PepChip protein kinase profiles of normal (top) and tumour tissue. Credit: PEPSCAN: DATA COURTESY OF J. TUYNMAN & D. RICHEL ACADEMIC MEDICAL CENTER, THE NETHERLANDS

Finding the right reagent or assay for the job in hand can be a daunting prospect in a field as complex as cell signalling. Some companies are taking a one-stop shopping approach; others are pursuing niche markets, specializing in, for example, antibodies, peptide substrates for kinases and proteases, enzymes, especially protein kinases, or protein and peptide microarrays, such as those from Sigma-Aldrich in St Louis, Missouri, PepScan Systems in Lelystad, the Netherlands, and Zeptosens in Witterswil, Switzerland. Even companies usually thought of as having a molecular biology focus are getting in on the act, as evidenced by the acquisition of Molecular Probes in Eugene, Oregon, a leader in novel fluorescence-based technologies for labelling biological molecules, by Invitrogen of Carlsbad, California in 2003.

“I think it is fair to say that it's becoming increasingly difficult to be totally comprehensive in signal transduction,” says Konrad Howitz, director of molecular biology at BIOMOL in Plymouth Meeting, Pennsylvania. BIOMOL, now in its twenty-first year of operation, was one of the first companies to specialize in this area and to use signal transduction as a theme for a catalogue.

BIOMOL's recent product development has been aimed at developing enzymes, substrates, antibodies and inhibitors for the study of histone deacetylases, which play a role in the regulation of gene transcription and other biological processes involving chromatin, and sirtuins, which are protein deacetylases implicated in the regulation of ageing. BIOMOL recently merged with UK-based Affiniti Research Products, and now offers the Affiniti line of ubiquitin and proteasome research tools.

“We still find that the model of niche excellence is the one that appeals to us and our customer base,” says Ian Ratcliffe, president and chief operating officer of Upstate in Charlottesville, Virginia, another established company supplying cell-signalling tools. Ratcliffe says Upstate's customers are evenly split between academia and industry.

ZeptoSens cell lysate array. Credit: ZEPTOSENS

“We think of ourselves as a ‘content’ company,” says Ratcliffe, and so is always on the lookout for companies with novel detection technologies. One such is CIS bio, based in Bagnols-sur-Cèze, France, which sells reagents and assays based on time-resolved homogenous fluorescence resonance energy transfer (HTRF) for probing molecular interactions. The company's proprietary HTRF technology uses a luminescent europium (Eu3+)-based cryptate compound as donor to tag one of the interacting partners and a phycobiliprotein (XL665) as acceptor to tag the other. When the two partners bind, fluorescence resonance energy transfer (FRET) can be induced between the cryptate and XL665, which emits a long-lived fluorescence at 665 nm. CIS bio entered into partnerships with both Upstate and antibody company Cell Signaling Technology of Beverly, Massachusetts, in August this year — a move that will extend the reach of its HTRF technology in the life sciences. CIS Bio also recently linked up with detection-system manufacturers BMG LABTECH of Offenburg, Germany, Molecular Devices of Sunnyvale, California, and Tecan of Zurich, Switzerland, to develop HTRF-compatible fluorimeters or upgrade kits for optimizing existing equipment. Upstate is also collaborating with Dharmacon of Lafayette, Colorado, to develop small interfering RNA (siRNA)-based products as an alternative to gene knock-outs, and with Evident Technologies on the quantum dot front (see ‘Quantum dots begin to show their true colours’, page 247).

In September, Serologicals Corporation, which also owns Chemicon of Temecula, California, announced plans to acquire Upstate. Ratcliffe sees it as a good fit, combining the company's strengths in phosphorylation, nuclear function, drug discovery and screening with Chemicon's expertise in developing tools for neurobiology. “There's little overlap but very complementary ranges of products,” he says.

Companies such as Amersham Biosciences, now part of GE Healthcare, aim to offer integrated solutions. “We're looking at this holistically and we're not interested in just providing a small part of the process. We're interested in providing innovative solutions that go across the biology, the hardware and software and into the informatics,” says John Anson, vice-president of development at GE Healthcare Biosciences. These products range from image analysers for cell-based assays (IN Cell Analyzer 1000 and 3000 and LEADseeker) to pH-sensitive cyanine dyes for tracking the internalization of cell-surface receptors and GFP-based live-cell translocation assays developed in collaboration with BioImage of Soeborg, Denmark.

Diane Gershon