Questions and Answers for RFA-AI-21-065, Systems Biology for Infectious Diseases (U19, Clinical Trial Not Allowed)

NIH published the funding opportunity announcement (FOA) RFA-AI-21-065, Systems Biology for Infectious Diseases (U19, Clinical Trial Not Allowed) on September 27, 2021.

Questions and Answers

NIAID envisions that the Systems Biology Centers will generate and integrate systems datasets to develop informative computational models for infectious diseases guiding in vitro, in vivo, and clinical studies. Ideally, these models will improve forecasting of disease onset and severity, simulate/predict variability in host responses to vaccines and therapeutics, and assist in identification of candidate targets for interventions.

The due date remains January 14, 2022, at 5:00 p.m. local time. If you are experiencing difficulties from the COVID-19 public health emergency, refer to Section II, Question 3 in the COVID-19 Flexibilities Frequently Asked Questions. Moreover, the NIH Policy on Late Submission of Grant Applications still stands.

A reissued FOA builds on the foundations developed under a previous FOA, RFA-AI-16-080 in this case. A reissued FOA can allow for renewal applications as well as new applications, as indicated in Section II. Award Information. Renewal applications can include projects that use data generated under RFA-AI-16-080, and the reissued FOA also allows for new applications with new/independent projects and datasets.

NIAID intends to commit $10 million in FY 2023 to fund four or five awards.

You may request budgets for direct costs of up to $1,500,000 each year. Application budgets need to reflect the actual needs of the proposed project.

There is a minimum requirement of two research projects with a maximum of three research projects. In addition, your application must include an “Overall” component that provides an overview of the entire program.

The following cores are required with a maximum of one each:

  • Administrative Core
  • Data Management and Bioinformatics Core
  • Technology Core
  • Modeling Core

Yes, a Systems Biology Center application may include investigators across a consortium of different institutions.

The RFA encourages interdisciplinary teams with expertise in clinical biology, microbiology, immunology, infectious diseases, microbiome, vector biology, high-throughput experimental and “omics” technologies, together with experts in mathematics, physics, bioinformatics, computational biology, machine learning, and statistical methods and modeling.

NIAID DMID supports a Systems Biology Program for Infectious Diseases to encourage development and use of high-throughput experiments, computing infrastructure, and increasingly sophisticated data processing and modeling algorithms.

This iteration is now positioned to implement models that have clinical applications in real-world scenarios. Moreover, this iteration emphasizes a “reverse translational research” or “bedside to benchtop (and back)” approach, integrating clinical data, systems biology datasets, and advanced technologies in the context of infectious diseases. It also includes secondary data analyses.

This re-issue seeks to:

  • Transform clinical data/metadata to predict onset, severity, and outcomes across infectious diseases, forecast responses to vaccines and therapeutics, and/or identify candidate targets for interventions.
    • Integrate clinical metadata, large datasets, and technologies in the context of infectious diseases.
    • Apply findings to predict disease outcome and inform treatment options.
    • Validate and obtain mechanistic insight from laboratory studies.
    • Refine predictive models to improve accuracy.
  • Emphasize best practices for high quality (FAIR) data generation and dissemination.
  • Support research across pathogens to promote technology/data development, which can be adopted in other communities.

This initiative will support Systems Biology Centers across bacteria, viruses, fungi, parasites and their vectors. Pathogens must be associated with human disease. Pathogens highlighted in the NIAID priority pathogens list are encouraged. Applications studying other human pathogens are acceptable, however, they should significantly advance the systems biology field and its associated technologies.

Projects that solely target Influenza viruses are considered non-responsive and will not be reviewed.

Projects in response to this announcement may study influenza but should primarily focus on pathogens other than influenza since a dedicated systems biology initiative for influenza exists (RFA-AI-21-017).

In addition, projects with a sole focus on HIV are considered non-responsive and will not be reviewed.

In this iteration, Centers should be positioned to move beyond standard systems biology data generation and analysis of infectious diseases. Centers are expected to move into validation, application, and implementation of models derived from systems biology datasets.

In addition, systems biology approaches that either identify candidate interventions (e.g., therapeutics, vaccine effectiveness) and/or characterize their effectiveness should have a direct link to real-world applicability.

Yes. Animal models offer experimental platforms for model validation, iteration, and refinement. They also provide an ability to obtain mechanistic insight into signatures obtained from clinical data.

However, as noted in the RFA, systems biology studies with a sole focus on “Animal models and/or cell lines in the absence of human clinical samples” are considered non-responsive and will not be reviewed. For a list of studies considered non-responsive, refer to Section I Research Objectives and Scope.

Yes. The objective of the Systems Biology Program is to improve prevention, diagnosis, and treatment modalities for infectious diseases through a more robust understanding of differential disease outcomes. The application should include multi-omic data and model generation in the context of these interventions, as described in the RFA.

Yes. Since each program includes at least two research projects, a technology core, data dissemination core, and modeling core, there are opportunities to mature systems biology processes while also integrating clinical data/metadata into models that forecast disease onset, severity, and/or efficacy of interventions.

Yes, as noted in the RFA, prospective sample collection is allowed for the first 2 years. If samples for the proposed studies are to be collected from an independently-funded clinical research project or trial, you may include the following costs: the costs of re-consenting study participants, and additional sample collection, preparation, and shipping.

We encourage applicants to also include projects with clinical samples “in hand,” leveraging pre-existing cohorts so projects can initiate immediately if awarded.

Yes. Foreign institutions and foreign components are allowed. Therefore, the PD/PI, project lead, core lead, and/or key personnel may be located at a foreign institution.

Direct your questions to the scientific/research contact shown in Section VII. Agency Contacts of RFA-AI-21-065.

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