The nanoscale reading of DNA sequences is envisioned to take place at a nanogap defined by a pair of nanoelectrode tips as a DNA molecule moves through the gate base by base. The rationale is that the four different nucleotide bases and their various sequences, each with a distinct chemical composition and structure, should be associated with a specific signature of tunneling current across the two tips. We propose to carry out calculations of the atomic and electronic structure and transport properties of DNA and DNA-carbon nanotube (DNA-CNT) hybrid systems, using a multiscale approach that we have recently developed. The immediate motivation for the proposed work is to gain insight at the quantum level of the unusual electronic and transport properties of these systems that could lead to new types of miniature devices for chemical/biological applications such as probes and sensors and DNA-sequencing technologies. The proposed studies will elucidate the effect of changes of the electronic structure and associated bonding properties in the presence of solvent and counter ions on the nature of the DNA and DNA-CNT intrinsic conductance. The calculations will employ three different but complementary methods: 1) the self-consistent charge density functional tight-binding (TB) method;2) the fully self-consistent ab initio calculations using the SIESTA and/or ONETEP approach;and 3) our recently developed multiscale approach which couples ab initio and empirical schemes. These approaches are unique in providing insight into the electronic structure which plays a key role for the interatomic forces and the transport, in contrast to empirical quantum-chemical methods which do not allow an accurate description of nucleic acid interactions. More specifically, we propose to study: (1) The atomic and electronic structure of A, B, lamda, and overstretched ribbon-like structures and the effect of (i) sequence, (ii) water and (iii) counterions;(2) The role of structure and environment in the transport properties;(3) The effect of charged environment (presence of electrons or holes) on defect reactions which may give rise to DNA cleavage pertinent to oxidative damage;and (4) The effect of diameter/curvature of the CNT on the transport properties of DNA-CNT hybrid systems. Our recently developed non-equilibrium transport TB approach also will be used to study the non-linear effect of bias.