Opportunities

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

 

Medicinal Chemistry

PhD Project Name: New drugs against TB: Novel inhibitors of DprE1.

Tuberculosis (TB), an infectious disease most commonly caused by Mycobacterium tuberculosis, claims ~ 2 million lives each year. Benzothiazinones (BTZs) target the essential M. tuberculosis cell wall building enzyme DprE1. BTZs are pro-drugs, activated in the bacterium by reduction of an essential nitro group to a nitroso derivative which then specifically reacts in the active site of DprE1, inactivating the enzyme. While this covalent mechanism imparts exquisite activity to the compounds, the required nitro group represents a liability in terms of toxicity and in vivo metabolism. Recently, the crystal structure of DprE1 was published and we aim to combine this new structural information with the extensive information available in the existing program to develop novel antitubercular compounds without the nitro group liability. This project aims to develop new lead compound classes targeting M. tuberculosis and will involve structure based design and medicinal chemistry.  It will leverage the existing expertise within the group in developing in vivo active compounds targeting DprE1.

 

PhD Project Name: PhD in CNS active Anti-inflammatory Compounds

Interleukin 1β is a key component of the innate immune response vital for host protection against invading pathogens and aiding in cellular and tissue repair. However, IL-1β is also a potent pyrogen and dysregulation leads to a wide variety of diseases including auto inflammatory disorders. We have recently discovered a series of compounds which modulate IL-1β through targeting the NLRP3 inflammasome signalling cascade. These small heterocyclic molecules also show early signs of activity in central nervous system disorders. This project will aim to examine the full potential of the structural class in disorders of the CNS (multiple sclerosis, Alzheimer’s and Parkinson’s disease) while also exploring the therapeutic potential of the class as a whole through structure activity relationship and mode of action studies. Ultimately new optimised drug leads will be generated for development. This is primarily a medicinal chemistry project but is highly interdisciplinary requiring a dedicated scientist keen to expand their skills and knowledge as the project requires.

 

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.

 

PhD Project Name: Project in Antifungal Drug Discovery

The human pathogenic fungus Cryptococcus neoformans is a common cause of fatal fungal meningioencephalitis in immunocompromised individuals, typically AIDS patients and persons undergoing immunosuppressive treatment such as transplant and chemotherapy.  In sub-Saharan Africa, cryptococcosis is the second most deadly infectious disease behind only malaria.  Infections of humans caused by pathogenic fungal species such as C. neoformans are highly refractive to pharmacological intervention due to similarities in our shared eukaryotic physiology. Antifungals are few in number, often expensive, frequently toxic to humans, and have notoriously variable efficacy across the spectrum of human fungal pathogens.

The aim of this medicinal chemistry PhD is to develop promising new antifungal lead compounds. An approach of particular interest is exploiting differences in essential proteins that are well characterised in both the human host and the fungal pathogen to gain selective antifungals through structure based drug design. We have already conducted an extensive screening campaign where a number of hits have been selected for further work. This project will require a talented and creative synthetic chemist willing to work across multiple scientific disciplines to progress the project.

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Structural Biology / Antibiotic Mode of Action

PhD Project Name: Structural Biology Investigation of Bacterial Lipid II-Glycopeptide Antibiotic Interactions
We seek a motivated and talented student interested in structural biology and label-free analysis, with a focus on structural NMR and X-ray crystallography, for a project investigating the interactions of glycopeptide antibiotics with their bacterial target.  Extensive biophysical characterisation (X-Ray crystallography, NMR, Surface Plasmon Resonance and Isothermal Titration Calorimetry) will be conducted on a range of known and novel glycopeptides of varying structure, and the complexes they form with Lipid II and mutated Lipid II.  The physical analysis will be integrated with state of the art modelling and simulation techniques to provide an unprecedented ability to model structural alterations and predict binding affinities that correlate with antimicrobial activity and the results used to design new theoretical constructs.  The applicant must be willing to learn a range of techniques to drive this multidisciplinary project.

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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.

 

PhD Project Name: Project in NLRP3 inflammasome in Gram-positive infections and ageing

Highly motivated candidates, with an interest immunology and innate immunity are sought for a PhD project looking at age dependent changes in the NLRP3 inflammasome against Gram-positive bacteria. Mouse in vivo work, cellular and biochemical assays, as well as microscopy/live animal imaging techniques will be extensively used to explore the role of NLRP3 inflammasome cascade initiated after infection in adult and aged animals. Candidates will be expected to be familiar with basic immunological concepts, and be prepared to learn animal handling and immune assays/techniques.

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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.

 

Click here to download an expression of interest form.

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