Staff profile

Dr David A Dougan

ARC Australian Research Fellow, Lab Head

Faculty of Science, Technology and Engineering

School of Molecular Sciences
Department of Biochemistry
La Trobe Institute for Molecular Science

Physical Science 4 room 381B/381 (L), Melbourne (Bundoora)

 

Qualifications

BSc Hons, PhD (La Trobe).

Area of study

Biochemistry and Molecular Biology

Brief profile

David Dougan completed his PhD at the Division of Biomolecular Engineering, CSIRO (Melbourne) where he worked on antibody engineering. For his postdoctoral research he joined the lab of Prof. Bernd Bukau - first at the University of Freiburg where he developed his interest in AAA+ proteins and their modulation by adaptor proteins. After three years in Freiburg he moved to the ZMBH (Center for Molecular Biology Heidelberg) set in the picturesque town of Heidelberg where he took up a new appointment as a project leader in Prof. Bukau's lab continuing his work on adaptor proteins and regulated proteolysis in Escherichia coli.

In 2004, he was awarded a QEII Fellowship by the Australian Research Council (ARC) and returned to Australia to set up a joint lab with Dr. Kaye Truscott where he has continued his work on AAA+ proteins and their modulation by specific adaptor proteins, but with a new twist. Currently, David is an ARC Australian Research Fellow, and work in his lab is supported by the ARC.

 

Honours & Awards

2011: ARC, Australian Research Fellowship

2010: Vice-Chancellor Excellence in Research Award (La Trobe University)

2004: ARC, Queen Elizabeth II Research Fellowship

2005: Lorne Young Investigators Award

2004: Ramaciotti Establishment Award

2003: Biology of Molecular Chaperones Poster Award, Tomar, Portugal

 

Lab news

  • Congratulations to Erica Brodie & Jyotsna Nagpal - our 2013 Lorne Protein Structure & Function poster prize winners.
  • Congratulations to Ralf Ottofueling - poster prize winner at the 2012 Lorne Conference on Protein Structure & Function. 

Research interests

Regulators of proteolytic machines

- Stress response pathways

Teaching units

  • Biochemistry and Molecular Biology (Honours)
  • Masters of Biotechnology and Bioinformatics

Recent publications

Book Chapters

Gur E. Ottofueling, R. & Dougan D.A. (2013). Machines of destruction – AAA+ proteases and the adaptors that control them. In Regulated Proteolysis in Microorganisms. Dougan D.A. (ed) Subcellular Biochemistry 66, 3-33.

Miceviski, D. & Dougan D.A. (2013). Proteolytic regulation of stress response pathways in Escherichia coli. In Regulated Proteolysis in Microorganisms. Dougan D.A. (ed) Subcellular Biochemistry 66, 105-128.

Journals 

Lowth B.R., Kirstein-Miles J., Saiyed T., Brötz-Oesterhelt H., Morimoto R.I., Truscott K.N., Dougan D.A. (2012). Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX. J Struct Biol. 179(2), 193-201.

Dougan, D.A. (2012), "Protein homeostasis in mitochondria: AAA+ chaperones & proteases", in Houry, W.A. (ed.), Protein Homeostasis: Folding proteins and maintaining the protein-protein interaction networks, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/bio)

Dougan, D.A., Micevski, D and Truscott, K.N. (2012). The N-end rule pathway: From recognition by N-recognins, to destruction by AAA+ proteases. BBA Molecular Cell Research. 1823(1), 83-91.

Dougan D.A. (2011). Chemical activators of ClpP: Turning Jekyll into Hyde. Chem. & Biol. 18, 1072-1074.

Truscott, K.N. Bezawork-Geleta, A. and Dougan, D.A. (2011). Unfolded Protein Responses in Bacteria and Mitochondria: A Central Role for the ClpXP Machine. IUBMB life. 63, 955-963.

Dougan, D.A., Truscott, K.N. and Zeth, K. (2010). The bacterial N-end rule pathway: expect the unexpected. Mol. Micro. 76, 545-558.

Truscott, K.N., Lowth, B.R., Strack, P.R. & Dougan, D.A. (2010). Diverse functions of mitochondrial AAA+ proteins: protein activation, disaggregation, and degradation. Biochem. Cell Biol. 88, 97-108.

