Opportunities

ABOUT US

Our group is defined by our commitment to our community principals. We strive to serve the community by discovering and developing better solutions for good health.  We are a diverse, multi-cultural inclusive group where each member of our team is recognised, accepted and embraced. We respond to the needs of our community and encourage a culture of helping others to promote effective communication and improve the sharing of scientific knowledge.

We continually examine and monitor progress via regular project and group meetings and annual performance reviews that provide the opportunity for everyone to communicate ideas, provide constructive feedback and advice and share positive experiences.

The Cooper Group is a safe and respectful workplace, where each member feels secure and valued. The University of Queensland’s comprehensive workplace safety policies provide an effective framework for a healthy and safe work environment. Our individuals accept responsibility and accountability for safe and respectful working practise.

 

Researchers

Jobs at UQ
http://www.uq.edu.au/staff/

We are always interested to hear from researchers with a strong interest in our research programmes and who have the potential to make significant impact.   We welcome approaches from talented scientists who can construct innovative and original research programmes allied to our general research focus.   We expect that such individuals can generate support for their stay with internationally competitive fellowships such as:

All countries:

Further information
info-coopergroup@imb.uq.edu.au

 

Students

PhD Studentships
Expressions of interest from prospective postgraduate students are welcome at any time. To discuss the PhD projects detailed below please contact: info-coopergroup@imb.uq.edu.au

If you have read the project summaries below and would like to submit an expression of interest, click here to download an expression of interest form. Please apply via UQjobs link and attach your CV, cover letter and expression of interest form.

Individual supervisors will invite selected applicants to submit a full application and will provide advice about university scholarship applications at this time.

If you require information on availability of PhD places please contact Amanda Carozzi at postgrad-office@imb.uq.edu.au

For other information on student opportunities at the Intstitute for Molecular Bioscience click here.


We currently have projects available in the following areas:
Medicinal Chemistry | Structural Biology / Antibiotic Mode of Action |Computer Aided Drug Design | Inflammation | Diagnostics & Dengue |Chemistry | Microbiology | Neurodegenerative Disease

 

Medicinal Chemistry

PhD Project Name: Medicinal Chemistry Development of a GPCR Receptor Agonist to Reduce Inflammation

Excessive inflammatory response results in a range of serious medical conditions.  Neutrophil mobilisation is a key component of the inflammatory cascade resulting from injuries such as ischemia.  A series of short peptides designed for an inflammation pathway GPCR target have recently show unexpected activity at a related GPCR that has been validated as an attractive therapeutic possibility. These peptides contain a key structural motif that is ripe for exploitation in a peptidomimetic hit-to-lead drug discovery project.  Initial studies will focus on exploring the structure-activity relationship (SAR) around the active peptides, followed by a concerted effort to improve potency and drug-like properties via peptide to small molecule peptidomimetic strategies.  We seek a motivated and talented student interested in medicinal chemistry, with a focus on peptidomimetic design, chemical synthesis and structural NMR willing to learn a range of techniques to drive this multidisciplinary project.

 

 

Computer Aided Drug Design

PhD Project Name:  Predictive model and knowledge base system for antimicrobial activity

As part of the ongoing antimicrobial research, we are interested in developing a comprehensive knowledge base system for antimicrobial drug discovery, especially against Gram-negative bacteria such as E. coli, P. aeruginosa and K. pneumonia. The aim of the knowledge base system is to collect and link all information relevant for the discovery of novel antibacterial compounds, including chemical and microbiological information, using modern chemo- and bio-informatic data management and classification (ontology) system. The main aim is to use the system build comprehensive predictive models for antimicrobial activity, using various machine learning methods based on the chemical structure of a compound. The project will utilize the vast amount of in-house data generated from the many different antibacterial drug discovery projects as well as from high-through put screening campaigns specifically design for this project. These predictive models will be an integral part of our antibacterial drug discovery projects. We are looking for highly motivated candidates interested in data modeling and machine learning, data and knowledge management, as well as strong interest in chemoinformatics and bioinformatics.  

 

PhD Project Name: Drug delivery and Membrane penetration of Antibacterial Compounds

How and why do small molecules (drugs) penetrate bacterial membranes?

As part of the ongoing antimicrobial research, we are interested in developing a comprehensive predictive system for antimicrobial activity, especially against Gram-negative bacteria such as E. coli, P. aeruginosa and K. pneumonia. The aim of the project is to use a mechanistic approach in the development of novel compounds. Gram-negative bacteria possess an innate resistance to many of the antibacterial compound classes due to their additional outer membrane, limiting penetration and accumulation of active compounds within the bacterial cell. It is currently difficult to predict the likelihood of activity against Gram-negative bacteria, due to the lack of information on how and why compounds penetrate bacterial membranes. The aim of the project is to study the outer and inner membrane penetration of various antibacterial compounds, utilizing a vast range of different assay technologies (visualization, labeled and label-free assays, chemical analytical technologies), accessible out our facilities. We looking for high motivated candidates interested in microbiology, biochemical and biological assay development, as well as with a strong interest in the discovery of novel active compounds against bacteria, including interest in chemical analysis. 

 

PhD Project Name: Novel ligand based screening methods using multi-conformational information

Most drug discovery and development projects rely on ligand based virtual screening methods, in which no structural information of the target enzyme or protein is known and the selection of novel potentially active compounds is only based on a chemical information of known active (and non-active) compounds. Current ligand based methods lack or under-represent the three-dimensional spatial information of compounds. The project aims to stream line the workflow and incorporate off-target activity, pharmacokinetic property and localization prediction in the process. The aim is to optimize the ligand based screening methods for mainly cell-based and in vivo assays which require additional properties such as cell penetration, metabolic stability and low off-target activity, which are mostly ignored in current methodologies. The project will have access to a wide range of chemo/bio-informatic tool kits, statistical tool kits and workflow management systems (pipeline pilot), as well as a high-performance computer infrastructure. For this project we are looking for highly motivated candidates with an interest in computer based data modeling and molecular modeling, and an interest in novel drug discovery. The candidates will be working within multiple drug discovery projects and will require good communication skills. 

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Inflammation

PhD Project Name: The biological role of the C5L2 receptor

Inflammation is a protective biological response the human body instigates when challenged with a harmful stimulus. It is crucial in innate immunity and is tightly regulated. The complement cascade plays a significant role in this innate immune response, where C3aR and C5aR receptors play a huge role in regulation. The C5a receptor is of particular interest to us it has been implicated in a range of disorders including inflammation, chronic lung disease, arthritis, bacterial pneumonia and sepsis. The second known, but not well characterized C5a receptor C5L2, has been reported to be a decoy receptor for C5aR (crucial receptor for mediating inflammation). The group is currently undertaking preliminary studies to determine how and if C5L2 and C5aR interact with one another and the individual will be involved in a continuation of this work. The individual will be involved in deciphering signalling mechanisms, and finding a therapeutic use for this receptor with the help of the chemistry team to design and synthesise ligands.

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Diagnostics & Dengue

PhD Project Name: Biomimetic supported membranes on magnetic nanoparticles

Solid supported lipid bilayers are biomimetic reconstructions that can closely reproduce the natural environment of cell-membrane bound probes, thus insuring proper surface orientation, molecular arrangement and fluidity for binding. We propose to immobilize supported lipid bilayer on magnetic nanoparticles and to introduce suitable receptors on the surface to generate a library of novel probes for biosensing and biophysical studies. The major aim of the PhD project is the development of a library of functionalized supported lipid bilayers on magnetic particles and to develop novel nanotechnologies for biosensing. In addition, extensive biophysical characterization of the conjugates will provide novel insight on the mechanism of interaction with the target molecules.

 

Chemistry

PhD Project: Re-tooling metronidazole – next generation 5-nitroimidazole antimicrobials

Metronidazole, a World Health Organization ‘essential medicine’, is a small molecule antibiotic characterised by an imidazole ring functionalised with a nitro group in the 5-position. It demonstrates broad versatility in the clinic, targeting a wide range of anaerobic microbes from protozoa, including Giardia lamblia, Trichomononas vaginalis, and Entamoeba histolytica, to bacteria, such as Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Upon entering the target organism, it exerts its mechanism of action through cell-based reduction to a short-lived nitroso free radical, which causes cytotoxicity through nonspecific binding to microbial DNA.

