Single molecule investigation of nucleic acids free energy landscapes: Bringing together computational models and laser tweezer experiments

Objective

In the last decade the increasing ability in the manipulation of small systems has led to a flourishing of single molecule studies. Optical tweezers and atomic force microscopes are proving extremely versatile tools and they are currently enabling us to access the inner functioning of biomolecules at an unprecedented level of detail. In particular, in the vast scenario of emerging experimental applications made possible by these techniques, experiments of mechanical unfolding and refolding of proteins or RNA's hold particular promise as tools for the detection of folding intermediates and misfolded states. These alternative configurations correspond to local minima of the free energy of the molecule and their characterization is fundamental in order to understand the folding process as well as all large conformational rearrangement in biomolecules. They are however difficult to detect by means of traditional experiments of thermal or chemical denaturation because of the unavoidable averaging effects inherent in bulk techniques. Single molecule experiments circumvent this limitation and provide and efficient tool to locate the most relevant free energy minima accessible to the molecule. The objective of this research is to explore the free energy landscape of large functional RNA's such as riboswitches and ribozymes by a combined use of computational tools and mechanical stretching experiments. Especially we aim at characterizing all intermediate and misfolded states both from the thermodynamical and structural point of view. Particular care will be devoted to the investigation of the microscopic details of the transition between competing metastable minima of the free energy, thus helping elucidate the mechanisms of conformational plasticity in functional RNA's.

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.

• natural sciences biological sciences biochemistry biomolecules nucleic acids
• natural sciences biological sciences biochemistry biomolecules proteins
• natural sciences physical sciences optics microscopy
• natural sciences biological sciences genetics RNA
• natural sciences physical sciences optics laser physics

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Biomechanics
• Molecular biophysics
• Statistical physics

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

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.

• FP7-PEOPLE-IEF-2008 - Marie Curie Action: "Intra-European Fellowships for Career Development"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-IEF-2008
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.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator