Postgraduate research student:
David Simpson

DNA is a double stranded polymer of four distinct monomer units (deoxyribonucleotides). The strands and held together by hydrogen bonding between the monomer units. The sequence of monomer units is used to direct the synthesis of proteins in the body and hence is valuable in the early diagnosis of genetic disease.

When double stranded DNA is subjected to elevated temperatures or to extreme pH the hydrogen bonding is disrupted and the two strands separate. On removal of extreme conditions the separated strands will bind to each other to reproduce the original structure. Due to the specificity of binding between the monomer units, the newly formed structure will not differ from the original structure.

This property of DNA provides a simple way to search for specific monomer sequences. If a single stranded DNA molecule which has the appropriate monomer sequence to bind a target DNA sequence is synthesised, it can be used as a probe for that sequence. All that is required is a method with which to determine whether this process, named hybridisation, has occured. Many methods are available to detect hybridisation but most are insensitive to single mismatches. If the sequence to either side of a mismatch is correct the probe and target will often bind, giving a false positive.

The aim of my project at UEA was to develop a method sensitive to such mismatches. The structure of DNA is such that it is probable that long range electron transfer along the polymer backbone is possible. Mismatches are postulated to disrupt this conductivity. If one end of the DNA polymer was attached to an electrode and a redox active molecule was attached to the other, with the conductivity of the double helix, the electrode could be used to oxidise and reduce the redox active molecule. The presence of a mismatch would prevent such oxidation and reduction. This process can be monitored by cyclic voltammetry.