Key Dates

Related Announcements

• May 5, 2020 - Research Project Grant (Parent R01 Clinical Trial Required). See NOFO PA-20-183.
• May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required). See NOFO PA-20-194.
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.
• November 9, 2020 - Stephen I. Katz Early Stage Investigator Research Project Grant (R01 Basic Experimental Studies with Humans Required). See NOFO PAR-21-039.
• November 9, 2020 - Stephen I. Katz Early Stage Investigator Research Project Grant (R01 Clinical Trial Not Allowed). See NOFO PAR-21-038.
• July 22, 2021 - Molecular Imaging of Inflammation in Cancer (R01 Clinical Trial Not Allowed). See NOFO PAR-21-294.
• March 21, 2022 - Technology Development Research for Establishing Feasibility and Proof of Concept (R21 - Clinical Trial Not Allowed). See NOFO PAR-22-126.
• March 21, 2022 - Focused Technology Research and Development (R01 Clinical Trial Not Allowed). See NOFO PAR-22-127.
• August 20, 2021 - Small Grants for New Investigators to Promote Diversity in Health-Related Research (R21 Clinical Trial Optional). See NOFO PAR-21-313.
• January 11, 2022 - Exploratory/Developmental Bioengineering Research Grants (EBRG) (R21 Clinical Trial Optional). See NOFO PAR-22-091.
• May 24, 2022 - Maximizing Investigators' Research Award (R35 - Clinical Trial Optional). See NOFO PAR-22-180.
• June 2, 2022 - PHS 2022-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed). See NOFO PA-22-176.
• June 2, 2022 - PHS 2022-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed). See NOFO PA-22-178.
• June 9, 2022 - Research Opportunities for New and "At-Risk" Investigators to Promote Workforce Diversity (R01 Clinical Trial Optional). See NOFO PAR-22-181.
• September 8, 2022 - Bioengineering Research Grants (BRG) (R01 Clinical Trial Optional). See NOFO PAR-22-243.
• November 18, 2022 - Trailblazer Award for New and Early Stage Investigators (R21 Clinical Trial Optional). See NOFO PAR-24-022.

Issued by

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of General Medical Sciences (NIGMS)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

Purpose

The purpose of this Notice of Special Interest (NOSI) is to announce that the National Center for Complementary and Integrative Health (NCCIH), the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of General Medical Sciences (NIGMS) are encouraging new applications to advance research activities relevant to synthetic biology.

Background

One of the great challenges in biomedical research is to be able to quantitatively predict, test, and harness the complex dynamics of biological systems. Synthetic biology is the design and construction of new biological parts and systems, and the re-design of existing and natural biological systems for specific purposes. In contrast to the traditional genetic engineering approach, which usually focuses on individual genes and proteins, synthetic biology adopts a more systematic approach targeting entire pathways, networks, and whole organisms with quantitative control and modulation. Gaining new insights into the complex and dynamic biological pathways of designer cells and tissues and developing cell-based and cell-free diagnostics and therapies are at the frontiers of biomedical science. Enabling these de novo biological systems will require the ability to design and build complex pathways with endogenous or novel functions and with predictable and quantitative responses to endogenous or environmental signals. Achieving this paradigm will allow the testing of hypotheses on complex biological systems and the development of novel therapeutic strategies and diagnostic capabilities. To improve the reach and impact of engineering biology on human health, an integrative research plan based on collaborations of synthetic biologists with computational scientists, cell biologists, engineers, geneticists, developmental biologists, and/or physician scientists is strongly recommended.

