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Building bridges through collaboration – a pathway for interdisciplinary research

2002; Elsevier BV; Volume: 13; Issue: 1 Linguagem: Inglês

10.1016/s0962-8924(02)00003-x

1879-3088

Alan Rick Horwitz,

Interdisciplinary Research and Collaboration

Interdisciplinary research is a linchpin of major scientific progress and innovation. Over a century ago, in his book Advice for a Young investigator, Santiago Ramón y Cajal wrote about the importance of identifying and mastering new technologies with which to attack important research problems [1Swanson N. Swanson L.W. Santiago Ramón y Cajal Advice for a Young Investigator. MIT Press, 1999Google Scholar]. In his era, for example, the advances in chemistry and microscopy were combined to propel the development of histological methods and produce new descriptions of nerve cell organization in the central and peripheral nervous systems. The continued development of microscope technologies, from light to EM, and novel contrast methods, including fluorescence and, more recently, fluorescence resonance energy transfer (FRET), have been a driving force for studying cells, even to the present day. Thus, technical advances continue to fuel discovery in cell biology. The contributions of Linus Pauling, considered by many to be the father of molecular biology, similarly illustrate the power of interdisciplinary research [2Marinacci B. Linus Pauling in His Own Words, Selections from his Writings, Speeches, and Interviews. Simon and Schuster, 1995Google Scholar]. For example, in the late 1930s, he first applied the newly emerging discipline of quantum mechanics, which had largely focused on descriptions of simple atomic structures, to address the chemical bond in the context of molecular structure; he then used his structural knowledge to outline the major themes of protein structure. These insights, in turn, were used to elucidate the molecular basis of a genetic disease (sickle cell anemia) and pioneer research in molecular evolution. Interdisciplinary research is even more important and necessary today. The initiatives in genomics, proteomics and structural biology, for example, are creating large databases of information that need to be organized, analyzed and connected to important biological questions and interpreted in the context of specific diseases. The increased complexity of more traditional investigative, hypothesis-driven research cries out for interdisciplinary approaches. The growing thirst for reagents, materials and sophisticated measurements requires contributions from neighboring disciplines. Finally, the increased interest in biological research from investigators in disciplines such as engineering and mathematics is making areas such as cell biology focal points of their interest. While the importance of interdisciplinary research is evident, the challenges in executing it are formidable. The concepts, ideas and technologies of chemistry, physics, mathematics, engineering and computer science that impact on biological research are now highly complex and not readily accessible to most cell biologists. Likewise, the overwhelming literature and experimental detail of cell-biological research similarly limits access to a researcher who has a new technique or idea from another discipline but has not worked in cell biology. The result is that it is increasingly difficult for individual laboratories to do innovative research at disciplinary interfaces. Biologists who attempt it often misuse the technology or misinterpret their data, and physical scientists often do not understand the biological questions or appreciate the nature and complexity of the biological systems. All of this points to interdisciplinary collaborations as an efficient mechanism for executing multidisciplinary research. Collaborative, interdisciplinary research poses unique challenges. Those interested in participating need to be cognizant of the cultural differences among diverse disciplines with respect to collaboration and credit, as well as disciplinary elitism and related issues. More formidable, however, are mechanisms to catalyze interactions among researchers in different disciplines and thus generate matches that combine state-of-the-art cell biology with cutting-edge technology in another discipline. Despite the challenges, there are many examples of highly successful, investigator-initiated contacts that have produced very significant contributions (Box 1) .Box 1. Some interdisciplinary contributions to cell biology1.MathematicsAnalysis of high-throughput initiatives (genomics and proteomics)Improved computational algorithmsNovel modeling strategies2.ChemistrySynthesis of small-molecule inhibitorsCombinatorial screens for inhibitorsNovel reagentsNovel biomaterials3.Physics and physical chemistryNew fluorescence techniquesNew approaches to structural analysisMeasurement and analysis of physical propertiesNew microscopies4.ComputationalWeb-based organization of data into useful, searchable databases (knowledge bases)Interactive, web-based modeling platformsCorrelative modeling of biological phenomena5.EngineeringHigh-throughput and quantitative measurementsSystems modeling of biological processesOptimization of cellular processesMicro/nano-fabricated devices 1.MathematicsAnalysis of high-throughput initiatives (genomics and proteomics)Improved