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Preapplication Webinar for RFA-AT-19-003, Center for Natural Product Technology, Methodology, and Productivity Optimization (U41 Clinical Trial Not Allowed)


Purpose of the Webinar
On Tuesday, February 12, 2019, the National Institutes of Health (NIH) National Center for Complementary and Integrative Health (NCCIH) hosted a preapplication technical assistance webinar to provide information for applicants about the funding opportunity announcement (FOA) for the Center for Natural Product Technology, Methodology, and Productivity Optimization (NP-TEMPO), RFA-AT-19-003, one of the components of the NIH Consortium for Advancing Research on Botanicals and Other Natural Products (CARBON).

Webinar Speakers

  • D. Craig Hopp, Ph.D., Deputy Director, Division of Extramural Research, NCCIH
  • Ashlee Tipton, Ph.D., Scientific Review Officer, Office of Scientific Review, NCCIH
  • Anita McRae-Williams, M.A., Outreach Communications Program Manager, Division of Extramural Research, NCCIH (Webinar Moderator).

In addition, Shelley Headley, Chief Grants Management Officer, Office of Grants Management, NCCIH, was available to answer participants’ questions.

Background on the Funding Opportunity

This funding opportunity is part of the larger group of projects that make up the CARBON program, which includes botanical research centers and a nuclear magnetic resonance (NMR) data repository. The researchers who carry out the various CARBON projects are expected to work closely together.

The objective of NP-TEMPO is to develop and disseminate technologies, methodologies, or approaches that will improve upon, and ultimately change, the landscape of natural products research. This is a funding opportunity for innovative, cutting-edge research, not a “plug-and-play” of existing technology. The projects should push the boundaries of existing capabilities and address current research challenges or bottlenecks.

Specific Areas of Research Interest

The areas of specific interest for NP-TEMPO are:

  • Innovative computational approaches for better characterization of network-level pharmacologic interactions between complex mixtures and complex biological systems
  • Methodologies that can identify active components with reduced reliance on bioactivity-guided fractionation
  • Tools to quickly identify biological targets for natural products
  • Novel approaches for rapid dereplication of active components in complex mixtures
  • Development of high-content phenotypic assays capable of capturing multiple mechanisms of action, including identification of previously unknown mechanisms of action or novel targets
  • Novel tools for chemical and biological annotation of complex mixtures that can qualitatively and/or quantitatively establish the presence of multiple active constituents (e.g., additive, synergistic, or antagonistic) in a complex mixture.

Topics that are not appropriate for this funding opportunity (although they may be well suited for other FOAs) include:

  • Tools that are limited in their application to a particular structure, target, disease, condition, or natural product source rather than being broadly applicable
  • Methodologies to improve production of individual natural products
  • Projects focused on tools to modify natural products
  • Creation of natural product libraries
  • Tools focused on chromatographic fractionation or purification of natural products
  • Synthetic biology tools
  • Development of tools and technologies that do not address existing bottlenecks or challenges.

Structure of the U41

The U41 mechanism is a cooperative agreement. This differs from a standard grant mechanism in that NIH staff will be heavily involved in the project, with regular, frequent communication with grantees.

Applications must propose at least three and not more than four research projects, each of which addresses a critical challenge in natural products research. For each, it is important to specify what bottleneck is being addressed and how much risk is involved. Projects with zero risk are not appropriate. Projects could have high risk if the reward is also high.

An Administrative Core is required.

Technology Demonstration Projects (TDPs) are an integral part of this initiative. The TDPs should test the limits of your technology. TDP partners should have outside funding; your technology should be attractive enough so that they are willing to engage with you without being paid to do so. Applications should describe a strategy for how collaborators for TDPs will be recruited and replaced, but TDP partners should not be named in the application. Providing a list of potential partners would make the review process more complicated because the people on the list would not be eligible to serve as reviewers.

Eligibility and Budget

Principal investigators can be from almost any U.S.-based institution, such as a university, nonprofit organization, or small business. Foreign collaborators are allowed, but applications from foreign institutions are not. Institutions may submit more than one application if the proposed projects are scientifically distinct.

The budget for this initiative will be up to $700,000 in direct costs per year. This excludes consortium costs. The budget must include funds for key personnel to travel to the annual CARBON meeting.

NCCIH and the NIH Office of Dietary Supplements expect to fund up to two U41 awards.

