I. Symbiotic control of insect-transmitted diseases of plants and animals

Insects are vectors for many of the most deadly plant and animal diseases and are a crucial link in these disease cycles. In the past, cultural methods or insecticide treatments have been used to control insect vectors. These methods are still widely practiced, but in many cases insects have evolved resistance to insecticides. In some areas of the world, notably Africa, public health measures used in developed countries to reduce vector populations are difficult to apply. Clearly, new methods are necessary to aid in the control of insect-vectored diseases.

Symbiotic control is a method that takes advantage of basic microbial ecology. The phenotype of all plants and animals is the product of genetic and environmental effects. One large environmental effect is provided by the microorganisms that form various kinds of sybioses with plants and animals. In symbiotic control, we genetically engineer symbiotic microbes to deliver effector proteins that can interfere with disease causing organisms. In this way, we can alter the disease-causing phenotype of insect vectors by modifying the bacteria that they normally carry.

Blocking mosquito transmission of malaria to humans. We are genetically modifying two species of bacteria to deliver antimalarial effector proteins. Malaria is the most widespread and dangerous insect-transmitted human disease in the world. It infects more than 500 million people (ca. 1 in 14 humans) and causes between 1 and 2 million deaths each year. The incidence of malaria is increasing and new measures to combat it are desperately needed.

Both Pantoea agglomerans and Asaia borogensis are bacterial species that are found in the midguts of Anopheles gambiae, the most important malaria vector mosquito in Africa. We are developing secretion systems for use in both of these species in order to secrete anti-malarial effectors into the midgut of An. gambiae. These effector molecules include single chain antibodies that bind directly to the Plasmodium parasites that cause malaria and to receptors on the mosquito midgut epithelium that the parasite uses to invade mosquito tissues. We are also developing ways to control the gene expression of antimalarial effector genes and methods to develop genetically stable strains of bacteria carrying these effectors.

II. Microbial ecology of mosquitoes

A related focus of my lab is uncovering the microbiota of mosquitoes in Pennsylvania with an eye toward expanding our repertoire of microbes suitable for symbiotic control. We are identifying a large number of culturable bacteria found in mosquitoes and also working to uncover the complete gut and ovary microbiomes of several species of Pennsylvania mosquitoes in collaboration with Gina Lamendella at Juniata College and Mike Hutchinson at the PA Dept. of Environmental Protection. Abundant culturable strains are being tested for their ability to colonize different mosquito tissues and for their ability to block the development of malaria parasites in Anopheles.

- Akerley, B.J. and Lampe, D.J. 2002. The GAMBIT system for analysis of virulence and essential genes. Methods in Enzymology 358:100-8.

- Lampe, D. J., K. K. O. Walden and H. M. Robertson 2001. Loss of transposase-DNA interaction may underlie the divergence of mariner-family transposable elements and the ability of more than one mariner to occupy the same genome. Molecular Biology and Evolution 18: 954-961.