Professor David Craik

ARC Laureate Fellow

Institute for Molecular Bioscience
d.craik@imb.uq.edu.au
+61 7 334 62019

Overview

David Craik is in the Division of Chemistry and Structural Biology at the Institute for Molecular Bioscience, The University of Queensland, Australia. He discovered the cyclotide family of circular proteins and has characterized the structures of many animal toxins including conotoxins from cone snail venoms. He heads a research team of 35 researchers whose current work focuses on applications of circular proteins, toxins and NMR in drug design.

He is author of over 600 scientific papers, including 6 in Nature/Nature Communications/Nature Neoroscience/Nature Structural Biology/Nature Chemical Biology/Nature Chemistry, 1 in Science, 9 in PNAS and 8 in Angewandte Chemie. He is a Fellow of the Australian Academy of Science and has received numerous awards for his research, including the Ralph F. Hirschmann Award from the American Chemical Society (2011), Ramaciotti Medal for Excellence in Biomedical Research (2014), GlaxoSmithKline Award for Research Excellence (2014), the Vincent du Vigneaud Award from the American Peptide Society (2015) and the FAOBMB Award for Research Excellence (2015). He is an Honorary Professor of Jinan University, Guangzhou and has an Honorary Doctorate from Kalmar University in Sweden.

Biography

David Craik obtained his PhD in organic chemistry from La Trobe University in Melbourne, Australia and undertook postdoctoral studies at Florida State and Syracuse Universities before taking up a lectureship at the Victorian College of Pharmacy in 1983. He was appointed Professor of Medicinal Chemistry and Head of School in 1988. He moved to University of Queensland in 1995 to set up a new biomolecular NMR laboratory and is currently an Australian Research Council Laureate Fellow.

Key Discoveries

David Craik has made discoveries of new classes of proteins, generated new knowledge on their structure and function, and used this information to design and chemically re-engineer new classes of protein-based drug leads and agricultural pest control agents. In particular, his major achievements are:

  • the discovery of cyclotides, the largest known family of circular proteins. As well as a circular backbone, cyclotides contain a knotted arrangement of cross-linking disulfide bonds, making them remarkably stable. His discovery of these proteins was sparked in part from anecdotal reports of medicinal practices in Africa where women make a tea from the plant Oldenlandia affinis by boiling it in water and sipping it during labour to accelerate child birth. He determined the structure of the bioactive component of this medicinal tea and found that it had an unprecedented head-to-tail cyclic peptide backbone combined with a cystine knot.
  • the first structural and functional characterizations of prototypic circular proteins in higher organisms - Professor Craik was one of the first to recognize that other families of ribosomally synthesized cyclic peptides exist. As examples from bacteria and animals emerged, Professor Craik was at the forefront of their structural characterization, reporting the first structures of theta-defensins from animals and the threaded lasso peptide microcin J25 from bacteria, as well as new examples of cyclic peptides from plants.
  • the development of artificially cyclized peptide toxins as drug leads – he developed an orally active peptide that is 100 times more potent than the leading clinically used drug for neuropathic pain.

Research Training

Professor Craik has trained more than 60 PhD students. He was awarded UQ’s Research Supervision Excellence Award in 2007 on the basis of his mentoring and innovations in postgraduate training, including his “writing retreats” to mentor students and postdocs on science writing skills. He was awarded an honorary doctorate from Kalmar University, Sweden for his contributions to international student exchange programs.

Professional Activities

Professor Craik founded and chaired the 1st, 2nd and 3rd International Conferences on Circular Proteins (2009, 2012 and 2015). He is on the Boards of nine international journals and on the Council of the American Peptide Society. He is the director two Brisbane-based biotech companies. He is on the Scientific Advisory Boards of James Cook University’s Centre for Biodiscovery and Molecular Development of Therapeutics (BMDT) and the University of Wollongong’s Illawara Health and Medical Research Institute (IHMRI). He conceived and supports a publicly accessible database Cybase on circular proteins (www.cybase.org.au) and another database on conotoxins (www.conoserver.org).

