Cracking Proteomics Bottlenecks

Courtesy of NextGen Sciences As a company that develops breast cancer protein chips, Cambridge, UK-based NextGen Sciences experiences the pitfalls of proteomics research on a daily basis. One of the bottlenecks at the moment, says CEO Kevin Auton, is the need to produce enough different proteins to meet the demands of therapeutic groups both internally and for corporate clients. Resolving complex protein mixtures into their component parts is another ongoing problem. In September, NextGen Sciences launched two platforms that overcame some of these challenges. The first release, the expressionfactory™, automates every facet of parallel protein expression and purification--from putting genes into fusion vectors and growing proteins in vivo or in vitro, to isolating and analyzing the proteins for use in subsequent applications. Researchers at NextGen Sciences who used the system to manufacture proteins for use in breast cancer chips quickly found themselves in an informatics quagmire. "One of the things we discovered in doing this is when you start going parallel rather than one gene-one vector at a time, you very quickly lose track of what on earth is going on," says Auton. NextGen Sciences solved this by developing an Oracle™-based laboratory information management system, called IMS™, that integrates the Sapphire™ sample tracking program from Bridgewater, NJ-based LabVantage Solutions. The database is integrated with the system's robotics to simplify automation programming as well. "We have an expert system that allows you to clone and express hundreds of proteins in parallel using a variety of different strategies, all of which can be done in silico in the database system before you begin. And then once you're happy with that process, the whole thing gets sent to the robot, [which] basically performs as an expert technician performing all the processes in one box," Auton explains. The expressionfactory can run up to 21 different processes all on an integrated system; other robotics platforms automate small parts of the process but are not tied to a database or LIMS, he says. Auton claims that the expressionfactory can extend the work of a PhD scientist fivefold and allow technical workers to spend more time on process development. Though only recently launched, the expressionfactory has already been tested by scientists at pharmaceutical companies and in academia. Paul Hawtin, senior research scientist at AstraZeneca in Cheshire, UK, evaluated the instrument and says he was impressed by how well it was engineered. He says the system could allow his group to evaluate a large number of protein constructs under various expression conditions in parallel, but that it is not necessarily the solution to all protein-production problems. "It's not going to produce enough protein to, for example, start a crystallography trial," says Hawtin. But it will lead his team in the right direction, helping them to identify the correct construct, which they could then scale up to production level "and hopefully get protein at the milligram level." SOLVING 2-D NIGHTMARES NextGen Sciences' second product release, the a2DE, is a benchtop two-dimensional gel electrophoresis system that completely automates what Auton calls a "ghastly" procedure for separating mixtures of proteins, a sentiment with which many proteomics researchers would likely concur. Two-dimensional gel electrophoresis is notoriously difficult to master, and researchers in the field of proteomics have long called for a reliable way to automate the process. NextGen Sciences' team of biologists and engineers tackled the problem with a number of patent-pending innovations that enable users to simply load a sample and walk away; the system performs the first-dimensional focusing and then automatically casts the second-dimension gel in situ using gradients set by the user. Three gels can run simultaneously using independently programmed gradients. "We've automated the process of 2-D electrophoresis, made it reproducible, made it possible to run very large gels so you get good resolution, and make it so easy that most degree-qualified scientists can use the system with a minimum of training," says Auton. NextGen Sciences has previewed the $140,000 (US) system at conferences, and Auton says that he is encouraged by potential customers' reactions to it. "Halfway into the process, when they realize the a2DE will actually cast a gradient gel under their computer control, which is something that most people can't do in their labs, you can see the light suddenly come on in their eyes, and they break into a big smile," Auton says. "The response has been incredibly positive." --Aileen Constans function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Cracking Proteomics Bottlenecks

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