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Science, Technology and Engineering |
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Research FellowDepartment of BiochemistryMSP2: Characterization and development of a malaria vaccine antigen
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Dr Christopher Adda Research Fellow, Anders lab Phone: +61 3 9479 1157 |
Our focus is on the asexual stage of the life cycle of the malaria parasite, Plasmodium falciparum , in which merozoites rupture either from the liver cells or the red blood cells and proceed to invade other red blood cells. It is these merozoites that are particularly vulnerable to attack by the immune system and hence, there are a number of merozoite proteins that are important vaccine candidates. Our efforts are focused on the merozoite surface and in particular the merozoite surface protein 2 (MSP2), which we are developing into a vaccine. The MSP2 vaccine development project is funded by the Malaria Vaccine Initiative , based in the US. We are also working in close collaboration with GroPep Pty Ltd to develop processes for large-scale production of the vaccine to be used in the initial human trials. My role in the vaccine project includes developing assays for the in-process characterisation and evaluation of the vaccine product as well as pre-clinical efficacy studies of different vaccine formulations.
An important part of developing a vaccine is to understand the functional role and properties of the vaccine candidates so that they can be produced in a way that induces the optimal immune response. A part of my role on the MSP2 vaccine project is to characterise the properties of MSP2 and better understand how the protein functions on the merozoite surface. Our initial studies have shown that recombinant MSP2 is an unstructured molecule that forms a soluble fibre. The fibrils formed by MSP2 have been shown to have similar properties to amyloid suggesting that MSP2 may have a role as a functional amyloid on the merozoite surface. By understanding of the biology of the malaria parasite strategies can be developed to rid the world of this disease.
Publications
Chandrashekaran IR, Adda CG, MacRaild CA, Anders RF, Norton RS. (2010) Inhibition by flavonoids of amyloid-like fibril formation by Plasmodium falciparum merozoite surface protein 2. Biochemistry. 49(28):5899-908.
Yang X, Adda CG, MacRaild CA, Low A, Zhang X, Zeng W, Jackson DC, Anders RF, Norton RS. (2010) Identification of key residues involved in fibril formation by the conserved N-terminal region of Plasmodium falciparum merozoite surface protein 2 (MSP2). Biochimie. 92(10):1287-95.
Anders RF, Adda CG, Foley M, Norton RS. (2009) Recombinant protein vaccines against the asexual blood stages of Plasmodium falciparum. Hum Vaccin. 6(1):39-53. Review.
Adda CG, Murphy VJ, Sunde M, Waddington LJ, Schloegel J, Talbo GH, Vingas K, Kienzle V, Masciantonio R, Howlett GJ, Hodder AN, Foley M, Anders RF. (2009) Plasmodium falciparum merozoite surface protein 2 is unstructured and forms amyloid-like fibrils. Mol Biochem Parasitol. 166(2):159-71.
Zhang X, Perugini MA, Yao S, Adda CG, Murphy VJ, Low A, Anders RF, Norton RS. (2008) Solution conformation, backbone dynamics and lipid interactions of the intrinsically unstructured malaria surface protein MSP2. J Mol Biol. 379(1):105-21.
Yang X, Adda CG, Keizer DW, Murphy VJ, Rizkalla MM, Perugini MA, Jackson DC, Anders RF, Norton RS. (2007) A partially structured region of a largely unstructured protein, Plasmodium falciparum merozoite surface protein 2 (MSP2), forms amyloid-like fibrils. J Pept Sci. 13(12):839-48.
Low A, Chandrashekaran IR, Adda CG, Yao S, Sabo JK, Zhang X, Soetopo A, Anders RF, Norton RS. (2007) Merozoite surface protein 2 of Plasmodium falciparum: expression, structure, dynamics, and fibril formation of the conserved N-terminal domain. Biopolymers 87(1):12-22.
Rekas A, Adda CG, Andrew Aquilina J, Barnham KJ, Sunde M, Galatis D, Williamson NA, Masters CL, Anders RF, Robinson CV, Cappai R, Carver JA. (2004) Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity. J Mol Biol. 340(5):1167-83.
Adda CG, Anders RF, Tilley L, Foley M. (2002) Random sequence libraries displayed on phage: identification of biologically important molecules. Comb Chem High Throughput Screen. 5(1):1-14.
Adda CG, Tilley L, Anders RF, Foley M. (1999) Isolation of peptides that mimic epitopes on a malarial antigen from random peptide libraries displayed on phage. Infect Immun. 67(9):4679-88.
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