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FP6

CIDNA Résumé de rapport

Project ID: 505669
Financé au titre de: FP6-NMP

Final Report Summary - CIDNA (Control of assembly and charge transport properties of immobilized DNA)

CIDNA was created with a view on opening new avenues in deoxyribonucleic acid (DNA)-based biophysics, biochemistry and biotechnology with special focus on high temporal and spatial resolution towards the mesoscopic and single-molecule levels. The objectives were to be approached by cooperation between 10 internationally recognised scientific partners and an industry partner active at the cutting edge of biotechnology.

CIDNA opened new areas in DNA science by its broad perspectives and its boundary-traversing approaches. These areas relate to the design and synthesis of tailored reporter molecules, and precisely controlled charge transfer pathways in DNA structures, rationalised and substantiated by computational modelling. Moreover, CIDNA contributed to a detailed understanding of folding and unfolding processes of DNA duplexes and its modifications. The necessary DNA modifications comprise base replacement or semicapping by aromatic molecules as well as backbone locking by restricting the mobility of the sugars (locked nucleic acid (LNA)).

On the basis of detailed understanding of active components studied in solution, CIDNA opened areas where novel DNA structures as well as large supramolecular architectures can be immobilised on solid supports and controlled in the ensemble and at the single-molecule level. Electrical field effects on the topology of DNA constructs and single-molecule conductivity in novel "switch" patterns were observed.

New kinds of synthetic DNA-based molecular systems with specific structures were a major CIDNA achievement. The modifications pertain to fluorescent and redox marker groups as well as multifarious pendant groups suitable for linking single- and double-strands to solid supports. Dye-labelled DNA and LNA containing double strands were instrumental for detailed studies of the charge transfer mechanisms. Their design, synthesis and structural characterisation held innovative discoveries per se.

The elucidation of the controversially discussed mechanisms of short-range charge injection and long-range charge transport through double-stranded oligonucleotides in solution were a CIDNA starting point and an area brought to blossom by CIDNA's interdisciplinary efforts. These successful studies involve design, synthesis, nuclear magnetic resonance (NMR) structural analysis, charge transfer dynamics, and computational modelling. The dynamics of purine oxidation initiated by semicapped rhodamine reveals two conformations, which differ in their electronic coupling to guanine.

The "multi-dimensional" scientific network established by CIDNA led to the most detailed understanding to date of charge transfer in DNA. This understanding was based on NMR structural analysis of the DNA duplex in parallel to the resolution of ultrafast time-resolved dynamics and cutting-edge theoretical and computational efforts. This combined attack on a problem by members of the CIDNA may serve as a paradigm for future studies on the structure and function of complex biological units.

Along these lines, mapping of the dynamics of DNA bound to a gold surface and the effects of both, electric fields and surface packing, was initiated. This was the first time that lifetime profiles of reporter dyes attached to a defined position in the DNA structure were instrumental for the control of conformational changes controlled by an electrochemical potential. These pilot experiments on the mesoscopic scale of the confocal microscope were suited to direct the future experimental strategy for the assessment of the properties of immobilised biosystems involving biopolymers as DNA, proteins, and complex architectures involving both. The dynamic surface mapping of immobilised DNA provides the bridge to novel CIDNA-based scientific strategies.

STM, particularly the electrochemically controlled in situ STM, supported the feasibility of visualising and controlling a single-molecule DNA-system in an aqueous medium, i.e. under biological conditions. The accumulation of individual and joint results within the CIDNA teams led to a new conceptual framework in experiment and theory which asks for fast and consequential continuation in order not to lose momentum and European leadership in this competitive field of biotechnology.

Major channels of disseminating the knowledge accumulated by the members of the CIDNA teams were international, refereed journals, where CIDNA results were or were about to be published. CIDNA results were also communicated at major international conferences and in lectures at prominent scientific institutions, where CIDNA members often enjoyed the status of invited speakers. Since CIDNA members taught at universities, the results of this programme became an important part in science education.

Although four patents were filed, there is, however, no doubt that given adequate funding, several other CIDNA results would be directly suitable for both national and international patent filing. Most of the members of the CIDNA consortium extended their relations or developed new relations with industry during the duration of the project. The most important contacts were directed towards companies active in high-value analysis products for gene expression and global provision of locked nucleic acids, microscopy and laser applications.

In addition, CIDNA results were disseminated in other ways addressing broader audiences: several book chapters and a monograph emerged from the programme. While stringently scientifically oriented, the scopes of these monographs went beyond the CIDNA objectives and set these into broader perspectives of bioelectrochemistry and electrochemical sensors for genomics and proteomics.

CIDNA results were communicated to wider audiences including engineers, administrators as well as scientists from nearby fields and decision-makers in science policy. CIDNA members considered it as an important obligation to communicate new results to the young generation. In this spirit, results were communicated during high-school teaching stimulating interest in science. Overall the CIDNA scientific communication and dissemination therefore accorded with expectations laid down in the proposal and initially stated objectives.

The most effective plan of dissemination of CIDNA results in the future was active and fast continuation of DNA research to which the present programme provided such successful basis. This would lead to intense industrial contacts on the one hand and to academic and public lecturing, patents and scientific publications on the other.

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Maria Elisabeth MICHEL-BEYERLE
Tél.: +49-89-28913400
Fax: +49-89-28913026
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