computational algorithmsNovel modeling strategies2.ChemistrySynthesis of small-molecule inhibitorsCombinatorial screens for inhibitorsNovel reagentsNovel biomaterials3.Physics and physical chemistryNew fluorescence techniquesNew approaches to structural analysisMeasurement and analysis of physical propertiesNew microscopies4.ComputationalWeb-based organization of data into useful, searchable databases (knowledge bases)Interactive, web-based modeling platformsCorrelative modeling of biological phenomena5.EngineeringHigh-throughput and quantitative measurementsSystems modeling of biological processesOptimization of cellular processesMicro/nano-fabricated devices Recently, several mechanisms have emerged to catalyze this kind of research. Some institutions have initiated cross-disciplinary programs – for example, the Harvard Institute of Chemistry and Cell Biology (ICCB; http://iccb.med.harvard.edu/), which combines chemistry and cell biology, and the Stanford Bio-X program (http://cmgm.stanford.edu/biochem/biox/intro.html), a cross-disciplinary initiative in bioengineering, biomedicine and biosciences. Federal funding agencies, such as the NIH, have developed initiatives that also foster cross-disciplinary research. The National Institute of General Medical Sciences (NIGMS) has taken the lead with bold and innovative initiatives that seek to promote integrative and collaborative approaches to solve complex problems in biomedical science (http://www.nigms.nih.gov/funding/collab.html). One of them is the Large-Scale Collaborative Project Award or ‘Glue Grant’. To date, four of these have been awarded (http://www.nigms.nih.gov/funding/gluegrants.html), and each has an interdisciplinary character including a strong bioinformatics component and outreach to their respective research communities. The Alliance for Cell Signaling (http://cellularsignaling.org), for example, is addressing the mechanisms by which cellular signaling networks regulate cell behavior. The goal is to develop and utilize a set of standardized assays of signaling intermediates and endpoints in response to single and multiple stimuli and to model these responses using a variety of bioinformatic approaches. The Cell Migration Consortium (http://www.cellmigration.org) is addressing major barriers to progress in migration research through collaborative, interdisciplinary developmental initiatives. These include determining the structure of large migration-related organelles, modeling migration-related processes, developing novel reagents for assaying signals in space and time, developing new imaging technologies, characterizing the ‘migration proteome’, generating new biomaterials and producing genetically altered mice. The two other Glue Grants support collaborative research to study carbohydrate-binding proteins and ligands (http://glycomics.scripps.edu) and the host response to trauma and burn (http://www.mgh.harvard.edu/gluegrant/). Over the coming months, Trends in Cell Biology will feature reviews that highlight the fruits of collaborative approaches to cell-biological research (Box 2) . The articles will discuss a variety of topics, including engineering approaches to optimizing cell function, structural modeling, an interactive, web-based modeling platform, combinatorial chemistry approaches to identifying small-molecule inhibitors, analyses of large-scale proteomic and genomic studies, and imaging modalities for the study of signaling networks. These reviews will illustrate the power of collaborative and interdisciplinary approaches and the synergies they convey. Hopefully, they will also stimulate and lower the barrier for others to engage in research at disciplinary interfaces.Box 2. Articles for the interdisciplinary biology series in Trends in Cell BiologyCell-biological applications of transfected-cell microarraysWu, R.Z., Bailey, S.N. and Sabatini, D.M. (2002) Trends Cell Biol. 12, 485–488Computational modeling of the EGF receptor system: a paradigm for systems biologyWiley, H.S., Shvartsman, S.Y. and Lauffenburger, D.A. (see this issue)Imaging signaling networksMeyer, T. and Teruel, M.An array of insights: application of DNA chip technology in the study of cell biologyPanda, S, Sato, T., Hampton, G. and Hogenesch, J.Virtual cell softwareSmith, A.E., Macara, I and Loew, L.Systematic proteomic studiesBoone, C., Bader, G. and Hogue, C.Proteomics approaches to elucidating protein kinase signal transduction pathwaysCantley, L. and Yaffe, M.Chemical genetics in cell biologyMayer, T.Chemistry for imaging and functional studies in cell biologyBogyo, M. Cell-biological applications of transfected-cell microarraysWu, R.Z., Bailey, S.N. and Sabatini, D.M. (2002) Trends Cell Biol. 12, 485–488Computational modeling of the EGF receptor system: a paradigm for systems biologyWiley, H.S., Shvartsman, S.Y. and Lauffenburger, D.A. (see this issue)Imaging signaling networksMeyer, T. and Teruel, M.An array of insights: application of DNA chip technology in the study of cell biologyPanda, S, Sato, T., Hampton, G. and Hogenesch, J.Virtual cell softwareSmith, A.E., Macara, I and Loew, L.Systematic proteomic studiesBoone, C., Bader, G. and Hogue, C.Proteomics approaches to elucidating protein kinase signal transduction pathwaysCantley, L. and Yaffe, M.Chemical genetics in cell biologyMayer, T.Chemistry for imaging and functional studies in cell biologyBogyo, M.