Research Objectives

The overarching goal(s) of this Notice of Special Interest are to:

1. Develop tools and technologies to control and reprogram biological systems
2. Apply synthetic biology approaches for the development of biomedical technologies
3. Increase the fundamental understanding of synthetic biology concepts as they relate to human health
4. Gain fundamental biological knowledge through the application of synthetic biology approaches
   

NCCIH Statement of Interest

NCCIH supports a diverse portfolio of natural products research and mind and body interventions. Natural products include botanicals, pre/probiotics, and products marketed as dietary supplements. Mind and body approaches include various meditation approaches (e.g., mindfulness), hypnosis or guided imagery, meditative movement approaches (e.g., yoga, tai chi, qi-gong), body-based approaches (e.g., spinal manipulation, massage, mobilization, acupuncture), a combination of these approaches (e.g., meditation and yoga, such as in mindfulness-based stress reduction (MBSR)), or complex interventions including music and art therapy.

NCCIH is especially interested in research that uses systems biology technology to better understand the biosynthesis and beneficial functions of natural products. This also includes support for development and application of synthetic biology approaches to assess mechanisms of action and causal effects of beneficial microbes in human. NCCIH encourages applications to this initiative aimed at elucidating biosynthetic pathways for high value, natural products from diverse organismal resources and developing ways to improve their production in either native or heterologous hosts. In the context of this initiative, high value, natural products are defined as those which have well established therapeutic properties for humans. Use of systems biology for the engineering and production of compounds which are not known from a natural source are considered low priority for NCCIH.

Examples of research of interest to NCCIH include, but are not limited to:

• Use of synthetic biology tools to identify biosynthetic gene clusters or pathways responsible for the biosynthesis of natural products derived from plants, fungi, bacteria, and marine organisms
• Use of synthetic biology tools to improve production of plant based natural products from their native sources
• Use of synthetic biology tools to assemble biosynthetic machinery and optimize yield for natural products derived from plants, fungi, bacteria, and marine organisms into heterologous hosts
• Develop novel synthetic biology methods and tools to study beneficial mechanisms of probiotics intervention
• Develop biosynthetic sensors of the hallmarks for mind and body interventions for animal-based model system
  

NCI Statement of Interest

The National Cancer Institute (NCI) supports a broad-based portfolio of cancer research and development projects encompassing basic, translational, clinical, and epidemiological inquiries.This includes support for the development and application of novel enabling technologies in a broad range of cancer research. NCI strongly encourages multidisciplinary collaborations between synthetic biologists and cancer biologists or translational cancer researchers in developing novel solutions to tackle critical cancer problems. Some general examples that are relevant to this NOSI include, but are not limited to:

• Developing novel synthetic biology methods and tools relevant to cancer research and cancer management
• Using synthetic biology methods to develop novel cell, tissue, and animal based model systems to study the fundamental mechanism of cancer development, progression, and/or response to treatment
• Using synthetic biology methods to develop and evaluate novel diagnostic, preventive, and therapeutic approaches relevant to human cancer
  

NHLBI Statement of Interest

The National Heart, Lung and Blood Institute (NHLBI) provides global leadership for research, training, and education programs to promote the prevention and treatment of heart, lung, and blood diseases and sleep disorders and enhance the health of all individuals so that they can live longer and more fulfilling lives. Participation in this NOSI directly addresses the NHLBI strategic goals related to a desire to better understand human health and resilience, to stimulate discoveries in the diagnosis and prevention of disease and to facilitate the translation of discoveries from basic research into clinical practice.

Application of synthetic biology approaches to heart, lung, blood and sleep (HLBS) diseases research holds great potential to advance fundamental knowledge and pathogenic mechanisms. Synthetic biology tools and platforms also have the potential to significantly accelerate translational and implementation research in HLBS disease areas. Recent progress in engineering of synthetic gene circuits demonstrate compelling opportunities for application of synthetic biology to advance clinical applications. These opportunities span the entire range from areas of therapeutics, programmable therapy-delivery systems, regenerative medicine (e.g., tissue/organoid engineering, bioengineered vasculature and vascular beds, cell-seeded scaffolds, etc.) and biosensors, to biomarkers of cell-fate tracking assays and health monitoring systems. Given the multidisciplinary expertise involved, NHLBI strongly encourages multidisciplinary collaborations between HLBS subject-matter experts (including legal/bioethics/policy experts where appropriate) and synthetic biology researchers.

