Jürgen Bosch, PhD
Center & Institute Affiliation(s):
615 N. Wolfe Street
Baltimore , Maryland 21205
PhD , Technical University of Munich , 2003
MS , Technical University of Munich , 1998
Our current research interest is focused on the Plasmodium parasite, the causative agent of Malaria, leading to 300-500 million infections per year and more than 1.2 million deaths worldwide [Murray et al.,The Lancet (2012) vol. 379 (9814) pp. 413-431].
The complex life cycle of the malaria parasite involves switching between mosquito and human hosts. Plasmodium is thereby constantly threatened by the host immune system, from which it evades by hiding inside of human liver- and red blood-, as well as mosquito midgut cells. This strategy requires the parasite to traverse various host membranes and undergo dramatic conversion processes to accommodate its rapidly changing environment. In my lab, we are interested in the intricate molecular mechanisms underlying these multiple host cell passages and the metabolic conversion processes in between (for more details visit our website at http://lupo.jhsph.edu).
Using a targeted structure based drug design approach, we employ X-ray crystallography, virtual library screening (VLS), and surface plasmon resonance (SPR) methods to study important key players of these plasmodial mechanisms, with the ultimate aim to develop novel, drug-like compounds to future therapeutic use.
Malaria; crystallography; drug design; Glideosome; Invasion machinery; Egress; Autophagy; Proteases; Surface Plasmon Resonance; SPR; protein protein interaction; FBDD; Fragment Based Drug Design; Interface inhibitors; Biophysics; Biochemistry; Plasmodium; Atg8; Atg3; Atg7; Toxoplasma; Cryptosporidium; structure based drug design; SBDD; Aldolase; MTIP; GAP50
Small molecule drug bound to an essential protein interface of a plasmodial protein.
Hain A.U.P., Bartee D., Sanders N., Miller A., Sullivan D., Levitskaya J., Freel Meyers C., Bosch J., Identification of an Atg8-Atg3 protein-protein interaction inhibitor from the Medicines for Malaria Venture Malaria Box active in blood and liver stage Plasmodium falciparum parasites. (epub ahead of print, Journal of Medicinal Chemistry )
Jayabalasingham B., Voss C., Ehrenman K., Romano J.D., Smith M.E., Fidock D.A., Bosch J., Coppens I.
Autophagy. 2013 Dec 12;10(2). [Epub ahead of print] PubMed PMID 24342964
Adelaide U.P. Hain, Ryan R. Weltzer, Holly Hammond, Bamini Jayabalasingham, Rhoel R. Dinglasan, David R. M. Graham, David R. Colquhoun, Isabelle Coppens, Jürgen Bosch Structural characterization and inhibition of the Plasmodium Atg8-Atg3 interaction . Journal of Structural Biology (2012)
Boucher L.E., Bosch J.
Development of a multifunctional tool for drug screening against Plasmodial protein-protein interactions via Surface Plasmon Resonance J. Mol. Recognit. (2013) vol 26 (10) pp. 496-500 (DOI: 10.1002/jmr.2292) PubMed PMID 23996492
Ipsita Pal-Bhowmick, John Andersen, Prakash Srinivasan, David L. Narum, Jürgen Bosch , Louis H. Miller
The binding of aldolase and GAPDH to the cytoplasmic tails of Plasmodium falciparum merozoite DBL and RH ligands. mBio (2012)
Bosch et al. Crystal structure of GAP50, the anchor of the invasion machinery in the inner membrane complex of Plasmodium falciparum. Journal of structural biology (2012) vol. 178 (1) pp. 61-73