A Center of Excellence in
Marine Genomics

Membrane Physiology

Stopping Malaria in its Tracks

The Krogh principle states that for many problems there is an animal of choice on which it can be most conveniently studied. To understand the problem of how animals absorb digested food and keep their acids and salts in balance, the larva of the African malaria mosquito, Anopheles gambiae, is proving to be a good choice. The Membrane Transport Group, comprising two Whitney research laboratories, has cloned over 30 genes encoding proteins that transport nutrient amino acids and ions across cell membranes (transporters).

Ions are molecules or atoms that have lost an electron and have a positive charge (cations) or gained an electron and have a negative charge (anions). Paul Linser's lab focuses on carbon dioxide, bicarbonate anions and chloride anions while my lab focuses on hydrogen, sodium and potassium cations. 

What if . . . we were able to develop new generations of insecticides that are able to target the alkaline conditions of the mosquito larvae digestive system? These new insecticides would kill mosquito larvae but leave other insects, fish and humans unaffected.

There are a number of proteins that use energy from ATP breakdown to move hydrogen ions (H+) across membranes. In the same sense that electrons carry electric currents through wires, ions carry electric currents through fluids.
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The simplest such current carrier is H+, which is a proton. The proteins that break down ATP are called ATPases; the one we study was first found in cell vacuoles and is called a Vacuolar-type ATPase or V-ATPase for short. This protein can do only one thing - pick up H+s from inside cells and move them outwardly across the cell membrane. This separation of positive H+s from negative charges that remain in the cell creates a voltage that can drive other anions and cations across the membrane. We are cloning transporters that use this H+ gradient to move ions across membranes. All of these membrane proteins work together to maintain internal pH, remove excess salts and absorb nutrients from food.

Our long-term objective is to identify molecular mechanisms responsible for these physiological processes that are necessary for larval survival. They may provide targets for the development of mosquito control measures that are specific to mosquitos and are environmentally benign.



William R. Harvey, Ph.D.

Professor of Physiology and Functional Genomics & Environmental and Global Health

 

Dr. Bill Harvey did his undergraduate work at Tufts University followed by a Fulbright Scholarship in educational psychology at Edinburgh University. He received his M.A. and Ph.D. in biology at Harvard University followed by postdoctoral work in membrane biophysics at Copenhagen and a Guggenheim Fellowship in membrane physiology at Cambridge University in the UK

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