Objective
Plasma cells are responsible for secretion of immunoglobulins (Ig) into the bloodstream, which constitute the humoral immune response. XBP-1 is a transcription factor necessary for the terminal differentiation of B cells into plasma cells. XBP-1 is required for the synthesis and the maintenance of high levels of Ig, and plays a critical role in setting the conditions for their assembly and secretion. Multiple myeloma (MM) is the cancer of plasma cells, and in most cases this cancer retains the capacity to secrete high levels of Ig. MM is impervious to conventional chemotherapies, and constitutes 2% of total deaths from cancer. Recent evidence shows that XBP-1 promotes survival of MM cells. Since XBP-1 is destroyed with a half-life of minutes, we shall explore the mechanisms responsible for its degradation, as factors that may promote MM survival. We shall express recombinant XBP-1, and study its degradation by the proteasome in a cell free assay. In addition, we will use an RNA interference screening to identify genes required for the degradation of XBP-1. Bortezomib is a newly approved drug for MM, which blocks the proteasome.
The reasons why MM shows remarkable sensitivity to bortezomib are unknown. Utilizing cells resistance to proteasome inhibition, we will strive to identify genes and biochemical pathways that confer resistance of MM to treatment with bortezomib. This study may identify novel targets and pathways for the therapy of MM, and provide better understanding of the regulation of XBP-1 levels.
The overall aim is to combat cancer by broadening the knowledge base on molecular mechanisms underlying chemotherapy resistance. In accordance with the IRG objectives, my proposal will implement and transfer to Europe the technology developed at the Whitehead Institute in Cambridge, Mass. USA, where I spent the last 5 years (postdoctoral training), and will strengthen the existing collaboration with Whitehead researchers.
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 biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
FP6-2004-MOBILITY-12
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Funding Scheme
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.
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
JERUSALEM
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.