Objective
The progression of cells through mitosis is tightly regulated to ensure the integrity of chromosomal transmission and cell division. The proper orchestration of mitotic progression is controlled by the balanced activity of mitotic kinases and counteracting phosphatases. Misregulation of these controls can be detrimental causing loss of entire chromosomes and aneuploidy. Considering that mitotic kinases are only expressed in actively dividing cells, targeting these kinases for cancer management is highly desirable. To this end, we are validating the mitotic kinase Greatwall Kinase (Greatwall) as a target for cancer therapy. Initial studies show that siRNA knockdown of Greatwall leads to rapid cell death in a number of transformed cell lines. Surprisingly, we found that untransformed RPE cells with low Greatwall protein and mRNA levels remained unaffected after Greatwall knock down. Moreover, Greatwall levels fluctuate dramatically among different cancer cell lines and are generally low in non-transformed tissues. Seminal studies using Xenopus egg extracts and drosophila larvae show that Greatwall has an important role in the cell cycle control of rapidly dividing embryonic cells and it is possible that some tumor cells have reverted back to this state of dependency on Greatwall. This makes Greatwall even more promising as an anti-cancer agent as its activity is dispensable in somatic cells but critical to the survival and proliferation of cancer cells. In light of these findings, I aim to pursue target validation studies with Greatwall, elucidate synergistic effects using known mitotic kinase inhibitors, and work closely with a team of medicinal chemists to characterize novel small-molecule Greatwall modulators. Nonspecific interactions between known mitotic kinase inhibitors and normally dividing cells often lead to unwanted side-effects. Targeting Greatwall provides an opportunity to circumvent this undesirable outcome and advance translational research.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
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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.
FP7-PEOPLE-2011-IIF
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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
BN1 9RH Brighton
United Kingdom
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.