Antibiotic Conjugates: Joining Together to Fight Antimicrobial Resistance

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Supervisor – Associate Professor Mark

With a near-empty antibiotic pipeline and growing antimicrobial resistance, there is a global search for novel approaches to treat infections. This project will investigate three innovative new approaches to address this urgent unmet need, all based on a core concept where existing antibiotics are functionalised so they have a chemical handle that can be used to attach other moieties. It builds on an advanced platform of bespoke derivatised antibiotics that we have developed over the past five years.

AIM 1. Antibiotic-antibiotic hybrids: Combine the power of two classes of antibiotics.  Combination therapy, where two or more distinct drugs are co-administered, is routinely used to overcome resistance in diseases such as cancer and viral infections, but rarely used for bacterial infections. We will systematically link pairs of different antibiotics and compare these dual-acting covalent antibiotic-antibiotic hybrids against the matching non-linked combination to assess synergistic efficacy against resistant bacteria.

AIM 2. Antibiotic-adjuvant hybrids: Supplement antibiotic activity with other mechanisms.  Antibiotics will be coupled with moieties that increase or supplement the parent antibiotic efficacy, creating antibiotic-conjugated adjuvantsSiderophores can increase antibiotic cellular penetration. Biofilm disrupting agents can improve the efficacy of antibiotics that struggle to penetrate and kill biofilms associated with resistance. Antivirulence factors target pathogen excretions that promote adhesion, invasion and colonisation.

AIM 3. Immune activation: Leverage the immune system to help fight infections.  This aim will explore how we can activate the immune system to more effectively eliminate infections, by using antibiotics as markers that label bacteria for destruction by triggering an antibody-based immune response. Based on the Antibody Recruiting Molecule approach that has been developed for other diseases, we will functionalise surface-binding antibiotics by linking them to small molecules capable of eliciting an antibody response and bacterial killing by human phagocytes.

All three aims will rely on our expertise in antibiotic development to advance promising candidates through a validated progression of assays that assess both antimicrobial activity and drug-like properties, culminating in testing for in vivo efficacy, toxicity and pharmacokinetics.

Preferred educational background

Applications will be judged on a competitive basis taking into account the applicant's previous academic record, publication record, honours and awards, and employment history.

A working knowledge of synthetic organic chemistry would be of benefit to someone working on this project.

The applicant will demonstrate academic achievement in the field(s) of synthetic or medicinal chemistry and the potential for scholastic success.

A background or knowledge of small molecule and peptide synthesis is highly desirable.

*The successful candidate must commence by Research Quarter 1, 2022. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

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