Dr Horst Schirra
Dr Horst Schirra

Dipl.-Chem. (University Frankfurt) Chemistry, Dr. sc. nat. ETH Zurich
Position: Lecturer; Director, Molecular Biosciences Honours Program

Room: 126A
Building: 76 Molecular Biosciences
Phone: +61 7 336 54878
Email: h.schirra@uq.edu.au

Biography

After undergraduate studies in Chemistry at the Johann-Wolfgang-Goethe University Frankfurt (Germany), I completed my PhD at the Swiss Federal Institute of Technology (ETH) Zurich (Switzerland) and the Max-Planck-Institute for Biochemistry in Martinsried (Germany). In 1999 I joined UQ, first in the Centre for Drug Design and Development and later in the Institute for Molecular Bioscience, supported by an ARC Postdoctoral Fellowship and a Queensland Smart State Fellowship. In 2009 I took up an independent academic position in the School of Chemistry and Molecular Biosciences. I am currently the Director of the School’s Molecular Biosciences Honours Program.

Research Interests and Collaborations

NMR-based Metabonomics and Structural Systems Biology

My main research interest is the delicate interplay between protein structure, dynamics and folding with protein function - by itself and embedded in the context of the whole metabolism of a living organism. I study these relationships with nuclear magnetic resonance (NMR) spectroscopy and a variety of other biochemical and biophysical techniques.

In this context, we want to understand how external triggers, such as drugs, illness, mutations etc., influence and change the metabolism of a subject. We study these metabolic changes by investigating the chemical composition of biofluids with NMR spectroscopy. Changes in the metabolic profile of e.g. urine are studied by multivariate statistical analysis and let us pinpoint, which parts of the subject's metabolism are disturbed. Thus, we can draw conclusions on the mechanism of action of the original trigger.

Current projects range from clinical science and medical applications to environmental science. They involve the study of the effects of growth hormone receptor mutations in mice, the mechanism of phosphine resistance in C. elegans, as well as several projects aimed at developing NMR metabonomics as a tool for clinical diagnosis.

Part of this research theme is to push the boundaries of NMR-based metabonomics by integrating the technique with genomic and proteomic methods and by expanding the toolbox of computational methods to analyse metabonomic data.

Obesity development, related diseases, and clinical diagnosis
One large focus of my research is the application of NMR-based metabonomics in clinical science, speciafically the development of obesity and related diseases. In collaboration with Mike Waters (IMB) and Lars Nielsen (AIBN), we are investigating the effects of growth hormone receptor mutations in transgenic mice, which are an excellent animal model-for late-onset obesity. In collaboration with Gary Leong (IMB), we are investigating the metabolic and clinical effects of childhood obesity as part of the KOALA childhood obesity research program. And in collaboration with Louise Conwell (Royal Children’s Hospital), we are studying the effects of childhood obesity on the development of type 2 diabetes. In addition, I am involved in several collaborations aiming at using NMR-based metabonomics in clinical diagnosis (e.g. Robert A Gardiner, UQCCR).

Environmental Research
The second research focus is the application of NMR-based metabonomics and systems biology in environmental research. In collaboration with Gene Wijffels (CSIRO) and Ross Tellam (CSIRO), we study the metabolic and physiological effects of various stressors on livestock. In collaboration with Paul Ebert (SCMB) we are studying the mechanism of phosphine resistance in C. elegans. And in collaboration with Leon Hugo (QIMR) and Jeremy Brownlie (Griffith University), we are studying the metabolic changes in the development of A. aegypti, the mosquito involved in transmission of Dengue fever.

Structural biology of plant defence proteins
How do plants defend themselves against predators? As they cannot run away, they have evolved a large arsenal of chemical and biochemical defense mechanisms, among them several families of biologically important proteins, such as proteinase inhibitors and plant defensins. In collaboration with David Craik (IMB) we are investigating the three-dimensional structure of these proteins with NMR-spectroscopy and study their biochemical and biophysical properties, as well as their mechanism of protein folding.

Selected Publications

Clarke R. A., Schirra H. J., Catto, J. W., Lavin, M. F., Gardiner, R. A (2010): Markers for Detection of Prostate Cancer, Cancers 2, 1125-1154.
 
Schirra, H. J., Anderson, C. G., Wilson, W. J., Kerr, L., Craik, D. J., Waters, M. J. & Lichanska, A. M. (2008): Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study, PLoS ONE 3, e2764.
 
Schirra, H. J. & Craik, D. J.: Structure and Folding of Potato Type II Proteinase Inhibitors (2005): Circular Permutations and Intramolecular Domain Swapping, Protein Peptide Lett. 12, 421-431.
 
Korsinczky, M. L. J. K., Schirra, H. J., Rosengren, K. J., West, J., Condie, B. A., Otvos, L., Anderson, M. A. & Craik, D. J. (2001): Solution structures by 1H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant.  Journal of Molecular Biology 311, 579-591
 
Schirra, H. J., Renner, C., Czisch, M., Huber-Wunderlich, M., Holak, T. A. & Glockshuber, R. (1998): Structure of Reduced DsbA from Escherichia coli in Solution. Biochemistry 37, 6263-6276.

Funded Projects

ARC Discovery Project 2010-2012
M Waters, H Schirra, L Nielsen
From genotype to phenotype- systems biology bridging the gap
Total value of grant : $330,000

Australian Dental Research Fund 2010
P Ford, A Shah, R Marshall, H Schirra
Characterization of inflammatory responses of co-cutures of epthelial cells,  macrohages and lymphocytes exposed to Porphyromnas gingivalis

Teaching

Physical Chemistry, Biochemistry, Systems Biology, NMR-spectroscopy 
  • CHEM1020: Energetics and Reactivity
  • BIOC3005: Systems Biology
  • Molecular Biosciences Honours Program Director

Awards

  • 2004: Queensland Smart state Fellowship
  • 2001: ARC Australian Postdoctoral Fellowship
  • 1994: PhD Fellowship, Studienstiftung des deutschen Volkes, Germany
  • 1994: Kèkule Fellowship, Fonds der Chemischen Industrie, Germany
  • 1988: Undergraduate Scholarship, Studienstiftung des deutschen Volkes, Germany

Other Activities

  • 2010: “It’s Magic and it’s Science”: Experimental Show