Objective
Lymphoid organ development results from a complex interplay of genetically controlled molecular and cellular networks. While most of the molecular mechanisms underlying lymphoid organogenesis remain unknown, recent findings demonstrate that homeodomain transcription factors are essential to these processes. One such homeoprotein is Pbx1 that binds DNA with a subset of Hox proteins, including the Hox11 oncoprotein aberrantly accumulated in T-cell acute leukemia. Like Hox11, Pbx1 was originally isolated as a proto-oncogene in pre-B-cell leukemia. By using knockout mouse models, cellular and biochemical approaches, we demonstrated that Pbx1 and Hox11 loss of function mutations result in reduced spleen mesenchymal proliferation accompanied by spleen agenesis. Furthermore, we established a genetic network regulating spleen mesenchymal expansion and demonstrated the essential role of the Pbx1-Hox11 transcriptional pathway during spleen ontogeny. Although a few Pbx1- and Hox11-targets have been identified, the growth-related transcriptional networks orchestrated by these homeoproteins during lymphoid organogenesis remain mostly unknown. Our research objective is to perform a comprehensive search for direct Pbx1 and Hox11 growth-related target genes and de-convolute the global gene regulatory network governed by these homeoproteins during lymphoid organogenesis. We plan perform a comprehensive analysis to uncover genes differentially expressed in wild type and single Pbx1 and Hox11 mutant embryonic spleens. Next, our studies will focus on those direct downstream targets that are likely responsible for the cellular proliferation/differentiation defects observed in these mutant spleens. We will validate these potential targets by performing in situ hybridization and immunohistochemistry analysis on embryonic spleen sections and further corroborate whether Pbx1 and/or directly control these targets by chromatin immunoprecipitation and transcriptional assays.
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- engineering and technology electrical engineering, electronic engineering, information engineering information engineering telecommunications telecommunications networks mobile network
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology leukemia
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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.
FP7-PEOPLE-2007-4-3-IRG
See other projects for this call
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
20132 MILANO
Italy
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.