NHLBI encourages technologies and approaches outlined in this NOSI that include, but are not limited to:

• Engineer cell therapy or nanotechnologies that can deliver gene therapy to correct gene defects in HLBS disorders (e.g. Cystic Fibrosis, Primary Ciliary Dyskinesia, Alpha-1 Anti-trypsin Deficiency, Familial Hypercholesterolemia, Hypertrophic Cardiomyopathy, Arrhythmias, Sickle Cell Disease, Beta Thalassemia, Insomnia, etc.)
• Development of innovative gene circuits/edits to modify existing gene expression pathways to create new approaches for treating HLBS diseases or vascular/cardiovascular remodeling and/or study of HLBS-related mechanobiology
• Development of synthetic biology methods to engineer organoids, tissues, novel cell-based, and/or animal-based model systems to study the fundamental mechanism of HLBS-related disease or condition development, progression, and/or response to treatment
• Leverage systems biology, AI/ML technologies, and synthetic biology methods to predict and develop new therapeutic target identification for regenerative cell therapy strategies for HLBS disorders or for the advancement of fundamental understanding of HLBS disease pathogenesis
• Create digital health theragnostics (e.g. biological sensors, cell-sensors, wearable monitors) that can help track, treat, and study HLBS disorders pathophysiology over time
• Leverage systems biology and/or AI/ML technologies to predict and develop new therapeutic target identification for regenerative cell therapy strategies
• Model HLBS-related metabolic pathways to understand and identify differences due to sex as a biological variable (SABV)
• Development of regenerative therapies for treatment of vascular injury, acute cardiac injury, and heart dysfunction
• Engineer cells to produce therapeutic proteins that can reduce or stop inflammatory and/or destructive responses in the pulmonary and cardiovascular systems
• Development of innovative modeling systems and software tools to more accurately reproduce the unique properties of blood and bone marrow
• Development of novel, non-viral, in vivo gene therapy products to treat rare hematologic diseases such as hemophilia A, hemophilia B, Sickle Cell Disease and von Willebrand Disease
• Development of safe, well-functioning designer platelets and red blood cells for therapeutic and diagnostic uses.
• Design genetically engineered stem cells to enhance the nation’s blood supply by generating universal donor red blood cells that are available off the shelf by a high-throughput process
• Use synthetic biology approaches to develop models of homeostatic sleep to better understand the mechanistic underpinnings that drive perceptions of sleepiness and fatigue, including validated biomarkers for sleep health
• Develop systems-level models of circadian clock synchrony across the body that coordinate biological function to better understand the role of circadian rhythms in disease pathogenesis

Note: NHLBI will only accept applications in response to PA-20-183 and PA-20-185. For PA-20-183, only mechanistic clinical trials will be accepted in accordance with NOT-HL-19-690. Applicants wishing to propose non-mechanistic clinical trials may consider applying to one of the NHLBI clinical trial mechanisms described at https://www.nhlbi.nih.gov/grants-and-training/clinical-trial-development-continuum.

NIA Statement of Interest

The National Institute on Aging (NIA) supports multiple portfolios on diverse aspects of aging, from social and behavioral research to the basic biology of aging, encompassing epidemiological, clinical, translational, behavioral, neurobiological and basic studies. This includes support for the development and application of novel enabling technologies in a broad range of aging research. In joining this NOSI, NIA encourages multidisciplinary collaborations between synthetic biologists and investigators from all aspects of aging research to develop novel synthetic biological tools and approaches.

Areas of interest to NIA include, but are not limited to:

• Develop biosynthetic reporters of the hallmarks of aging for laboratory animals or for lab animal and human-derived organoid and cell culture systems
• Develop tools and technologies to control and reprogram aging systems for accelerated or delayed aging
• Apply synthetic biology approaches for the development of biomedical technologies to track geroscience-based interventions in preclinical studies
• Develop synthetic biology tools and technologies applicable to multiple morbidities in aging populations
• Apply synthetic biology approaches for re-programming and re-wiring the aging and/or diseased neural systems
  

NIAID Statement of Interest

The NIAID mission is to conduct and support basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. NIAID has a unique mandate, which requires the Institute to respond to emerging public health threats. Synthetic biology technology represents a foundation to improve our ability to prevent, diagnose, and treat infectious and immune-mediated diseases and to better understand complex host immune responses to such diseases. NIAID encourages collaboration between synthetic biologists and infectious disease scientists and/or immunologists for either basic or translational applications.

