BPharm(Hons), PhD
Position: 
NHMRC postdoctoral (overseas) research fellow
Room: 
1120
Phone: 
+61 (7) 3346 9893
Biography: 

Dr Moyle received a PhD (Dec 2006) and a Bachelor of Pharmacy (Hons I) (Dec 2001) from The University of Queensland (UQ); graduated from the Pharmaceutical Society of Australia pre-registration pharmacist-training course (Nov 2002); and is registered with the Pharmacy Board of Australia. He currently works as a National Health and Medical Research Council postdoctoral research fellow with Professor Istvan Toth (School of Chemistry & Molecular Biosciences, UQ) and is a casual lecturer in the UQ School of Pharmacy.

Dr Moyle works in the fields of medicinal chemistry and chemical biology, investigating subunit vaccine development, and outcomes associated with histone post-translational modifications. During his PhD, Dr Moyle developed methods that enabled the synthesis of pure, lipid adjuvanted peptide vaccines, using advanced chemical ligation techniques. In addition, the conjugation of mannose to combined prophylactic/therapeutic human papillomavirus type-16 vaccines, to target dendritic cells, was demonstrated to significantly improve vaccine anti-tumour activity (PM2). This work, conducted with leading researchers at the QIMR Berghofer Medical Research Institute (Prof Michael Good & Dr Colleen Olive), established Dr Moyle’s national and international profile in the field of vaccine development, resulting in 11 peer reviewed papers, including top journals in the field (J Med Chem; J Org Chem), as well as 6 review articles and 2 invited book chapters.

Dr Moyle recently worked in the laboratory of one of the world’s premier chemical biologists, Professor Tom Muir (the Rockefeller University, NY, USA). During this time he developed an extensive knowledge of techniques for protein expression, bioconjugation, bioassays, and proteomics, which represent an essential skill set required for this proposal. As part of this work, Dr Moyle developed novel synthetic routes to generate site-specific ADP-ribose conjugated peptides and proteins. This research was hailed as a major breakthrough in the field, leading to several collaborations, and an exemplary publication in the prestigious chemistry journal JACS (PM1). This vast body of work identified the enzyme (PARP10) responsible for mono-ADP-ribosylation of histone H2B, and demonstrated interactions between this modification and several proteins, including BAL, which is associated with B cell lymphomas. In addition, a number of robust chemical methods were developed to enable the synthesis of a complete library of methyl-arginine containing histones, which were incorporated into synthetic chemically-defined chromatin to investigate the site-specific effects of arginine methylation on histone acetylation. This work led to a collaboration with colleagues at Rockefeller to investigate the effects of histone arginine methylation on transcription.

Research Focus and Collaborations: 

Dr Moyle investigates the use of (semi)synthetic peptides/proteins as tools to study the function of biomedically important proteins and post-translational modifications, as well as their utility for developing novel therapeutic agents. His research has heavily focused on developing technologies for producing new or improved vaccines through the attachment of Toll-like receptor (TLR) and/or dendritic cell targeting groups  (e.g. mannose) to synthetic peptide antigens, to stimulate protective immune responses and increase vaccine potency. Dr Moyle is particularly interested in the use of biological and synthetic lipids (e.g. Pam3Cys) as immunostimulatory molecules, and has published extensively in the field. In addition, he is interested in the development of techniques to attach other important immunostimulatory molecules to proteins (e.g. poly(I:C), CpG DNA, and monophosphoryl lipid A), to further tailor elicited immune responses. He has used such techniques to develop vaccines targeting S. pyogenes, human papillomavirus type-16 and H. pylori, and has trained numerous students and postdoctoral researchers in these areas.

In addition, Dr Moyle is interested in the use of advanced synthetic methodologies combined with recombinant protein technologies to produce proteins incorporating non-natural groups, or to enable the production of large amounts of site-specific, chemically-defined proteins for biological assays. He is especially interested in the assortment of post-translational modifications associated with histones, with a focus on ADP-ribosylation and arginine methylation. Dr Moyle has developed techniques to produce large amounts of site-specific ADP-ribosylated or methyl arginine containing histones, which have enabled biochemical analysis of the protein interactions and effects associated with these modifications. Through this work, Dr Moyle developed an interest in advanced cloning, protein expression, and protein interaction technologies.

Selected Publications: