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Biomedical subjects

Anthony A James

Publications and source records attributed to Anthony A James.

25 records · Page 2Linked to original sources

Engineering Plasmodium-refractory phenotypes in mosquitoes.

A remarkable number of effector mechanisms have been developed for interfering with malaria parasite development in mosquitoes. These effector mechanisms affect different aspects of parasite biology and therefore could be targeted synergistically to reduce the probability of emergence of parasite resistance to any one mechanism. The use of these mechanisms will depend on how efficiently and safely they can be introduced into existing mosquito populations.

Animals↗

Blocking malaria parasite invasion of mosquito salivary glands.

Release of genetically engineered mosquitoes resistant to parasite infections has been proposed as a novel way to control malaria transmission, and several important advances have been made in anticipation of testing this approach. In particular, the development of synthetic effector genes that block parasite development in mosquito hosts has exploited a number of different mechanisms that result in parasite-resistant phenotypes, and those that target specifically the sporozoites are reviewed here. The use of a number of synthetic genes based on different mechanisms in transgenic mosquitoes will make the selection of resistant parasites unlikely.

Animals↗

Gene vector and transposable element behavior in mosquitoes.

The development of efficient germ-line transformation technologies for mosquitoes has increased the ability of entomologists to find, isolate and analyze genes. The utility of the currently available systems will be determined by a number of factors including the behavior of the gene vectors during the initial integration event and their behavior after chromosomal integration. Post-integration behavior will determine whether the transposable elements being employed currently as primary gene vectors will be useful as gene-tagging and enhancer-trapping agents. The post-integration behavior of existing insect vectors has not been extensively examined. Mos1 is useful as a primary germ-line transformation vector in insects but is inefficiently remobilized in Drosophila melanogaster and Aedes aegypti. Hermes transforms D. melanogaster efficiently and can be remobilized in this species. This element is also useful for creating transgenic A. aegypti, but its mode of integration in mosquitoes results in the insertion of flanking plasmid DNA. Hermes can be remobilized in the soma of A. aegypti and transposes using a common cut-and-paste mechanism; however, the element does not remobilize in the germ line. piggyBac can be used to create transgenic mosquitoes and occasionally integrates using a mechanism other than a simple cut-and-paste mechanism. Preliminary data suggest that remobilization is infrequent. Minos also functions in mosquitoes and, like the other gene vectors, appears to remobilize inefficiently following integration. These results have implications for future gene vector development efforts and applications.

Animals↗

Development and applications of transgenesis in the yellow fever mosquito, Aedes aegypti.

Transgenesis technology has been developed for the yellow fever mosquito, Aedes aegypti. Successful integration of exogenous DNA into the germline of this mosquito has been achieved with the class II transposable elements, Hermes, mariner and piggyBac. A number of marker genes, including the cinnabar(+) gene of Drosophila melanogaster, and fluorescent protein genes, can be used to monitor the insertion of these elements. The availability of multiple elements and marker genes provides a powerful set of tools to investigate basic biological properties of this vector insect, as well as the materials for developing novel, genetics-based, control strategies for the transmission of disease.

Aedes↗

Germline transformants spreading out to many insect species.

The past 5 years have witnessed significant advances in our ability to introduce genes into the genomes of insects of medical and agricultural importance. A number of transposable elements now exist that are proving to be sufficiently robust to allow genetic transformation of species within three orders of insects. In particular all of these transposable elements can be used genetically to transform mosquitoes. These developments, together with the use of suitable genes as genetic markers, have enabled several genes and promoters to be transferred between insect species and their effects on the phenotype of the transgenic insect determined. Within a very short period of time, insights into the function of insect promoters in homologous and heterologous insect species are being gained. Furthermore, strategies aimed at ameliorating the harmful effects of pest insects, such as their ability to vector human pathogens, are now being tested in the pest insects themselves. We review the progress that has been made in the development of transgenic technology in pest insect species and conclude that the repertoire of transposable element-based genetic tools, long available to Drosophila geneticists, can now be applied to other insect species. In addition, it is likely that these developments will lead to the generation of pest insects that display a significantly reduced ability to transmit pathogens in the near future.

Animals↗