Molecular Plant Biotechnology

Overview

Overview

Expression of recombinant proteins in plants, molecular basis of the N-glycan biosynthesis pathway in plants. Intracellular molecular processes of glycan biosynthesis and protein transport.

Leader: Ao.Univ.Prof. Mag. Dr. Herta Steinkellner

Orientation

The research area encompasses basic research with application-oriented aspects in the field of molecular cell biology and biotechnology. The aim is to understand the molecular cellular processes involved in the expression of recombinant proteins in plants in order to use these optimally for the production of biopharmaceuticals. Of particular interest is above all the investigation and the targeted modification of posttranslational modifications such as glycosylation.

Specific tasks:

  • Biosynthesis of  recombinant secretory proteins in plants
  • Intracellular transport of (recombinant) proteins in plants
  • Subcellular compartmentation 
  • Molekular mechanisms of glycan-biosynthesis and targeted manipulation thereof (Glycan engineering)

Curriculum Vitae

Projects

Publications

selected publications

In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants. Hurtado J, Acharya D, Lai H, Sun H, Kallolimath S, Steinkellner H, Bai F, Chen Q. Plant Biotechnol J. 2019  doi: 10.1111/pbi.13194.

Advanced Plant-Based Glycan Engineering. Montero-Morales L, Steinkellner H. Front Bioeng Biotechnol. 2018 doi: 10.3389/fbioe.2018.00081. eCollection 2018. Review.

Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody. Mire CE, Geisbert JB, Fenton KA, Agans KN, Flyak AI, Deer DJ, Steinkellner H, Bohorov O, Goodman C, Hiatt A, Kim DH, Pauly MH, Whaley KJ, Crowe JE Jr, Zeitlin L, Geisbert TW. Sci Transl Med. 2017, 9. pii: eaai8711. doi: 10.1126/scitranslmed.aai8711.

Recombinant plant-derived human IgE glycoproteomics. Montero-Morales L, Maresch D, Castilho A, Turupcu A, Ilieva KM,  Karagiannis SN, Lupinek C, Oostenbrink C, Altmann F, Steinkellner H. J Proteomics. 2017 Apr 8. pii: S1874-3919(17)30121-5. doi: 10.1016/j.jprot.2017.04.002.

Engineering of complex protein sialylation in plants. Kallolimath S, Castilho A, Strasser R, Grünwald-Gruber C, Altmann F,  Galuska CE, Galuska SP, Werner S, Werneburg S, Hildebrandt H, Gerardy-Schahn R, Steinkellner H. Proc Natl Acad Sci U S A. 2016 ;113:9498-503. doi: 10.1073/pnas.1604371113.

Monoclonal antibody therapy for Junin virus infection. Zeitlin L, Geisbert JB, Deer DJ, Fenton KA, Bohorov O, Bohorova N, Goodman C, Kim D, Hiatt A, Pauly MH, Velasco J, Whaley KJ, Altmann F, Gruber C, Steinkellner H, Honko AN, Kuehne AI, Aman MJ, Sahandi S, Enterlein S, Zhan X, Enria D, Geisbert TW. Proc Natl Acad Sci U S A. 2016 Apr 4. pii: 201600996. 

Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants. Dicker M, Tschofen M, Maresch D, König J, Juarez P, Orzaez D, Altmann F, Steinkellner H, Strasser R. Front Plant Sci. 2016 Jan 29;7:18. doi: 10.3389/fpls.2016.00018.

Glycan modulation and sulfoengineering of anti-HIV-1 monoclonal antibody PG9 in plants. Loos A, Gach JS, Hackl T, Maresch D, Henkel T, Porodko A, Bui-Minh D, Sommeregger W, Wozniak-Knopp G, Forthal DN, Altmann F, Steinkellner H, Mach L. Proc Natl Acad Sci U S A. 2015 ;112(41):12675-80. doi: 10.1073/pnas.1509090112.

Processing of complex N-glycans in IgG Fc-region is affected by core fucosylation. Castilho A, Gruber C, Thader A, Oostenbrink C, Pechlaner M, Steinkellner H, Altmann F. MAbs. 2015;7:863-70. doi: 10.1080/19420862.2015.1053683.

