Network Structure, Organization and Operation. The nature of the science plays the central role in determining the proposed Network structure. Specifically, that structure facilitates the “flow” of samples to analysis centers, followed by metabolomic assays, data analyses, replication and functional validation studies – all conducted by different nodes in the Network. The Bridging Projects and, in the future, Pilot Projects, will be the source of these samples. The samples from these projects will undergo metabolomic analysis with a variety of “platforms” – platforms located in different institutions. The data generated, both metabolomic data and related clinical or laboratory-based data, must then be transferred to the central database, followed by its use to perform statistical and pathway-based analyses. Throughout this process, integrated “Research Teams” for each individual project will monitor the progress of the projects, discuss the data and plan functional and/or pharmacogenomic follow-up studies designed to test hypotheses generated with the metabolomic data (Figure 1). Creating and sustaining ongoing scientific dialog among all contributing disciplines within the Network will be essential for the success of each project, a lesson already learned during “pilot” studies conducted with support from the NIH R24 and RC2 grants that have sustained the formative stages of the proposed Pharmacometabolomics Network.
The PMRN network consists of a series of “Cores”, including an “Administrative Core”, a “Metabolomics Analytical Core” that includes all of the analytical platforms, a “Database and Data Governance Core” and an “Informatics Core”, all of which are linked to “Bridging Projects” and, eventually, to “Pilot Projects”. The flow of samples and information through this matrix is depicted in a slightly different fashion, and the geographic locations of the individual institutions within which these “Cores” and “Projects” are based is shown on the map in the Institutions page.
Committee Structure. Two of the major committees proposed for the Pharmacometabolomics Research Network are the Steering Committee and the External Advisory Committee. The Steering Committee will be composed of the PI and Co-PI for this proposal as well as one representative from each group of Cores (i.e., one representative from the “Analytical Cores”, one from the “Informatic Cores”, etc.) and one representative from the “Bridging Projects/Pilot Projects”. This group was purposely designed to be relatively small. However, its composition will change over time as a result of “staggered” membership terms, designed so there will not be complete turnover of membership at any time in order to ensure “institutional memory” within the Steering Committee. The Steering Committee will serve as a focus for major policy discussions and will meet once a month by teleconference. It will also meet “in person” at each of two annual face-to-face meetings of the Network. However, the Steering Committee will not make final decisions on policy issues, but rather will make recommendations to the “All-PIs” group that will also meet once per month by teleconference and will make all major policy decisions. The External Advisory Committee will meet with the Network during one of the two annual “face-to-face” meetings of all Network participants. This Committee will be composed of senior advisors who will represent the spectrum of expertise represented within the Network. The External Advisory Committee will evaluate the progress of the Network, but the term Advisory was used to describe this committee purposely to indicate that every effort should be made to avoid a “site-visit-like” atmosphere during these meetings. The External Advisory Committee will, of course, both advise Network participants and NIGMS, but it should not view itself as a “site-visit-team”. If it does its job well, this group will play a key role in helping to advance the science pursued by the Network. No names for possible members of the External Advisory Committee have been included in this application in order to avoid potentially excluding those individuals from consideration for the review panel for this application.