antigen-specific immune responses. Several recent scientific reports demonstrated that Notch signalling pathway is involved in the differentiation and function of T lymphocytes, including the subsets responsible of immune response regulation.

What is the Euro-Thymaide project and how Notch signalling cell interactions can help in understanding auto-immune diseases ?

The Euro-Thymaide project is the first European Research Integrated Project (IP) developing a novel approach of autoimmunity management by exploring the major biological functions of the thymus. The thymus is an organ located just behind the breastbone, that is responsible for the development of T lymphocytes, the type of white blood cells ensuring cellular immunity.
The thymus is the site for generation of T-cell diversity against the world of infectious non-self antigens, while it also programs central self-tolerance, i.e. the inability of T-cells to attack the components of the host.
The discovery of the intrathymic expression of a great number of tissue-specific antigens has revolutionized our knowledge of the mechanisms underlying the establishment of immune self-tolerance and the development of autoimmune diseases. Many tissue-specific self-antigens are presented to T cells during their differentiation in the thymus. If a developing T cell recognizes any of these antigens, it will be censored, or programmed to death, according to a process called clonal deletion.
T cells that survive this process will be tolerant to most of self-proteins. In addition the thymus is responsible for the generation of self-specific regulatory T cells that inactivate in periphery self-reactive T cells having escaped the thymus censorship.

Dr Isabella Screpanti, partner in the Euro-Thymaide project, is studying the implication of Notch3 signalling mechanisms in T-cell development and its relevance in the control of autoimmune diseases. Indeed, Notch3 transgenic mice were demonstrated to be resistant to the development of experimentally induced autoimmune diabetes.

Twenty-three partners are collaborating in EURO-THYMAIDE consortium to understand the mechanisms of autoimmunity resulting from the impairment of thymus-dependent central self-tolerance.

We can expect that this unique cross-border research network which involves academic research groups, hospitals and SMEs from 12 Countries can rapidly lead to new insights into mechanisms of autoimmune diseases, and will concurrently provide an unique platform for innovative diagnostics and for disease-specific therapies.

Type 1 diabetes is the first prototypic target of the EURO-THYMAIDE project.

References:   www.eurothymaide.org
                     w3.uniroma1.it/embo_notch
  
This project is supported by funding under the Sixth Research Framework Programme of the European Union. The University of Liege is the coordinator of the project.