ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Millions of people in the U.S. and across the globe are afflicted by prolonged pain after surgery and/or by chronic pain. We will develop means of treating such pain with a single local injection that would last for days to weeks. We will also develop systems where that pain relief would be triggered on demand when desired by patients, adjusted to the patient’s needs, and last as long as the patient feels is necessary.

PI_NAMEs: KOHANE, DANIEL S (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Accounting;addiction liability;Address;Anesthesia procedures;Biocompatible Materials;Biomedical Engineering;Charge;chronic pain;Clinical;Communication;COVID-19;design;Devices;Drug Delivery Systems;Drug Synergism;Drug usage;Energy-Generating Resources;Event;Formulation;General Anesthesia;Hour;improved;Inflammation;Injectable;Injections;Journals;Letters;Light;Local anesthesia;Local Anesthetics;nano;nanoscience;Nature;Nerve;Nerve Block;novel;novel strategies;Operative Surgical Procedures;Opioid;opioid use;Pain;Pain management;pain relief;Paper;Patients;Perioperative;Persistent pain;Persons;Pharmaceutical Preparations;Postoperative Pain;Procedures;Reaction;Research;Safety;Saxitoxin;Science;side effect;Site;Sodium Channel Blockers;Steroids;System;systemic toxicity;Technology;Tetrodotoxin;Time;Tissues;Toxic effect;ultrasound;Water;Work

PROJECT_TITLE: Prolonged duration and triggered local anesthesia


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: ATLANTA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Lung transplantation is a costly and life-saving procedure with the drawback of poor long-term survival secondary to development of chronic rejection. In this application, we will investigate the mechanism and potential therapeutic targets for a particular aggressive form of chronic rejection.

PI_NAMEs: LAMA, VIBHA N (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: 3-Dimensional;Allografting;antagonist;anti-CD20;Antibodies;antibody-mediated rejection;B-Cell Activation;Bone Marrow;Bortezomib;Cell Maintenance;Cells;chemokine;Chronic;Communication;cost;cytokine;Data;Development;donor-specific antibody;Drug Targeting;experimental study;Exudate;Failure;Fibrosis;Functional disorder;hematopoietic tissue;Histologic;Homing;Human;Human Pathology;humoral immunity deficiency;IL6ST gene;Immune;immune activation;immune cell infiltrate;Immune response;Immunoglobulin G;Immunoglobulin-Secreting Cells;In Situ;In Vitro;in vivo;Infiltration;Inflammatory;Injury;innovation;insight;Interleukin-6;Interleukins;Investigation;JAK2 gene;Life;Ligands;Longitudinal Studies;LoxP-flanked allele;Lung;lung allograft;lung development;Lung Transplantation;Lymphoid Tissue;Lymphoplasmacytic Infiltrate;Maintenance;Mature B-Lymphocyte;Mesenchymal;mesenchymal stromal cell;Modality;Modeling;monocyte;Mononuclear;mouse model;Mus;novel;Outcome;paracrine;Paracrine Communication;Pathogenesis;Pathology;Perivascular Fibrosis;pharmacologic;Phenotype;plasma cell differentiation;Plasma Cells;Plasmablast;Pleura;Population;pre-clinical;preclinical study;prevent;Procedures;Prognosis;Proteasome Inhibitor;Proteins;Publishing;recruit;Regulation;response;rituximab;Role;Secondary to;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Source;spatiotemporal;STAT3 gene;Stromal Cell-Derived Factor 1;Stromal Cells;Syndrome;targeted treatment;Testing;Therapeutic;therapeutic target;Time;Transgenic Mice;transplant model;Transplant Recipients;Transplantation;Up-Regulation;Work

PROJECT_TITLE: Pathogenesis of Restrictive Allograft Syndrome Post-Lung Transplantation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(05)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: Nashville

ORG_DEPT: CHEMISTRY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative The proposed research is relevant to public health because of the need to develop and study new treatments for resistant bacterial infections and aggressive cancers. Carbohydrates and their conjugates are present on the surface of all cell types and are key transmitters of biological information. This proposal addresses the synthesis, modification, and evaluation of carbohydrates that have potential to be used as novel treatments for human disease.

