Assoc. Prof Heinrich Hoppe Research
Protozoan parasite cell biology
Drug discovery bioassays
Current research interests
Malaria parasite cell biology
Malaria bioassays for drug screening
Malaria is caused by protozoan parasites that are transmitted to humans by Anopheles mosquitoes and cause disease through the cyclical invasion, modification and destruction of host red blood cells. Plasmodium falciparum is the parasite species predominantly responsible for malaria morbidity and mortality. It is routinely maintained in continuous in vitro cultures, which has significantly aided research aimed at defining the cell biological properties of the organism, as well as efforts to discover novel therapeutics against it. However, many aspects of its fundamental biology remain superficially characterized. An example is its principal feeding mechanism, the ingestion of host red blood cell cytoplasm by endocytosis. The general topology and organization of the endocytic process and pathway have been reasonably well described, but its detailed features and molecular mechanisms remain largely unknown. An ongoing interest of the group is to address this area of research through the use of transgenic parasites and fluorescence and electron microscopy techniques.
A second research interest is in developing and performing bioassays in support of malaria drug discovery projects. The utility of therapeutic drugs is constantly threatened by the specter of resistance, which has already severely compromised the use of two of the three major classes of antimalarials. Consequently, global malaria research efforts focus extensively on the discovery and development of novel antimalarial compounds to augment the alarmingly limited arsenal of existing drugs. Compounds are prepared by synthetic chemistry and natural product extraction by a large number of research groups and their antimalarial potencies routinely evaluated in in vitro parasite cultures. In addition to performing these standard assays, the group is exploring a number of novel methods for interrogating the antimalarial properties of experimental test compounds.
- Tasmiyah Khan (MSc student)
- Dustin Laming (MSc student)
- Thandeka Moyo (BSc Hons student)
- Travis Basson (BSc Hons student)
Undergraduate teaching courses
- Drug Discovery (BSc Hons module)
- Pathogen-host cell interactions (BSc Hons module)
- Protein trafficking and organelle formation
- Amino acids & Proteins
- Membranes & Transporters
- Electrophoresis and Immunological Techniques
- Protein-protein interactions
- Gravestock, D., A.L. Rousseau, A.C.U. Lourens, H.C. Hoppe, L.A. Nkabinde & M.L. Bode. 2012. Novel branched isocyanides as useful building blocks in the Passerini-amine deprotection-acyl migration (PADAM) synthesis of potential HIV-1 protease inhibitors. Tetrahedron Letters (accepted)
- Rossouw, C.L., A. Chetty, F.S. Moolman, R. Anandjiwala, L. Birkoltz, H.C. Hoppe & D.T. Mancama. 2012. Thermo-responsive non-woven scaffolds for “smart” 3D culture. Biotechnology and Bioengineering (accepted)
- Bode, M.L., D. Gravestock, S.S. Moleele, C.W. van der Westhuyzen, S.C. Pelley, P.A. Steenkamp, H.C. Hoppe, T. Khan & L.A. Nkabinde. 2011. Imidazo[1,2-a]pyridine-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors. Bioorganic and Medicinal Chemistry 19:4227-4237.
- Feng, T-S, E.M. Guantai, M.J. Nell, C. Medlin, K. Ncokazi, T.J. Egan, H.C. Hoppe & K. Chibale. 2011. Effects of highly active novel artemisinin-chloroquinoline hybrid compounds on B-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum. Biochemical Pharmacology 82: 236-247.
