Dr Paul Gary Young
PhD Molecular Medicine (University of Auckland); MSc Medicine (First Class Honours) (University of Auckland); BSc Biochemistry / Molecular Genetics (Massey University)
Paul is a Research Fellow in Structural Biology at the School of Biological Sciences. His current research involves using Xray-crystallography and electron microscopy to solve the structures of various proteins involved in bacterial pathogenesis, which include proteins involved in bacterial pili generation and adhesion. He leads a Health Research Council funded project that is developing multi-component vaccines that spontaneously covalently ligate together within bacteria.
Research | Current
We have projects focused on cell adhesins from GAS. The surface of S. pyogenes is decorated with numerous virulence factors to aid adhesion and colonization. Prominent amongst GAS virulence factors are pili. Pili (or fimbriae) are proteinaceous filaments that extend from the bacterial surface. They are involved in cell adhesion and biofilm formation.
We are interested in the structure of pilins and the mechanism of pilus assembly. The structures of pilins have been instrumental in understanding how they are assembled, why they are incredibly stable and how the adhesion at the tip works. GAS pili are built from multiple copies of a single major or backbone pilin (BP), that forms the shaft, with an adhesive pilin at the tip and typically an anchor pilin at the base, all covalently linked like beads on a string.
Furthermore, as pili are highly immunogenic we are currently investigating the use of the pilins as a target for a vaccine against GAS. We are also developing other multi-component vaccines against GAS and Staphylococcus aureus. Our research aims to develop a radical new method for producing multi-component complexed protein vaccines using a spontaneously-forming scaffold. Our extremely stable protein scaffold, which captures and glues multiple antigens together in a precisely defined way, is engineered utilising intramolecular ester bonds that we discovered in the bacterial proteins. Our goal is to incorporate this scaffold into laboratory bacteria to create a system that pre-assembles a complex multi-component vaccine that can be produced with a simple ‘one-step’ purification.
Other new projects/interests include the engineering of enzymes to degrade plastics and the use of electron diffraction to solve protein structures from microcrystals.
Areas of expertise
Synthetic biology, protein engineering, protein expression and purification. Structural biology, protein characterization by X-ray crystallography, small-angle X-ray scattering and electron microscopy.
Selected publications and creative works (Research Outputs)
- Young, P. G., Raynes, J. M., Loh, J. M., Proft, T., Baker, E. N., & Moreland, N. J. (2019). Group A Streptococcus T Antigens Have a Highly Conserved Structure Concealed under a Heterogeneous Surface That Has Implications for Vaccine Design. Infection and immunity, 87 (6).10.1128/iai.00205-19
Other University of Auckland co-authors: Thomas Proft, Nikki Moreland, Jacelyn Loh
- Hanson-Manful, P., Whitcombe, A. L., Young, P. G., Atatoa Carr, P. E., Bell, A., Didsbury, A., ... Moreland, N. J. (2018). The novel Group A Streptococcus antigen SpnA combined with bead-based immunoassay technology improves streptococcal serology for the diagnosis of acute rheumatic fever. Journal of Infection, 76 (4), 361-368. 10.1016/j.jinf.2017.12.008
Other University of Auckland co-authors: Thomas Proft, Rod Dunbar, Nikki Moreland, Alicia Didsbury, Alana Whitcombe
- Raynes, J. M., Young, P. G., Proft, T., Williamson, D. A., Baker, E. N., & Moreland, N. J. (2018). Protein adhesins as vaccine antigens for Group A Streptococcus. Pathogens and disease, 76 (2).10.1093/femspd/fty016
Other University of Auckland co-authors: Thomas Proft, Nikki Moreland
- Langley, R. J., Ting, Y. T., Clow, F., Young, P. G., Radcliff, F. J., Choi, J. M., ... Fraser, J. D. (2017). Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors. PLoS Pathogens, 13 (9).10.1371/journal.ppat.1006549
Other University of Auckland co-authors: Ries Langley, Fiona Radcliff, John Fraser
- Kwon, H., Young, P. G., Squire, C. J., & Baker, E. N. (2017). Engineering a Lys-Asn isopeptide bond into an immunoglobulin-like protein domain enhances its stability. Scientific Reports, 7, 42753-undefined. 10.1038/srep42753
Other University of Auckland co-authors: Christopher Squire
- Young, P. G., Yosaatmadja, Y., Harris, P. W. R., Leung, I. K. H., Baker, E. N., & Squire, C. J. (2017). Harnessing ester bond chemistry for protein ligation. Chemical Communications, 53 (9), 1502-1505. 10.1039/c6cc09899a
Other University of Auckland co-authors: Christopher Squire, Ivanhoe Leung, Paul Harris
- Raynes, J. M., Frost, H. R. C., Williamson, D. A., Young, P. G., Baker, E. N., Steemson, J. D., ... Atatoa Carr, P. E. (2016). Serological evidence of immune priming by group A streptococci in patients with acute rheumatic fever. Frontiers in Microbiology, 7, 1-6. 10.3389/fmicb.2016.01119
Other University of Auckland co-authors: Thomas Proft, Nikki Moreland, Rod Dunbar, Jacelyn Loh, John Steemson
- Ting, Y. T., Harris, P. W., Batot, G., Brimble, M. A., Baker, E. N., & Young, P. G. (2016). Peptide binding to a bacterial signal peptidase visualized by peptide tethering and carrier-driven crystallization. IUCrJ, 3 (Pt 1), 10-19. 10.1107/S2052252515019971
Other University of Auckland co-authors: Margaret Brimble, Paul Harris