Objective
"Gene expression studies rely on high throughput techniques, which do not take in account conceptual limits. I will overcome this situation by exploiting two biological facts. First, RNAs that are important in tissue function are a subset of the global mass, but are always associated with the ribosomal machinery and as such should be identified. Second, gene expression is the outcome of dynamic fluctuations that with time create a unique expression pattern. We need to dynamically label cell populations that undergo stress and follow them to generate a gene expression signature. To achieve my goal, I will consider: 1. Translational stress generated by viral infection or accumulation of misfolded proteins; 2. human CD4+ T lymphocyte subsets which are key to orchestrate immune responses; 3. EIF6 model of metabolic reprogramming.
1. Activation of eIF2alpha phosphorylation by viral infection generates a translational response in which silent mRNAs containing upstream ORFs (uORF) are translated. I will exploit this observation to construct the first in vivo reporter model of translational stress. We will label genetically cells that have translational stress, to identify all the changes that a single cell undergoes after viral infection/accumulation of undegraded proteins.
2. I will selectively sequence for the first time mRNAs and ncRNAs associated with the ribosomal machinery in human cells with a defined functional status.
3. Spectacular data have shown that translation factor eIF6 regulates tumorigenesis by inducing a profound metabolic reprogramming. This observation suggests that, in vivo, translation acts upstream of transcription. We will model how a short translational input results in a complex epigenetic change.
Significance: a revolution in finding biomarkers/drug targets. Generate a map of predictors of the process from stress to disease. Dscriminate biologically active sequences from background. Define how transient translation reshapes gene expression."
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
- social sciences political sciences political transitions revolutions
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics RNA
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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-2013-ADG
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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
20122 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.