Objective
Quiescin sulfhydryl oxidase (QSOX), which catalyzes disulfide cross-linking in proteins, is up-regulated in many tumor types. QSOX is the only disulfide catalyst to undergo regulated secretion from cells, but the biological role of the enzyme, its substrates, and its mechanistic link to cancer are obscure. In addition to determining the first X-ray crystal structures of QSOXs, we recently discovered that QSOX is required for incorporation of laminins into basement membrane extracellular matrix (ECM). Fibroblasts depleted of QSOX make defective ECM that fails to support adherence and migration of tumor-derived cells in co-culture, but ECM composition and cell migration are restored by supplying recombinant QSOX exogenously. Our observations suggest a role for QSOX in building a microenvironment favorable for tumor cell survival and migration. We are motivated by a number of observations to expand our studies of QSOX enzymes. First, QSOX is ideally suited for single-molecule fluorescence resonance energy transfer experiments, which will shed light on hitherto invisible steps in the QSOX reaction cycle. Second, we have evidence for additional functions of QSOX with intriguing links to lipid metabolism and lipid storage diseases, and we are compelled to discover the pathways involved. Third, the modulation of tumor/stromal interactions is a promising direction for anti-metastatic cancer therapy, so the QSOX inhibitors we are developing may find use in the clinic as well as in the laboratory. Fourth, the complex QSOX expression patterns in developing and adult mammals prompted us to generate a conditional QSOX knockout mouse with which to explore QSOX function in vivo. In consolidating my laboratory, I will continue to rely heavily on my strengths as a structural biologist while pushing forward the frontier of our understanding of oxidative protein folding and assembly in cell and matrix biology, a fascinating subject that spans the Angstrom to the organism.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- engineering and technology materials engineering crystals
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
ERC-2012-StG_20111109
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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.
Host institution
7610001 Rehovot
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.