Research Interests

  • Discovery of bioactive peptides and peptide-based drug design
    The Craik group focuses on the discovery and applications of small disulfide-rich proteins as leads in drug design. Such proteins often have potent biological activities and, because of their cross-linking disulfide bonds, usually have well defined three-dimensional structures that can be determined using NMR spectroscopy. NMR is one of the main techniques we use in the laboratory. The proteins we study come from animal and plant sources, as well as "designer" proteins we produce in the lab. In particular we have been exploring the bioengineering of circular proteins, based on our discovery of a naturally occurring family of cyclic proteins called cyclotides. By cyclising proteins and creating embedded knots within the structures using disulfide bonds we are able to significantly enhance the stability of proteins. We are applying our technology to the design of drugs for pain, cancer (prostate cancer, chronic myeloid leukeamia and melanoma), cardiovascular disease, multiple sclerosis, and metabolic diseases (obesity and diabetes). Our goal is to overcome current limitations on the use of conventional proteins as drugs, i.e. their poor bioavailability and susceptibility to degradation in vivo. We are currently determining relationships between structure and activity in a wide range of cystine knot proteins, including those from plants, cone-snail venoms, snakes, spiders and frogs. Cystine knot proteins have applications in agriculture as well as in the development of pharmaceuticals, and in collaboration with Dr Marilyn Anderson at La Trobe University we have been examining the insecticidal properties of a range of disulfide rich proteins. The cyclotide proteins discovered in our laboratory show particular promise as "natural" insecticides against pests in a range of crop plants.
  • Production of-based pharmaceuticals in plants
    Our group is interested in using plants as ‘biofactories’ for producing high value peptide-based pharmaceuticals. The peptides are either expressed in the leaves of plants, which are harvested to allow extraction of the pharmaceutical product for conventional formulation or tableting. Alternatively, we can express the therapeutic peptides specifically in the seeds of plants so that the seed becomes the bio pill. This technology has the potential to make high-tech ‘designer’ medicines available to patients in developing countries as well as the potential to lower the costs of production of refined pharmaceuticals. This work is supported by a grant from the Australian Research Council and the Clive and Vera Ramaciotti Foundation.
  • Structural biology of peptides and proteins
    We use NMR spectroscopy to determine the structures of a wide range of peptides and proteins so that we can understand fundamental biological processes and use structural information for the development of pharmaceuticals or next generation agrichemicals. NMR allows structures to be determined in solution under physiologically relevant conditions.

Research Impacts

Professor Craik is known internationally for his pioneering work on the discovery and study of naturally occurring circular proteins. Gene-encoded circular proteins were unknown when he started working on them in the 1990s, but it is now clear that their unique topology makes them remarkably stable compared to conventional proteins. Circular proteins are exciting leads for drug design and protein engineering applications, where resistance to breakdown by enzymes is critically important. In one example, Professor Craik's lab has been working on using a peptide from cone snail venom as a pain relief drug 100 times more potent than morphine. Circular proteins also have considerable potential as natural insecticides, diagnostic probes, and as tools in neuroscience. He has developed methods for using plants as ‘biofactories’ to make these peptides.

Specific Measures of Impact

  • Editor of two books; NMR in Drug Design (CRC Press) and Plant Cyclotides (Academic Press)
  • Author of more than 600 papers; h-index 76; Citations 21,000
  • Professor Craik has given more than 500 presentations over his career, including 112 Plenary/invited lectures at national and international conferences and university colloquia or industry forums in 23 countries over the past 5 years.
  • Numerous international and national awards including the Adrien Albert Award (Royal Australian Chemical Institute, 1993); ANZMAG Medal (Australian & New Zealand Society for Magnetic Resonance, 2004); Royal Australian Chemical Institute H G Smith Medal (2006); American Chemical Society Ralph F. Hirschmann Award in Peptide Chemistry (2011); Josef Rudinger Memorial Lecture Award, European Peptide Society (2012); La Trobe University Distinguished Alumnus Award (2013); GlaxoSmithKline Award for Research Excellence (2014); Ramaciotti Medal for Excellence in Biomedical Research (2014); Vincent du Vigneaud Award (American Peptide Society, 2015); Australian Research Council Australian Laureate Fellowship (2015); FAOBMB Award for Research Excellence (Federation of Asian and Oceanian Biochemists and Molecular Biologists, 2015); $1million Ramaciotti Biomedical Research Award (2015)
  • Fellow of the Australian Academy of Science
  • Fellow of the Royal Australian Chemical Institute, the Royal Society of Chemistry and member of six other learned societies.

