Centre for Superbug Solutions - Project's List

Principal Advisor: Prof Matt Sweet (IMB)

Associate Advisor: Prof Mark Schembri (IMB)

For bacterial pathogens to colonise the host and cause disease, they must first overcome frontline defence of the innate immune system. Innate immune cells such as macrophages engage a suite of direct antimicrobial responses to destroy engulfed bacteria, including free radical attack, lysosomal degradation, nutrient starvation, metal ion poisoning, and lipid droplet-mediated delivery of antimicrobial proteins. A detailed understanding of such pathways can provide opportunities to manipulate macrophage functions to combat antibiotic-resistant bacterial infections. This project will explore the regulation of specific macrophage antimicrobial responses, with the goal of manipulating the functions of these cells to combat infections caused by uropathogenic E. coli, a major cause of urinary tract infections and sepsis.

Principal Advisor: Prof Mark Schembri (m.schembri@uq.edu.au)

Associate Advisors: Dr Nhu Nguyen (kn.nguyen@uq.edu.au) and Dr Zack Lian (IMB; z.lian@uq.edu.au) 

Biofilms are surface-attached clusters of bacteria encased in an extracellular matrix and are significantly associated with increased antibiotic resistance. This project will apply molecular microbiology methods to understand the structure, function and regulation of biofilms produced by uropathogenic E. coli that cause urinary tract infections, and investigate new strategies to disrupt biofilms. The project will build skills in cutting edge genetic screens, molecular microbiology, genome sequencing, bioinformatics, microscopy, imaging and animal infection models. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

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 and a leading cause of sepsis. The last decade has seen an unprecedented rise in antibiotic resistance among UPEC, resulting in high rates of treatment failure and mounting pressure on healthcare systems. This project will explore how UPEC cause disease and become resistant to antibiotics, with a goal to identify new approaches to treat and prevent infection.

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisor: A/Prof Adam Irwin (UQ Centre for Clinical Research)

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, and mechanisms that enable E. coli to cause severe infection in new-born infants. This project will identify and characterise common genomic features of E. coli that cause neonatal meningitis, and employ molecular microbiology methods in conjunction with animal models to understand disease pathogenesis and antibiotic resistance. Our goal is to develop new diagnostic and therapeutic interventions to prevent this life-threatening disease.

Principal Advisor: Professor Waldemar Vollmer (w.vollmer@uq.edu.au)

Associate Advisor: Prof Mark Schembri (m.schembri@uq.edu.au)

Gram-negative bacteria use some of their most abundant cellular proteins connect the outer membrane with the underlying cell wall (peptidoglycan) layer and this tight connection protects the cell from many toxic molecules and even antibiotics. However, most of the known peptidoglycan-interacting proteins are poorly characterised and we lack a comprehensive inventory of these proteins and their functions in key pathogens. In this project, the PhD student will develop novel proteomics approaches to identify all peptidoglycan-bound proteins in important Gram-negative pathogens, and then identify peptidoglycan-interacting proteins that fortify the cell envelope when bacteria encounter host defence factors and antibiotics. In addition to state-of-the art molecular biology and high-throughput microbiology screening techniques, the student will use cell biology and biochemical methodologies to gain understanding of the cellular roles of new cell envelope proteins identified. The student will benefit from working in an outstanding research environment and in research groups with a strong expertise in bacterial cell envelope biology and pathogenicity. The expected outcomes will be important to develop new strategies to fight infections caused by antibiotic resistant bacteria.

Principal Advisor: Dr Larisa Labzin (IMB)

Associate Advisor: A/Prof Kirsty Short (UQ School of Chemistry and Molecular Biosciences)

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.

Principal Advisor: Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Associate Advisor: Dr Brian Forde (b.forde@uq.edu.au); Dr Rudi Sullivan (rudi.sullivan@imb.uq.edu.au)

The current spread of antimicrobial resistance is a major concern for public health because the pipeline of antibiotic drug development is almost empty. Hence, there is an urgent need to discover new ways to inhibit and kill disease-causing bacteria by new drugs to be developed. The bacterial cell wall envelope is an ideal target for antibiotics because it is essential for a bacterial cell and not present in humans, and target sites are better accessible for drugs than internal ones. Indeed, some of the most successful antibiotics in history (e.g., the beta-lactams) inhibit bacterial cell wall synthesis. The PhD student will generate a web-based platform of the cell envelope proteins encoded in the available genomes of thousands of bacterial strains and species, and perform bioinformatic analysis of the distribution and abundance of key essential proteins of cell envelope biogenesis, to predict promising new target sites for antibiotic action (computational part). The PhD student will then validate selected target sites identified, using genetic and molecular biology methodologies in important bacterial pathogens (experimental part). The focus will be to identify new targets present in bacteria that are resistant to known antibiotics, aiming to discover new mechanisms to kill pathogenic bacteria.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Prof Gabrielle Belz (Frazer 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. 

