Objective
NF-kB is a family of transcription factors that coordinately control hundreds of genes involved in many steps of inflammatory processes, from microbial killing to cancer. When inflammatory stimuli hit the cell surface, NF-kB undergoes several cycles of nucleus-to-cytoplasm translocations, resulting in oscillations of nuclear NF-kB concentrations and activity.
At single cell level, live imaging and mathematical modeling suggest that NF-kB oscillations are selected over other non-oscillatory dynamics.
At population level there is significant heterogeneity, mainly due to cell asynchrony. Mathematical models reproducing population heterogeneity indicate absence of coupling between dynamics of individual cells. This behaviour is thought to be adaptive by enabling a wider multiplicity of responses, but this has not been tested. Moreover, due to collective heterogeneity, the link of NF-kB dynamics to gene expression in a tissue as a whole is far from being clear.
Analyses of mathematical models of the NF-kB system using my expertise on Nonlinear Dynamics and Chaos Theory showed that complex oscillatory population dynamics are possible. Furthermore, regimes for coherent collective behaviours (synchrony) can be found. These regimes entail the use of periodic stimulations with different intensities and/or periods, suggestive of acute and chronic inflammatory conditions.
My project proposes to mathematically explore and experimentally validate complex population dynamics. In vivo quantitative imaging of NF-kB dynamics in GFP-p65 knock-in cells upon repetitive stimulations will provide data to build models on NF-kB collective behaviours. Transcription profiles of synchronized cells will be incorporated into the model. By increasing our understanding on NF-kB collective dynamics, we expect to contribute to strategies for the control of diseases with a huge social impact, like septic shock, autoimmune diseases and cancer, in which the deregulation of NF-kB plays a pivotal role
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.
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences clinical medicine oncology
- natural sciences mathematics applied mathematics mathematical model
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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-IEF
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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
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.