Examples of research of interest to NIAID include, but are not limited to:

• Basic research including novel cell, tissue, and animal-based model systems to better understand the complexities of infectious disease and immune disorders, and/ or immune responses in such diseases/disorders
• Tools and technologies to facilitate design and development of novel sensors, therapeutics, antibodies, or vaccine approaches to overcome roadblocks in infectious disease diagnosis, prevention, treatment and eradication/cure
• Translational and clinical studies for precise detection, targeting and treatment of a wide range of infectious and immunological diseases, including remodeling of the disease microenvironment
• Use of synthetic biological methods to understand mechanisms of immune function in general and across the lifespan
  

NIBIB Statement of Interest

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) is interested in projects focused on the development of modular platform technologies to enable a new paradigm of biomedical intervention. Through this NOSI, the NIBIB seeks applications with a particular emphasis on technologies to enable synthetic biology approaches or that are driven by synthetic biology approaches.

Examples of research of interest to NIBIB include, but are not limited to:

• Engineered genetic circuits
• Engineered cells and tissues for therapeutic and diagnostic applications
• Sensors, processors, actuators, and other modules for biological control
• Biosensor assays for analyte detection and contrast agents and probes for imaging
• Computational models and methods to drive the design, development, testing, and validation of synthetic biology technologies for human health

A complete list of programmatic interests in NIBIB can be found at: https://www.nibib.nih.gov/research-funding.

Furthermore, the NIBIB mission does not include the development of new technologies to address basic research questions in cellular processes, functions, and structure. For research leading to the development of such technologies, applicants should consult the National Institute of General Medical Sciences (NIGMS).

NOTE: For applications submitted to this NOSI that propose clinical trials, NIBIB will only support applications proposing early-stage clinical trials through Phase I, first-in-human, safety, feasibility, or other small clinical trials that inform the early-stage technology development in the submitted application. NIBIB will not support applications proposing Phase II, III, IV or pivotal clinical trials, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern.

NICHD Statement of Interest

The NICHD is interested in projects that focus on basic and applied synthetic biology research to (1) better understand typical and atypical development or (2) the pathophysiology, and ultimately treatment, of diseases within its mission. Synthetic biology approaches should serve as novel enabling technologies to understand embryonic and fetal development or to diagnose, prevent, and treat diseases of interest to the NICHD.

Research topics that are of interest to NICHD that fall within the scope of this NOSI include, but are not limited to:

• Construction and utilization of transgenic synthetic biology tools and approaches in animal model systems for the systematic and quantitative study of embryonic developmental processes.
• Generation and evaluation of synthetic biology tools to record information on developmental events and exposures that contribute to the origins of health and disease.
• Utilization of synthetic biology approaches and tools as diagnostic, prognostic, predictive, or therapeutic synthetic biomarkers for use in populations and conditions of interest to the NICHD.
• Creation of synthetic biology tools to advance research on endogenous tissue or limb regeneration.
• Development of synthetic biology constructs to deliver therapeutic payloads to targeted tissue niches or cell types for the treatment of a condition of interest to the NICHD.
  

