Overview/Mission
DBCAB, formerly known as the Developmental Biology and Structural Variation Branch, focuses on deciphering the biological causes of structural congenital anomalies. Understanding the etiology of these errors in embryonic development provides the most promising route for improving prevention, diagnosis, and implementation of evidence-based treatments for patients and families affected by these rare diseases and conditions.
In addition to studies focused on identifying and elucidating the roles of gene variants, environmental perturbations, and other factors causing structural congenital anomalies, DBCAB supports studies to advance our understanding of the fundamental processes underlying formation and differentiation of the embryo. This basic knowledge is crucial for understanding how the process of embryogenesis can go awry. Major program areas for the branch include early embryonic development and differentiation, biophysics/biomechanics of development, developmental neurobiology, organogenesis, regeneration, regenerative medicine, systems developmental biology, and developmental genetics, including genomic analysis of human structural congenital anomalies. The branch also administers the Gabriella Miller Kids First Pediatric Research Program, led by the NIH Common Fund, as well as NIH-wide coordination of research on congenital anomalies.
We are interested in applications that align with the following research priorities. For more information about NICHD’s research themes, cross-cutting topics, and aspirational goals, visit the plan’s Scientific Research Themes and Objectives.
Congenital Anomalies
Strategic Plan Theme 1: Understanding the Molecular, Cellular, and Structural Basis of Development
Gap: Understanding the genetic and environmental origins of a spectrum of structural congenital anomalies is needed to identify potential targets and determine optimal timing for intervention strategies.
Priority: Identification, validation, and functional characterization of human genetic variants associated with structural congenital anomalies using cutting edge technologies in model systems. Provide support for the model organism resources that provide the necessary infrastructure to facilitate this research.
Gene Regulatory Networks
Strategic Plan Theme 1: Understanding the Molecular, Cellular, and Structural Basis of Development
Gap: Our understanding of developmental gene regulatory networks is incomplete. A comprehensive picture is necessary to fully understand typical and atypical vertebrate development and the function of genomic variants associated with congenital anomalies. Currently available linear pathway models are insufficient to capture the highly dynamic and complex genetic control mechanisms that govern vertebrate embryonic development.
Priority: Research focused on at providing comprehensive analyses of gene regulatory networks at the single- and multi-cellular level for all developmental stages using model organisms and human cell-based models. Further research that uses this information to create predictive computational models of the complex gene regulatory networks that coordinate vertebrate embryogenesis.
-Omics for Developmental Biology
Strategic Plan Theme 1: Understanding the Molecular, Cellular, and Structural Basis of Development
Gap: New and emerging functional -omics (genomics, epigenomics, proteomics, metabolomics, etc.) technologies have not yet been systematically applied to analyze the dynamics of endogenous developmental processes at the genetic, molecular, and cellular levels.
Priority: Research on the spatial and temporal analyses of developmental processes at the single cell- and tissue-level using ‘omics approaches to advance knowledge of determinants of typical and atypical development.
Stem Cells and Regeneration Biology
Strategic Plan Aspirational Goal: Advance the ability to regenerate human limbs by using emerging technologies to activate the body’s own growth pathways and processes
Gap: Currently, our understanding of any regenerative process is in its infancy, and reliable, experimentally accessible models to understand these processes are lacking.
Priority: Research using emerging tools and evolutionarily divergent models to understand the biology of tissue regeneration with an emphasis on endogenous stem cells.
Mechanics and Biophysics of Development
Strategic Plan Theme 1: Understanding the Molecular, Cellular, and Structural Basis of Development
Gap: Technical limitations have hampered our understanding of biomechanical forces that play essential roles in typical and atypical embryonic development.
Priority: Research that uses novel concepts, approaches, tools, and techniques to advance knowledge of the biophysical and mechanical forces that act in concert with genetic mechanisms to drive embryonic morphogenesis.
- Biophysics/Biomechanics of Development: Examines how biophysical forces and mechano-transduction contribute to morphogenetic events regulating embryonic development and patterning
- Developmental Genetics and Genomics: Identifies and characterizes the genes, genetic networks, and epigenetic factors that control developmental processes to understand how alterations in them lead to structural congenital anomalies
- Developmental Neurobiology: Examines mechanisms that control the early pattern of the developing nervous system, neurogenesis, differentiation, axonal guidance, neural crest differentiation and migration, and neural tube formation and defects
- Early Embryonic Development: Seeks to explain the cellular and molecular mechanisms directing the zygote to establish the embryonic plan for developing a complex, multicellular organism
- Organogenesis: Studies mechanisms underlying typical development of organ primordia against which aberrations can be better understood
- Regenerative Biology: Examines key biological events underlying tissue regeneration by supporting research in model organisms
- Stem Cell Biology: Promotes research on basic stem cell biology essential for creating therapeutic opportunities to maximize functional integration and clinical recovery
- Systems Developmental Biology: Links isolated molecular and mechanistic descriptions of developmental processes into a foundational framework
- Congenital Anomalies Initiative: : Aims to capitalize on genomic and other biomedical discoveries to further understand the mechanisms responsible for structural congenital anomalies and increase collaborations between basic, translational, and clinical researchers
- Gabriella Miller Kids First Pediatric Research Program (Kids First): NIH-wide program supported through the NIH Common Fund and administered by DBCAB that fosters collaborative research to uncover the causes of childhood cancers and congenital anomalies and support data sharing with the pediatric research community
- Kids First Data Resource Portal
: An interoperable data resource that enables cloud-based access, discovery, and analysis of whole genome sequences to accelerate collaborative pediatric research leading to improved prevention, diagnosis, and treatments for patients and their families with congenital anomalies or childhood cancers; the branch also funds community resources, animal model systems, research tool development, and training to facilitate the efforts of developmental biology researchers
- Kids First Data Resource Portal
Highlights
- Science Update: Cellular metabolism regulates developmental rates, suggests NIIH-funded study
The study findings also suggest the potential to manipulate developmental rates at the cellular level. - Media Advisory: NIH-funded scientists generate a mouse embryo model that develops neural tubes
These embryoids offer a promising model system for research into factors affecting mammalian embryonic development and disease. - Some recent findings from DBCAB-supported researchers include the following:
- The Gene Ontology knowledgebase in 2023. This comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs) covers organisms and viruses and includes three components: a computational knowledge structure describing functional characteristics, annotations, and mechanistic models of molecular pathways. (PMID: 36866529)
- Reconstruction and deconstruction of human somitogenesis in vitro. This research demonstrates that major patterning modules involved in somitogenesis, including the clock and wavefront, anteroposterior polarity patterning and somite epithelialization, can be dissociated and operate independently within in vitro systems. (PMID: 36543321)
- Evolutionary divergent mTOR remodels translatome for tissue regeneration. Rapid activation of protein synthesis during injury response plays a crucial role in axolotl limb regeneration. The mTORC1 pathway is a key signal that mediates tissue regeneration and translational control in axolotls. An axolotl mTOR protein was engineered in human cells, inducing a state supporting rapid protein activation. This study provides another missing link in our understanding of vertebrate regenerative potential. (PMID: 37495694)
- The Gene Ontology knowledgebase in 2023. This comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs) covers organisms and viruses and includes three components: a computational knowledge structure describing functional characteristics, annotations, and mechanistic models of molecular pathways. (PMID: 36866529)
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