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Drug Discovery, Issue 6 2013 / 15 December 2013 / Sergio C. Chai, Asli N. Goktug and Taosheng Chen, High Throughput Screening Center, Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital
Liquid handlers are ubiquitous and essential tools in every aspect of the drug discovery arena. Innovations in the past few decades resulted in a sizeable array of devices. With so many choices, it is important to identify appropriate instrumentation for a particular screening strategy, which should be based on unique capabilities and limitations. Intense advances in the design of liquid handling devices have broadened the capabilities to screen larger collections of compounds at a faster pace with increased reliability and efficiency. These innovations drift towards miniaturisation, in large part to reduce cost and increase throughput. A wide selection of fluid handlers has been developed for every aspect of drug discovery, which incorporate different technologies for discrete functions. Although this segment focuses on instrumentation relevant to the screening of small organic molecules, the perspectives presented herein can be valuable in the handling of oligonucleotides or biologics…
As RNA interference (RNAi) enters its teenage years from the first critical observations, it has now reached a multi-billion pound industry. There are few research areas that have expanded as quickly and spectacularly as the field of RNAi. The potential of RNAi initially sparked a functional genomics gold rush. Different uses of this technology in genomewide screens have identified genes involved in fundamental biological processes. There are now hundreds of research papers reporting genome-wide screens using cell culture to investigate the building blocks of the cell. However tempting it may be to speculate that this technology could be the new magic bullet to all our research needs, especially after some of the previous successes, some basic aspects of the RNAi technology and screening process still need to be addressed and improved upon. This review will investigate the strengths and weaknesses of our current technology, suggesting improvements and highlighting some of the novel growth areas in this field.
Our foundations of cell biology rely upon an understanding of cellular pathways, the components of which have been investigated over the last 40 years or so. Recent embellish – ment of the pathways has been carried out using models in cell culture with RNAi technology1. Many techniques have been used to reveal the functions of core pathway proteins, but few have sparked the imagination like the RNAi screen with the potential to systematically knock down the expression of every gene in the genome.
The pharmaceutical industry has significantly influenced laboratory automation trends in the past two decades. The need to screen large collections of chemical entities in a short time with minimised consumption of reagents has driven a strong demand of parallelisation, automation, simplification and miniaturisation solutions from the suppliers of instruments, labware and assay technologies. Currently, the levels of automation and miniaturisation seem to have reached a plateau and the new paradigms are flexibility and information content.
In this article, an overview regarding advances in assay formats for specific target classes and options that should be considered when considering hardware will be given. There has been a significant growth in the assay and automation technologies that are available for compound screening activities and it is essential to evaluate a variety of these before beginning a drug discovery program, the aims of these being to ensure the most relevant assay formats that are available are adopted.
Over the past decade we have seen a significant realignment of activities associated with drug discovery and this will continue for a multitude of reasons. Within the pharmaceutical industry we have seen significant changes e.g. a decrease in the numbers of drugs that are being approved by the regulatory authorities and the looming expiration of patented drugs, both of which have an immediate and direct consequence on revenue streams. In light of these issues, the pharmaceutical industry is responding appropriately. These changes have included a re-assessment of the strategies being employed in the pre-clinical phase of drug discovery, some of which are discussed in relation to automation solutions.
Participants: Dr Gordon R Alton, President and CEO, Altonyx Consulting / Dr Scott Bowes
Scientist, Novartis / Dr Sheraz Gul, Vice President and Head of Biology, European ScreeningPort /
Chris Molloy, Vice President of Corporate Development, IDBS
In 2010 a diverse group of scientists, engineers and professionals from around the world will come together once again for this laboratory automation event. At LabAutomation2010 participants will develop long-lasting connections through networking and expand their minds by exploring cutting-edge information and strategies.
There has been a continuous move by the large commercially orientated players involved in Drug Discovery to initiate novel methods to increase income streams and productivity. An example of the former has been the acquisition of companies and their drug pipelines and in the case of the latter, rationalisation of internal Research & Development activities. This is well illustrated by GlaxoSmithKline Pharmaceuticals which have formed small focused research units called the Centres for Excellence in Drug Discovery (CEDD) and the Discovery Performance Units (DPU) each of which having increased accountability1.
Among the challenges for the pharmaceutical industry, declining research productivity and increasing research costs take a prominent position. This is often put in the context of efforts in the pharmaceutical industry to automate and “industrialise” research activities, combinatorial chemistry and High Throughput Screening being the most prominent examples. An argument is being put forward that the industry replaced scientists with robots and scientists’ ingenuity with mindless screening. It is then concluded that the investments into automation were misguided and led to a decline in research productivity.
High Throughput Screening (HTS) has for many years now been playing a central role in drug discovery efforts to aid the identification of small molecule chemical entities that are capable of modifying the activity of disease relevant targets1. In order to make HTS a viable option to provide appropriate starting points for drug discovery efforts, large libraries of compounds are required that contain diverse chemical space.
From around the world, a diverse and highly innovative group of academicians, scientists, engineers, post-doctoral associates, graduate students, and business leaders will converge at LabAutomaton2009. The show will be held on 24-28 January 2009, at the Palm Springs Convention Centre, Palm Springs, California.
Laboratory automation development is being increasingly outsourced to the commercial market according to a recent industrial member survey by the Association for Laboratory Automation (ALA). ALA polled 400 of its members in industry with 14 questions and received 72 responses representing 47 different companies in the Pharma, Biotech and Agriculture Science sectors (an exceptionally good response). This article discusses the four questions that pertain to how the practitioners of laboratory automation in industry get their job done.
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