The ACTV research group has a multi-disciplined and inclusive approach to understand how the design and synthesis of peptide-based materials and nanomaterials influences their ability to:
1. target microbes or cancer cells in the development of antimicrobial and anticancer peptide-based materials; and
2. stimulate immunity in the development of vaccines to oral bacteria or cancer.
We use a chemical biology approach to understand how our materials induce their biological effect and how we are able to enhance this to improve efficacy. We employ a range of organic/peptide synthetic, immunological and microbial approaches to achieve the goals of the team to produce peptide-based materials that can be used clinically for microbial infections and cancer treatment.
The ACTV research group has the view that interdisciplinary, equitable and inclusive research is the catalyst for both scientific parsimony and paradigm shift.
Research Projects
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By 2050, it is predicted that more people will die from bacterial infections than cancer. Currently, multidrug resistant (MDR) bacterial infections cause >700,000 deaths/year and incur an estimated annual treatment cost of >US $20 billion. Antimicrobial resistance is considered “one of our most serious health threats” and thus new, potent and selective antimicrobial agents that do not induce resistance like traditional antibiotics are urgently required.
We have 3 primary areas of research: (1) Antimicrobial nanomaterials – we are investigating antimicrobial nanomaterials, termed Structurally Nanoengineered Antimicrobial Peptide Polymers (SNAPPs) with collaborator Prof Greg Qiao (Dept Chemical Engineering, Uni Melbourne)and the Selenium nanoparticles with collaborator Prof Andrea O’Connor (Dept Biomedical Engineering, Uni Melbourne).
This research uses novel and established assays in an iterative chemical biology approach to modify these antimicrobial nanomaterials to enhance killing of MDR bacteria in solution and on surfaces. (2) Antimicrobial peptides (AMPs) targeting oral bacteria – the oral cavity is a reservoir for transferable antibiotic resistance, a phenomenon increased in patients with chronic periodontitis. Our research in collaboration with Prof Eric Reynolds and Prof Stuart Dashper investigates methods for narrowing the activity spectrum of AMPs to target only periodontal pathogens, reduce cytotoxicity, and leave unharmed bacteria associated with oral health. (3) Enhancing antimicrobial peptide activity and antibiotic adjuvants – our research in collaboration with Prof John Wade (Florey Department of Neuroscience and Mental Health, Uni Melbourne) and Prof Frances Separovic (School of Chemistry, Uni Melbourne) is investigating how structural changes in AMPs and proline-rich AMPs enhances activity and how these peptides can function as “antibiotic adjuvants”, to potentiate or restore the activity of the antibiotic towards MDR bacteria. This project will use an iterative chemical biology approach to modify AMPs or SNAPPs to enhance their activity and antibiotic adjuvant properties.
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Cytotoxic T lymphocytes (CTL) are critical for immunosurveillance and killing of virus-infected cells and cancer cells. Many viral infections and squamous cell carcinomas (SCC) occur at mucosal sites; however, parenteral vaccination does not induce mucosal immunity. For the vaccine to induce a protective CTL response, it needs to be administered via a mucosal route and deliver its antigen cargo to dendritic cells. Further, the vaccine will need to activate these cells to induce both CTL and T helper (Th) cell antigen-specific responses, which is necessary for strong effector and memory CTL responses. We have demonstrated that nanoparticles are effective mucosal vaccine delivery vehicles and different pattern recognition receptor (PRR) ligands used to functionalise antigen-loaded nanoparticles can enhance or abrogate CTL and Th responses. The overall aim of our research is to combine novel technologies for an integrated, preclinical evaluation of novel calcium phosphate nanoparticle vaccines and compare their ability to induce CTL responses via mucosal or parenteral immunisation. Our research focuses on: (1) Determining the immuno-stimulatory capability of antigen and molecular adjuvant loaded calcium phosphate nanoparticles in vitro. (2) Determining the immuno-stimulatory capability of calcium phosphate nanoparticle vaccines in vivo. (3) Evaluating the efficacy of calcium phosphate nanoparticles as mucosal vaccines to induce protective CTL responses.
Directly targeting cancer with peptide therapeutics is a major goal of the ACTV research group. Our research is investigating the abilities of peptides to target and kill cancer cells directly or to target specific cells in the tumour microenvironment that support the growth and spread of cancer with the aim to eliminate this support and aid in cancer cell eradication.">
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The initial interaction of bacteria and bacterial products with mucosal tissue and the immune response induced are fundamental to bacterial infection and disease. We are focused on investigating how antibiotic susceptible and resistant bacteria differ in their interactions and what materials they produce (e.g. outer membrane vesicles, OMVs) to aid infection. We are also interested in discovering how oral bacteria interact with the host to cause disease and how they are associated with systemic conditions (e.g. oral, pancreatic and bowel cancer). We have already found that there is synergy between pathogenic and non-pathogenic bacteria in causing disease and immunopathology. Our research has a focus on: (1) mucosal and systemic immune responses to single and multi-bacterial species infection; (2) what and how bacterial factors such as OMVs interact with immune cells; (3) how bacteria effect immune cell trafficking into the mucosa and the effect of infection by multiple bacteria; (4) how OMVs aid infection of antibiotic susceptible and resistant bacteria and oral bacteria that cause chronic periodontitis.
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Our Team
Dr Negar Yazdani
