Centre for Superbug Solutions - Project's List

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisor: A/Prof Sumaira Hasnain (Mater Research Institute); A/Prof Jana Vukovic (UQ School of Biomedical Sciences); A/Prof Adam Irwin (UQCCR)

Neonatal meningitis is a devasting disease with high rates of mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis and the most common cause of meningitis in preterm neonates. Despite this, we have limited knowledge about the global epidemiology of E. coli that cause neonatal meningitis, genomic relationships between different strains, key virulence genes directly associated with capacity to cause disease, and mechanisms of relapse in newborns that suffer repeat infection. This project will identify and characterise common genomic features of E. coli that cause neonatal meningitis, and employ molecular methods in conjunction with animal models to define key mechanisms in the pathogenic cascade of infection. Our goal to develop new diagnostic and therapeutic interventions to prevent this life-threatening infection.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Vollmer Waldemar (IMB)

Associate Advisor: 

Antimicrobial resistance is a global health emergency. The growing number of drug-resistant pathogens is making common infections more and more difficult to treat. Gram-negative bacteria, a major cause of infections in recent years, are resistant to almost all antibiotics, leaving no option for treatment at all. BREAKthrough is a Doctoral Network which aims to make these bacteria susceptible to today’s standard-of-care antibiotics. Since the bacteria’s outer membrane prevents antibiotics from entering the cell, the project will develop new compounds that ultimately damage the outer membrane and allow antibiotics to break through the bacterial cell wall. BREAKthrough is funded under Horizon Europe’s Marie Skłodowska-Curie Actions (MSCA) programme.

Project Website: https://breakthrough-project.eu/

The project is integrated into the BREAKThrough EU ITN project and offers unique opportunities for research collaborations and training for the PhD student. The student will undertake secondments (each 2 months) at Newcastle University (UK) and Vrije Universiteit Amsterdam (The Netherlands).

Gram-negative bacteria have a multi-layered cell envelope with an outer membrane that is tightly connected to the underlying peptidoglycan cell wall layer. The outer membrane protects the cell from many toxic molecules and lysins, and the peptidoglycan layer confers osmotic stability and its biosynthesis is the target of some of our best antibiotics. Growing and dividing bacteria transport all outer membrane components (lipopolysaccharide, outer membrane proteins, phospholipids) through the pores of the net-like peptidoglycan and insert them into the outer membrane, using dedicated and sophisticated multi-protein machineries. One of these, the BAM complex, folds outer membrane beta-barrel proteins (OMPs, porins) into the outer membrane. How outer membrane biogenesis is coordinated with peptidoglycan growth is largely unknown. The PhD project will follow our recent work showing that peptidoglycan maturation controls the activity of the BAM complex (Mamou et al., Nature 2022). The PhD student will use a range of techniques in molecular biology, microscopy and protein biochemistry to decipher how BAM proteins interact with peptidoglycan and other cell envelope factors, and how these interactions affect BAM function in the test tube and cell. The project is expected to discover molecular mechanisms that can be targeted by new molecules that disrupt cell envelope coordination in bacteria.  

Candidate profile

• Keen interest in molecular biosciences.

• Excellent interpersonal and team-working skills.

• Motivated to work in a research team and undertake collaborative research with BREAKthrough partners, willingness to undertake medium term (2 months) research secondments in Europe. 

• Knowledge and practical experience in bacterial growth, microscopy, genetic methods, protein biochemistry.

• Master degree in Microbiology, Biochemistry, or a related discipline

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Larisa Labzin (IMB)

Associate Advisor: A/Prof Kirsty Short (SCMB)

Emerging viruses such as Highly Pathogenic Avian Influenza, HPAIV and SARS-CoV-2 can cause deadly outbreaks that decimate wild and domestic animal populations or cause global pandemics. . Some species, particularly bats and wild birds, can carry these viruses with minimal disease, meaning they can easily spread viruses between farms, states and even countries. The immune response is the best protection against viral infection, yet in susceptible species (such as chickens and pigs), immune overactivation may cause collateral tissue damage, driving disease pathology. This PhD project will study how the immune systems of different species recognise viral infections. This research will determine if viral reservoir species (such as ducks and bats) mount a specific kind of immune response that allows them to tolerate viruses, which is distinct to susceptible species (such as chickens and pigs). This project will utilise cell biology, imaging, molecular cloning, and virology to identify new ways to prevent pandemic virus outbreaks and protect vulnerable species.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Prof Gabrielle Belz (Fraser Institute)

An opportunity exists for a PhD position in the molecular immunology of malaria. The focus of this project will be to apply cutting-edge technologies to understand the molecular basis of protective immunity to malaria. It will take advantage of controlled human infection models and as well as animal models to explore the mechanisms underlying protective immunity to malaria and immune responsiveness. Using a range of interdisciplinary approaches including immune profiling, transcriptomics, proteomics, and small molecule characterization, the project aims to define the critical cells and signalling pathways required for protective immunity against malaria. It is anticipated that this research will have broad application to a wide range of infectious and chronic diseases, with important implications for vaccination.  

Subject areas: Immunology, Molecular immunology, Systems biology, Vaccinology, Malaria

Eligibility: Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements). Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required. 