PI_NAMEs: TOWNSEND, STEVEN D. (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TITLE: Bioorganic Approaches Toward Novel Antimicrobial Agents and Chemotherapeutics

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ORG_CITY: SYRACUSE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE These studies investigate the essential mechanisms underlying how the actin and microtubule cytoskeletons are assembled and coordinated by the individual and combined effects of several disease-relevant regulatory proteins. This research uses biochemical and cell-based analyses to assess how profilin and specific biomolecular condensate forming proteins impact the individual assembly and coordination of cytoskeletal polymers. These studies will provide new insight into the underlying shared features of several cancers and severe neurological disorders.

PI_NAMEs: RIDILLA, JESSICA L. (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;Address;Biochemical;Biological Process;biological systems;Biomimetics;Cell Nucleus;Cell Physiology;Cells;Cytoplasm;Cytoskeleton;Disease;DNA biosynthesis;DNA Repair;genetic regulatory protein;Goals;In Vitro;Individual;innovation;insight;Malignant Neoplasms;Membrane;Microfilaments;Microscopy;Microtubules;Molecular;Monitor;Morphogenesis;Motility;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;optogenetics;Phagocytosis;Physical condensation;Physiological;Polymers;Positioning Attribute;profilin;Proteins;Research;Resolution;single molecule;System;tool;Visualization

PROJECT_TITLE: Mechanisms of coordinated actin and microtubule dynamics

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


NIH_SPENDING_CATS: Genetics

ORG_CITY: NEW YORK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Protein-nucleic acid interactions are central to many biological processes, including the defense mechanisms in prokaryotes against invading DNA and translesion synthesis (TLS) mechanisms in eukaryotes for replicating through DNA lesions. We will uncover the role of protein nucleic acid interactions in these basic cellular processes.

PI_NAMEs: AGGARWAL, ANEEL K. (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Area;Bacteriophages;Biological Process;Cell Physiology;Cells;Complex;coping;Cryoelectron Microscopy;Defense Mechanisms;DNA;DNA biosynthesis;DNA Damage;DNA lesion;DNA Restriction-Modification Enzymes;DNA-Directed DNA Polymerase;Eukaryota;Eukaryotic Cell;genome integrity;Genotoxic Stress;Immunity;Infection;Invaded;Nucleic Acids;Oligonucleotides;Periodicity;Polymerase;Population;prevent;Prokaryotic Cells;Proteins;Research;Role;Signal Transduction;Structure;success;System;Work

PROJECT_TITLE: Protein-nucleic acid interactions in basic cellular processes

STUDY_SECTION: MRAE

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - E Study Section[MRAE]


NIH_SPENDING_CATS: Neurosciences;Nutrition

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PUBLIC HEALTH RELEVANCE This research program aims to discover the three-dimensional structures and to understand the fundamental mechanisms of two classes of proteins that reside within cellular membranes: ion channels and enzymatic membrane proteins. The ion channels under study regulate the flow of potassium, calcium, and chloride across cellular membranes and they are thereby involved in cognition, neuronal signals, muscle contraction, cellular motility, fluid secretion and a host of other processes; the enzymatic membrane proteins under study catalyze crucial post-translational chemical reactions in the cellular construction of signaling molecules (such as hormones and protein signaling complexes) that act to control cell growth and cell differentiation in normal tissues and can contribute to cancer progression when mutated or coopted by oncogenic signaling networks. The molecular, structural, and functional principles obtained from the studies will provide fuller understandings of the inner workings of these intricate protein machines and may inspire new approaches to intervene in diseases that include cancer, cystic fibrosis, immune disorders, and obesity.