Principal Advisor: Prof Waldemar Vollmer (IMB)

Associate Advisor: Mr Alun Jones (IMB); Prof Rob Capon (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.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Prioetti (IMB); A/Prof Jessica Mar (AIBN)

This PhD project aims to develop and apply computational approaches that integrate systems biology and molecular immunology to understand host-pathogen immunity and predict immune control of malaria. The project will utilise systems-based immunology and multi-omics approaches to profile the host immune response in controlled infection models of malaria at molecular, cellular, transcriptome and proteome-wide scale.

The overall aim will be to develop and apply omics-based technologies and computational tools, including network theory and machine learning, to integrate multiple high-dimensional datasets and reveal novel insights into host-pathogen immunity and predict immune responsiveness and parasite control. Modelling of large-scale existing datasets, including those generated by single-cell RNA-sequencing technologies, may also be a feature of this project. The opportunity to identify new knowledge and integrate this with experimental data produced by our laboratory will be instrumental to extending the impact of these bioinformatics analyses.  This project will provide an opportunity to be at the forefront in cutting-edge technologies and advances in computational analysis of integrated high-dimensional omic data.

Eligibility:

Entry: BSc Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: Experience with programming languages, mathematics, statistics and/or background in immunology and molecular sciences, with an interest in integrating the fields of immunology and bioinformatics.

Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged.

Principal Advisor: Dr Brian Forde (b.forde@uq.edu.au)

Associate Advisors: Dr Patrick Harris (UQCCR, p.harris@uq.edu.au), Dr Kym Lowry (UQCCR, k.lowry@uq.edu.au)

Hospital-acquired infections (HAIs) present significant healthcare challenges globally, affecting patients in both developed and developing nations. In Australia alone, over 165,000 patients suffer from HAIs annually, with antimicrobial resistance (AMR) compounding the issue by limiting treatment options and worsening patient outcomes. Prospective whole-genome sequencing (WGS) has emerged as an optimal approach for rapidly identifying transmission of multi-drug resistant (MDR) bacteria. However, current surveillance methods primarily rely on culture-based isolation of specific pathogens, followed by  detailed genomics characterisation of individuals, which is labour-intensive, prone to selection bias, and fails to provide insights into community dynamics and interactions between patients and the hospital environment. This project aims to pioneer an alternative approach: prospective metagenomic surveillance. By leveraging high-throughput metagenomics, this project seeks to profile overall community structure, characterise community dynamics, and identify and control pathogen transmission in clinical settings. The research will involve developing new workflows and pipelines to integrate metagenomic surveillance into routine clinical practice, thereby enhancing infection control strategies and patient care

Principal Advisor: Prof Mark Schembri (m.schembri@uq.edu.au)

Associate Advisor: Dr Brian Forde (b.forde@uq.edu.au), Dr Patrick Harris (UQCCR; p.harris@uq.edu.au), Dr Minh-Duy Phan (IMB; m.phan1@uq.edu.au)

Antimicrobial resistance (AMR) is a major threat to global human health. In 2019 alone, there were an estimated 4.95 million deaths associated with bacterial AMR, with uropathogenic E. coli (UPEC) a leading pathogen associated with urinary tract infections, sepsis and high rates of antibiotic resistance. This project will use cutting edge genetic screens, molecular microbiology, genome sequencing and bioinformatics to understand how plasmids contribute to the spread of antibiotic resistance in UPEC. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Prioetti (IMB)

An opportunity exists for a PhD position in molecular immunology, where cutting-edge technologies will be applied to understand the molecular basis of the link between EBV and Multiple Sclerosis. Epstein-Barr virus (EBV) is the top identified causative agent of Multiple Sclerosis, but how this occurs is not known. This project aims to apply an innovative approach using proteome-wide screening of EBV to identify the subset of EBV proteins from the complete EBV proteome that triggers MS. It will compare responses in individuals with different stages of MS and apply sophisticated computational analytics to identify specific EBV proteins that predict MS disease. This EBV signature of MS could be translated into a clinic-friendly point-of-care test. If successful, this project could revolutionize the diagnosis and management of MS, providing patients with a quicker and more accurate diagnosis and enhanced quality of life.

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.

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.

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Prioetti (IMB)

An opportunity exists for a PhD position in vaccine engineering. Vaccines are one of the most effective health care interventions but remain a challenge for many diseases, and in particular intracellular pathogens such as malaria where T cell responses are particularly desirable. We have been exploring novel  approaches to rationally design an effective vaccine against challenging disease targets. By taking advantage of recent advances in genomic sequencing, proteomics, transcriptional profiling, and molecular immunology, we have discovered unique targets of T cell responses or antibody response. This project will test these antigens as vaccine candidates by assessing immunogenicity, protective capacity and biological function using different vaccine platforms. By designing an effective vaccine from genomic data, this project is expected to result in significance advances in vaccinology as well as immunology, with important public health outcomes.

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.

Principal Advisor: Prof Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Associate Advisors: Prof Rob Capon (IMB); Dr Zeinab Khalil (IMB); Dr Alun Jones (IMB); Dr Rudi Sullivan (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. Our group works on the key essential membrane steps of cell wall synthesis, 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 novel, innovative assays to measure the activities of membrane-bound cell wall enzymes. The PGR student will then use these new assays to search for new inhibitors from Nature that inhibit the bacterial cell wall in the Australian Soil for Science microbe collection. 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.