The Walter and Eliza Hall Institute of Medical Research

Dr Thomas Nebl

Details

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Division: Systems Biology and Personalised Medicine

Research Overview

I am a senior research officer at The Walter & Eliza Hall Institute and currently manage the WEHI Proteomics Laboratory. Our facility uses mass spectrometry as the key technology to solve complex problems presented by how a biological system works.

Parasite-host interactions

Most of my research is a direct continuation of proteomics approaches I developed in collaboration with research groups of the WEHI Infection and Immunity Division over the past ten years. The apicomplexan parasites Plasmodium falciparum and Toxoplama gondii infect millions of people worldwide and cause a major global health burden due to malaria or toxoplasmosis disease, respectively. These obligatory parasites depend on the invasion of host cells for survival and proliferation, but the underlying molecular mechanisms remain poorly understood.

As part of a highly productive team I pursue integrated, multi-disciplinary research aimed at dissecting signaling networks regulating apicomplexan invasion and solving other complex problems related to parasite-host interactions.

Serum proteomics

One of the main priorities of the WEHI Proteomics laboratory will be to implement robust quantitative proteomics workflows, both isotopic-labeling and label-free approaches. Figuring out what to measure (i.e. determining what proteins serve as biomarkers for disease processes) and how to perform the measurements (i.e. identify the protein and measure its concentration, sort out signal/noise issues) constitute significant challenges in biological experiments.

My future efforts will focus on establishing proteomics technologies for the high-throughput screening of human serum samples, and utilizing quantitative approaches for the discovery of potential biomarkers of human diseases such as malaria or rheumatoid arthritis.

Research Projects

• Dissection of phosphorylation networks mediating apicomplexan host cell invasion
• Immunoprotoemics analysis of human antibody responses to Plasmodium falciparum
• Serum proteomics approaches for the discovery of human disease biomarkers

Major Publications

1. Nebl T, Prieto JH, Kapp E, Smith BJ, Williams MJ, et al. 2011 Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex. PLoS Pathog 7(9): e1002222. doi:10.1371/journal.ppat.1002222
2. Leykauf K, Treeck M, Gilson PR, Nebl T, Braulke T, Cowman AF, Gilberger TW,Crabb BS. Protein kinase a dependent phosphorylation of apical membrane antigen 1plays an important role in erythrocyte invasion by the malaria parasite. PLoSPathog. 2010 Jun 3;6(6):e1000941. PMID: 20532217; PubMed Central PMCID: PMC2880582.
3. Gilson PR, O'Donnell RA, Nebl T, Sanders PR, Wickham ME, McElwain TF, deKoning-Ward TF, Crabb BS. MSP1(19) miniproteins can serve as targets for invasioninhibitory antibodies in Plasmodium falciparum provided they contain the correct domains for cell surface trafficking. Mol Microbiol. 2008 Apr;68(1):124-38. PMID: 18333885.
4. Sanders PR, Cantin GT, Greenbaum DC, Gilson PR, Nebl T, Moritz RL, Yates JR3rd, Hodder AN, Crabb BS. Identification of protein complexes indetergent-resistant membranes of Plasmodium falciparum schizonts. Mol BiochemParasitol. 2007 Aug;154(2):148-57. Epub 2007 Apr 27. PMID: 17553576.
5. Takizawa N, Smith TC, Nebl T, Crowley JL, Palmieri SJ, Lifshitz LM, EhrhardtAG, Hoffman LM, Beckerle MC, Luna EJ. Supervillin modulation of focal adhesionsinvolving TRIP6/ZRP-1. J Cell Biol. 2006 Jul 31;174(3):447-58. PMID: 16880273; PubMed Central PMCID: PMC2064240.
6. Gilson PR, Nebl T, Vukcevic D, Moritz RL, Sargeant T, Speed TP, Schofield L,Crabb BS. Identification and stoichiometry ofglycosylphosphatidylinositol-anchored membrane proteins of the human malariaparasite Plasmodium falciparum. Mol Cell Proteomics. 2006 Jul;5(7):1286-99. Epub Apr 2006 PMID: 16603573.
7. Nebl T, De Veer MJ, Schofield L. Stimulation of innate immune responses bymalarial glycosylphosphatidylinositol via pattern recognition receptors. Parasitology. 2005;130 Suppl:S45-62. PMID: 16281992.
8. Sanders PR, Gilson PR, Cantin GT, Greenbaum DC, Nebl T, Carucci DJ, McConvilleMJ, Schofield L, Hodder AN, Yates JR 3rd, Crabb BS. Distinct protein classesincluding novel merozoite surface antigens in Raft-like membranes of Plasmodiumfalciparum. J Biol Chem. 2005 Dec 2;280(48):40169-76. Epub 2005 Oct 3. PMID: 16203726.
9. Oh SW, Pope RK, Smith KP, Crowley JL, Nebl T, Lawrence JB, Luna EJ. Archvillin, a muscle-specific isoform of supervillin, is an early expressed component of the costameric membrane skeleton. J Cell Sci. 2003 Jun 1;116(Pt 11):2261-75. Epub 2003 Apr 23. PubMed PMID: 12711699.
10. Nebl T, Pestonjamasp KN, Leszyk JD, Crowley JL, Oh SW, Luna EJ. Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem. 2002 Nov 8;277(45):43399-409. Epub 2002 Aug 28. PubMed PMID: 12202484.

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