Potential applicants are urged to contact Dr. Hopp, the scientific/research contact for this FOA, to discuss their ideas and ask questions. Please make the initial contact by email at

Review Perspective

The completeness, compliance, and responsiveness of your application are of the utmost importance because applications that are incomplete, noncompliant, or not responsive to the RFA will not be reviewed.

For this initiative, letters of support are among the factors that determine compliance.

For the overall component, a letter of institutional commitment from the dean or another official of similar rank must be included. For a consortium that includes multiple institutions, similar letters of support from each participating institution must be included. For the technology research projects, letters of support from other key personnel should be attached to the relevant application component.

The U41 includes multiple components. Compliant applications will include an Overall Component, Administrative Core, and three or four Technology Research Projects.

Page limitations for the Research Strategy are as follows:

  • Overall Component: 6 pages
  • Administrative Core: 6 pages
  • Technology Research Projects: 12 pages per project.

Applications must be responsive to the Research Objectives of the RFA. Responsiveness will be determined by program staff. When reading the FOA, it is helpful to refer to the “Specific Areas of Research Interest” and to search for words like “must,” “should,” and “need.”

Review Structure

The review of multicomponent applications, such as those submitted in response to this U41, differs from that of typical R01 applications. For the U41, reviewers will first discuss each research project separately and provide a numerical impact score for each of them. These scores will not be released to the principal investigators. Next, reviewers will discuss and provide a merit descriptor for the administrative core. The merit descriptors will not be released to the principal investigators. Following that discussion, the reviewers will discuss the overall component and provide a numerical impact score. The average score of the overall component will be released to the principal investigators.

The overall component and technology research projects will be assessed based on the five standard review criteria, Significance, Investigators, Innovation, Approach, and Environment. Each of the five standard review criteria will receive a criterion score. In addition to the scored review criteria, reviewers will also assess additional review criteria. Together, all these criteria will be taken into consideration in determining the Overall Impact Score. Additional language has been added to the standard five review criteria for this RFA, and there are different review criteria for each component. All aspects that reviewers will be asked to address in their critiques match exactly what applicants are asked to address in the application. Therefore, it is important for applicants to read the review criteria carefully.

The administrative core will not receive a numerical score. Instead it will receive a merit descriptor (outstanding, acceptable, unacceptable). Cores do not have standard review criteria. Instead, they have specific review criteria that should be addressed in the application. These criteria are described in the FOA.

Letters of intent are requested but not required. They should include the title of the proposed project, principal investigator’s name and institution, and names of key personnel and their institutions. Send letters of intent to Dr. Martina Schmidt at

Applications submitted in response to this FOA will be reviewed by a Special Emphasis Panel. Reviewers will be selected based on their specific area of expertise in the target areas of the FOA and the science proposed in the applications. Reviewers will be oriented to use the review criteria added to this FOA and the additional review criteria in their assessments.

Questions and Answers

Q: Can you elaborate on what is meant by adaptation of existing technology?
A: An example that would not qualify as an adaptation of existing technology would be simply adding natural products to a tissue-on-a-chip method. That would be implementation of existing technology rather than adaptation. An example from recent research that would qualify as adaptation involves electron cryomicroscopy (cryo-EM). This innovative tool was developed for proteins and other macromolecules. In the past few months, efforts have been made to adapt cryo-EM to the structures of small molecules. To do this, the technology had to be modified to make it suitable for the new use.

Q: The areas of interest don’t mention the microbiome explicitly. Would microbiome technology be considered responsive to this FOA?
A: It could be if the technology isn’t limited only to the human microbiome. A project that’s applicable to a variety of complex systems – such as plant or marine microbiomes as well as the human microbiome – could be responsive. The choice of TDPs would be important. As long as you can make a case that your technology is broadly applicable and addresses a bottleneck in natural products research, it would be acceptable.

Ms. Carow commented at this point about the roles of grants management personnel and program officials. The grants management office is responsible for the negotiation of the award, the administration of the project, and the interpretation of grants management policies. Program officials are responsible for the scientific, programmatic, and technical aspects of the project. Grants management and program officials work together in overall project administration. If you are awarded a grant, make sure that the authorized business official from your institution works with the grants management office.

Dr. Hopp commented that all too often, people submit applications that are not aligned with NCCIH’s interests. He encouraged potential applicants to contact him to see if their ideas are well suited for this FOA and to ask questions.