Objective
Following initiation of protein synthesis, the nascent polypeptide must journey through the exit tunnel of the ribosome. Although this has typically been deemed a passive process, it is established that certain peptide sequences interact with rRNA components and ribosomal proteins lining the walls of the tunnel to bring protein synthesis to a complete halt. In many cases, translational arrest is dependent upon the presence of a small cofactor – such as an amino acid or an antibiotic – acting in concert with the specific peptide being synthesized.
In order to gain a deeper insight into the process of nascent chain-mediated translational arrest, I propose to focus on two complementary objectives:
First, I will obtain high-resolution structures of ribosome nascent chain (RNC) complexes by X-ray crystallography in order to understand the mechanistic aspects of this process. Current strategies for preparing RNC complexes rely on cell-free expression systems and produce samples of varying quality and unknown stoichiometry. Here, I propose to prepare peptidyl-tRNAs by attaching chemically synthesized peptides onto tRNAs expressed in vivo, using small RNA enzymes known as a flexizymes. Peptidyl-tRNAs obtained in this manner will be added to the ribosome in trans to obtain RNC complexes, thereby sidestepping some of the problems that result from ribosomal peptide synthesis in cis.
Second I will explore the functional diversity of nascent chain-mediated arrest by developing an in vitro selection/evolution method that will enable the identification of cis-regulatory nascent peptides capable of inhibiting the ribosome with the help of small molecules. By integrating the structure and sequence data obtained from our studies, we will develop a predictive algorithm for identifying regulatory peptide sequences within genomic data and we will begin to assess the biological extent and distribution of nascent chain-mediated events in a systematic manner.
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 earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences genetics RNA
- natural sciences chemical sciences organic chemistry amines
- 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.
FP7-PEOPLE-2013-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
75654 PARIS
France
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.