Professor, Sanford Orkin Eminent Scholar
M.D., 1972 University of Buenos Aires
Ph.D., 1977 Federal University of Rio de Janeiro
Ph.D., 1979 University of Buenos Aires

RESEARCH

Our strategy is to search for metabolic pathways in parasites that may be essential for their survival but may not find an equivalent counterpart in the host. Currently our efforts are concentrated on the mechanisms by which pH and calcium homeostasis are maintained by different trypanosomatids (T. cruzi, T. brucei, and Leishmania sp.) and malaria parasites (P. falciparum, P. berghei) and more specifically in the biochemical and molecular characterization of a new organelle that we have discovered and named the acidocalcisome [see figure]. This organelle is acidic due to the presence of a vacuolar H+-ATPase and a vacuolar H+ -pyrophosphatase. In addition, it has a Ca2+-ATPase, for Ca2+ uptake, and a Ca2+ channel, for Ca2+ release. In addition, we are studying the signaling mechanisms that occur in the parasites and in the host cells during their interaction. Recent developments in the study of the basic biochemistry of these parasites have resulted in the discovery that bisphosphonates, drugs widely used in the treatment of benign and malignant diseases characterized by increased bone resorption, could have a role as lead antiparasitic agents.

Acidocalcisomes as viewed in a trypanosome.

CONTACT INFORMATION

(706) 542-8104, rdocampo@cb.uga.edu

DOCAMPO-MORENO LAB PAGE

OF NOTE

• Member of the Editorial Board of Molecular and Biochemical Parasitology (1983-present), Experimental Parasitology (2005-2009), and The Biochemical Journal (2005-2008); Associate Editor of The Journal of Eukaryotic Microbiology (2004-2007); Guest Editor of Acta Tropica (2002-2005), and Microscopy and Microanalysis (2004)
  
• Member, Brazilian Academy of Sciences (1999-present)
  
• Burroughs Wellcome Fund New Initiatives in Malaria Research Award (1999-2001) and Burroughs Wellcome Fund Visiting Professor in the Microbiological Sciences (2000-2001)
  

Schematic representation of a typical acidocalcisome. Ca2+ uptake occurs in exchange for H+ by a reaction catalyzed by a vacuolar Ca2+-ATPase that is inhibited by vanadate. A H+ gradient is established by a bafilomycin A1-sensitive vacuolar H+-ATPase and an aminomethylenediphosphonate (AMDP)-sensitive vacuolar H+-PPase. Ca2+ release occurs in exchange for H+ and is favored by sodium-proton exchange. An aquaporin allows water transport. Other transporters (for Mg, Zn, Fe, Pi, PPi, Arginine, Lysine, etc) are probably present. The acidocalcisome is rich in pyrophosphate, short- and long-chain polyphosphate (poly P), magnesium, calcium, sodium, and zinc. An exopolyphophatase (PPX), a pyrophosphatase (PPase) and a poly P kinase (PPK) are also present. Not all these enzymes are necessarily present in all acidocalcisomes described and their internal composition may also vary (from Docampo et al., Nat. Rev. Microbiol. 3, 251-261, 2005).

REPRESENTATIVE PUBLICATIONS

Rohloff, P., Montalvetti, A., and Docampo, R. (2004) Acidocalcisomes and the contractile vacuole are involved in osmoregulation in Trypanosoma cruzi. J. Biol. Chem. 279, 52270-52281

Seufferheld, M., Lea, C., Vieira, M., Oldfield, E., and Docampo, R. (2004) The H+-pyrophosphatase of Rhodospirillum rubrum is predominantly located in polyphosphate-rich acidocalcisomes. J. Biol. Chem. 279, 51193-51202.

Ruiz, F. A., Lea, C. R., Oldfield, E., and Docampo, R. (2004) Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J. Biol. Chem. 279, 44250-44257.

Montalvetti, A., Rohloff, P., and Docampo, R. (2004) A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi. J. Biol. Chem. 279, 38673-38682.

Luo, S., Rohloff, P., Cox, J., Uyemura, S. A., and Docampo, R. (2004) Trypanosoma brucei plasma membrane-type Ca2+-ATPase 1 (TbPMC1) and 2 (TbPMC2) genes encode functional Ca2+-ATPases localized to the acidocalcisomes and plasma membrane, and essential for Ca2+ homeostasis and growth. J. Biol. Chem. 279, 14427-14439.

Lemercier, G., Espiau, B., Ruiz, F.A., Vieira, M., Luo, S., Baltz, T., Docampo, R., and Bakalara, N. (2004) A pyrophosphatase regulating polyphosphate metabolism in acidocalcisomes is essential for Trypanosoma brucei virulence in mice. J. Biol. Chem. 279, 3420-3425.

Uyemura, S.A., Luo, S., Vieira, M., Moreno, S.N.J., and Docampo, R. (2004) Oxidative phosphorylation and rotenone-insensitive malate- and NADH-quinone oxidoreductase in Plasmodium yoelii yoelii mitochondria in situ. J. Biol. Chem. 279, 385-393.

Docampo, R., de Souza, W., Miranda, K., Rohloff, P., and Moreno, S.N.J. (2005) Acidocalcisomes- conserved from bacteria to man, Nat. Rev. Microbiol. 3, 251-261.

Smith, S.A., Mutch, N.J., Baskar, D., Rohloff, P., Docampo, R., and Morrissey, J.H. (2006) Polyphosphate modulates blood coagulation and fibrinolysis. Proc. Natl. Acad. Sci. U.S.A., 103, 903-908.

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