CooperGroup

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:

• ARC Australian Postdoctoral Fellowship
• EU residents: FP7 Marie Curie International Outgoing Fellowships (IOF)
• German: Deutsche Forschungsgemeinschaft Research Fellowships
• Japanese: Japan Society for the Promotion of Science Postdoctoral fellowships for Research Abroad
• Swiss: Swiss National Science Foundation Postdoctoral fellowships
• USA: National Science Foundation International Research Fellowship Program (IRFP)

All countries:

• Endeavour Research Fellowships

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

 

Students

PhD Studentships
Expressions of interest from prospective postgraduate students are welcome at any time.

If you require further information on availability of PhD places please contact Amanda Carozzi (a.carozzi@imb.uq.edu.au)

We currently have projects available in the following areas:
Medicinal Chemistry | Structural Biology / Antibiotic Mode of Action |Computer Aided Drug Design

 

Medicinal Chemistry

Novel antibiotics to combat drug resistant bacteria

Multi-drug resistant (MDR) Gram-negative bacteria have spread considerably in recent years and are now causing untreatable, lethal infections worldwide. This has resulted in a dire medical need for new antibiotics to treat infections caused by MDR Gram-negative pathogens, which is exacerbated by the lack of suitable drug candidates in the pharmaceutical pipeline.
The aim of this project is the synthesis and biological evaluation of lipopeptides active against Gram-negative bacteria and the study of their mode of action. It involves the chemical synthesis of lipids and lipid-like molecules, solid phase peptide synthesis, and 3-D structure elucidation using NMR and MS techniques, as well as the characterization of membrane interactions and intracellular targets using SPR, NMR, and TOF-MS.
The Cooper group has experienced medicinal and analytical chemists, biochemists and biologists that will provide guidance throughout the project. The University of Queensland was ranked 65 in the world University rankings 2012-13 and the Institute for Molecular Biosciences (IMB) is the source of many high-impact publications and is well-appointed with state-of-the art equipment (http://www.imb.uq.edu.au).
This project will suit a candidate with a medicinal chemistry or chemistry background with a strong interest in biology and interdisciplinary research.

 

 

Structural Biology / Antibiotic Mode of Action

PhD Project: Structural Biology Investigation of Bacterial Lipid II-Glycopeptide Antibiotic Interactions
Glycopeptide antibiotics such as vancomycin are a last line of defence in the treatment of serious infections caused by drug resistant Gram-positive bacteria such as MRSA.  They bind to the C-terminal Lys-DAla-DAla tripeptide component of Lipid II, thereby inhibiting a key step in biosynthesis of the bacterial cell wall peptidoglycan. Mutations in the peptidoglycan structure have led to widespread vancomycin resistance in recent years. However, changes to the backbone of the proximal Ala-D-ɣ-Glu/Gln residues in Lipid II have not been observed in resistant bacteria.  We have developed novel vancomycin derivatives containing additional functional groups designed to target the full-length Lipid II sequence and bacterial membrane.  These analogues are highly potent against resistant Gram-positive bacteria.
As part of this project, we are developing a comprehensive understanding of glycopeptide-ligand interactions with native and resistant forms of Lipid II in a physiologically relevant membrane environment.  Extensive biophysical characterisation (X-Ray crystallography, NMR structural determination, Surface Plasmon Resonance and Isothermal Titration Calorimetry) will be conducted on a range of glycopeptides that vary in the type and position of lipophilic, basic and glycosyl groups, 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. Promising theoretical constructs will be synthesised and tested against a panel of resistant bacterial strains.

We seek a motivated and talented student interested in structural biology, with a focus on structural NMR, X-ray crystallography and label-free analysis, willing to learn a range of techniques to drive this multidisciplinary project.

 

 

Computer Aided Drug Design

Chemoinformatics for Drug Design and Development
A comprehensive chemo- and bioinformatics infrastructure is essential for competitive drug design and development to process and analyse the ever increasing amount of data. The Cooper Group currently maintains a large chemical database of biological data, including bioactivity and specific organism and disease based information. We also aim to include genomic, proteomic and metabolomics information, combining chemoinformatic and bioinformatics. Several research projects are thereby available:

• Predictive modelling system for antimicrobial activity

As part of the ongoing antimicrobial research, we are interested in developing a comprehensive predictive modelling system for antimicrobial activity. The aim is to use various machine learning methods to build prediction of antimicrobial activity based on the chemical structure of a compound. The aim is to not only predict the overall likelihood of a compound to be active against different classes of bacteria (such as Gram-positive, Gram-negative or mycobacteria); but also to provide prediction on membrane penetration, compound delivery and localisation within the bacterial cell. This model will have a profound impact on our current and future antibacterial drug development programs.

• Data analysis system for antimicrobial drug discovery

As part of the antimicrobial research we are currently extending our databases with more and more genomic and proteomic data, including metagenomic data collected to distinguish disease state from normal state of various microbiomes (i.e. gut, lung, skin); and metagenomic data collected to distinguish pathogenic and/or resistant bacteria from non-pathogenicbacteria. This large and complex amount of data will be linked with the chemical and biological information of antibacterial compounds, including chemical and biological onotologies. This will require novel data analysis and visualisation tools, combining chemoinformatic with bioinformatics methods. This system will provide the central data repository and analysis platform for our antibacterial drug development programs. 

• Novel ligand based screening methods using multi-conformational information

Several of our 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. The selection of novel potentially active compounds is based on chemical information of known active (and non-active) compounds. Current ligand based methods lack or under-represent the three-dimensional spatial information of compounds, especially its variation, due to different conformations of a compound. The aim of the project is to develop novel ligand based screening methods using multi-conformational descriptors. The goal is to provide a framework for improved ligand based screening and scaffold hopping applications.