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Discussions among ABRF members during their February meeting in Savannah, Georgia, revealed concern about the future of resource facilities amidst the broadening scope of biomedical science as it evolves toward integrative “systems biology” 1–3. Here I argue that, despite this anxiety, resource facilities will continue to play an expanding and increasingly essential role in biomedical research. Despite this reassuring outlook, however, I believe the character of the work undertaken by facilities will change, most particularly in increasing demands for intellectual involvement. ABRF should embrace this change with enthusiasm, and provide strong leadership to advance its progress and realize the opportunities it presents.
Among the most striking changes in biomedical science that have taken place over the last three decades is the widespread expansion in studies that involve collaboration between multiple groups of investigators. Such collaboration occurs when the work requires the participation of individuals with special expertise or access to special samples. An illustration of the extent of this change is provided by a sampling of papers in biology and biomedicine published by three journals of high visibility and prestige, Nature, Science, and Cell, over the last three decades (Table 11).). Papers appearing in January 1975, 1985, 1995, and 2005 are classified as collaborative or noncollaborative according to the authors’ institutional affiliations. The incidence of collaborative reports is seen to have risen from 25% to 74% during this period. Biology has indeed become a collaborative, multidisciplinary enterprise.
One facet of this profound change in biological research is the expansion of reliance upon core facilities. Centralized laboratories equipped with complex, expensive instruments and staffed by individuals skilled in acquisition and interpretation of the data derived from them are now commonplace in both academic and commercial institutions. Institutions establish core facilities because they recognize that advanced technologies must be provided to maintain or improve institutional competitiveness. They recognize that they can afford to provide these technologies only with centralization.
Systems biology has promoted this trend. Among the procedures essential to the systems approach now routinely conducted in core facilities are highly parallelized methods for genotyping,4 RNA expression analysis,5 protein expression analysis,6 and metabonomics.7 High throughput procedures for assigning functions to macromolecules and assessing macromolecular activity levels are also gaining more general currency. Examples include the use of RNA inhibition (RNAi) in arrays of cultured cells,8 qualitative binding assays in protein microarray platforms,9 and quantitative binding measurements made by surface plasmon resonance.10 It is indeed through the implementation of such techniques that systems biology has become established as a communal aspiration of biomedical science.
I contend that the trend toward increasing reliance upon core facilities will persist, for they will continue to be called upon to implement further novel experimental procedures for systems biology. This task will involve streamlining the techniques, reducing turn-around times, teaching students how to use the new methods, and working with manufacturers to reduce costs.
When these efforts are successful, some technologies may be amenable to translation to commercial and clinical laboratories. For example, considerable oligonucleotide and peptide synthesis is presently performed in large commercial houses. Such divestment, I believe, frees core laboratories to fulfill the role for which they are best suited—the implementation of new and exciting vehicles for biological discovery—and represents a benefit rather than a detriment to core facilities.
The challenge for core facilities, then, is to find ways to function effectively in an environment where the technologies they are being called upon to deploy are crucial for driving biomedical research forward, yet are still to some extent immature. I believe that to be successful in this environment requires first a willingness to become proactively involved in projects at the highest level of intellectual input. The background and goals of every project must be understood in detail in order to apply the most appropriate techniques. Data must be evaluated not only at the technical level. The strength of the biological conclusions that can be drawn must also be assessed. For example, the interpretation of microarray expression data demands attention both to data quality and to statistical methods for data interpretation. Similarly, the elucidation of protein interactions by co-immunoprecipitation demands not only the ability to interpret the mass spectral data both qualitatively and quantitatively, but also careful attention to precipitation conditions and formulation of appropriate controls both negative and positive.
Facilities’ success also depends upon planning for the future based upon a thorough understanding of the nature of the biological questions being addressed and in-depth familiarity with the latest methodological literature. Core facilities must accept responsibility for identifying the most effective methods of accomplishing research goals. Simply continuing to perform procedures derived from today’s technology without anticipating and working to implement tomorrow’s methods will consign a facility to obsolescence. Careful scientific judgment is required to make such assessments, and correctly anticipating demands for new capabilities is vital to scientific productivity. Oftentimes, more than one platform is available for acquiring the information that is needed, and it falls to facility personnel to make or guide choices between alternative methods. For example, it has only recently become clear that genotyping and loss of heterozygosity are likely henceforth to be accomplished most effectively with DNA microarrays in a high throughput context,4 but, until recently, capillary electrophoresis and mass spectrometry were also vying for attention.11 Aside from scientific productivity, the decision to invest in a platform can have important financial consequences. In the future, what will be the best methods for identifying and assessing the function of small RNA species? How will the dynamic range problem in proteomics be definitively solved? Such questions should be the subject of active inquiry by core facilities right now.
Success further depends upon recruiting staff with a high level of scientific sophistication, and hence garnering the salaries and benefits commensurate with such skills. Core facility management requires additional expertise and possibly special training in project management techniques. Furthermore, operating as part of a multidisciplinary team often requires considerable skill in communicating information to collaborators, and not infrequently requires considerable diplomacy. It is greatly advantageous to structure core labs in ways that promote communication between individuals working on interdependent aspects of a single project. Multidisciplinary cores tend to promote such communication.
Another key requirement for deploying many contemporary techniques is computational support, including access to suitable computers and software, help with database management, and availability of statistical or bioinformatic expertise. Adequate resources of these kinds may require expenditures equal to or even greater than those made in deploying the analytical methods themselves. Among the reasons are the exceedingly heavy demands on processor and communications speed, memory, and storage space, and the specialized nature of the skills to make best use of the hardware involved.
Clearly, institutional resources are needed to create core laboratories. Once a decision to invest in a technology has been made, the arguments for centralizing its availability in a core facility are frequently compelling. These arguments include the ability to regulate access in a way that is equitable on an institution-wide basis, and the control of costs through shared infrastructure, including computational support. Although the cost may be high, the benefits of creating productive core laboratories are correspondingly great, and include enhanced productivity and visibility of research, and competitive advantage in recruiting excellent faculty.
Success in this evolving environment does not entail elimination of small core facilities. At the February meeting of ABRF in Savannah, voice was given to fears that small cores are liable to be “squeezed out” in the era of systems biology. However, I see compelling reasons to believe that small cores will continue to be formed to pioneer and deploy new, special methods, and will grow as their work becomes recognized. Some may diversify their services as growth takes place. The existing large multidisciplinary cores all arose in this way. Others will not diversify in this way, but will nonetheless continue to provide crucial services.
A primary goal of ABRF, I believe, should be to assist its member cores in meeting these challenges. Among the specific actions that would provide most benefit at the present time are the following:
We are at a juncture when the opportunities for core laboratories to expand and to extend the contributions they make to biomedical science are unprecedented, but cores must adapt and strengthen their capabilities to meet the challenges those opportunities present.