U54AG079753

The Jackson Laboratory Senescence Tissue Mapping Center (JAX-SEN TMC) - Project Summary/Abstract

Overall, the Jackson Laboratory (JAX) Cellular Senescence Network Mouse Tissue Mapping Center (JAX-SEN) represents a multi-modal interdisciplinary effort that draws upon existing, longstanding aging research programs at JAX, our role as a consortium site of KAPP-SEN, a funded SENNET human tissue mapping center, and JAX's close collaboration with UCONN Health.

JAX-SEN is organized around three cores nested in the well-resourced environment for aging research and multi-omics profiling at JAX. JAX-SEN will profile senescent cells in kidney, adipose tissue, placenta, pancreas, heart, and hypothalamus, selected for their clinical relevance to chronic diseases of aging, the domain expertise of the JAX-SEN leadership team in the biology of these tissues, and the overlap of four of the tissues with KAPP-SEN.

We will leverage cutting-edge mouse resources including the Diversity Outbred, which offers unparalleled genetic diversity for modeling a range of molecular senescence phenotypes, and new inbred (C57BL/6J) transgenic mice that express P16 and P21 driven fluorescent tags to allow visualization enrichment for specific senescent cell subsets.

The Biological Analysis Core will apply a multitude of analytical modalities to selected tissues (bulk and single cell and single nucleus RNAseq, Visium spatial transcriptomics, multiplexed antibody-based imaging, multiplexFISH, imaging mass spectrometry including lipidomics, metabolomics, proteomics, 3D tissue reconstruction from serial sections), and will re-evaluate these technologies throughout the project period to ensure our approaches align with those of other centers and that we maximally benefit from the technology development efforts in SENNET.

These profiling activities will yield subcellular resolution of biomolecular content in senescent cells not possible with human samples, along with an expanded set of senescent cell biomarkers.

The Data Analysis Core will combine robust computational capability with scalable and reproducible scientific workflows to develop and implement network-wide open data and metadata standards. The Data Analysis Core will benefit from JAX's unique mouse research resources to establish the diversity of senescence by integrating with expression quantitative trait locus and protein quantitative trait locus data in DO mice and JAX bioinformatics resources, e.g., Mouse Genome Informatics, Mouse Phenome Database, Monarch Initiative.

The integrative mining of JAX-SEN data will lead to novel methods for multi-modal 3D map reconstruction from imaging data and will yield an important resource for SENNET interpretation and enrichment of human senescent cell data.

Finally, the Administrative Core will provide strong oversight of project progress and nurture a culture of collaborative, dynamic scientific exchange within JAX-SEN. It will also maximize JAX-SEN's engagement in the consortium through collaborative activities that will help optimize data generation activities and create new research synergies. In so doing, JAX-SEN will help achieve the goal of SENNET to generate an unprecedented atlas of mouse senescent cells and new biomarkers of senescence for human analysis and therapeutic application.

Jackson Laboratory

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.310 - Trans-NIH Research Support

National Institute on Aging (NIA) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Bar Harbor, Maine 04609 United States

Single Zip Code

Cellular Senescence Network: Murine Tissue Mapping Centers (U54 - Clinical Trial Not Allowed) (RFA-RM-22-003)

Amendment Since initial award the total obligations have increased 343% from $2,486,085 to $11,008,025.