- Feng, T-S, E.M. Guantai, M.J. Nell, C.E.J. van Rensburg, H.C. Hoppe & K. Chibale. 2011. Antiplasmodial and antitumor activity of dihydroartemisinin analogs derived via the aza-Michael addition reaction. Bioorganic and Medicinal Chemistry Letters 21: 2882-86
- Botha, M., A.N. Chiang, P.G. Needham, L.L. Stephens, H.C. Hoppe, S. Külzer, J.M. Przyborski, K. Lingelbach, P Wipf, J.L. Brodsky, A. Shonhai & G.L. Blatch. 2011. Plasmodium falciparum encodes a single cytosolic type I Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock. Cell Stress and Chaperones 16: 389-401
- Coetzee, J., S. Cronje, L. Dobrzanska, H.G. Raubenheimer, M.J. Nell, C.E.J. van Rensburg & H.C. Hoppe. 2011. First N-heterocycliv ylideneamine gold(I) complexes: characterisation and screening for antitumour and antimalarial activity. Dalton Transactions 40: 1471-83
- Vaid, A., R. Ranjan, G. Verma, W.A. Smythe, H.C. Hoppe & P. Sharma. 2010. PfPI3K, a phosphatidylinositol-3 kinase in Plasmodium falciparum, is exported to the host erythrocyte and is involved in haemoglobin trafficking. Blood 115:2500-07
- Toomey, D., H.C. Hoppe, M.P. Brennan, K.B. Nolan & A.J. Chubb. 2009. Genomes2Drugs: identifies target proteins and lead drugs from transcriptome data. PLoS ONE 4(7):e6195
- Birkholtz, L-M., G. Blatch, T.L. Coetzer, H.C. Hoppe, E. Human, J. Morris, Z. Ngcete, L. Oldfield, R. Roth, A. Shonhai, L. Stephens & A.I. Louw. 2008. Heterologous expression of plasmodial proteins for structural studies and functional annotation. Malaria J. 7:197
- Pesce, E.-R., P. Acharya, U. Tatu, W.S. Nicoll, A. Shonhai, H.C. Hoppe & G.L. Blatch. 2008. Functional analysis of Pfj4, an Hsp40 from Plasmodium falciparum. Int J Biochem Cell Biol 40: 2914-26
- Roberts, L., T. Egan, K.A. Joiner & H.C. Hoppe . 2008. Differential effects of quinoline anti-malarials on endocytosis in Plasmodium falciparum. Antimicrob Agents Chemother 52: 1840-1842.
- Smythe, W.A., K.A. Joiner & H.C. Hoppe. 2008. Actin is required for endocytic trafficking in the malaria parasite Plasmodium falciparum. Cellular Microbiol 10: 1079-1085
- van Wyk, A.W.W., K.A. Lobb,M. Caira, H.C. Hoppe & M.T. Davies-Coleman. 2007.Transformations of manool. Novel tri- and tetracyclic norditerpenoids with in vitro activity against Plasmodium falciparum. J Natural Products 70: 1253-1258
- Rautenbach, M., M.Vlok, M. Stander & H.C. Hoppe. 2007. Inhibition of malaria parasite blood stages by tyrocidines, membrane-active cyclic peptide antibiotics from Bacillus brevis. Biochim Biophys Acta-Biomembranes 1768: 1488-1497
- Wiehart, U.I.M., M. Rautenbach & H.C. Hoppe. 2006. Selective lysis of erythrocytes infected with the trophozoite stage of Plasmodium falciparum by polyene macrolide antibiotics. Biochem Pharmacol 71:779-790.
- Yang, M., I. Coppens, S. Wormsley, P. Baevova, H.C. Hoppe & K.A. Joiner. 2004.The Plasmodium falciparum VPS4 homolog mediates multivesicular body formation. J Cell Science 117:3831-3838
- Hoppe, H.C., D.A. van Schalkwyk, U.I.M. Wiehart, S.A. Meredith, J. Egan & B.W. Weber. 2004. Antimalarial quinolines and artemisinin inhibit endocytosis in Plasmodium falciparum. Antimicrob Agents Chemother 48: 2370-2378
- Ngô, H.M., M. Yang, K. Paprotka, M. Pypaert, H. Hoppe & K.A. Joiner. 2003. AP-1 in Toxoplasma gondii mediates biogenesis of the rhoptry secretory organelle from a post-Golgi compartment. J Biol Chem 278: 5343-5352.
- Robibaro, B., H.C. Hoppe, M. Yang, I. Coppens, H.M. Ngô, T.T. Stedman, K. Paprotka & K.A. Joiner. 2001. Endocytosis in different lifestyles of protozoan parasitism: role in nutrient uptake with special reference to Toxoplasma gondii. Int J Parasitol 31: 1343-1353.
- Liendo, A., T.T Stedman, H.M. Ngo, S. Chaturvedi, H.C. Hoppe & K.A. Joiner. 2001. Toxoplasma gondii ADP-ribosylation factor 1 mediates enhanced release of constitutively secreted dense granule proteins. J Biol Chem 276: 18272-18281.
- Hoppe, H.C. & K.A. Joiner. 2000. Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii. Cellular Microbiol 2: 569-578.
- Hoppe, H.C., M. Yang, H. M. Ngô & K.A. Joiner. 2000. Targeting to the rhoptry organelles of Toxoplasma gondii involves evolutionarily conserved protein sorting mechanisms. Nature Cell Biol 2: 449-456
- Ngô, H.M., H.C. Hoppe & K.A. Joiner. 2000. Differential sorting and post-secretory targeting of proteins in parasitic invasion. Trends Cell Biol10: 67-72.