the c. elegans genome sequencing project: a beginning
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Parasitology Today, vol. 8, no. 5, 1992 153
for direct embryotoxic and embryo- static drug effects, and support our hypothesis that sustained alterations of biological and immunological processes interfere with a delicate dynamic para- site-host equilibrium and with parasite reproduction.
We know from our investigations of old O. volvulus populations in the OCP area that a low reprodua:ivity and slow turnover of mf production are associ- ated both with a significant decrease in the total number of intrauterine stages and with a significant increase in ab- normal embryos I (a development that can obviously be reversed by external manipulation, eg. iverrnectin treat- ment3). Hence, the observed qualitative or quantitative alterations of the em- bryonic stages 4 following annual or semi-annual retreatment with iver- mectin might result from reduced re-
productivity owing to immunological changes, at least to a certain extent. So, we would like to extend the classical view of drug evaluation that only focusses on the death or survival of the parasite. Since ivermectin-facilitated immunity is of significant relevance for mass treatment campaigns, immuno- logical alterations in the host and the complex impact of single and repeated ivermectin treatment on the worm population and its reproductive capacity are in need of further clarification.
Acknowledgements Our onchocerciasis research and ivermectin trials are being supported by WHO (TDR, ID No. 890067), the STD-2 and STD-3 Programmes of the Commission of the European Communities (contract no. ST2-0066-D) and the German Association for Technical Cooperation (gtz).
References I Schulz-Key, H. et al. (1989) Trap. Med. Para-
sitol. 40, 493494 2 Greene, B.M. et al. (1989) in Ivermectin and
Abamectin (Campbell, W.C., ed.), pp 311-323, Springer
3 Awadzi, K. et al. (1986) Ann. Trap. Med. Pamsitol. 80, 433-442
4 Schulz-Key, H. (I 990) Acta Leiden. 59, 27-43 5 Albiez, E.J. et at. (1988) Trap. Med. Parasitol.
39, 93-99 6 Duke, B.O.L. et at. ( 1991 ) Trap. Med. Parasital.
42, 175-180 7 Vande Waa, E.A. ( 1991 ) Parasitology Today 7.
194-199 8 Schulz-Key, H. et al. (1987) Zentralbl. Bakteriol.
265, 492-493 9 Schulz-Key, H. and Karam, M. (1986) Para-
sitology Today 2, 284-296 10 Karam, M., Schulz-Key, H. and Remme, J.
(I 987) Acta Trap. 44, 445-457
Hartwig Schulz-Key, Peter Soboslay and Wolfgang Hoffmann are at the Institute of Tropical Medicine, University of Tdbingen, Wilhelmstrasse 27, D-7400 Tdbingen, FRG.
The C. elegans Genome Sequencing Project: a Beginning J. Sulston, Z. Du, K. Thomas, R. Wilson, L. Hillier, R. Staden, N. Halloran, P. Green,
J. Thierry-Mieg, L. Qiu, S. Dear, A. Coulson, M. Craxton, R. Durbin, M. Berks, M. Metzstein, T. Hawkins, R. Ainscough and R. Waterston Nature 356, 37-41
Genomic sequencing projects (worm or human) have their detrac:ors. Why not obtain biological knowledge from con- ventional studies of mutation and mol- ecules? Why not follow the more cost- effective route of complementary DNA sequencing? Sulston starts to answer these questions in this report of the completion of the sequence determi- nation of 0. I% of the Caenorhabditis elegans genome, 121298 base pairs of DNA cloned in three cosmids isolated
from chromosome III. From each cos- mid he constructs two types of library: a small-insert library, consisting of I-3 kb fragments shotgun-cloned into vectors that produce single-strand templates, and a large-insert library of 6-9kb fragments. The small-insert clones are sequenced and the information so arranged as to yield a number of nonoverlapping, continuous chunks (contigs) of sequence. The ends of the large inserts are sequenced and
matched to the ends of contigs. Then, fluorescent primers are generated from the ends of the contigs to enable a 'filling-in' of the appropriate sequence complementary to the large insert clone. Their sequence data reveal the presence of 34 genes (out of an esti- mated 6500-40000), some of which encode proteins of known function. Of course, nothing new is gained about knowledge of nematode biology, but the serving-up of all C elegans gene (plus intervening) sequences, which Sulston claims will be on the table within five years (at a projected cost of $0.50 per residue), will surely lead to such knowledge. Stay tuned.
A Recombinant Sporozoite Surface Antigen of Thei ler ia parva Induces Protection in Catt le A. Musoke, S. Morzaria, C. Nkonge,
E. Jones and V. Nene Proc. Nat l Acad. Sci. USA 89, 5 14-5 1 8
The protozoan parasite Theileria parva, transmitted by the three-host tick, Rhipicephalus appendiculatus, causes East Coast Fever (ECF) and puts at risk over 20 million cattle in eastern, central and southern Africa. To date, immunization against T. parva has been by infection with live sporozoites, combined with treatment with a long-acting oxytetra- cycline (the major effector mechanism of immunity appears to be major histo- compatibility complex class I-restricted cytotoxic T lymphocytes, or CTLs). However, not only is the resulting
~) r992, EPsevier Science Publishers Ltd (UK)
immunity parasite-stock specific, but there are terrible logistical problems associated with delivering cryopreserved sporozoites to ECF-risk areas. Mono- clonal antibodies that recognize a 67 kDa stage-specific surface antigen (p67) of sporozoites neutralizes sporozoite infectivity. This gene, which encodes 709amino acid (aa) residues and con- tains a 29 base pair intron, is transcribed during sporogeny. When recombinant p67 sequences were fused to the first 85 aa residues of a nonstructural gene of influenza virus A, and the partially
purified recombinant antigen used to immunize nine Boran cattle (6-9 months old) on homologous challenge with T. parva sporozoites, sporozoite-neu- tralizing antibodies were produced and six cattle were provided with protection. The two cattle that showed a mild ECF reaction generated a CTL response against schizont-infected cells and were immune on subsequent chal- lenge with a lethal dose of T. parva sporozoites. This ability to develop immunity against both the sporozoite and schizont stages is a desirable feature of a vaccine strategy; perhaps by modi- fying antigen preparation, dose and frequency of application, an efficient vaccine protocol against theileriosis is on the horizon.