Project ECOPOD

ECOPOD - Environmentally Controlled Polymorphism of non-B DNA structures

Project Number / Acronym	322104 / ECOPOD
Funding scheme	7th Framework Programme – People
Call identifier	FP7-PEOPLE-2012-CIG
Start Date / Duration	1st October 2012 / 48 months
Project Cost	EU funding 100.000 €
Project Coordinator / Person in charge of scientific aspects	Masaryk University, Prof. Vladimír Sklenář vladimir.sklenar@ceitec.muni.cz
Researcher	Dr. Lukáš Trantírek lukas.trantirek@ceitec.muni.cz

Repetitive blocks of guanine- and cytosine-rich sequences, such as those occurring in centromeric and telomeric DNA regions and promoter regions of protein coding genes, have ability to form G- and C-quadruplex structures, respectively. These non-B DNA structures are involved in more than 40 pathological human conditions including cancer. From a biophysical point of view, a common property to both G- and C-rich sequences is their inherent sensitivity to non-specific, physical-chemical environmental factors promoting their conformational polymorphism. Despite significant effort, motivated by both biological significance and biotechnological and biomedical applications of these non-B DNA motifs, the mechanistic nature of the environmentally induced effects remains poorly understood. The mechanistic insight and revealing of relationships between the DNA sequence and its folding topology in relation to its environment is essential for both rational design of novel nanomaterials and ways for their manipulations as well as for related biomedical applications. In this project, we propose systematic investigations of the influence of non-specific physical-chemical factors on structure of the DNA quadruplexes. In parallel, we propose characterization of these structures under the physiological conditions in vivo using state-of-the-art method of in-cell NMR spectroscopy. The acquired information will help to identify physiologically relevant structures of G- and C-quadruplexes.

Figure 1. Polymorphism of non-B DNA structures in telomeric (A), centromeric (B), and oncogene promoter (C) DNA regions. MC stands for molecular crowding.

Project aims:

1. Characterization of the folding topologies and conformational polymorphism of the G- and C-rich DNA sequences under native-like conditions.

2. Identification of environmental factors modulating structure and conformational equilibrium of non-B DNA structures in relation to primary DNA sequence.