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During my postgraduate studies and postdoctoral fellowship, I gained experience in a wide range of chemical biology techniques as well as in initiating and managing collaborations. Building on a background in chemistry and biochemistry, I developed my skills in peptide chemistry and NMR spectroscopy during my PhD in Australia, synthesizing a variety of disulfide-rich cyclic peptides and elucidating their structures and dynamics by NMR spectroscopy. I have gained further experience in protein chemistry, solid phase peptide synthesis and protein ligations during my postdoctoral fellowship in Vienna, collaborating with Syntab Therapeutics on a project involving synthesis and development of synthetic antibodies for cancer therapy. I have recently taken up a UQ Development Fellowship to establish my independent research area in synthesis and structural biology of posttranslationally modified proteins.

The molecular evolution of 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. P450s are involved in the biosynthesis of an unequalled range of potent, biologically active natural products in microbes, plants and animals, including many antibiotics, plant and animal hormones, signalling molecules, toxins, flavours and fragrances. We are studying how P450s have evolved to deal with novel substrates by reconstructing ancestral precursors and evolutionary pathways, to answer such questions as how did the koala evolve to live on eucalyptus leaves, a toxic diet for most mammals.

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. For example, recently we 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. Importantly, 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.

Synthetic biology of enzymes for clean, green, solar-powered chemistry in drug development, bioremediation and biosensors. We have identified ancestral enzymes that are extremely thermostable compared to their modern counterparts, making them potentially very useful in industry, since they can withstand long incubations at elevated temperatures. They can be used as ‘off the shelf’ reagents to catalyse useful chemistry, such as in in drug discovery and development, fine chemicals synthesis, and cleaning up the environment. Working with drug companies, we are exploring how they can be best deployed in chemical processes and what structural features make them efficient, robust and specialized. We are also immobilizing P450s in virus-like-particles as ‘designer’ reagents that can be recovered from reactions and reused. To make such processes cheaper and more sustainable, we are using photosynthesis to power P450 reactions for clean, green biocatalysis in microalgae.

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.

Present Position

I am an ARC Future Fellow at the Centre for Advanced Imaging and associated with the University of Oxford as a Senior Visiting Research Fellow.

Previous Positions

• August 2007 to March 2013: Scientific Coordinator and Applications manager of the Centre of Advanced Electron Spin Resonance (CAESR) at the Oxford University, UK.
• 2002-July 2007: Project leader (“Ober-assistent”) in the Physical Chemistry Department at the Swiss Federal Institute of Technology (ETH), Zürich. I was a project leader in the electron paramagnetic resonance group of Prof. Arthur Schweiger.
• 1999-2002: Postdoctoral position at ETH, Zurich. In the group of Prof. Arthur Schweiger I used CW and pulse EPR as a tool to investigate the geometric and electronic properties of transition metal complexes.
• 1996-1999: Doctor of Philosophy from the Chemistry Department of the University of Newcastle, Australia, Advanced Coal Characterization by Nuclear Magnetic Resonance. The project was funded by the Collaborative Research Centre for Black Coal Utilization and I was supervised by the University of Newcastle (Prof. Marcel Maeder), BHP Research Melbourne (Dr. Brian Smith) and Callcott Coal Consulting (Dr. Tom Callcott).
• 1995: Researcher at BHP Central Research Laboratories, Newcastle, Australia. I developed experimental techniques to measure the conductivity and the permeability of coal as it pertains to coke ovens.
• 1992-1995: Researcher at Oakbridge Research Center, Newcastle, Australia. I worked on high temperature Nuclear Magnetic Resonance (NMR) for coal characterization (for my Bachelor of Science Honors thesis). This was a collaboration between the CSIRO Coal and Energy Division (North Ryde, Sydney), Oakbridge Research Centre and the University of Newcastle.