Castilho A, Windwarder M, Gattinger P, Mach L, Strasser R, Altmann F, Steinkellner H. (2014) Proteolytic and N-Glycan Processing of Human Alpha-1 Antitrypsin Expressed in Nicotiana benthamiana. Plant Physiol. 2014 Oct 29. pii: pp.114.250720.

Strasser R, Altmann F, Steinkellner H. (2014) Controlled glycosylation of plant-produced recombinant proteins. Curr Opin Biotechnol. 30C:95-100. doi: 10.1016/j.copbio.2014.06.008. Review.

Loos A, Gruber C, Altmann F, Mehofer U, Hensel F, Grandits M, Oostenbrink C, Stadlmayr G, Furtmüller PG, Steinkellner H. (2014) Expression and glycoengineering of functionally active heteromultimeric IgM in plants. Proc Natl Acad Sci U S A. 111:6263-8. doi: 10.1073/pnas.1320544111.

Schneider JD, Marillonnet S, Castilho A, Gruber C, Werner S, Mach L, Klimyuk V, Mor TS, Steinkellner H. (2014)  Oligomerization status influences subcellular deposition and glycosylation of recombinant butyrylcholinesterase in Nicotiana benthamiana. Plant Biotechnol J. doi: 10.1111/pbi.12184

Schneider JD, Castilho A, Neumann L, Altmann F, Loos A, Kannan L, Mor TS, Steinkellner H. (2013) Expression of human butyrylcholinesterase with an engineered glycosylation profile resembling the plasma-derived orthologue. Biotechnol J. 2013 Oct 16. doi: 10.1002/biot.201300229

Castilho A, Neumann L, Gattinger P, Strasser R, Vorauer-Uhl K, Sterovsky T, Altmann F, Steinkellner H. (2013) Generation of biologically active multi-sialylated recombinant human EPOFc in plants. PLoS One.8:e54836. doi: 10.1371/journal.pone.0054836. 

Jez J, Castilho A, Grass J, Vorauer-Uhl K, Sterovsky T, Altmann F, Steinkellner H. (2013). Expression of functionally active sialylated human erythropoietin in plants. Biotechnol J. 8:371-82. doi: 10.1002/biot.201200363.

Castilho A, Neumann L, Daskalova S, Mason HS, Steinkellner H, Altmann F, Strasser R. (2012). Engineering of sialylated mucin-type O-glycosylation in plants. J Biol Chem. 287:36518-26. doi: 10.1074/jbc.M112.402685. 

Jez J, Antes B, Castilho A, Kainer M, Wiederkum S, Grass J, Rüker F, Woisetschläger M, Steinkellner H. (2012). Significant impact of single N-glycan residues on the biological activity of Fc-based antibody-like fragments. J Biol Chem. 287:24313-9. doi: 10.1074/jbc.M112.360701.

Zeitlin L, Pettitt J, Scully C, Bohorova N, Kim D, Pauly M, Hiatt A, Ngo L, Steinkellner H, Whaley KJ, Olinger GG. (2011) Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proc Natl Acad Sci U S A. 108:20690-4.


Funding Agencies


Collaborations

  • Department für Chemie, Universität für Bodenkultur Wien; contactperson: Dr. Friedrich Altmann
  • Department of Biotechnology, BOKU-WIEN, contactperson: Renate Kunert, Karola Vorauer-Uhl
  • Oxford Brooks University, Oxford UK , contactperson: Chris Hawes
  • Universität Heidelberg, D, contactperson: David G. Robinson 
  • University Gent, B, contactperson: Ann Depicker
  • UC Irvine School of Medicine, USA, contactperson: Donald Forthal
  • Arizona State University, USA contactperson: Charles Arntzen
  • Mapp biopharmaceuticals, Inc, San Diego, USA, contactperson: Kevin Whaley
  • Icon Genetics GmbH, Bio-Zentrum Halle, Deutschland, Victor Klimyuk