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Molecular evolution of protease substrates involved in carcinogenesis by in vivo selection of retroviral display libraries

Objective

The transition from benign to malignant phenotype involves the protease-mediated breakdown of basement membrane surrounding a primary cancer, allowing cells to escape and initiate metastatic tumours. The complex proteolytic machinery responsible for this process is supplied and regulated by the invading cells and the stromal cells. This proposal describes highly innovative strategies based on molecular evolution of retrovirus peptide display libraries to determine the substrate specificities of these proteases under physiological conditions, to generate programmable retroviral targeting vectors selective for sites of tumour invasion and to clone novel tumour associated proteases. The project will facilitate the improvement of molecular evolution technologies, the understanding of tumour invasion and the development of anti-cancer therapeutics.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

CAMBRIDGE DRUG DISCOVERY HOLDINGS LIMITED
Address
Cambridge Science Park 10, Milton Road
CB4 0FG Cambridge
United Kingdom

Participants (3)

HOSPITAL UNIVERSITARIO CLINICA PUERTA DE HIERRO
Spain
Address
4,San Martin De Porres 4 Clínica Puerta De Hierro
28035 Madrid
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Address
Allée D'italie 46 Ecole Normale Supérieure De Lyon
69364 Lyon
PAUL-EHRLICH-INSTITUT, FEDERAL AGENCY FOR SERA AND VACCINES
Germany
Address
Paul-ehrlich-straße 51-59
63225 Langen