Keywords

structural biology · protein interactions · metalloenzymes · metal complexes · electron transfer · Iron sulphur clusters · pulse EPR · CW EPR · DEER · PELDOR ·HYSCORE · ENDOR · ESEEM · density functional theory · molecular dynamics

A/Prof Landsberg's undergraudate and Honours studies, majoring in Chemistry, were completed at Central Queensland University and the CSIRO (JM Rendel laboratories) before he moved to the University of Queensland to study a PhD in Biochemistry (awarded 2003). He then moved to a postdoctoral position at the Institute for Molecular Bioscience, spending time as a Visiting Scientist at Harvard Medical School (2008) and securing promotion to Senior Research Officer upon his return to IMB in 2009. He additioanlly spent time as a Visiting Scientist at the Victor Chang Cardiac Research Institute in 2010 and 2011.

In 2016, he joined UQ's School of Chemistry and Molecular Biosciences as a Group Leader in Cryo-EM and Macromolecular Structure and Senior Lecturer in Biochemistry and Biophysics, where he was promoted to Associate Professor in 2019. He has secured >$13.5M in competitive research funding since 2012, including major grants from the Australian Research Council and National Health and Medical Research Council. He his research has been presented at over 70 national and international conferences and research institutions.

Professor Mobli is a structural biologist and a group leader at the University of Queensland's Australian Institute for Bioengineering and Nanotechnology (AIBN). He is well known internationally for his contributions to the basic theory of multidimensional nuclear magnetic resonance and its applications to resolving the molecular structure of peptides and proteins, as well as studying their physiochemical properties and function. Mehdi's contributions to the field has been recognised by being appointed an Executive Editor of the AMPERE society's journal "Magnetic Resonance", and to the advisory board of the international Biological Magnetic Resonance Data Bank (BMRB) as well as serving on the board of directors of the Australia and New Zealand Society for Magnetic Resonance (ANZMAG). He is a former ARC Future Fellow and recipient of the ASBMB MERCK medal, the Australia Peptide Society's Tregear Award, the ANZMAG Sir Paul Callaghan medal and the Lorne Proteins Young Investigator Award (now Robin Anders Award).

Prof. Mobli's research group focuses on characterising the structure and function of receptors involved in neuronal signalling, with a particular focus on developing new approaches for the discovery and characterisation of modulators of these receptors through innovations in bioinformatics, biochemistry and and biophysics. This work has led to publication of more than 100 research articles attracting over 6,000 citations.

Megan O’Mara is a Professor and Group Leader at the Australian Institute for Bioengineering and Nanotechnology (AIBN), UQ. Her group uses multiscale modelling techniques to understand how changes in the biochemical environment of the cell membranes alters membrane properties and modulates the function of membrane proteins. She has research interests in multidrug resistance, computational drug design and delivery, biopolymers, and personalized medicine. Megan completed her PhD in biophysics at the Australian National University in 2005 before moving to the University of Calgary, Canada, to take up a Canadian Institutes of Health Research Postdoctoral Fellowship. In 2009, she returned to Australia to join University of Queensland’s School of Chemistry and Molecular Biosciences as a UQ Postdoctoral Fellow, before commencing an ARC DECRA in 2012 where she continued her computational work on membrane protein dynamics. In 2015, Megan joined the Research School of Chemistry, Australian National University in 2015 as Rita Cornforth Fellow and Senior Lecturer. In 2019 she was promoted to Associate Professor and was Associate Director (Education) of the Research School of Chemistry ANU in 2019-2021. In April 2022 she relocated to AIBN.

Karnaker's research interests are natural products, peptide-based drug discovery and development, formulation chemistry and non-viral gene delivery system. Karnaker co-inventor and developed a novel, bioresponsive disulphide-linker technology, which has been used for non-viral vectors, peptide-therapeutics for pain and cancer treatment. Karnaker is also keen interest for topical, mucosal drug delivery using a range of dendrimer, nano and microbubbles, lipid and polymer-based nanoparticle systems in conjugation with both biological and physical stimuli-responsiveness.

Karnaker received a PhD in Pharmaceutical Chemistry from The University Queensland under the supervision of Dr Harendra Parekh and Dr Defang Ouyang. Prior to PhD, he completed a Master degree in Pharmaceutical Analysis and Quality assurance (India). Also worked as analytical research and development chemist for one year in a Pharma company. Since 2016, he his working with Dr Parekh team on a range of Industry-funded research projects and his role involves from ideation, research plan, execution, product delivery to industry partners on major platforms such as peptide-based therapeutics, gene therapy and sol-gel technology.