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Waldemar Vollmer (IMB)

Associate Advisor: Prof Alun Jones (IMB)

The PhD project addresses the global burden of Antimicrobial Drug Resistance (AMR) by developing new assays for antibiotic discovery. The bacterial cell wall is targeted by some of our best antibiotics (e.g., beta-lactams, glycopeptides) and remains an attractive target for antibiotic drug discovery. Our group investigates the molecular mechanisms underpinning cell wall synthesis during growth and division of a bacterial cell. We pioneered the development of biochemical assays to monitor the activities and interactions of essential enzymes required for the synthesis of peptidoglycan, identified the first activators of peptidoglycan synthases and deciphered the activation mechanism. The PGR student will be trained in a wide range of molecular biology, (analytical) biochemistry and bacterial cell biology techniques and use these to develop innovative assay for key peptidoglycan enzymes that built and remodel the cell wall in pathogenic bacteria. The PGR student will then use the new assays to screen compound libraries to identify inhibitors. Hit compounds will be characterised by cellular and biochemical techniques and assessed for their potential to be developed into new antibiotics.

Reference:1. Egan et al. 2020. Regulation of peptidoglycan synthesis and remodelling. Nature Reviews Microbiology 18, 446–460.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: A/Prof Mark Blaskovich (IMB)

Associate Advisor: Prof Kristofer Thurecht (CAI); Dr Anthony Verdosa (IMB)

Infections caused by drug resistant bacteria pose a significant threat to global human health, with predicted annual mortality of 10 million by 2050. Most research is focused on developing better therapies, but improving diagnosis could quickly have substantial impact by reducing unnecessary antibiotic use and enhancing therapeutic efficacy. There is no current clinical technology capable of specifically identifying bacterial infections by imaging the site of a bacterial infection. Suspected chronic infections, such as endocarditis and prosthetic joint infections, are particularly difficult to accurately diagnose without invasive techniques. A whole-body imaging diagnostic that could simultaneously determine whether an infection was present and rapidly pinpoint the site of the infection, then monitor the efficacy of subsequent treatment, would directly inform targeted treatment, leading to substantial health and economic benefits. This project will extend our current research on fluorescent tracers that bind to the surface of bacteria with high specificity and selectivity. We will replace the fluorophore component of these tracers with radioisotope chelating ligands, creating new constructs suitable for positron emission tomography (PET) whole body imaging. These tracers will be tested both in vitro and in mice to demonstrate specific PET imaging of bacterial infections.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Waldemar Vollmer (IMB)

Associate Advisor: Prof Alun Jones (IMB)

There is an urgent need to develop new antibiotics to address the global challenge of antimicrobial drug resistance (AMR). The membrane steps in bacterial cell wall biogenesis include verified targets for antibiotics (e.g. daptomycin, teixobactin) which cause death and lysis of a bacterial cell. We study the key essential steps of cell wall synthesis at the cell membrane, including the synthesis of lipid-linked precursor, the polymerisation of the cell wall and the recycling of the carrier lipid. The PGR student will receive extensive training in molecular biology, biochemistry and mass spectrometry techniques and develop new assays to measure the activities of membrane-bound cell wall enzymes. The PGR student will then use the new assays in proof-of-principle studies to screen for new inhibitors. The student will characterise the activity of hit molecules by bacterial cell biology techniques and assess their potential to be developed into new antibiotics. 

References:
1. Egan et al. 2020. Regulation of peptidoglycan synthesis and remodelling. Nature Reviews Microbiology 18, 446–460.
2. Oluwole et al. 2022. Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients. Nature Communications 13:2278.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisor: Prof Matt Sweet (IMB)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of ~175M cases. UTI is also a major precursor to sepsis, which affects ~50M people worldwide each year, with a mortality rate of 20-40% in developed countries. Uropathogenic E. coli (UPEC) is the major cause of UTI (>80%) and a leading cause of sepsis. The last decade has seen an unprecedented rise in antibiotic resistance among all significant bacterial pathogens, including UPEC. One pandemic multidrug resistant UPEC clone, ST131, is the cause of ~20% of all UTIs and ~50% of all E. coli bloodstream infections. This project will explore how UPEC ST131 cause disease, with a goal to identify new approaches to treat and prevent infection.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Dr Jessica Rooke (IMB)

Associate Advisor: Prof Ian Henderson (IMB); Prof Matt Sweet (IMB)

Salmonella enterica is a broad host range pathogen that is distributed globally. Worryingly, S. enterica strains are becoming increasingly resistant to routinely used antibiotics, leading to the World Health Organisation classifying S. enterica as a high priority pathogen for which alternative treatments are desperately needed. By understanding how Salmonellainfects a host, novel therapies and vaccines can be designed to prevent disease. Recent evidence suggests that pathogen-lipid interactions are important for pathogens to survive in the host and that Salmonella has a unique, conserved lipase that is essential for these interactions. This project aims to establish the molecular mechanism by which Salmonella interacts with host lipids to enable evasion and manipulation of host immune responses. These investigations will provide novel insights into fundamental Salmonella biology and aid in the development of more effective strategies to treat Salmonella infections, such as novel drug targets and/or novel vaccine candidates.

*Qualifies for the Global Challenges Scholarship.

Principal Advisor: Professor Alpha Yap (IMB)

Must commence by Research Quarter 1, 2023

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.

Driven by the introduction of antibiotics and vaccines, deaths from infectious diseases declined markedly during the 20th century. These unprecedented interventions paved the way for other medical treatments; cancer chemotherapy and major surgery would not be possible without effective antibiotics to prevent and treat bacterial infections. The evolution and widespread distribution of antibiotic-resistance elements, and the lack of new antimicrobials, threatens the last century of medical advances; without action the annual death toll from drug-resistant infections will increase from 0.5 million in 2016 to 10 million by 2050. New treatments are desperately needed including new antibiotics and alternative treatments such as phage. This project will address the molecular basis for the basis of phage interaction with the bacterial cell envelope and the potential for using this knowledge to treat antibiotic resistant infections.

 *Qualifies for an Earmarked Scholarship.