The long term goal of the proposed project is the elucidation of the entire DNA sequence of the Caenorhabditis elegans genome. 100mb in size. the present application is for a pilot project, in which appriate methods will be developed and the first 2Mb of the sequence will be acquired. C. elegans is the subject of intensive studies, which are making great contribution to developmental and cellular biology. The extensive physical map of the genome provides an excellent point of departure for sequencing, and the relatively small DNA content and low level of repetitive sequences mean that the information density is high. The intended sequencing strategy relies heavily on the use of synthetic oligonucleotides to provide controlled start points for chain termination sequencing reactions. This will allow sequence data to be systematically collected, from the physically mapped clones for the first strand, and from genomic DNA for the second. Automated sequencing machines now appear to provide improved efficiency of sequence data collection and their value will be explored. Editing and database management programs will be improved, to speed assembly of the finished sequence. Analysis of this sequence through the application of increasingly sophisticated computer software and hardware will reveal much of the genome's information. This information will be of immense value both for studies of C. elegans and for the interpretation of sequencing of the C. elegans genome will aid in formulating effective strategies to sequence the much larger human genome.