Professor Elizabeth Gillam

Professor

School of Chemistry and Molecular Biosciences
Faculty of Science

Affiliated Professor

Centre for Plant Science
Queensland Alliance for Agriculture and Food Innovation
e.gillam@uq.edu.au
+61 7 336 51410

Overview

Cytochrome P450 Enzymes: biological catalysts of unprecedented versatility.

Cytochrome P450 enzymes (CYPs, P450s) especially those responsible for drug metabolism in humans, are the unifying theme of the research in our lab. These fascinating enzymes are catalysts of exceptional versatility, and functional diversity. In humans they are principally responsible for the clearance of a practically unlimited variety of chemicals from the body, but are also critical in many important physiological processes. In other organisms (plants, animals, bacteria, fungi, almost everything!) they carry out an unprecedented range of functions, such as defense, chemical communication, neural development and even pigmentation. Recently we have discovered that P450s are present within cells in the Fe(II) form, a finding that has led to a radical revision of the dogma concerning the P450 catalytic cycle, and has implications for the control of uncoupling of P450 activity in cells.

The capabilities of P450s are only just coming to be fully recognized and structural studies on P450s should yield critical insights into how enzyme structure determines function. Moreover, the biotechnological potential of P450s remains yet to be exploited. All of the specific research themes detailed below take advantage of our recognized expertise in the expression of recombinant human cytochrome P450 enzymes in bacteria. Our group is interested in finding out how P450s work and how they can be made to work better.

Artificial evolution of P450s for drug development and bioremediation: a way of exploring the sequence space and catalytic potential of P450s. The demonstrated catalytic diversity of P450 enzymes makes them the ideal starting material for engineering sophisticated chemical reagents to catalyse difficult chemical transformations. We are using artificial (or directed) evolution to engineer enzymes that are more efficient, robust and specialized than naturally occurring enzymes with the aim of selecting for properties that are commercially useful in the areas of drug discovery and development and bioremediation of pollutants in the environment. The approach we are using also allows us to explore the essential sequence and structural features that underpin all ~12000 known P450s so as to determine how they work.

P450s in brain: relevance to mental illness and neurodegenerative diseases. While P450s are responsible for the metabolic clearance of drugs from the human body, this is not always a benevolent process: sometimes metabolites are generated that are chemically reactive and may cause mutagenic or other toxic effects. Moreover P450s are involved in the synthesis and degradation of important endogenous chemicals, physiological roles which can be affected by drugs and dietary chemicals. We are particularly interested in the role of P450s in brain chemistry. P450s localised in mitochondria have recently been shown to contribute to the neurotoxicity of some drugs and can lead to oxidative damage to mitochondria, possibly contributing to the development of neurodegenerative diseases.

Biosketch:

After graduating from UQ with first class Honours in Biochemistry, Elizabeth took up a Royal Commission for the Exhibition of 1851 Overseas Scholarship to pursue doctoral work at Oxford University then undertook postdoctoral work at the Center in Molecular Toxicology and Department of Biochemistry at Vanderbilt University School of Medicine with Prof. F.P. Guengerich. She returned to UQ in 1993 to take up a position in Pharmacology and joined the School of Chemistry and Molecular Biosciences in 2009 as a Professor of Biochemistry.

Research Impacts

Our research is leading to the development of more sustainable, environmentally friendly, chemical processes to accelerate drug development and improve the safety of medicines. Our studies into the evolution of catalytic promiscuity in P450s reveal how organisms have evolved to deal with chemicals in the environment and provide insights as to how enzymes develop novel functions. The work we and our colleagues have done to characterise the expression of P450s in the brain has suggested novel therapeutic strategies for the treatment of certain mental disorders and better prediction of susceptibility to neurodegenerative diseases.

Qualifications

  • Doctor of Philosophy, Oxf.
  • Bachelor of Science (Honours), The University of Queensland

Publications

View all Publications

Supervision

  • Doctor Philosophy

  • Doctor Philosophy

  • Doctor Philosophy

View all Supervision

Available Projects

  • We are using artificial (or directed) evolution to engineer enzymes that are more efficient, robust and specialized than naturally occurring enzymes for application in drug discovery and development and cleaning up the environment. The approach we are using also allows us to explore the essential sequence and structural features that underpin all ~12000 known P450s so as to determine how they work.

  • P450s localised in mitochondria have recently been shown to contribute to the neurotoxicity of some drugs and can lead to oxidative damage to mitochondria. Genetic differences between individuals affect the expression of P450s in mitochondria and may contribute to susceptibility to diseases such as Alzheimer’s. (To be conducted in collaboration with Prof. Peter Dodd and Dr. Simon Worrall.)

View all Available Projects

Publications

Book Chapter

  • Zaugg, Julian, Gumulya, Yosephine, Gillam, Elizabeth M. J. and Bodén, Mikael (2014). Computational tools for directed evolution: a comparison of prospective and retrospective strategies. In Elizabeth M. J. Gillam, Janine N. Copp and David F. Ackerley (Ed.), Directed evolution library creation: methods and protocols 2nd ed. (pp. 315-333) New York, NY, United States: Humana Press. doi:10.1007/978-1-4939-1053-3_21

  • Behrendorff, James B. Y. H., Johnston, Wayne A. and Gillam, Elizabeth M. J. (2013). DNA shuffling of cytochrome P450 enzymes. In Ian R. Phillips, Elizabeth A. Shepherd and Paul R. Ortiz de Montellano (Ed.), Cytochrome P450 protocols 3rd ed. (pp. 177-188) New York, NY, United States: Humana Press. doi:10.1007/978-1-62703-321-3_16

  • Johnston, Wayne A. and Gillam, Elizabeth M. J. (2013). Measurement of P450 difference spectra using intact cells. In Ian R. Phillips, Elizabeth A. Shepherd and Paul R. Ortiz de Montellano (Ed.), Cytochrome P450 protocols 3rd ed. (pp. 189-204) New York, NY, United States: Humana Press. doi:10.1007/978-1-62703-321-3_17

  • Jackson, Colin J., Gillam, Elizabeth M. J. and Ollis, David L. (2010). Directed evolution of enzymes. In Lewis Mander and Hung-Wen Liu (Ed.), Comprehensive natural products II chemistry and biology (pp. 723-749) Oxford, England, Unied Kingdom: Elsevier.

  • Gillam, E. M. J. and Hunter, D. J. B. (2007). Chemical Defence and Exploitation: Biotransformation of Xenobiotics by Cytochrome P450 Enzymes. In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel (Ed.), Metal Ions in Life Sciences (pp. 477-560) West Sussex: John Wiley and sons.

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Joint Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • We are using artificial (or directed) evolution to engineer enzymes that are more efficient, robust and specialized than naturally occurring enzymes for application in drug discovery and development and cleaning up the environment. The approach we are using also allows us to explore the essential sequence and structural features that underpin all ~12000 known P450s so as to determine how they work.

  • P450s localised in mitochondria have recently been shown to contribute to the neurotoxicity of some drugs and can lead to oxidative damage to mitochondria. Genetic differences between individuals affect the expression of P450s in mitochondria and may contribute to susceptibility to diseases such as Alzheimer’s. (To be conducted in collaboration with Prof. Peter Dodd and Dr. Simon Worrall.)