Bourne and Gilman reply

Haggarty and Ramalho-Santos have misunderstood the goals, organization and scientific approach of the Alliance for Cellular Signalling. We urge readers to visit the alliance website and decide for themselves whether the critics are right.

Haggarty and Ramalho-Santos say that the alliance's decision to emphasize signalling in only two kinds of mouse cells is “biased and limited”. But an intense focus (highly reproducible observations on a few systems) is essential to obtain complete sets of quantitative data for sophisticated mathematical modelling and systems analysis. Any criticism should be in the other direction: for hedging our bets by choosing two cell types rather than one. We plan to look at all signalling inputs to these cells, not just those initiated by G-protein-coupled receptors.

Our critics have failed to distinguish between participating investigators in the alliance and alliance membership. Participating investigators (currently 51 at 21 different research institutions) will collaborate to run the scientific programmes of the alliance. Members of the B-lymphocyte and cardiac myocyte committees will prioritize work in seven alliance laboratories (not their own laboratories), and will make resultant data and analysis publicly available on the Internet so that all cell-signalling researchers can join in the effort. Our intention is to supply leads — for example the results of yeast two-hybrid screens and protein-interaction traps — for others to pursue and substantiate or discard.

A critical factor is Internet 2, which will permit real-time audio-visual communication with sharing of virtually any software application. We do not need to disseminate data in real time, but we must interact freely and regularly, as do the members of any research group.

We solicit members to act as consultants and to represent molecules by authorship of molecule pages as the core element of a signalling database. The job of authorship is the equivalent of writing and maintaining a structured review of the literature. Molecule pages can be collaborative; they will be peer reviewed and include comments and feedback. By facilitating bioinformatic searches for emergent properties of signalling networks, the standardized format of molecule pages should foster — not “minimize” — innovation and creativity. To date, we have received 180 applications for membership from residents of 15 countries, and we welcome and can accommodate many more. The list of molecules that need champions is a long one.

Conventional publication of data from the laboratories of participating investigators or members is not prohibited. The data to be placed on the Internet will be produced in dedicated alliance laboratories staffed by fully trained, full-time research scientists and technicians, not postdocs or students.