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Thermo Fisher Collaborates with ICR on Network Biology-Based Cancer Research


By Tony Fong

Thermo Fisher Scientific has entered into a collaboration with the UK's Institute of Cancer Research as part of a new integrative network biology initiative underway at the institute that is using proteomics and other –omics methods to decipher how cancer cell networks interact with each other in order to metastasize.

As part of the initiative, Thermo is outfitting ICR's new "state-of-the-art" proteomics laboratory with two of its LTQ Orbitrap Velos mass spectrometers, launched last month at the American Society of Mass Spectrometry conference [see PM 06/04/09], one TSQ Vantage triple quadrupole mass spec, a Kingfisher Flex automated sample preparation system, software, including Proteome Discoverer and Pinpoint, and reagents.

The company asked that financial terms of the deal not be disclosed.

The collaboration comes as the ICR embarks on a new strategy to combat cancer and develop more effective drugs. According to Rune Linding, head of the cellular and molecular logic team at the ICR, cancer research has traditionally focused on the function and behavior of individual genes and proteins.

With its new approach, which ICR calls "network medicine," analyses will shift to investigation of cancer cell networks and how they interact with each other and other tissues to spread.

"We are pushing the field of network medicine," Linding told ProteoMonitor in an e-mail this week. "We will use integrative network models based on protein, phenotype/genetic, and … deep DNA sequencing [data] to construct predictive models of cell behavior. These will allow us to identify sub-networks responsible [for] or key to the progression of complex regulatory diseases like cancer, diabetes, and neurological disorders."

Such an approach calls for high-performance instruments, and "the LTZ Orbitrap Velos and TSQ Vantage systems enable us to push the boundaries and analyze completely new aspects of cellular signaling networks and perform massive-scale studies of the dynamics in these networks," Linding added. "This is crucial as we believe the progression of cancer is due to changes in these molecular networks."

The Thermo Fisher instruments will be used to identify and quantify post-translationally modified peptides, with the resulting data then used to compare cell signaling networks. Presently, such work is done on a single-protein level, "but they're talking about signaling from all the signaling molecules to their receptors and back again, which is a massive demand on the instruments, and an even bigger demand on computation," said Anthony Sullivan, proteomics team leader for Thermo Fisher.

"It's going to lead to understandings of networks and phenotypes at the network level, and then eventually to the tailoring of personalized medicine," he added.

ICR has no history of proteomics research. "I know only of what we will do from now on," Linding said. But he added that the work he will be conducting will not duplicate research being conducted by the scores of other proteomics scientists working in the field of cancer.

"We are contributing [in] a completely new way," he said. 'We are not running samples; we are answering biological questions using quantitative methods, including mass spectrometry."

The proteomics laboratory is just becoming operational. When online, it will have a dedicated staff of 15 to 20 mass-spec personnel, Linding said. He said he did not know the exact size of the facility or the cost of creating it.

According to him, however, the new lab is "the most advanced ever built," with HEPA/carbon positive air pressure, air locks at entry, extreme temperature and humidity controls, and vibration and noise controls.

In addition to the Thermo Fisher platforms, the lab has MALDI tissue imaging equipment, and mass specs from Applied Biosystems.

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In addition to outfitting the laboratory with instruments and tools, Thermo will work with ICR computational scientists to "improve and enhance" the company's protein identification software, Sullivan said.

"We see the collaboration as being two-way from the point of view of us giving them preferential agreements with instruments and software, and us benefiting from them with scientific contributions on a collaborative basis," he said.

In particular, one goal for the company is further development and improvements to the Pinpoint software, used for quantitative analysis of selected-reaction monitoring-based targeted peptide assays, Sullivan said. Enhancements to the product would be based on feedback from the ICR.

Hardware development is not expected to result from the partnership, however.

As one of the largest players in the proteomics space, Thermo Fisher gets its share of requests for collaborations from researchers. It chose to enter into this one with ICR because Sullivan was impressed with the breadth of what Linding wanted to do, and, just as importantly, saw that ICR had the infrastructure, funding, and support to do the research.

However, it was largely by happenstance that the company was in a position to partner with ICR. Prior to this week's announcement on the collaboration, Thermo Fisher and ICR had no more than a typical vendor-customer relationship. And when ICR decided it was going to create its proteomics center, it had its eyes on ABI, the division within Life Technologies that houses its mass spec operations, as it supplier.

Sullivan, however, heard from a colleague about ICR's plans for a proteomics center, and soon Thermo Fisher's romancing of ICR was on. According to Sullivan, ICR was a reluctant potential partner in the beginning.

"They wanted to make sure we were serious about the collaboration," he said, and eventually, the process included "the involvement of many, many people" at Thermo Fisher, including Ian Jardine, vice president of global R&D.

A visit by ICR members to Thermo Fisher's Biomarker Research Initiatives in Mass Spectrometry, or BRIMS, center in Cambridge, Mass., was influential in completing the deal, Sullivan said. After seeing that facility, how the instruments performed, and the kind of work that was being done, ICR added Thermo Fisher to its portfolio of vendors.

In his e-mail, Linding said "We are working across all divisions within Thermo. We are collaborating with all R&D divisions, including Bremen, San Jose, and Boston. The new partnership includes [a] focus on RNAi/genomics and software development. Both parties are realizing that to handle future proteomics data, much more effort is needed to [be] put [into] analysis."

The two partners also plan on developing training programs for students "longer term," Linding said. Research will be on new methods for quantitative proteomics with the goal of pushing biology "not to just create long lists of phospho-sites. We are interested in the specific sites changes through time, [chemistry], or disease progression."

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