NIGMS Statement of Interest

The National Institute of General Medical Sciences (NIGMS) supports basic research that increases our understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment, and prevention. NIGMS welcomes applications that fall within its mission to address fundamental research questions. NIGMS encourages technologies and approaches related to synthetic biology that include, but are not limited to:

• Establishing in vivo or cell-free means of producing useful natural and unnatural biological and/or chemical materials
• Producing models for the characterization and testing of complex cellular and metabolic processes (e.g., the microbiome)
• Development of safer, more effective, targeted early-stage delivery strategies, including the synthetic readout and control systems for controlled release of molecules of interest
• Synthetic reporter and genome-editing systems for single cell genome-wide genotype-phenotype mapping
• Synthetic reporter, genome-editing and transcriptional control tools for the reliable and reproducible construction of synthetic control devices and gene networks
• Transforming basic and applied biomedical research into new technologies (e.g., biosensors, bioswitches, nanosensors, and nanodevices)

The Institute places great emphasis on supporting investigator-initiated research grants. For this NOSI, NIGMS will not accept applications that include research which meets the NIH definition of a clinical trial.

Application and Submission Information

Applicants must select the IC and associated NOFO to use for submission of an application in response to this NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that NOFO. Non-responsive applications will be withdrawn from consideration for this initiative. In addition, applicants using NIH Parent Announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those NOFOs are acceptable and based on usual application-IC assignment practices.

This notice applies to due dates on or after May 16, 2023 and subsequent receipt dates through May 17, 2026.

Submit applications for this initiative using one of the following notices of funding opportunity announcements (NOFOs) or any reissues of these announcements through the expiration date of this notice.

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For this NOSI, NHLBI and NIGMS will not accept applications that include research which meet the NIH definition of a clinical trial nor applications to PA-20-183.
• For PA-20-183, NHLBI will only accept mechanistic clinical trials, in accordance with NOT-HL-19-690. Applicants wishing to propose non-mechanistic clinical trials may consider applying to one of the NHLBI clinical trial mechanisms described at https://www.nhlbi.nih.gov/grants-and-training/clinical-trial-development-continuum.
• For funding consideration, applicants must include NOT-EB-23-002 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applicants planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with an NIH Program Officer listed on this NOSI well in advance of the grant receipt date.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Hye-Sook Kim, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-827-6910
Email: hye-sook.kim@nih.gov

Jiayin (Jerry) Li, M.D., Ph.D.
Division of Cancer Biology
National Cancer Institute (NCI)
Telephone: 240-276-6210
Email: jiayinli@mail.nih.gov

Solita Chiayeng Wang, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute (NCI)
Telephone: 240-276-6624
E-mail: Chiayeng.wang@nih.gov

Rahul G. Thakar, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Phone: 301-827-8151
E-mail: rahul.thakar@nih.gov

Fei Wang, Ph.D.
National Institute on Aging (NIA)
Phone: 301-496-6402
E-mail: fei.wang@nih.gov

Reed Shabman, Ph.D.
Division of Microbiology and Infectious Diseases (DMID)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6433
Email: reed.shabman@nih.gov

Brigitte Sanders, DVM, Ph.D
Division of AIDS (DAIDS)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3209
Email: sandersbe@niaid.nih.gov

Conrad Mallia, Ph.D.
Division of Allergy, Immunology, and Transplantation (DAIT)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3491
Email:cmallia@niaid.nih.gov

Jermont Chen, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4778
Email: jermont.chen@nih.gov

Tuba Fehr, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4774
Email: tuba.fehr@nih.gov

Aaron C. Pawlyk, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-7299
Email: pawlykac@mail.nih.gov

Miljan Simonovic, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Email: miljan.simonovic@nih.gov

Peer Review Contact(s):

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s):

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Telephone:301-594-3788
Email: debbie.chen@nih.gov

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: hines@mail.nih.gov

Francesca Alicia Hunter
National Heart, Lung and Blood Institute (NHLBI)
E-mail: francesca.hunter@nih.gov

Jessi Perez
National Institute on Aging (NIA)
Phone: (301) 402-7739
E-mail: jessi.perez@nih.gov

Dhana Khurana
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2966
Email: khuranav@mail.nih.gov

Ruthann McAndrew
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-496-8521
Email: Ruthann.mcandrew@nih.gov

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@nih.gov

Lisa Moeller
National Institute of General Medical Sciences (NIGMS)
E-mail: moellerl@mail.nih.gov