The purpose of this Notice of Scientific Interest (NOSI) is to support research in the area of physics and mechanics of embryonic development. Applicants should propose hypothesis-driven developmental biology research with the prospect of gaining new and critical information about tissue mechanics relevant to vertebrate development and understanding the basis for developmental disorders. Interdisciplinary research through collaborations between developmental biologists, physicists and engineers is encouraged.

Background

In the past, research on developmental biomechanics was focused on developing theoretical models and using in vitro experimental approaches for model validation. However, it is now well recognized that morphogenesis occurs through interactions between multiple tissue layers, and that physical parameters contributing to these processes are not displayed appropriately when studying individual cells in culture. The challenge is to match theoretical models to experimental data and integrate the analyses across time and space so that cellular mechanisms can be linked to tissue-level behavior. Consequently, to better understand the role of the physical and mechanical forces exerted during development, the focus of this NOSI is to promote studies aimed at understanding biomechanics of morphogenesis in vivo.

In recent years, there has been considerable progress towardunderstanding the genetic control of morphogenesis. It is evident that regulated gene expression determines the chemical environment of cells and tissues and thereby regulates biophysical processes. In turn, changes in physical forces feedback to regulate gene function and cell fate. Advancing our knowledge of the physical aspects of development will thus provide a broader view of how the genome of multicellular organism functions in association with physical forces to specify final shape and architecture of an organ and/or an entire organism.

Research Objectives

The objective of this research program is to advance our knowledge of the contributions of biophysical and biomechanical processes during normal and abnormal embryonic development. This will be achieved by encouraging applications with innovative concepts and approaches for studying developmental tissue mechanics in living organisms. While achieving this goal will depend on the availability of reliable non-invasive measuring devices, developing such tools is not the focus of this NOSI. However, this NOSI runs in parallel with a companion NOSI (NOT-HD-19-038) that uses the NIH Exploratory/Developmental grant mechanism (R21) with similar scientific goals, but with additional scope to promote the development of new and innovative tools, including non-invasive devices, for reliable measurement of physical parameters of cells and tissues in vivo and in tissue explants, in the context of complex tissue layers.

Potential Research Areas

Research projects proposed in response to this NOSI are intended to advance our knowledge of the biophysical and biomechanical aspects of embryonic development. High impact interdisciplinary research through collaborations between developmental biologists, physicists and engineers is encourage. Studies can be focused at any level from the molecular and cellular, to tissue and organ level. However, it is important to note that the goal is to promote studies conducted in vivo, as emphasized below:

• The research activities must be confined to embryonic development.
• In vivo experimental systems to be used are confined to multicellular vertebrate or invertebrate animal models.
• Theoretical model- or hypotheses-driven studies conducted in tissue explants and/or cell culture-based in vitro experimental systems must be extended to include in vivo systems.

Examples of activities that this NOSI intends to support include, but are not limited to the following:

• Studies to identify and quantitatively assess the biophysical and biomechanical processes contributing to the morphogenetic events that occur during embryonic development.
• Studies to determine how coordination between gene regulatory networks and biophysical forces regulate key morphogenetic processes.
• Studies to identify mechanistic commonalities across various morphogenetic events.
• Studies aimed at understanding how disruptions in biophysical and biomechanical processes might lead to known structural developmental disorders.
• Studies to refine non-invasive tools for in-depth analyses of the temporal and spatial dynamics of developmental processes, as well as quantitative measurement of physical parameters contributing to these processes.

Application and Submission Information

This notice applies to due dates on or after February 5, 2020 and subsequent receipt dates through November 8, 2022.

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

• PA-19-056 NIH Research Project Grant (Parent R01, Clinical Trial Not Allowed)
• PAR-19-158 Bioengineering Research Grants (BRG) (R01 Clinical Trial Not Allowed)

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 funding consideration, applicants must include NOT-HD-19-037 (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.

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