PI_NAMEs: LONG, STEPHEN BARSTOW (contact)

PROJECT_TERMS: Active Sites;acyl group;Address;analog;Anions;ATP Synthesis Pathway;Attention;Binding;Biochemistry;Calcium;calcium uniporter;Catalysis;Cell Differentiation process;cell growth;cell growth regulation;cell motility;Cell Volumes;Cells;Cellular Membrane;chemical reaction;Chemicals;Chloride Channels;Chlorides;Cognition;Complex;Cryoelectron Microscopy;Cystic Fibrosis;Disease;Electrophysiology (science);Enzymatic Biochemistry;enzyme structure;Enzymes;Erinaceidae;Eukaryota;experimental study;Family;Fluids and Secretions;ghrelin;Hormones;Human;Immune response;Immune System Diseases;Integral Membrane Protein;Ion Channel;Ions;Lipids;lipophilicity;Malignant Neoplasms;Membrane;Membrane Lipids;Membrane Potentials;Membrane Proteins;Mitochondria;Molecular;Molecular Conformation;Molecular Machines;Muscle Contraction;Mutate;Mutation;Neurons;neurotransmission;Neurotransmitters;Normal tissue morphology;novel strategies;Obesity;Oncogenic;Phosphorylation;Physiological Processes;Post-Translational Protein Processing;Potassium;Process;programs;Property;Proteins;public health relevance;Reaction;Research;Retinal Degeneration;Signal Transduction;Signaling Molecule;Signaling Protein;Structure;three dimensional structure;tumor progression;Water;X-Ray Crystallography

PROJECT_TITLE: Mechanisms of Ion Channels and Enzymatic Membrane Proteins


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Narrative: Protein misfolding is associated with numerous devastating neurodegenerative, cardiovascular, and kidney disorders, as well as certain forms of cancer. We seek to understand the role of protein disaggregases, which can solubilize misfolded proteins and restore the proteins to their native folds and functions. We seek to better understand how these agents maintain cellular health and how they counter cellular stress, because with this understanding we might gain new insights into how they fail in disease, ultimately leading to new insights into how disaggregases can be modulated to develop new therapeutics.

PI_NAMEs: JACKREL, MEREDITH E. (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Award;Biology;Cardiovascular Diseases;Cells;Cellular Stress;Disease;disease phenotype;Engineering;Enhancement Technology;Ensure;Health;Heart Diseases;Human;Human Activities;insight;Kidney Diseases;Life;Malignant Neoplasms;member;misfolded protein;Neurodegenerative Disorders;novel therapeutics;Phase;Play;prevent;programs;Protein Family;protein folding;protein misfolding;Proteins;proteostasis;Research;restoration;Role;Stress;Structure;System;Testing;Therapeutic;therapeutically effective;Variant

PROJECT_TITLE: Elucidating the roles of protein disaggregases and developing enhanced diaggregases to counter diverse protein-misfolding disorders

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


ORG_CITY: STANFORD

ORG_DEPT: PATHOLOGY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Planar cell polarity (PCP) signaling controls the polarization of cells within the plane of an epithelium, orienting asymmetric cellular structures, cell divisions and cell migration, and is well conserved from Drosophila to vertebrates. This proposal aims to dissect the essential logic and underlying molecular and cell biological mechanisms of PCP signaling by leveraging the experimental tractability of the Drosophila model system, combining novel genetic tools, single molecule imaging and powerful biochemical approaches to probe previously inaccessible problems in PCP signaling. The proposed work will both enhance our knowledge of fundamental mechanisms as well as lay the groundwork for potential therapeutic interventions for PCP related pathologies.

