Dr Rachel Stephenson

Research Fellow

School of Chemistry and Molecular Biosciences
Faculty of Science
r.stephenson@uq.edu.au
+61 7 334 69893

Overview

I completed a Bachelor of Science with a dual major in Biochemistry and Chemistry followed by a Bachelor of Science with First Class Honours in Chemistry from Massey University in New Zealand where my honors project focused on hydrogel development for the release of bioactive peptides into the gut. I completed a PhD at Massey University (New Zealand) investigating synthetic anti-cancer drugs based on the cyclic sugar, cyclodextran.

Following the completion of my doctoral studies, I worked as a Research Officer at the New Zealand Veterinary Pathology/Epicentre (Massey University) before relocating to the Department of Diagnostic Medicine and Pathobiology at Kansas State University (USA) where I worked as a Postdoctoral Fellow on the detection and surveillance of zoonotic diseases for the swine industry.

Combining my knowledge of synthetic peptides with my passion for vaccine development research, I relocated to the School of Chemistry and Molecular Biosciences (the University of Queensland, Australia) where my research now focuses on synthetic vaccine and adjuvant design strategies for infectious diseases, including group A Streptococcus, cancer and tropical diseases, including schistosomiasis.

Research Interests

  • Group A Streptococcus glycoconjuagte vaccines
    Carbohydrates are an abundant and structurally diverse biomolecule present on a cells surface, representing a unique feature and important recognition marker for the immune system. Identification of a highly conserved antigenic epitope of group A Streptococcus is an important challenge in the development of a universal group A Streptococcus vaccine. This project aims to build a new multi-component glycoconjugate vaccine for the delivery of Group A Streptococcus (GAS) antigens.
  • Cyclic peptides as vaccine delivery platforms
    Cyclic peptides represent useful scaffolds for the multivalent presentation of peptide epitopes to the immune system. Their constrained conformation allows presentation of structural elements in a well-defined orientation, improving resistance against proteolytic degradation. With this in mind, the project would involve a structure-activity study investigating the role of antigens attached to the cyclic ring. It would be expected that an immune response would change with different antigen attachment positions, making it an exciting project.
  • Peptide delivery systems
    Peptides as drugs may suffer from issues including an inability to reach their site of action, poor absorption, and degradation. Using chemical modification and characterisation we can improve the targeting, circulation time, stability, potency, etc of peptide-based therapeutics.
  • Subunit Vaccine Development
    Vaccination is one of the most effective public health strategies undertaken. Instead of using whole killed pathogens, next-generation vaccines use pathogen-derived peptides, allowing fine control when tailoring the vaccine. Group A Streptococcus vaccines are of particular significance to Australia with increasing incidences of rheumatic fever and rheumatic heart disease, which can be fatal. We focus on technologies that enable the site-specific incorporation of potent vaccine adjuvants into peptide and carbohydrate-based antigens, and the targeting of these vaccines to specific cell populations enhancing vaccine efficacy.

Research Impacts

My past research focused on the development of synthetic strategies for the synthesis of multi-functional peptide-sulfonamide drug candidates, followed by in vitro immunological assessment for applications in biomedical research. These experimental investigations revolved around novel solid phase peptide synthesis chemistry and chemical conjugation techniques, leading to cell-based immunological analysis of novel anti-cancer drug candidates.

Switching focus from Chemistry to Virology/Immunology, I used my Chemistry knowledge to develop and optimise protein-based multiplex diagnostic assays (Luminex and ELISA) for diseases affecting the swine industry (e.g. porcine reproductive and respiratory syndrome virus, bovine viral diarrhoea, African swine fever). As some of these diseases were absent from the USA, this collaborative effort ensured that imported meat and animals continued to be free from disease.

I have applied my research background towards an interdisciplinary approach at the School of Chemistry & Molecular Biosciences (University of Queensland), where my current educational research as a research-focused academic in Medicinal Chemistry revolves around the structure-immunological assessment of synthetic peptide-based subunit vaccines for the prevention and/or treatment of human diseases, including group A Streptococcus infection, Schistomisasis and cancer. This research aims to address the importance of synthetic immune-stimulants in subunit vaccine design, as well as improving the technological methods around multi-component vaccine development, supporting the growth of peptide-based vaccine development.

This research is carried out through multiple UQ collaborations and has been funded by the NHMRC (Australia) and more recently, Meat and Livestock Australia.

Qualifications

  • Bachelor of Science, Massey University
  • Bachelor of Science (Honors), Massey University
  • Doctor of Philosophy, Massey University

Publications

View all Publications

Supervision

View all Supervision

Available Projects

  • Many glycoconjugates (sugars) have been identified and used for the increased targeted delivery of vaccines. Our lipid-peptide carrier systems have been shown to have self-adjuvant properties. This project aims to evaluate immunological responses by increased targeting towards dendritic and macrophage cells using glycoconjugates in the treatment of group A Streptococcus infection. Project aims: 1) the chemical synthesis of a series of dendritic delivery systems containing different glycoconjugates, 2) in vitro uptake studies, and 3) toxicology assessment.

