Investigating electrostatic effects on DNA compaction: applications to gene delivery and transcription regulation.
Date of Issue2009
School of Biological Sciences
The general aim of the project is to obtain a principal understanding of the interactions of counterions, multivalent ions and charged ligands with DNA and other biopolyelectrolytes. We are interested in understanding the general mechanism and importance of electrostatic interactions for inducing and stabilizing such condensed forms of rod-like biopolymers in biological systems with biomedical applications. The specific aims are: (i) To experimentally determine the ability of different polyvalent ligands to condense DNA and other biopolyelectrolytes and how this depends on structural features of ligands and biopolymer. (ii) To establish the physical basis in terms of molecular interactions, for this condensation. (iii) To use this knowledge in the practical design of new gene delivery agents. Specifically, a new class of polyamine mimetics that are ~peptides will be developed. (iv) To identify the electrostatic role in polyanion-polycation interaction of DNA with histone protein tails and other chromatin regulating proteins involved in transcriptional regulation. These aims will be realized using a combination of experimental approaches such as light scattering, fluorescence and NMR, in combination with computer modeling based on Monte Carlo and molecular dynamics simulations.