PI_NAMEs: AXELROD, JEFFREY D. (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Adult;Behavior;Biochemical;Biochemistry;Biological;Biological Models;Cell division;cell motility;Cells;Cellular Structures;Complex;Coupled;Defect;Development;Dissection;Drosophila genus;Epithelium;Eye;Feedback;fly;Genetic;genetic approach;Goals;Hair;innovation;interest;Knowledge;Logic;mathematical model;Medical;Molecular;molecular asymmetry;molecular imaging;molecular scale;novel;Pathology;Physiological Processes;planar cell polarity;polarized cell;Process;Proteins;response;Role;segregation;Side;Signal Transduction;single molecule;System;system architecture;Technology;Therapeutic Intervention;Tissues;tool;Vertebrates;Work

PROJECT_TITLE: Planar cell polarity mechanisms and systems architecture


ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE This project will investigate how Gram-negative bacteria transport lipids across their envelope to build their outermost layer, the outer membrane. Our work will generate fundamental knowledge about the mechanism of function of transporters that are potential targets for new antibiotics. In the long term, this knowledge will help in the development of much needed novel antimicrobials that can treat infections caused by Gram-negative bacteria, which pose a serious threat to global health.

PI_NAMEs: RUIZ, NATIVIDAD  (contact)

PROJECT_TERMS: Antibiotics;antimicrobial;Applied Genetics;aqueous;ATP-Binding Cassette Transporters;Bacteria;Bacterial Physiology;Biochemical;Biogenesis;cell envelope;Cell Shape;Cell surface;Cell Wall;Cells;Detergents;Development;Diffuse;Ensure;Escherichia coli;Eukaryotic Cell;global health;Glycerophospholipids;Gram-Negative Bacteria;Growth;Hydrophobicity;Infection;Knowledge;Lipid Bilayers;lipid transfer protein;lipid transport;Lipids;Lipopolysaccharides;Membrane;membrane biogenesis;Membrane Lipids;Natural Resistance;novel;Organelles;Organism;pathogen;Peptidoglycan;periplasm;Permeability;Phospholipids;programs;Protein Family;protein transport;Proteins;Research;Site;Structure;System;Thinness;Travel;Work

PROJECT_TITLE: Envelope biogenesis in Gram-negative bacteria

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE RNA nucleoside modifications are universal modulators of post-transcriptional gene expression, impacting protein synthesis in all organisms . Despite decades of study and established links between the dysregulation of RNA modifications and disease, the molecular level function of most individual rRNA, tRNA and mRNA modification sites remains to be discovered. Our work will establish relationships between cellular components that shape the RNA modification landscape, evaluate the impacts of discrete tRNA and mRNA modifications on translation, and open new avenues of investigation into how RNA modifications broadly influence cellular stress responses.

PI_NAMEs: KOUTMOU, KRISTIN S (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Biological Process;Biology;Cells;Cellular Stress;chemical addition;Chemicals;Coupled;design;Disease;Enzymes;Etiology;Foundations;Gene Expression;Gene Expression Regulation;Health;Human;human disease;Individual;Intellectual functioning disability;Intervention;Investigation;Knock-out;Knowledge;Life;Life Cycle Stages;Link;Malignant Neoplasms;Maps;Medical;Messenger RNA;Mitochondrial Diseases;Modification;Molecular;Mutation;Nucleosides;Organism;Outcome;Positioning Attribute;Post-Transcriptional RNA Processing;posttranscriptional;Production;Protein Biosynthesis;Proteins;Pseudouridine;response;Ribosomal RNA;RNA;Role;Shapes;Site;Stress;therapeutic RNA;therapeutically effective;transcriptome;Transfer RNA;Translations;Work

PROJECT_TITLE: Mechanisms of translational control

STUDY_SECTION: MRAF

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - F Study Section[MRAF]


ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Development and Applications of Bioorthogonal Chemistry Narrative This application seeks to combine the powers of genetic code expansion with bioorthogonal chemistry to develop new tools and capabilities for the studies of transmembrane receptor dynamics, intracellular enzyme functions, and antibody-based diagnostics in living systems. The demonstration of these new capabilities and their use in biomedical systems are expected to provide novel mechanistic insights into three major classes of drug targets crucial for clinical translation.

