Objective
Background: Retrovirus-induced tumours acquire in time increasing numbers of proviruses in their genome, which are required for the activation of additional (onco)-genes that contribute to tumour progression.
Insertional mutagenesis in oncogene-bearing transgenic mice is therefore a powerful strategy to identify genes that cooperate with the transgene in the formation and progression of tumours.
In the host lab, the Tiam1 gene was identified by retroviral insertional mutagenesis in combination with selection for invasive T-lymphoma cells. The Tiam1 gene was also frequently activated (>70%) in T-lymphomas induced by retroviral infection of tumour-prone transgenic Em-Pim1 mice.
Tiam1 thus seems to play a critical role in the initiation and progression of T-lymphomas. Tiam1 encodes an activator of the Rho-like GTPase Rac. Rho-GTPases regulate a wide variety of cellular processes including cytoskeletal rearrangements, cell migration, and gene transcription.
Objectives: In this proposal we want to uncover the signalling pathways that act downstream or parallel of Tiam1and that are essential for lymphomagenesis in vivo. To this end, we propose to perform an insertional mutagenesis screen on tumour-prone transgenic Eµ-Pim1 mice in a Tiam1-deficient background.
Strategy: T-lymphomas will be induced in Tiam1-deficient Eµ-Pim1 mice by Moloney Murine Leukemia virus (M-MuLV) infection. Targeted genes will be identified using improved Splinkerette PCR. The sequence data will be mapped and used to identify common insertion sites. The involvement of the gene targets in lymphomagenesis will be confirmed by in vitro and in vivo analyses.
Results: The obtained results are expected to give insight into the downstream signalling pathways of Tiam that are acting in the development and progression of lymphomas in vivo. These gene products may turn out to be targets for the development of diagnostic tools or novel anti-cancer therapies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
Netherlands
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