NOTCH AND POLARITY

Modulation of the Notch receptor activity through the regulation of the epithelial apical-basal polarity in Drosophila melanogaster

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 Obiettivo del progetto (Objective)

'Several lines of evidence suggest an interplay between apical-basal polarity (ABP) and Notch (N) signaling in epithelia. Available data indicate that modulation of N signaling can occur through both direct regulation of the activity and mislocalization of either the receptor or the ligand. The purpose of this project is to understand how N activity can be modulated by differential regulation of apical-basal components or, in general, subcellular domains. A genetic screen among genes involved in ABP, ranging from regulators of vesicular trafficking or protein sorting to polarity regulators themselves, will help us identify the components underlying this modulation. Further genetic analysis together with molecular biology and biochemistry studies will help understand the molecular mechanisms of N activity modulation by ABP. Both ABP regulators and N pathway members have been shown to be involved in crucial events during development and tissue homeostasis, such as control of epithelial integrity and cell division, that, when distorted, can lead to tissue overgrowth and eventually cancer. Nevertheless, the molecular mechanisms underlying these processes are very poorly understood. This project will help shed light on these mechanisms.'

Introduzione (Teaser)

There's so much more to tough diseases than meets the eye, particularly at a molecular level. Identifying minute signals in certain tissue types could help treat these illnesses.

Descrizione progetto (Article)

There are numerous ways to study dangerous diseases such as cancer. One of these is to examine body tissue types called epithelia. This type of tissue is regulated by many different factors at the sub-cellular level. Although they play a key role in epithelial integrity, the molecular mechanisms underlying tissue regulation are poorly understood.

A lot of communication or signalling goes on in epithelial tissue, sometimes leading to overgrowth of tissue or even cancer. Understanding these signalling mechanisms is very important in treating implicated diseases.

Funded entirely by the EU, the NOTCH and Polarity project was named after two specific types of signalling mechanisms that are implicated in cancer and tissue overgrowth. The project aims to understand how both of these are involved in tissue homeostasis, such as control of epithelial integrity and cell division.

Rigorous laboratory tests have been undertaking on fruit flies or drosophila, using advanced digital analysis and images to understand the signalling process in epithelia. Close monitoring and documentation has already started unveiling the secrets of signalling and the role they play in diseases. For one, this is expected to reveal a key set of genes involved in the regulation of signalling mechanisms or 'pathways'.

Some of these pathways have been linked to Alzheimer's disease, different congenital diseases and malignancies such as leukaemia. Once these pathways and mechanisms are understood, the results will help design treatment strategies for these ailments. More concrete results are set to emerge at the conclusion of this project by the end of 2011.