Dr Andrew Osborne

Lecturer in Microbial Macromolecular Systems

Room: 602, Structural & Molecular Biology, Division of Biosciences, Faculty of Life Sciences, Darwin Building, UCL

Research interests

How proteins cross membranes
In all cells, from bacteria to humans, proteins have to be transported across membranes. For example, proteins that are secreted by bacteria have to be secreted across the bacterial plasma membrane. In human cells proteins that are targeted to the secretory pathway have to be translocated across the endoplasmic reticulum membrane. I am interested in the molecular mechanism of a particular protein translocation process in the malaria parasite.

In low income countries malaria is a leading cause of death, disproportionately effecting children. Plasmodium, a unicellular eukaryote, causes Malaria and is transmitted to humans via mosquito bites. Symptoms of the disease occur when the parasite enters the bloodstream, where it invades and replicates inside erythrocytes. Within the erythrocyte, Plasmodium resides in a membrane-bounded vacuole, the parasitophorous vacuole (PV). By exporting soluble and membrane proteins across the parasitophorous vacuole membrane, into the cytoplasm and to the surface of the infected erythrocyte, the parasite alters the solute permeability, cytoskeleton, and adhesion properties of its host cell.

Many exported proteins are required for immune evasion and parasite viability, making them excellent drug targets. Likewise components of the export machinery itself may also represent novel drug targets. The localization of some exported proteins to the surface of the infected erythrocyte makes them excellent vaccine candidates. Despite the importance of exported proteins to our understanding and potential treatment of malaria, how proteins are exported across the PV membrane is poorly understood.

andrew osbourne

Figure 1. Plasmodium resides in a membrane vacuole within an erythrocyte

Protein export into the human erythrocyte by the malaria parasite, Plasmodium
My research will address two major questions using cell biological, biochemical, and structural approaches:

  1. How are soluble exported proteins recognized and unfolded by the export apparatus?
  2. What is the molecular mechanism by which soluble proteins are translocated across the PV membrane?

To export proteins, the parasite likely has to assemble a secretion apparatus in the PV membrane. Many intracellular bacteria use secretion systems to translocate proteins across the membranes of their host cells. However, these secretion systems are not found in eukaryotes such as Plasmodium, indicating that the parasite uses a novel secretion apparatus to perform this essential function.

Review articles about protein export in the malaria parasite:
Signal-mediated export of proteins from the malaria parasite to the host erythrocyte Marti M, Baum J, Rug M, Tilley L, Cowman AF.


Osborne, A.R., Speicher K.D., Tamez P.A., Bhattacharjee S., Speicher D.W., Haldar K.The Host Targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum. Mol. Biochem. Parasitol. 2010 May;171(1):25-31.

Erlandson, K.J., Miller, S.B., Nam, Y., Osborne, A.R., Zimmer, J., and Rapoport, T.A. (2008) A role for the two-helix finger of the SecA ATPase in protein translocation. Nature 455: 984-987.

Erlandson, K.J., Or, E., Osborne, A.R., and Rapoport, T.A. (2008) Analysis of polypeptide movement in the SecY channel during SecA-mediated protein translocation.J. Biol. Chem. 283: 15709-15715.

Ménétret, J.F., Schaletzky, J., Clemons, W.M. Jr., Osborne, A.R., Skånland, S.S., Denison, C., Gygi, S.P., Kirkpatrick, D.S., Park, E., Ludtke, S.J., Rapoport, T.A., and Akey, C.W. (2007) Ribosome binding of a single copy of the SecY complex: implications for protein translocation. Mol. Cell 28: 1083-1092.

Osborne, A.R., and Rapoport, T.A. (2007) Protein translocation is mediated by oligomers of the SecY complex with one SecY copy forming the channel. Cell 129: 97-110.

Osborne, A.R., Rapoport, T.A., and van den Berg, B. (2005) Protein translocation by the Sec61/SecY channel. Annu. Rev. Cell. Dev. Biol. 21:529-50.

Osborne, A.R., Flett, A., and Smythe, E. (2005) Endocytosis assays in intact and permeabilized cells. Current Protocols. Unit 11.18.

Osborne, A.R., Clemons, W.M. Jr., and Rapoport, T.A. (2004) A large conformational change of the translocation ATPase SecA. Proc. Natl. Acad. Sci. USA 101: 10937-10942.

Ye, J., Osborne, A.R., Groll, M., and Rapoport, T.A. (2004) RecA-like motor ATPases - lessons from structures. Biochim. Biophys. Acta 1659: 1-18.

Antoniou, A.N., Ford, S., Alphey, M., Osborne, A.R., Elliot, T., and Powis, S.J. (2002) The oxidoreductase Erp57 efficiently reduces partially folded in preference to fully folded MHC class I molecules. EMBO J. 21: 2655-2663.

McLauchlan, H., Newell, J., Morrice, N., Osborne, A.R., West, M., and Smythe, E. (1998) A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits. Curr. Biol. 8: 34-45.



andrew osbourne Dr Andrew Osborne



Institute of Structural and Molecular Biology, University of London

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