Community Engagement

  • ABC Radio interview with David Curnow on “Medicines in Plants” 14th March 2016
  • Named one of the Best & Brightest in Queensland for 2015, Courier Mail, Q Weekend, Dec 5-6, 2015
  • Radio interview on conesnail envenomation, June 10th 2015 ABC News
  • UQ Alumni lecture, Singapore April 2015
  • Press release by the American Society on Microbiology on a new antimicrobial peptide from frog skin February 11th 2015
  • Catalyst documentary on “Plant Based Medicines”, aired 3rd Feb 2015, ABC2
  • Radio National interview November following GSK Award 2014 with Fran Kelly, 27th November 2014
  • Televised Press conference at American Chemical Society National Convention. March 2014 Dallas, USA
  • Approx. a dozen radio interviews in US, Canada, Australia associated with ACS Convention
  • Feature article on our research on ABC’s Science Online
  • Author of Wikipedia entry on cyclotides
  • Presentation to the Minister for State Development, April 2007
  • Press coverage (Courier Mail, UQ News) on development of lead compound for the treatment of pain 2010-2011
  • Invited public lecture at Florida Atlantic University 2011
  • European documentary on cone snail research televised in Europe in December 2013

Qualifications

  • PhD, La Trobe University
  • Bachelor of Science (Honours), La Trobe University

Publications

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Grants

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Supervision

  • Doctor Philosophy

  • Doctor Philosophy

  • Doctor Philosophy

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Available Projects

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Publications

Featured Publications

Book Chapter

  • Henriques, Sonia Troeira and Craik, David J. (2015). Discovery of peptide drugs from natural sources. In Ben M. Dunn (Ed.), Peptide chemistry and drug design (pp. 203-245) Hoboken NJ, United States: John Wiley & Sons. doi:10.1002/9781118995303.ch6

  • Akcan, Muharrem and Craik, David J. (2015). Engineering venom peptides to improve their stability and bioavailability. In Glenn F. King (Ed.), Venoms to Drugs: Venom as a Source for the Development of Human Therapeutics (pp. 275-289) Cambridge, United Kingdom: Royal Society of Chemistry. doi:10.1039/9781849737876-00275

  • Kaas, Quentin and Craik, David J. (2014). Conotoxins and other conopeptides. In Stéphane La Barre and Jean-Michel Kornprobst (Ed.), Outstanding Marine Molecules: Chemistry, Biology, Analysis (pp. 319-332) Weinheim, Germany: Wiley-VCH Verlag. doi:10.1002/9783527681501.ch14

  • Northfield, Susan E., Poth, Aaron, D'Souza, Charlotte and Craik, David J. (2014). Cyclotide analysis. In Robert A. Meyers (Ed.), Encyclopedia of Analytical Chemistry (pp. 1-18) Hoboken, NJ, USA: John Wiley & Sons. doi:10.1002/9780470027318.a9933

  • Akcan, Muharrem and Craik, David J. (2013). Synthesis of cyclic disulfide-rich peptides. In Knud J. Jensen, Pernille Tofteng Shelton and Soren L. Pedersen (Ed.), Peptide synthesis and applications 2nd ed. (pp. 89-101) New York, NY, United States: Springer Science + Business Media. doi:10.1007/978-1-62703-544-6_6

  • Craik, David J., Henriques, Sonia Troeira, Mylne, Joshua S. and Wang, Conan K. (2012). Cyclotide isolation and characterization. In David A. Hopwood (Ed.), Natural product biosynthesis by microorganisms and plants, part B (pp. 37-62) Burlington, USA: Elsevier. doi:10.1016/B978-0-12-394291-3.00024-1

  • Akcan, Muharrem and Craik, David J. (2011). Conotoxin-based leads in drug design. In Miguel Castanho and Nuno C. Santos (Ed.), Peptide drug discovery and development: Translational research in academia and industry (pp. 119-137) Weinheim, Germany: Wiley-VCH.

