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SULSA Bulletin

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Drug Discovery

Scottish Hit Discovery Facility

Researchers at SULSA universities can access industry-standard screening capabilities through collaboration with the SULSA-supported Scottish Hit Discovery Facility (SHDF) at the University of Dundee. The SHDF specialises in medium and high throughout screening of small molecule libraries against both molecular target and cell-based assays, and provides qualitycontrolled starting points for medicinal chemistry programmes.

The purpose-designed laboratories boast industry-standard equipment and software, with all standard screening technology outputs for isolated target and cell-based screening represented. The current screening capabilities of the unit are based around a series of compound sets amounting to a total of >90,000 compounds. These include known bioactive sets, gene family or biology focused sets and diversity sets. The large volume of data generated is managed within a secure, queryable database using purpose designed tools that link biological data to compound structure.

Contact
Dr David Gray
d.w.gray@dundee.ac.uk

Drug Discovery Portal

The Drug Discovery Portal (DPP), based at the University of Strathclyde, is a centralised resource for both chemists and biologists to work in tandem to enhance their drug discovery efforts. The DPP matches structures provided by chemists to targets provided by biologists, and uses advanced in silico screening for hit identification. The DPP also offers database creation and secure storage of proprietary molecules, virtual screening, druggability filtering and molecular docking analysis. DPP users can also access a proprietary collection of compounds synthesised by chemists, an extensive natural products collection, and a commercial collection from commercial suppliers.

More information is available from www.ddp.strath.ac.uk or contact-ddp@strath.ac.uk
 

Scottish Bioscreening Facility

The Scottish Bioscreening Facility originated as a joint SULSA and Wellcome Trust funded initiative to stimulate collaborations and enable large siRNA and compound library screens. The SBF is based around High Content Image Based Screening (HCS) with the GE IN Cell 2000©. This wide-field fluorescence microscopy platform is useful for high throughput image capture and analysis of numerous parameters in a biologically relevant context (e.g. whole cells).

The system uses automated microscopy of samples in a variety of sample containers ranging from samples mounted on microscopy slides to uniwell, 96 well, 384 well and even 1536 well microplates, capturing multiple fields of view per well and computer-assisted image analysis gives you values for biological systems with a greater statistical significance.

Cell imaging-based high content analysis (HCA) and high content screening (HCS) are essential tools in many areas of life science research and drug discovery.  High content analysis employs image based cellular assays in a high throughput imaging and analysis format. This allows researchers to increase the number of questions they can ask whilst simultaneously decreasing the time taken to achieve their results.

For more information about the facility click here.

Compound libraries

SULSA is supporting the development of unique compound libraries, which will be accessible to SULSA researchers for screening assays. 

The Strathclyde Natural Products Library comprises 5120 extracts from around the world. With coverage of 90% of plant families, it is one of the most biodiverse (and hence chemically diverse) collections available for screening.

The library can be accessed through collaboration with Strathclyde Innovations in Drug Research (SIDR) within the Strathclyde Institute of Pharmacy and Biomedical Sciences (University of Strathclyde). SIDR offers facilities for high throughput screening, fractionation of hit extracts, isolation of active compounds and determination of structures.

SIDR also provides access to the Maybridge Hitfinder ™ compound collection of 14,000 pure compounds specially selected for their chemical diversity and drug-like properties.

Contact
Professor Alan Harvey
a.l.harvey@strath.ac.uk

Scottish Biologics Facility

Biologic ligands including classical monoclonal antibodies (and their fragments), peptides and alternative binding scaffolds are invaluable tools for biomarker validation, diagnostic assay development, in vivo imaging and drug discovery. Using phage display technology, large antibody or protein libraries can be selected and screened for target binding, by displaying binding sites on the surface of bacteriophage. The SULSA-supported Scottish Biologics Facility (SBF) at the University of Aberdeen will offer antibody-library screening services against a wide range of targets including proteins, peptides and haptens. In addition, SULSA-researchers will be able to gain training in phage display based selection, screening techniques, antibody reformatting etc. through the experienced technologist working within the facility. The facility has recently increased its staff and has moved to new facilities on the University of Aberdeen's Forseterhill site. The process of establishing suitable protocols for antibody selection is now well underway. It is anticipated that the facility will be able to offer antibody selection as part of the next round of SULSA Translational Biology Screening (Q2 2010). 

Contact 
Prof Andy Porter
 
Soumya Palliyil
 
 

The Aberdeen Natural Products Library
Facility

The Aberdeen Natural Products Library Facility consists of a collection of over 400 pure natural products of plant, microbial and marine origin. Compounds can be provided as 20 mM stock solutions in DMSO in a 96-well plate format. Requests for different formats will also be considered. Data on antibacterial/antifungal activity and cytotoxicity is already available and can be used to select the most appropriate samples for bioassay. The compounds are produced by the recently established Marine Biodiscovery Centre in Aberdeen, which has considerable expertise in obtaining extracts and pure compounds from plants, microbes and marine organisms. The library is available to researchers at SULSA institutions for testing of diverse biological targets using various high throughput screening platforms.

Contact Professor Marcel Jaspars
m.jaspars@abdn.ac.uk  

Natural Products Library Presentation at the SULSA Facility Roadshow - 16 September 2010 - University of Aberdeen

Marine Biodiscovery Centre Compound and Extract Libraries

The centre brings together complementary expertise in biology, chemistry, compound isolation and characterisation. The centre has a library of extracts and pure compounds from marine organisms, because the marine environment provides a broad range of habitats and organisms that studies have indicated produce a diverse range of novel compounds and structures with potent biological activities. For more information click here (pdf).

Contact
Professor Marcel Jaspars
m.jaspars@abdn.ac.uk

SULSA High Throughput Screening Fund

Several Scottish universities offer excellent facilities and expertise for high throughput small molecule and biologics screening. But investigators can struggle to find sources of funding for screening, particularly when their research is at an early stage. The SULSA High Throughput Screening Fund was established to help bridge this gap. The choice of facility or laboratory for running the proposed screen is at the discretion of the applicant. Successful 2008 projects – seven projects in total, from six different universities – tackled diverse biological targets for a wide range of diseases, including cancer, inflammatory disease, pain associated with nerve damage, trypanosomiasis (sleeping sickness) and pneumococcal infection. The application form, guidelines and dates for the next round of applications are available on the SULSA website.

Contact
Janette Moore (SULSA Administrator)
j.m.moore@dundee.ac.uk

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