Drug discovery

Protein Production and Characterisation (PPC) is a key node that assists researchers with the expression, purification and analysis of their proteins of interest. The facility is open to all researchers and its main objective is to facilitate the production and characterisation of proteins that most often constitute major drug targets. Services include: 

• undertaking experiments to produce and characterise target proteins in state-of-the-art laboratories
• providing expert advice to users and training personnel (including students and staff). 

We work with three different expression hosts (bacterial, insect, and mammalian cells), and use highly-specialised protein purification and characterisation equipment. The flyer (right hand side) has more information about the PPC workflow, as well as our equipment and expertise.

Protein X-ray crystallography is one of the most powerful methods to visualise the molecular structure of a protein at atomic resolution. The structure, in turn, provides a better understanding of a protein’s functionally important sites and its mechanism of action.

This facilitates the development of efficient and specifically targeted drugs. Sydney Analytical facilities provide a platform for trained crystallographers to access these state-of-the-art instruments. In addition, our expert staff provide guidance and can assist researchers, especially those new to the field of X-ray crystallography, in determining the three-dimensional structure of their target protein.

Services offered include:

• protein crystallisation
• in-house crystal screening
• data collection at the Australian Synchrotron and data processing
• structure determination and refinement.

Download the flyer (right hand side) for more information about available Protein Crystallography equipment and expertise.

Synchrotron X-rays are much more intense than in-house sources, allowing much smaller crystals to be measured much more quickly. Our partners at ANSTO operate three protein crystallography beamlines at the Australian Synchrotron (MX1 and MX2, with MX3 due to open shortly) tuned for different types of problems. We can provide advice on their suitability for your experiment and how to access them.

Fragment-based drug discovery (FBDD) is a strategy that is growing rapidly in popularity. Rather than rely on large libraries of complex molecules, FBDD involves a small, carefully curated library of molecules that are about half the size of typical drugs. A drug target is screened against the library and ‘hits’ can then be chemically expanded to create lead compounds that bind with high affinity. The approach can be used to target enzymes as well as less traditional targets such as protein-protein or protein-nucleic acid interactions, and even membrane proteins.

Sydney Analytical use a fragment library curated by the medicinal chemists at the Monash Fragment Platform. Our primary screening methods are Nuclear Magnetic Resonance (NMR) and Surface Plasmon Resonance (SPR). Please see the attached flyers for more information about our FBDD workflow, as well as our equipment and expertise.

Learn more about FBDD workflow and equipment available by downloading the PDFs on the right hand side.

Small cyclic peptides can be large enough to block protein-protein interactions but small enough to display drug-like properties, making them ideal candidates for drug discovery. Cyclic peptide display screening (CPDS) allows for the rapid parallel synthesis and screening of trillions of molecules against virtually any expressible protein target, yielding diverse ligands with very high affinity (typically low nM) and selectivity.

Learn more about cyclic peptide display by downloading the brochure on the right hand side. 

The following equipment is available to user working in the drug discovery laboratories:

• PC2 Lab 
• Prometheus Panta
• Refeyn TwoMP Mass Photometer
  
• BioSafety and Cytotoxic cabinets 
• Bio-Rad micropulser and neon electroporators 
• Countess cell counter 
• Seahorse XF24-3 
• IncuCyte Zoom 
• Cytation 3 
• PheraStar plate reader 
• Incushakers 
• C3 Homogeniser 
• AKTA FPLC purification systems 
• Gradient station 
• Beckman Optima L-80XP ultracentrifuge 
• Biacore T200 
• Blitz 
• BioRad Trans-Blot Turbo transfer system 
• Bio-rad T100 thermal cycler 
• RotorGeneQ 
• Uncle protein stability screening platform

The RASTRUM™ 3D Cell Culture Platform enables the generation of physiologically representative 3D cell models (mono-cultures and co-cultures, HTP models and organoid models) that can be used for drug screening, personalised medicine and investigative biological studies.

The RASTRUM™ 3D cell culture platform allows for rapid and reproducible 3D cell model generation in an automated manner in order to study a range of disease and tissue types. Here is a short two minute video on the technology.