Single molecule DNA sequencing in gold

The human genome contains 3164.7 million nucleic acid bases (adenine, guanine, cytosine, thymine) and it is estimated that the length of all the DNA strands in a single cell (if all the strands were placed end to end) is about two metres. The human genome sequence was completed at the start of the millennium; this resulted in significant public and scientific interest in understanding the DNA sequence 'code' and how it is 'translated'. The sequence of the genome provides information about our ancestry, hereditary diseases, our features (such as eye, skin or hair colour) and our physiological 'make-up'. In order to truly understand the genome sequence it would be desirable to have simpler DNA sequencing methods so that many more genomes could be sequenced. Currently, methods require expensive reagents, are laborious and take a long time. Despite the fact that the human genome was sequenced a decade ago and better DNA sequencing methods have been since developed, a simple, cheap, fast, accurate DNA sequencing method is still an important goal. In our view, what is needed is a small scale technology, something that works like a hard disk drive, where a tiny read head is scanned past the stored information (the DNA strand) and the information (the sequence) is read directly without need for any complex processing of the genomic DNA molecule. We propose to flow DNA molecules through a nanopore that will act as a 'read head' and detect and identify the nucleic acids in the DNA sequence by their response to laser excitation. Identifying the DNA base sequence in this way will be highly ac curate, and capable of detecting damage or modification to particular bases from environmental or cellular processes which can control the switching on and off of genes. DNA sequencing techniques are crucial to obtain a better understand of all organisms, not just humans, and a fast, cheap DNA sequencing method will be able to answer many more questions as well as also provide a diagnostic tool. These studies will provide proof of concept data appropriate to demonstrate a very new DNA sequencing approach.