  • Daly, Norelle L., Gruber, Christian W., Goransson, Ulf and Craik, David J. (2011). Cystine knot folding in cyclotides. In Folding of disulfide proteins (pp. 43-61) New York , NY, U.S.A.: Springer. doi:10.1007/978-1-4419-7273-6

  • Kaas, Quentin, Westermann, Jan-Christoph, Troeira Henriques, Sonia and Craik, David J. (2010). Antimicrobial Peptides in Plants. In Guangshun Wang (Ed.), Antimicrobial Peptides: Discovery, Design, and Novel Therapeutic Strategies (pp. 40-71) Wallingford, Oxfordshire, UK: CAB International. doi:10.1079/9781845936570.0040

  • Dornenburg, Heike and Craik, David J. (2010). Cyclotides. In Michael C. Flickinger (Ed.), Encyclopedia of industrial biotechnology: Bioprocess, bioseparation, and cell technology (pp. 1849-1866) Hoboken, N.J., U.S.A.: Wiley. doi:10.1002/9780470054581

  • Wang, Conan K., Huang, Yen-Hua, Greenwood, Kathryn and Craik, David J. (2010). Membrane binding of cyclotides. In Miguel A.R.B. Castanho (Ed.), Membrane-active peptides: Methods and results on structure and function (pp. 597-672) La Jolla, CA, U.S.A.: International University Line.

  • Craik, David J., Smith, Philippa A. and Clark, Richard James (2010). NMR-based screening and drug discovery. In Donald J. Abraham, David P. Rotella and Alfred Burger (Ed.), Burger's medicinal chemistry, drug discovery, and development 7th ed. (pp. 359-437) Hoboken, N.J.: Wiley. doi:10.1002/0471266949

  • Jan Westermann and Craik, David J. (2010). Plant peptide toxins from nonmarine environments. In Mander, Lewis and Liu, Hung-Wen (Ed.), Comprehensive natural products II: Chemistry and biology (pp. 257-285) Oxford,U.K.: Elsevier Science. doi:10.1016/B978-008045382-8.00115-5

  • Daly, N. L. and Craik, D. J. (2009). Folding motifs of cystine-rich peptides. In Johannes Buchner and Luis Moroder (Ed.), Oxidative folding of peptides and proteins (pp. 318-344) Cambridge, UK: Royal Society of Chemistry.

  • Rosengren, K. Johan, Daly, N. L. and Craik, D. J. (2009). NMR of peptide toxins. In Graham A. Webb (Ed.), Annual reports on NMR Spectroscopy x ed. (pp. 89-147) Oxford England U.K.: Academic Press Elsevier.

  • Jan Westermann and Craik, David J. (2008). NMR in peptide drug development. In Laszlo Otvos (Ed.), Peptide-Based Drug Design (Methods in Molecular Biology) (pp. 87-113) New York: Humana Press. doi:10.1007/978-1-59745-419-3

  • Craik, D. J. and Clark, R. J. (2008). Structure-based Drug Design and NMR-based screening. In R. A. Meyers (Ed.), Pharmacology from drug development to gene therapy (pp. 225-313) Weinheim: Wiley-VCH Verlag GMBH & Co.

  • Cemazar, M. and Craik, D. J. (2006). NMR and Structural Genomics in the Pharmaceutical Sciences. In Graham A. Webb (Ed.), Modern Magnetic Resonance Part 2: Applications in Medical and Pharmaceutical Sciences 1 ed. (pp. 1411-1419) Netherlands: Springer.

  • Schirra, H. J. and Craik, D. J. (2006). Overview of NMR in the Pharmaceutical Sciences. In Graham A. Webb (Ed.), Modern Magnetic Resonance Part 2: Applications in Medical and Pharmaceutical Sciences 1 ed. (pp. 1177-1184) Netherlands: Springer.

  • Craik, D. J. and Clark, R. J. (2005). Structure-based drug design and NMR-based screening. In Robert A Meyers (Ed.), Encyclopdeia of Molecular Cell Biology and Molecular Medicine 2nd ed. (pp. 517-605) Germany: Wiley-VCH.

  • Craik, D. J. and Clark, R. J. (2003). NMR and Drug Discovery. In Donald J Abraham (Ed.), Burger's Medicinal Chemistry and Drug Discovery, Vol 1, Drug Discovery 6th ed. (pp. 507-582) USA: John Wiley & Sons.

  • Craik, D. J. and Scanlon, M. J. (2000). Marine toxins as a starting point for drugs. In Luis M Botana (Ed.), Seafood and Freshwater Toxins Pharmacology, Physiology and Dection (pp. 715-740) New York: Marcel Dekker Inc.

  • Craik, D. J. and Scanlon, M. J. (2000). Pharmaceutical Applications of NMR. In Webb and GA (Ed.), Annual Reports on NMR Spectroscopy (pp. 115-174) USA: Academic Press.

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PhD and MPhil Supervision

Current Supervision

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Possible Research Projects

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