Assistant Professor
Department of Biochemistry and Molecular Biology
Bloomberg School of Public Health

jubosch@jhsph.edu

W8708 Hygiene Building
615 N. Wolfe Street Street
Baltimore, MD 21205

Office: 410-614-4742
Lab: 410-614-4894

Our current research interest is focused on the invasion machinery of the Plasmodium parasite, the causative agent of Malaria, leading to 300-500 million infections per year and more than 1 million deaths worldwide.

The complex life cycle of the Plasmodium parasite requires traversing various membranes and even changing hosts. An infected female Anopheles Mosquito injects sporozoites into the human host, which then invade liver cells. After transforming into the blood-stage, the newly formed merozoites are released into the blood cycle and invade erythrocytes, where the parasites are mostly invisible to the human immune system. Only during the rupture of the erythrocytes following the release of multiplied merozoites, the immune system reacts, leading to the typical symptoms of malaria, e.g. fever, flu-like symptoms, headache. An uninfected Anopheles mosquito can then ingest merozoites during a blood meal of an infected human and close the lifecycle of the parasite.

The invasion machinery, which is required to traverse host membranes is well conserved throughout the genus Apicomplexa including e.g. Toxoplasma and Cryptosporidium. Our aim is to gain structural insights via X-ray crystallography into the interacting partners of the invasion machinery. Based on our structural studies we try to identify novel compounds which render the interaction between these partners impossible, leading perhaps to a novel drug-like compound for future use in Malaria prevention and therapeutic treatment.

Selected Publications
Fan, E., D. Baker, S. Fields, M.H. Gelb, F.S. Buckner, W.C. Voorhis, E. Phizicky, M. Dumont, C. Mehlin, E. Grayhack, M. Sullivan, C. Verlinde, G. DeTitta, D.R. Meldrum, E.A. Merritt, T. Earnest, M. Soltis, F. Zucker, P.J. Myler, L. Schoenfeld, D. Kim, L. Worthey, D. LaCount, M. Vignali, J. Li, S. Mondal, A. Massey, B. Carroll, S. Gulde, J. Luft, L. DeSoto, M. Holl, J. Caruthers, J. Bosch, M. Robien, T. Arakaki, M. Holmes, I. Trong, and W.G.J. Hol. (2008) Structural genomics of pathogenic protozoa: an overview. Methods Mol. Biol. 426:497-513.

Bosch, J., S. Turley, C. Roach, T.M. Daly, L.W. Bergman, and W.G.J. Hol. (2007) The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery. J. Mol. Biol. 372:77-88.

Bosch, J., C.A. Buscaglia, B. Krumm, B.P. Ingason, R. Lucas, C. Roach, T. Cardozo, V. Nussenzweig, and W.G.J. Hol. (2007) Aldolase provides an unusual binding site for thrombospondin-related anonymous protein in the invasion machinery of the malaria parasite. Proc. Natl. Acad. Sci. USA 104:7015-7020.

Bosch, J., T. Tamura, N. Tamura, W. Baumeister W, and L.O. Essen. (2007) The beta-propeller domain of the trilobed protease from Pyrococcus furiosus reveals an open Velcro topology. Acta Crystallogr. D Biol. Crystallogr. 63:179-187.

Rockel, B., J. Bosch, and W. Baumeister. (2006) Structural studies of large, self-compartmentalizing proteases. In Protein Degradation Vol. 2 The Ubiquitin-Proteasome System, ed. by Mayer, Ciechanover, and Rechsteiner, 183-214. Germany: WILEY-VCH Verlag GmbH & Co. KGaA.

Bosch, J., M.A. Robien, C. Mehlin, E. Boni, A. Riechers, F.S. Buckner, W.C. Van Voorhis, P.J. Myler, E.A. Worthey, G. DeTitta, J.R. Luft, A. Lauricella, S. Gulde, L.A. Anderson, O. Kalyuzhniy, H.M. Neely, J. Ross, T.N. Earnest, M. Soltis, L. Schoenfeld, F. Zucker, E.A. Merritt, E. Fan, C.L. Verlinde, and W.G. Hol. (2006) Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase. J. Med. Chem. 49:5939-5946.

Bosch, J., S. Turley, T.M. Daly, S.M. Bogh, M.L. Villasmil, C. Roach, N. Zhou, J.M. Morrisey, A.B. Vaidya, L.W. Bergman, and W.G. Hol. (2006) Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor. Proc. Natl. Acad. Sci. USA 103:4852-4857.

Robien, M.A., J. Bosch, F.S. Buckner, W.C. Van Voorhis, E.A. Worthey, P. Myler, C. Mehlin, E.E. Boni, O. Kalyuzhniy, L. Anderson, A. Lauricella, S. Gulde, J.R. Luft, G. DeTitta, J.M. Caruthers, K.O. Hodgson, M. Soltis, F. Zucker, C.L. Verlinde, E.A. Merritt, L.W. Schoenfeld, and W.G. Hol. (2006) Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 A resolution reveals intriguing extra electron density in the active site. Proteins 62:570-577.

Caruthers, J., J. Bosch, F. Buckner, W. Van Voorhis, P. Myler, E. Worthey, C. Mehlin, E. Boni, G. DeTitta, J. Luft, A. Lauricella, O. Kalyuzhniy, L. Anderson, F. Zucker, M. Soltis, and W.G. Hol. (2006) Structure of a ribulose 5-phosphate 3-epimerase from Plasmodium falciparum. Proteins 62:338-342.