Due to limited commercial development of 5-nitroimidazole drugs following approval of first generation compounds in the 1960s, the influence of structural modifications of 5-nitroimidazole compounds on antimicrobial activity and resistance profiles is poorly understood. With evolving resistance threatening the long-term clinical utility of this important class of compounds, next generation agents with improved properties are needed. We seek a highly motivated candidate with an interest in medicinal chemistry to engage in our early stage drug discovery program investigating how structural modification of metronidazole influences activity and resistance. The candidate will combine extensive medicinal chemistry with the ability to perform microbiological profiling of generated analogues under anaerobic conditions. Preclinical mouse models of C. difficile, E. histolytica and G. lamblia infections will also be used to characterise compounds with promising in vitro activity.

 

Microbiology

PhD Project: Understanding C. difficile relapse, reinfection, Eagle effect and therapies

C. difficile has become an important pathogen in both hospital and community settings in the last 10 years, causing a significant health and economic burden. A rapid response by the scientific and medical community has been required to develop suitable treatments as relapse and reinfection is problematic. Only three antibiotics are clinically used as primary treatment for C. difficile, all of which fail to treat the infection in 10-30 % of cases. There is now a spotlight on non-antibiotic treatments, such as faecal transplant, to address relapse and reinfection rates, and an increased interest in antibiotics selective for C. difficile.


We have initiated a drug discovery program to investigate the activity of novel potent glycopeptide antibiotics on C. difficile infections, which will include in vivo mouse studies in collaboration with Dena Lyras at Monash University. In the course of this research we have identified an ‘Eagle effect’, in which low concentrations of antibiotics kill the bacteria, but higher concentrations lead to survival. We seek a motivated and talented student interested in microbiology and medicinal chemistry to continue and expand the current investigations into new methods to treat this urgent health threat.

 

PhD Project: Synthesis of anti-infective cyclic peptide drug leads and probes

Cyclic peptides are an emerging class of antibiotics that have great potential as new leads for antibacterial drugs. Previously, these products could only be obtained by from natural sources, which have limited the scope of analogues that can be produced and biologically evaluated. However, advances in synthetic methodologies has enabled our group to synthesise and screen hundreds of new cyclic peptides, as well as make probes that can be used for further studies including investigating their mode of action.


One of the peptides of interest is Bacitracin A, which is active against both Gram-positive and Gram-negative bacteria, and is used topically in ointments such as Neosporin. Two residues, D-asparagine and D-glutamic acid, are not required for antibacterial activity, so bacitracin A can be modified at these two positions with azide groups. These will be useful starting materials for generating both fluorescent probes and hybrid antibiotics via ‘click’ chemistry. The fluorescent probe(s) will be used to investigate the Bacitracin A molecular targets. Bacitracin is not used systemically due to toxicity; we will conduct structure-activity relationship studies to investigate whether it is possible to decouple toxicity from antibacterial activity. We also have other cyclic peptides and lipopeptides that would also be synthesised and biologically evaluated in this project. This project is suitable for a highly motivated student interested in synthetic / medicinal chemistry, with opportunities for extension into biochemical and microbiological assays for mode of action studies.

 

Neurodegenerative Diseases

Pharmacological targeting of innate immune neuroinflammation in Parkinson’s disease

We seek a motivated and talented student interested in investigating the innate immune and neuroinflammatory responses during Parkinson’s disease. The study of novel signaling pathways that mediate chronic neuroinflammation and progressive degeneration of dopaminergic neurons in Parkinson’s disease will be a major focus. A combination of in vitro primary culture systems, preclinical mouse models and clinical patient samples will be utilized to carry out these studies. The contribution of specific neuroinflammatory mediators to disease progression will be delineated using novel pharmacological inhibitors, genetically engineered mice and cutting edge Cell & Molecular Biology approaches. These studies will drive the development of therapeutic strategies that aim to mitigate disease progression in Parkinson’s disease.

 

PhD Project Name: Pharmacological targeting of innate immune neuroinflammation in Parkinson’s disease.

We seek a motivated and talented student interested in investigating the innate immune and neuroinflammatory responses during Parkinson’s disease. The study of novel signaling pathways that mediate chronic neuroinflammation and progressive degeneration of dopaminergic neurons in Parkinson’s disease will be a major focus. A combination of in vitro primary culture systems, preclinical mouse models and clinical patient samples will be utilized to carry out these studies. The contribution of specific neuroinflammatory mediators to disease progression will be delineated using novel pharmacological inhibitors, genetically engineered mice and cutting edge Cell & Molecular Biology approaches. These studies will drive the development of therapeutic strategies that aim to mitigate disease progression in Parkinson’s disease.

 

Click here to download an expression of interest form.

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