Douglas J. LaCount, Ph.D. Assistant Professor of Medicinal Chemistry and Molecular Pharmacology Phone: (765) 496-7835 E-mail: dlacount@purdue.edu Full directory listing

Specialization: Systems biology of malaria parasites; protein-protein interactions

Education

Research: Systems biology of malaria parasites; protein-protein interactions

Malaria continues to exert an enormous toll on people in developing countries. More than 100 million cases of malaria occur each year, resulting in more than 1 million deaths, most of them in African children under the age of 5. To make matters worse, the parasite is rapidly developing resistance to the commonly available anti-malarial drugs. There is an urgent need for new anti-malarial drugs and a better understanding of the parasite’s biology.

Despite the impact of malaria on global health, much remains to be discovered about most of the parasite’s proteins. More than 60 % of the malaria proteins are annotated as "hypothetical", and an even larger percentage of the proteins have never been experimentally characterized. To begin to address this issue, the Fields lab at the University of Washington, in collaboration with Prolexys Pharmaceuticals in Salt Lake City, Utah, performed a large-scale screen to identify protein-protein interactions in Plasmodium falciparum, the parasite that causes the most deadly form of malaria. From more than 32,000 yeast two-hybrid screens, we identified nearly 3,000 pairs of interacting proteins involving one quarter of the parasite’s proteins. Because protein-protein interactions can be used to infer functions for uncharacterized proteins (the principle of "guilt by association"), this dataset is providing a wealth of information about Plasmodium biology and has linked numerous "hypothetical" proteins to diverse processes, including host cell invasion, gene expression, RNA processing and translation.

Research in my lab will continue to focus on protein-protein interactions in P. falciparum. Projects include the identification of interactions between host and parasite proteins, follow-up studies on several of the interactions identified in the large-scale yeast two-hybrid screen, and exploitation of the information in the P. falciparum protein interaction map to identify critical parasite proteins.

Representative Publications

LaCount DJ, Vignali M, Chettier R, Phansalker A, Bell R, Hesselberth J, Schoenfeld LW, Ota I, Sahasrabudhe S, Kurschner C, Fields S, and Hughes R. A protein interaction network of the malaria parasite Plasmodium falciparum. 2005. Nature. 2005 Nov 3;438(7064):103-7.

Alexandrov A, Vignali M, LaCount DJ, Quartley E, De Vries C, De Rosa D, Babulski J, Mitchell SF, Schoenfeld LW, Fields S, Hol WG, Dumont ME, Phizicky EM, Grayhack EJ. A facile method for high-throughput co-expression of protein pairs. Mol Cell Proteomics. 2004 Sep;3(9):934-938. Epub 2004 Jul 07.

Barrett B, LaCount DJ, Donelson JE. Trypanosoma brucei: a first-generation CRE-loxP site-specific recombination system. Exp Parasitol. 2004 Jan-Feb;106(1-2):37-44.

LaCount DJ, Gruszynski AE, Grandgenett PM, Bangs JD, and Donelson JE. 2003. Expression and function of TbMSP (GP63) genes in African trypanosomes. Journal of Biological Chemistry, 278: 24658-64.

LaCount DJ, Barrett B, and Donelson JE. 2002 Trypanosoma brucei FLA1 is required for flagellar attachment and cell division. Journal of Biological Chemistry 277:17580–17588.

LaCount DJ, and Donelson JE. 2001. RNA Interference in African Trypanosomes. Protist 152:103-111.

LaCount DJ, El-Sayed NM, Kamir S, Wanless D, Turner CMR, and Donelson JE. 2001. The donor region and expression site for a variant surface glycoprotein in African trypanosomes. Nucleic Acids Research 29:2012-9.

LaCount DJ, Bruse S, Hill KL, and Donelson JE. 2000. Double-stranded RNA interference in Trypanosoma brucei using head to head promoters. Molecular and Biochemical Parasitology 111:67-76.