Kirstein, J., Moliere, N., Dougan, D.A. & Turgay, K. (2009). Adapting the machine: Adaptor proteins for Hsp100/Clp and AAA+ proteases. Nature Rev. Micro. 7, 589-599.

Ninnis, R.L., Spall, S.K., Talbo G.H., Truscott, K.N & Dougan, D.A. (2009). Natural substrates of the N-end rule pathway in Escherichia coli. EMBO J 28, 1732-1744.

 

Schuenemann V.J., Kralik S.M., Albrecht R., Spall S.K., Truscott K.N., Dougan D.A. & Zeth, K. (2009). Structural basis of N-end rule substrate recognition in Escherichia coli by the ClpAP adaptor protein ClpS. EMBO Reports 10, 508-514.

Erbse A.H., Wagner J.N., Truscott K.N., Spall S.K., Kirstein J., Zeth K., Turgay K., Mogk A., Bukau B. & Dougan D.A. (2008). Conserved residues in the N-domain of the AAA+ chaperone ClpA, regulate substrate recognition and unfolding. FEBS Journal 275, 1400-1410.

Kirstein J., Dougan D.A., Gerth U., Hecker M., Turgay K. (2007). The tyrosine kinase McsB is a regulated adaptor protein for ClpCP. EMBO J. 26, 2061-70.

Erbse, A., Schmidt, R., Bornemann, T., Schneider-Mergener, J., Mogk, A., Zahn, R., Dougan, D.A. & Bukau, B. (2006).

ClpS is an essential component of the N-end rule pathway in Escherichia coli. Nature 439, 753-756.

 

Kirstein J., Schlothauer T., Dougan D.A., Lilie H., Tischendorf G., Mogk A., Bukau B. & Turgay K. (2006). Adaptor protein controlled oligomerization activates the AAA+ protein ClpC. EMBO J. 25, 1481-1491.

Weibezahn, J., Tessarz, P., Schlieker, C., Zahn, R., Maglica, Z., Lee, S., Zentgraf, H., Weber-Ban, E.U., Dougan, D.A., Tsai, F.T., Mogk, A., Bukau, B. (2004).  Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB. Cell 119, 653-665.

 

Dougan D.A., Weber-Ban E. & Bukau, B (2003). Targeted delivery of an ssrA-tagged substrate by the adaptor protein SspB to its cognate AAA+ protein ClpX. Mol Cell. 12, 373-380.

 

Schlothauer, T., Mogk, A., Dougan D.A., Bukau, B. & Turgay, K. (2003). MecA and ClpC of Bacillus subtilis form a new bipartite chaperone system. Proc. Natl. Acad. Sci. U.S.A. 100, 2306-2311.

 

Zeth, K., Ravelli, R., Paal, K., Cusack, S. Bukau, B. & Dougan D.A. (2002). Structural analysis of the adaptor protein ClpS in complex with the N-terminal domain of ClpA. Nature Struct. Biol. 9, 906-911.

 

Dougan, D.A., Mogk, A., Zeth, K., Turgay, K., and Bukau B. (2002). AAA+ proteins and substrate recognition, it all depends on their partner in crime. FEBS Letters 529, 6-10.

 

Dougan, D.A., Reid, B.G., Horwich, A.L. & Bukau, B. (2002). ClpS, a substrate modulator of the ClpAP machine.  Mol. Cell 9, 673-683. 

  

Research projects

We are interested in a group of proteins referred to as AAA+ proteases that are responsible for general (protein quality control) and regulated protein turnover in bacteria and in some organelles of eukaryotes such as mitochondria. Together with their associated protein cofactors (adaptors) these molecular machines have an intrinsic ability to shape the proteome of their respective compartments thus contributing to key cellular events by controlling the stability of other proteins (substrates). Our research is directed toward gaining an understanding of the molecular mechanism of the AAA+ proteases, substrate delivery by adaptors and the identification of recognition motifs in protein substrates. A detailed understanding of this machinery will allow us to determine the contribution of regulated proteolysis to the temporal and spatial control of important cellular or organellar processes.