Collaborative Project: Mosquito Diuretic Peptides: Peptide Chemistry, In Vitro Physiology and In Vivo Endocrinology

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In sheer numbers, insects are the most successful species on earth. No one denies the many beneficial activities of insects as, for example, in the pollination of economically important crops, the production of silk, and most recently biological pest control (one insect predating on another). Everybody also knows about the potentially devastating effects of insects. Insects have been known to wipe out entire crops, contributing to world hunger. Insects are also known as the dreadful bearers of blood borne fatal diseases such as yellow fever, malaria, and elephantiasis. Since biblical time (the flight of locust) men have tried to cope with the undesirable impacts of insects on mankind. In modern times the most successful approach has been the use of pesticides; but pesticides - as we are now learning - have serious undesirable side-effects on man and animal alike. For this reason alternatives to insect control are needed. The present proposal marks the exploration of a new approach via attempts to interfere in the normal salt and water budget of the insect. This approach will be pursued in the blood-feeding yellow-fever mosquito (Aedes aegypti). Shortly after mating the female mosquito seeks a bloodmeal. She needs blood in order to obtain nutrients and proteins for her eggs. Having found a source, the female yellow-fever mosquito gorges herself, taking a meal 2-3 times her own body weight| Such a heavy payload prevents the mosquito from flying away, thereby threatening reproductive success (she must find a pond to deposit her eggs) and personal calamity (a swat). To guarantee the former and to avoid the latter, she must maintain flight capability and maneuverability, namely by quickly eliminating unwanted weight, in particular the unwanted salt and water portion of the bloodmeal. This she does by way of a hormone, the so-called diuretic, natriuretic hormone. In the upcoming grant period the PIs plan to purify and isolate this hormone, learn its structure and attempt to synthesize it. This work will be done in the laboratory of a peptide chemist, Dr. Hayes of Texas A&M University. At the same time Dr. Beyenbach (a transport physiologist) at Cornell University will study how the kidney in the mosquito works normally and under the influence of the hormone. And the laboratory of the insect endocrinologist, Dr. Hagedorn (University of Arizona) will investigate how the hormone is released in the mosquito, where it is made and stored, and what organs other than the kidney it affects. Three potential target sites for pest control via disrupting normal salt and water balance in the insect will be investigated: 1) by giving synthetic hormone causing the insect to lose salt and water when they need to be conserved, 2) by interfering with normal kidney function, e.g. preventing the action of the hormone and thereby reproductive success, and 3) by disrupting the normal feedback loop of salt and water balance by inhibiting the production or the release of the hormone, when the insects need the hormone.