Malaria is the most common and deadly parasitic disease in the world. Several factors have contributed to making malaria as serious a problem now as it was during the first half of the twentieth century. In any given year, there will be 300 to 500 million cases of malaria, and 1 to 3 percent of those who contract the disease will not survive. Over 90 percent of the cases and deaths occur in Africa. As bad as that is, some experts foresee as much as a 20 percent annual increase in Africa's rate of malaria-related illness and death. Each year the world over, malaria destroys, through premature death and disability, the equivalent of at least 35 million years of healthy, productive human life and to date, there is no effective subunit vaccine for malaria. The incidence of drug-resistant parasite is increasing worldwide. The sequencing of the Plasmodium falciparum (and Plasmodium yoelii), the Anopheles gambiae and the Homo sapiens (and Mus musculus) genomes, the three organisms that comprise the complex life cycle of the malaria parasite, is complete and will aid in the study of the complex interactions responsible for the disease. Our laboratory is undertaking the investigation of the protein-protein interactions involved in the invasion pathway to potentially identify new targets for immunologic or chemotherapeutic intervention.

The invasive stages of apicomplexan parasites actively penetrate host cells, an essential ability for maintaining an intracellular lifestyle. What has become clear is that numerous parasite and host cell components participate in the rapid invasion process. The process of parasite invasion also involves a unique actin-myosin-based motor that is localized between the plasma membrane and the inner membrane complex, a structure formed by two closely aligned membranes and supported by microtubules. Transmembrane proteins displaying adhesive properties were predicted to link the extracellular substrates with the motor. Studies are underway to analyze the proposed merozoite-specific parasite ligand that links the red blood cell being invaded to the parasite actin-myosin motor. Our approach utilizes proximity biotinylation and subsequent protein identification using mass spectroscopy to discuss proteins associated with the specialized secretory organelles of the parasite and proteins involved with the functioning of the parasite actin-myosin motors. Also, using structural information of the myosin-myosin light chain complex, we have potentially identified small molecule inhibitors of the invasion process.

Selected publications
(See all Lawrence Bergman's publications in PubMed.)

"Characterization of a Plasmodium falciparum orthologue of the yeast ubiquinone-binding protein, Coq10p"
Jenkins BJ, Daly TM, Morrisey JM, Mather MW, Vaidya AB and LW Bergman
PLoS One, e0152197, 2016

Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon
Meibalan E, Comunale MA, Lopez AM, Bergman LW, Mehta A, Vaidya AB and  JM Burns Jr., >
Eukaryot Cell. 14:371-384, 2015

"Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum"
Vaidya AB, Morrisey JM, Zhang Z, Das D, Daly TM, Otto TD, Spillman NJ, Wyvatt M, Siegl P, Marfurt J, Wirjanata G, Sebayang BF, Price RN, Chatterjee A, Nagle A, Stasiak M, Charman SA, Angulo-Barturen I, Ferrer S, Belen Jimenez-Diaz M, Martinez MS, Gamo F, Avery VM, Ruecker A, Delves M, Kirk K, Berriman M, Kortagere S, Burrows J, Fan E and LW Bergman
Nat. Commun. 5:5521, 2014

The structure of the D3 domain of Plasmodium falciparum myosin tail interacting protein MTIP in complex with a nanobody
Khamrui S, Turley S, Pardon E, Steyaert J, Fan E, Verlinde CL, Bergman LW and WG Hol
Mol Biochem Parasitol. 190:87-91, 2013

The compact conformation of the Plasmodium knowlesi myosin tail interacting protein MTIP in complex with the C-terminal helix of myosin A
Turley S, Khamrui S, Bergman LW and WG Hol
Mol Biochem Parasitol. 190:56-59, 2013

"Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials"
Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, DeGrado WF, Sinnis P, Scott RW and DC Greenbaum
Cell Host Microbe, 12: 815-823, 2012.

"Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria"
Cernetich-Ott A, Daly TM, Bergman LW and JM Burns, Jr.
Malar. J., 11: 265, Epub ahead of print, 2012.

"Crystal structure of GAP50, the anchor of the invasion machinery in the inner membrane complex of Plasmodium falciparum"
Bosch J, Paige MH, Vaidya AB, Bergman LW and WG Hol
J. Struct. Biol., 178: 61-73, 2012.

Elevated levels of the Plasmodium yoelii homologue of macrophage migration inhibitory factor attenuate blood-stage malaria.
Thorat S, Daly TM, Bergman LW and Jr. Burns JM.
Infection and Immunity, 78: 5151-5162, 2010.

Structure-based design of novel small-molecule inhibitors of Plasmodium falciparum
Kortagere S, Welsh WJ, Morrisey JM, Daly T, Ejigiri I, Sinnis P, Vaidya AB and Bergman LW.
Journal of Chemical Information and Modeling, 50: 840-849, 2010.

High mobility group protein HMGB2 is a critical regulator of plasmodium oocyst development.
Gissot M, Ting LM, Daly TM, Bergman LW and Sinnis P.
Journal of Biological Chemistry., 283: 17030-17038, 2008.

Functional characterization of a redundant Plasmodium TRAP family invasin, TRAP-like protein, by aldolase binding and a genetic complementation test.
Heiss K, Nie H, Kumar S, Daly TM, Bergman LW and Matuschewski K.
Eukaryotic Cell, 7: 1062-1070, 2008.

Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host.
Mikolajczak SA, Silva-Rivera H, Peng X, Tarun AS, Camargo N, Jacobs-Lorena V, Daly TM, Bergman LW, de la Vega P, Williams J, Aly AS and Kappe SH.
Molecular and Cellular Biology., 28: 6196-6207, 2008.

A combined transcriptome and proteome survey of malaria parasite liver stages.
Tarun AS, Peng X, Dumpit R. F, Ogata Y, Silva-Rivera H, Camargo N. Daly TM, Bergman LW and Kappe SH.
Proceedings of the National Academy of Sciences of the United States of America. 105: 305-310, 2008.

Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor.
Bosch J, Turley S, Daly TM, Bogh SM, Villasmil ML, Zhou N, Morrisey JM, Vaidya AB, Bergman LW and Hol WG J.
Proceedings of the National Academy of Sciences of the United States of America, 103: 4852-4857, 2006.