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Concept: Consortium for Advancing Research on Botanicals and Other Natural Products (CARBON.2)

Council Date: February 9, 2018        

Program Directors: Dr. Barbara C. Sorkin, Ph.D., Office of Dietary Supplements (ODS), NIH, and Dr. D. Craig Hopp, Ph.D., National Center for Complementary and Integrative Health (NCCIH), NIH    


Background 

Plants and plant-derived products are widely consumed for basic nutrition, to promote health and well-being, and for medicinal purposes in the United States and worldwide. Despite this prevalent use, the mechanisms of action and efficacy of many of these products have not been rigorously evaluated; the challenges of doing research on these complex materials continue to slow progress toward understanding their contributions to public health. ODS is congressionally mandated to support research initiatives to address this gap. Since 1999, ODS has fulfilled this mandate by partnering with NCCIH and other NIH components to support the Botanical Research Centers Program, now a component of the Centers for Advancing Research on Botanicals and Other Natural Products (CARBON) Program.

Based on the deliberations of an Expert Panel convened by ODS and NCCIH in 2013, the CARBON Program is one of the few in the United States focused on elucidating the mechanisms through which complex botanical products may affect resilience to environmental stressors (e.g., mutagens, diet, insufficient sleep). The Botanical Dietary Supplements Research Centers (BDSRC) awarded in July 2015 focused on identifying bioactive components of complex products and their bioactive metabolites, elucidating their cellular and molecular mechanisms of action, and describing the role of individual biological differences in modulating their activities. Additionally, in 2015, the program was broadened to include the U41 Centers for Advancing Natural Products Innovation and Technology, which have focused on cutting-edge methodological advances intended to break through persistent bottlenecks that have hindered natural products research. Each of the current BDSRC has developed collaborations with one or both simultaneously awarded U41 Centers. The BDSRC also collaborate with each other in areas of intersecting research interest, sharing materials and expertise to enhance understanding of the products under study. In calendar year 2017 alone, the Program Centers published 26 peer-reviewed papers, including one from newly developed inter-Center collaborations. Based on these promising indicators, this concept proposes enhanced support for such interactions. 

Purpose of Proposed Program

ODS and NCCIH seek to further accelerate progress in understanding how complex botanical and other natural products influence human health in order to acquire the data needed to guide clinical trial design and interpretation. This goal of enhancing progress toward translatable data should be achieved by supporting a range of networked, collaborative, transdisciplinary research centers and projects, and the development and dissemination of relevant good research practices and research resources.

Objectives

Through the CARBON Program, ODS and NCCIH propose to solicit and support cutting-edge transdisciplinary research that will synergistically combine a range of research disciplines and topics to generate causal, molecular, mechanistic data on actions of these products relevant to human health, with enhanced focus on data that can support optimal design of relevant clinical research. Emphasis will be placed on the development, dissemination, and utilization of advanced methodology, including computational, bioinformatics, and mathematical modeling approaches. While maintaining a focus on mechanistic research related to botanicals, the program will also include an increased effort in developing tools and resources for the broader natural products research community. A broadly networked Consortium, structured with the increased flexibility associated with cooperative agreements, is expected to expand the collaborative synergy seen in the current CARBON Program. The Centers and pilot projects constituting the planned Consortium should contribute significant advances to the full range of health-related botanical and natural products research needed to provide a solid foundation for clinical research, including but not limited to developing improved (faster, more comprehensive, and/or more accurately predictive) approaches to:

  • Natural product identification and characterization
  • Elucidation of causal, molecular mechanisms of action, including but not limited to intercomponent interactions between bioactive compounds, and molecular and cellular mechanism(s) required to generate clinically relevant biological effects
  • Modulation of natural product activities (including metabolism, safety, and efficacy) by host characteristics such as genetics, epigenetics, and environment.

We anticipate that conduct of this research will include and entail:

  • Application of state-of-the-art approaches, as well as the development of new methods or adaptation of cutting-edge methodologies from allied fields
  • Collaboration among Consortium components, and between Consortium Centers and other researchers with intersecting research interests, in pilot projects or other research, as appropriate
  • Development of relevant new research resources
  • Establishment of an environment suitable for training investigators to design, conduct, and participate in transdisciplinary botanical and other natural products research, and coordination on approaches that provide training support
  • Participation in an annual meeting of the full Consortium and other interested researchers, as well as additional meetings of subsets of the Consortium with intersecting research interests 
  • Coordination with relevant botanical clinical trials.