PI_NAMEs: LIN, QING  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Address;Alkenes;Alkynes;Antibodies;antibody diagnostic;Arrestins;beta-Lactams;Biochemical;biomaterial compatibility;Biomedical Research;Biophysics;Biosensor;Cell Cycle Kinetics;Cell surface;Cells;Chemicals;Chemistry;clinical translation;crosslink;Crosslinker;cycloaddition;design;Development;Drug Targeting;Endowment;Environment;Enzymes;Fluorescence Resonance Energy Transfer;fluorophore;G-Protein-Coupled Receptors;Genetic Code;GTP-Binding Proteins;Histone-Lysine N-Methyltransferase;Hydrogen Peroxide;hydrophilicity;Imaging problem;ImmunoPET;in vivo imaging;insight;interest;Lactams;Ligation;Lysine;Mammalian Cell;Mediating;Membrane;Molecular Biology Techniques;nanobodies;nephrotoxicity;novel;Organism;Penetration;Performance;Positron-Emission Tomography;radiotracer;Reaction;Reagent;receptor;Receptor Activation;Receptor Signaling;recruit;Reporter;Research Project Grants;Signal Transduction;System;tautomer;Tetrazoles;tool;tool development;Tracer;tumor;uptake


ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative The proposed studies will explore cellular stress response pathways that regulate protein homeostasis. Understanding these pathways will elucidate how cells maintain internal conditions that are conducive to life and give insights into the molecular basis of disease.

PI_NAMEs: BRANDMAN, ONN  (contact)

PROJECT_TERMS: Aging;Area;biological adaptation to stress;biophysical analysis;Biophysics;Cell Survival;Cells;Cellular biology;Cellular Stress;Disease;insight;Life;Messenger RNA;Molecular;Pathway interactions;Process;Protein Biosynthesis;Proteins;proteostasis;Quality Control;response;Ribosomes;Stress;Tail;tool;Translations

PROJECT_TITLE: Stress Response Pathways Regulating Protein Homeostasis


ORG_CITY: FLUSHING

ORG_DEPT: BIOLOGY

ORG_NAME: QUEENS COLLEGE

PHR: Cellular communication initiated by members of the Transforming Growth Factor beta (TGF-β) family of secreted signaling molecules plays important roles in normal and pathological biological processes. Signaling components mediate diverse outcomes that depend on the context, but how these outcomes are differentiated is poorly understood, increasing the likelihood of causing unintended consequences during the management of diseases and disorders. In this project, we will exploit the advantages of a simple model organism to uncover the conserved mechanisms that distinguish the roles of TGF-β signaling in fat metabolism and immunity from those in development.

PI_NAMEs: SAVAGE-DUNN, CATHY  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Activins;Address;Biochemistry;Biological Assay;Biological Process;Bone Morphogenetic Proteins;Caenorhabditis elegans;Cardiovascular Diseases;Cell Physiology;Communication;Data;Development;developmental disease;Disease;Disease Management;Family;Fatty acid glycerol esters;Genetic;Genomics;Goals;Growth Factor;Health;Homeostasis;Human;Image;Immune response;Immunity;insight;Knowledge;Ligands;lipid metabolism;Lipid Mobilization;Malignant Neoplasms;Mediating;member;model organism;Modeling;Molecular;mutant;Natural Immunity;Nematoda;Outcome;pathogen;pathogen exposure;pathogenic bacteria;Pathologic;Pathway interactions;Pattern;Peptides;Phenotype;Physiological;Physiology;Play;procollagen C-endopeptidase;protein function;receptor;Research;resilience;response;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Signaling Protein;Specificity;System;Testing;Tissues;Transducers;Transforming Growth Factor beta;transforming growth factor beta3;Vertebrates;Whole Organism

PROJECT_TITLE: TGF-beta Signaling Mechanisms in C. elegans Physiology and Homeostasis


ADMINISTERING_IC: AR

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: SEATTLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE - OVERALL Skeletal muscle dysfunction represents a significant and growing public health concern due to reduced quality of life and loss of independence for those affected. Muscle dysfunction and degeneration result from numerous pathological conditions including genetic diseases like muscular dystrophy and systems level conditions like diabetes, cancer and aging. The UW Resource Center for Translational Muscle Research (CTMR) will provide access to, and training on state of the art tools to recruit new investigators, accelerate research and disseminate news of exciting new successes in understanding and treating skeletal muscle dysfunction to improve the health status of the U.S. population.

