Details of Grant 

EPSRC Reference:	GR/S31068/01
Title:	Physical Mechanisms of the Sequence Dependence of DNA Aggregation and the Recognition of Homologous Genes
Principal Investigator:	Kornyshev, Professor AA
Other Investigators:	Seddon, Professor JM
Researcher Co-Investigators:	Dr S Leikin
Project Partners:	Institute for Theoretical Physics II Laboratoire de Physique Théorique National Institute of Child Health
Department:	Chemistry
Organisation:	Imperial College London
Scheme:	Standard Research (Pre-FEC)
Starts:	01 October 2003	Ends:	31 March 2007	Value (£):	385,382
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Biology Complex fluids & soft solids Theoretical biology
EPSRC Industrial Sector Classifications:	Chemicals Electronics Pharmaceuticals and Biotechnology
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Summary on Grant Application Form
PThis experimental and theoretical project lies at the interface of physical chemistry, soft matter physics and molecular biology, and is focussed on experimental verification of the Kornyshev-Leikin (KL) model of a 'snap-shot' recognition of homologous genes, extension of the KL-theory with account for DNA elasticity, experimental and theoretical investigation of sequence effects on the structure of DNA mesophases.We intend to investigate the effect of base-pair sequence homology on polycation-induced aggregation of double stranded DNA fragments and on intermolecular forces between adjacent DNA helices in aggregates. Based on the KL model predictions we expect lower sperm ine/spermidine concentration needed to induce aggregation of homologous DNA fragments and more attractive/less repulsive forces in aggregates. This would provide evidence that electrostatic recognition may contribute to homologous fragment pairing preceding genetic recombination in vivo.We will study effects of sequence homology on the structure and phase behaviour of DNA columnar and cholesteric mesophases. For instance, we expect changes in biaxial correlations and chiral interactions resulting in changes in the cholesteric pitch and in the cholesteric-hexagonal transition. Detecting such changes will open a way for characterising sequence-dependent interactions through the structural analysis of DNA liquid crystals. The theory part of the project focuses on exploring the effects of torsional elasticity, that relax the accumulated mismatch in the interaction of long non-homologous sequences, and studies in statistical mechanics of liquid crystal phases of DNA, assembled subject to the KL interaction potential.
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Organisation Website:	http://www.imperial.ac.uk