  • Cyclic peptides offer an attractive solution for presentation of short peptide antigens due to their stability and structurally constrained conformation. We identified that a cyclic deca-peptide plays a significant positive influence on the adjuvant activity of several lipid-antigen mixtures, leading to high immunological antibody titres and opsonisation of the model infection. Building on these exciting findings, this project aims to optimise the capacity of these cyclic delivery systems, leading to project skills in areas of peptide synthesis and analytical analysis, and in vitro and in vivo immunological assessment.

  • Vaccination is one of the most effective public health strategies ever undertaken. Instead of whole killed pathogens, next generation vaccines use pathogen derived peptides, allowing fine control when tailoring the vaccine. This project aims to examine a new multi-component self-adjuvanting cyclic carrier system for the delivery of Group A Streptococcus (GAS) antigens. Here, novel nanoparticle vaccine systems will be synthesised where both adjuvant and particulate carrier are contained in a single molecular entity. Project aims: 1) chemical synthesis of lipoamino acid libraries and a series of delivery system-GAS conjugates with different rearrangements, 2) in vitro biological stability studies, 3) in vitro uptake studies, and 4) biological activity assessment.

View all Available Projects

Publications

Book Chapter

  • Madge, Harrison Y.R., Stephenson, Rachel J. and Toth, Istvan (2021). Nanocarrier-based vaccine delivery systems for synthetic peptide vaccines. Handbook of Nanotechnology Applications. (pp. 509-535) Amsterdam, Netherlands: Elsevier. doi: 10.1016/b978-0-12-821506-7.00020-x

  • Hussein, Waleed H., Stephenson, Rachel J. and Toth, Istvan (2021). Preface. Peptide conjugation: methods and protocols. (pp. v-v) New York, NY USA: Humana Press.

  • Madge, Harrison Y. R., Stephenson, Rachel J. and Toth, Istvan (2020). Nanocarrier-based vaccine delivery systems for synthetic based peptide vaccines. Handbook of nanotechnology applications. (pp. 509-533) edited by Kajornsak Faungnawakij , Woei Jye Lau, Uracha Ruktanonchai and Kuakoon Piyachomkwan. Oxford, United Kingdom: Elsevier.

  • Eskandari, Sharareh, Stephenson, Rachel and Toth, Istvan (2016). Current boundaries in the formulation of lipid based delivery systems. Liposomal delivery systems: advances and challenges. (pp. 160-174) edited by Abdus Samad, Sarwar Beg and Iram Nazish. London, United Kingdom: Future Medicine. doi: 10.4155/9781910419083

Journal Article

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Master Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

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.

  • Many glycoconjugates (sugars) have been identified and used for the increased targeted delivery of vaccines. Our lipid-peptide carrier systems have been shown to have self-adjuvant properties. This project aims to evaluate immunological responses by increased targeting towards dendritic and macrophage cells using glycoconjugates in the treatment of group A Streptococcus infection. Project aims: 1) the chemical synthesis of a series of dendritic delivery systems containing different glycoconjugates, 2) in vitro uptake studies, and 3) toxicology assessment.

  • Cyclic peptides offer an attractive solution for presentation of short peptide antigens due to their stability and structurally constrained conformation. We identified that a cyclic deca-peptide plays a significant positive influence on the adjuvant activity of several lipid-antigen mixtures, leading to high immunological antibody titres and opsonisation of the model infection. Building on these exciting findings, this project aims to optimise the capacity of these cyclic delivery systems, leading to project skills in areas of peptide synthesis and analytical analysis, and in vitro and in vivo immunological assessment.

  • Vaccination is one of the most effective public health strategies ever undertaken. Instead of whole killed pathogens, next generation vaccines use pathogen derived peptides, allowing fine control when tailoring the vaccine. This project aims to examine a new multi-component self-adjuvanting cyclic carrier system for the delivery of Group A Streptococcus (GAS) antigens. Here, novel nanoparticle vaccine systems will be synthesised where both adjuvant and particulate carrier are contained in a single molecular entity. Project aims: 1) chemical synthesis of lipoamino acid libraries and a series of delivery system-GAS conjugates with different rearrangements, 2) in vitro biological stability studies, 3) in vitro uptake studies, and 4) biological activity assessment.

  • Immune-stimulant (adjuvant) development is an important area of vaccine research. This exciting project aims to investigate particle characteristics and immunogenicity for a library of lipopeptide vaccine constructs containing an asymmetric arrangement of the Group A Streptococcus (GAS) epitopes. Lipoaminoacids (lipid) are investigated for particle rearrangement properties following self-assembly. Project aims: 1) chemical synthesis of an asymmetric GAS vaccine library and 2) physiochemical characterisation, 3) in vitro uptake studies, and 4) toxicology assessment.