The Malaria Molecular Physiology Section conducts basic research on the transport of ions and nutrients across various membranes of the malaria parasite or its host cells. This work incorporates molecular biology and informatics, protein and lipid biochemistry, and biophysics. We recently used electrophyiological methods to identify an unusual ion channel on human red blood cells infected with P. falciparum which causes a severe form of malaria. This channel, the plasmodial surface anion channel (PSAC), is present at 1000 copies/cell, has unusual gating properties, and is permeable to a range of anions and nutrients known to be required for parasite growth. We proposed that PSAC mediates the first step in a sequential diffusive pathway of nutrient acquisition. Current projects in the lab include: 1) characterizing the mechanism of permeation through PSAC with various transport methods, 2) developing and testing specific PSAC blockers that may function as future antimalarials, 3) cloning the genes of various parasite transporters, and 4) heterologous expression of these transporters. These projects aim to understand the parasite's physiology and develop new strategies for control of malaria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000882-01
Application #
6503692
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lisk, Godfrey; Pain, Margaret; Gluzman, Ilya Y et al. (2008) Changes in the plasmodial surface anion channel reduce leupeptin uptake and can confer drug resistance in Plasmodium falciparum-infected erythrocytes. Antimicrob Agents Chemother 52:2346-54
Staines, Henry M; Alkhalil, Abdulnaser; Allen, Richard J et al. (2007) Electrophysiological studies of malaria parasite-infected erythrocytes: current status. Int J Parasitol 37:475-82
Alkhalil, Abdulnaser; Hill, David A; Desai, Sanjay A (2007) Babesia and plasmodia increase host erythrocyte permeability through distinct mechanisms. Cell Microbiol 9:851-60
Lisk, Godfrey; Scott, Seth; Solomon, Tsione et al. (2007) Solute-inhibitor interactions in the plasmodial surface anion channel reveal complexities in the transport process. Mol Pharmacol 71:1241-50
Hill, David A; Pillai, Ajay D; Nawaz, Fatima et al. (2007) A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel. Proc Natl Acad Sci U S A 104:1063-8
Lisk, Godfrey; Desai, Sanjay A (2006) Improved perfusion conditions for patch-clamp recordings on human erythrocytes. Biochem Biophys Res Commun 347:158-65
Lisk, Godfrey; Kang, Myungsa; Cohn, Jamieson V et al. (2006) Specific inhibition of the plasmodial surface anion channel by dantrolene. Eukaryot Cell 5:1882-93
Desai, Sanjay A (2005) Open and closed states of the plasmodial surface anion channel. Nanomedicine 1:58-66
Kang, Myungsa; Lisk, Godfrey; Hollingworth, Stephen et al. (2005) Malaria parasites are rapidly killed by dantrolene derivatives specific for the plasmodial surface anion channel. Mol Pharmacol 68:34-40
Desai, Sanjay A; Alkhalil, Abdulnaser; Kang, Myungsa et al. (2005) Plasmodial surface anion channel-independent phloridzin resistance in Plasmodium falciparum. J Biol Chem 280:16861-7

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