Research Assistant Scientist
Research Assistant Professor
Department of Environmental and Global Health
College of Public Health and Health Professions
University of Florida
P. O. Box 100188
Gainesville FL 32610-0188
Mosquito transmitted diseases such as malaria, dengue, West Nile virus and Rift Valley fever feature highly in the public health agenda. Malaria still kills millions of people in developing countries of Africa and Asia, while pathogens like dengue and rift valley fever are on the rise. Unlike HIV and tuberculosis that are transmitted directly from human to human, malaria is spread when an infected female Anopheles mosquito bites for a blood meal. A mosquito gets infected from an infected person, amplifies the parasite, and injects it into a naïve person where the parasite is again amplified.
The fight against malaria, as is with other arthropod borne diseases, is aimed at preventing sickness and death. For malaria, prompt and effective treatment is the first line of defense. The Plasmodium parasite often mutates conferring resistance to available drugs: hence the need to search for new, resistant proof drugs. If effective vaccines are developed, they will complement the drugs and help stop the deaths due to malaria. Equally effective is killing the mosquito vector through a variety of means to break the transmission cycle: with no or few mosquitoes present, the transmission cycle is broken.
My research goal is focused on finding environmentally safe ways to kill the vectors of disease. To achieve this goal, I study in detail, the biological processes occurring in the insect midgut after ingestion of food and how they affect mosquito survival. Understanding these processes may help in finding new techniques and tools offering the potential to reduce disease vector populations and/or prevent pathogen transmission without harming the environment.
I use techniques in molecular biology and immuno-cytochemistry to identify proteins and other factors within the alimentary canal and blood that influence the survival of insect and the pathogens they carry. In addition, I employ high resolution microscopy and histological techniques to study the cellular factors involved in nutrient absorption and other regulatory processes in mosquito gut that enable survival of the vector and pathogen.
The overall goal of this project is to understand the functional basis of nutrient amino acid uptake in the larval midgut of An. gambiae, the malaria vector mosquito. We have localized essential nutrient amino acid transporters in the midgut epithelium of An. gambiae larvae using immunohistological techniques. The identification of the cellular localization of these proteins is critical in defining the amino acids uptake mechanisms in the mosquito midgut. Our results established that the uptake of amino acid depends upon the antero-posterior and polar distribution of the NATs and is driven by electrochemical motive forces which are generated across epithelial cell membranes by the synergistic activity of the ATP pumps (H+ V-ATPase and Na+K+ATPase) and other ion transporters, notably Na+/H+ antiporter.
The anterior midgut lumen of larval mosquitoes can attain a pH of 11, which is the highest alkaline environment ever recorded in any biological membrane. This alkaline environment (pH = 11) is crucial for the larval nutrition and development and is believed to be useful in breaking down tannin-protein complexes.
My research in this area is geared to understanding the molecular factors responsible for the generation and maintenance of this high pH in the anterior midgut and how the pH is lowered in the posterior midgut. My hypothesis is that lumen alkalization is supported by a proton-translocating (H+) V-ATPase that imposes a transepithelial voltage; which supports lumen alkalization and absorption of nutrients. In the posterior midgut, a Na+/H+ antiporter cololcalizes with Nutrtient Amino acid transporters and H+VATPase. These proteins together function as a typical NHE, but in this case facilitating the uptake of amino acids in the posterior midgut cells, while also removing Na+ ion from the lumen resulting in a lower pH here.
Understanding this molecular machinery of lumen alkalization and its involvement with nutrition may aid in the identification of selective targets for control of mosquito vector populations.
Okech, B. A., Meleshkevitch, E. A., Miller, M. M., Popova, L. B., Harvey, W. R. and Boudko, D. Y., Synergy and Specificity of Na+: Aromatic Amino Acid Symporters in Model Alimentary Canal of Mosquito Larvae. (Submitted to Journal of. Experimental Biology)
Okech, B.A., Boudko, D. Y., Linser, P.J. and Harvey, W. R. 2008. Cationic Pathway of pH Regulation in Larvae of Anopheles gambiae J. Exp. Biol. 211 (In press)
Rheault, MR, Okech, BA, Keen, SBW, Miller, MM, Meleshkevitch, MM, Linser, PJ, Boudko, DY and Harvey, WR (2007) Molecular Cloning, Phylogeny and Localization of a First Alkali Metal Ion/Hydrogen Ion Antiporter a Metazoan Anopheles gambiae (AgNHA1). Journal of Experimental Biology, 210:3848 – 3861.
Okech, B A. Gouagna LC, Beier JC, Yan G, Githure JI. (2007) Larval habitats of Anopheles gambiae s.s. (Diptera: Culicidae) influences vector competence to Plasmodium falciparum parasites. Malaria Journal 6: 50
Okech, B, Arai, M, Matsuoka, H. (2006) The effects of blood feeding and exogenous supply of tryptophan on the quantities of xanthurenic acid in the salivary glands of Anopheles stephensi (Diptera: Culicidae). Biochemical and Biophysical Research Communications, 24;341(4):1113-8
Okech BA, Gouagna LC, Walczak E, Kabiru EW, Beier JC, Yan G, Githure JI. (2004) The development of Plasmodium falciparum malaria in experimentally infected Anopheles gambiae ss (Diptera: Culicidae) under ambient microhabitat temperature in western Kenya. Acta Tropica, 92 (2) 99 – 108.Okech BA, Gouagna LC, Kabiru EW, Walczak E, Beier JC, Yan G, Githure JI. (2004) Resistance to high temperatures of early midgut stages of natural isolates Plasmodium falciparum in artificially infected Anopheles gambiae (Diptera: Culicidae) mosquitoes. Journal of Parasitology, 90 (4) 764 – 768