A structural and transcription pattern for variant surface glycoprotein gene expression sites used in metacyclic stage Trypanosoma brucei.

African trypanosomes first express the variant surface glycoprotein (VSG) at the metacyclic stage in the tsetse fly vector, in preparation for transfer into the mammal. Metacyclic (M)VSGs comprise a specific VSG repertoire subset and their expression is regulated differently from that of bloodstream VSGs, involving exclusively transcriptional regulation during the life cycle. To identify basic structural and functional features that may be common to MVSG telomeric transcription units, we have characterized the anatomy and transcription of the telomere containing the ILTat 1.

The Leishmania mexicana proteasome.

As a start to understanding the importance of intracellular proteolysis in the protozoon Leishmania mexicana, the parasite proteasome has been purified and characterised. The L. mexicana proteasome is similar to proteasomes from other eukaryotes.

A highly conserved nematode protein folding operon in Caenorhabditis elegans and Caenorhabditis briggsae.

In the free-living model nematode, Caenorhabditis elegans, a protein-folding co-transcribed gene pair has previously been described. The degree and form of trans-splicing, orientation and spacing of the genes, and the co-ordinate co-expression of protein folding catalysts in the nematode's hypodermis indicated this to be a functionally important operon. This gene pair has now been cloned and compared in the related organism Caenorhabditis briggsae to identify evolutionarily conserved, functionally important features.

Roles of cysteine proteinases of trypanosomes and Leishmania in host-parasite interactions.

Trypanosomes and Leishmania contain an abundance of stage-regulated cysteine proteinases encoded by several gene families. Analysis of parasites rendered defective in cysteine proteinase function, either through genetic manipulation or through the use of specific inhibitors, has revealed roles for the enzymes in parasite virulence, in modulation of the host's immune response and in parasite differentiation.

The crk3 gene of Leishmania mexicana encodes a stage-regulated cdc2-related histone H1 kinase that associates with p12.

A cdc2-related protein kinase gene, crk3, has been isolated from the parasitic protozoan Leishmania mexicana. Data presented here suggests that crk3 is a good candidate to be the leishmanial cdc2 homologue but that the parasite protein has some characteristics which distinguish it from mammalian cdc2. crk3 is predicted to encode a 35.

VSG gene control and infectivity strategy of metacyclic stage Trypanosoma brucei.

As the metacyclic trypanosome stage develops in the tsetse fly salivary glands, it initiates expression of variant surface glycoproteins (VSGs) and does so by each cell activating, at random, one from a small subset of metacyclic VSG (M-VSG) genes. Whereas differential activation of individual VSG genes in the bloodstream occurs as a function of time, to evade waves of antibody, it is believed that the aim in the metacyclic stage is simultaneously to generate population diversity. M-VSG genes are activated in their telomeric loci and belong to monocistronic transcription units, unlike all other known trypanosome protein-coding genes, which appear to be transcribed polycistronically.

Activity of a trypanosome metacyclic variant surface glycoprotein gene promoter is dependent upon life cycle stage and chromosomal context.

African trypanosomes evade the mammalian host immune response by antigenic variation, the continual switching of their variant surface glycoprotein (VSG) coat. VSG is first expressed at the metacyclic stage in the tsetse fly as a preadaptation to life in the mammalian bloodstream. In the metacyclic stage, a specific subset (<28; 1 to 2%) of VSG genes, located at the telomeres of the largest trypanosome chromosomes, are activated by a system very different from that used for bloodstream VSG genes.

Cyclophilin and protein disulfide isomerase genes are co-transcribed in a functionally related manner in Caenorhabditis elegans.

The ubiquitous enzymes peptidyl prolyl cis-trans isomerase (PPI, EC 5.2.1.

Cathepsin B-like cysteine proteinase-deficient mutants of Leishmania mexicana.

Mutants null for the cathepsin B-like cysteine proteinase gene (cpc) of Leishmania mexicana have been generated by targeted gene disruption. The gene deletion was confirmed using a polymerase chain reaction (PCR) method with cpc-specific primers and genomic DNA isolated from the mutants. cpc was re-expressed in the null mutants from an episomal vector.

The relative significance of mechanisms of antigenic variation in African trypanosomes.

The large number of genes involved in antigenic variation in African trypanosomes has been the focus of a wide literature that describes an almost bewildering array of mechanisms for their differential activation. To the outsider searching for an underlying strategy for antigenic variation, this can appear as a rather disordered and confusing picture. Here, David Barry argues that an understanding of which mechanisms are significant, which ones are primarily inconsequential and which ones perhaps even arise from overdependence on laboratory models, might be achieved by turning attention to trypanosomes that have not undergone adaptation in laboratory conditions.

The multiple cpb cysteine proteinase genes of Leishmania mexicana encode isoenzymes that differ in their stage regulation and substrate preferences.

The cpb genes of Leishmania mexicana encode stage-regulated, cathepsin L-like cysteine proteinases that are leishmanial virulence factors. Field inversion gel electrophoresis and genomic mapping indicate that there are 19 cpb genes arranged in a tandem array. Five genes from the array have been sequenced and their expression analyzed.

The origins, dynamics and generation of Trypanosoma brucei rhodesiense epidemics in East Africa.

The history of sleeping sickness in East Africa has provoked controversy not only about the origins and spread of the disease, but also the identity of the causative organisms involved. Molecular methodology(1) has shed new light on the genetic makeup of the organisms involved in recent epidemics. Here, Geoff Hide, Andrew Tait, Ian Maudlin and Susan Welburn discuss these new data in relation to previous theories about the origins of epidemics in East Africa which emphasized the importance of the introduction of new strains.

A promotor directing alpha-amanitin-sensitive transcription of GARP, the major surface antigen of insect stage Trypanosoma congolense.

The major surface antigen of procyclic and epimastigote forms of Trypanosoma congolense in the tsetse fly is GARP (glutamic acid/alanine-rich protein), which is thought to be the analogue of procyclin/PARP in Trypanosoma brucei. We have studied two T.congolense GARP loci (the 4.