PI_NAMEs: DAVIS, JENNIFER MICHELLE;RAFTERY, DANIEL ;REGNIER, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: GARCIA-CAZARIN, MARY

PROJECT_TERMS: Acceleration;Address;Advocate;Affect;age related;Aging;analytical tool;Animal Model;Applications Grants;Area;Award;Basic Science;Biological Assay;Biology;Biomechanics;bone;Canada;Cancer Center;Cell Respiration;Cells;Child;Clinic;Clinical;Clinical Investigator;Clinical Research;Collaborations;Communities;computerized tools;Connective Tissue;Core Facility;cost effective;Data;Development;Device or Instrument Development;Devices;Diabetes Mellitus;Discipline;Disease;disease mechanisms study;early-career faculty;Education;Educational workshop;Engineering;Environment;Europe;Exercise;experience;Extramural Activities;Faculty;Functional disorder;Funding;Genetic Diseases;Genomics;Goals;Health Status;high reward;high risk;Home;Hospitals;Human;human stem cells;Image;improved;Individual;Infrastructure;Injury;innovation;insight;Institution;instrumentation;interdisciplinary approach;Interdisciplinary Study;interest;International;Length;Malignant Neoplasms;Measurement;Measures;Mechanics;Mentorship;Metabolic;Metabolism;metabolomics;Mission;Mitochondria;Modeling;Movement;multidisciplinary;Multiscale Mechanics;Muscle;muscle aging;Muscular Dystrophies;muscular system;Myopathy;NCI Center for Cancer Research;neuromuscular plasticity;Neuromuscular research;new therapeutic target;news;novel;novel strategies;novel therapeutics;Nursing Faculty;Organ;Organelles;outreach;Pathologic;Pathology;Patient-Centered Care;Pediatric Hospitals;Peripheral;Physicians;Population;Productivity;programs;Proteins;Proteomics;Public Health;Quality of life;Recording of previous events;recruit;Research;research and development;research faculty;Research Personnel;Research Training;Resources;sarcopenia;Scientist;Series;Services;Skeletal Muscle;skill acquisition;skills training;Speed;stem cell biology;stem cell model;Striated Muscles;Structure;success;symposium;Techniques;Technology;Testing;Therapeutic Agents;therapeutic development;therapeutic target;Time;Tissues;tool;tool development;Training;Training and Education;Translational Research;treatment research;treatment strategy;United States;Universities;Viral Vector;Washington;Work

PROJECT_TITLE: UW Center for Translational Muscle Research

STUDY_SECTION_NAME: Special Emphasis Panel[ZAR1 FY (M1)]


PI_NAMEs: REGNIER, MICHAEL  (contact)

PROJECT_TERMS: Acceleration;Administrator;Advertising;Advisory Committees;Area;Award;Biological Assay;Biomedical Research;Budgets;career development;cellular engineering;Clinic;Clinical;clinical development;Collaborations;commercialization;Communication;Communities;Complement;Core Facility;Creativeness;design;Development;Discipline;Disease;e-science;Education;Educational Curriculum;Educational workshop;Effectiveness;Environment;Europe;Evaluation;Event;experience;Faculty;Feedback;Fees;Funding;gene therapy;General Population;Goals;graduate student;Grant;improved;Individual;Industrialization;Industry;Informatics;innovation;Institution;interest;Journals;Knowledge;Leadership;lectures;Link;Marketing;medical schools;member;Mentors;Muscle;Muscle Cells;Myopathy;NCI Center for Cancer Research;novel;novel therapeutics;organizational structure;outreach;Pacific Northwest;Pathway interactions;Patients;Pediatric Hospitals;Pharmaceutical Preparations;Pilot Projects;Planet Earth;Positioning Attribute;Postdoctoral Fellow;preclinical development;Productivity;programs;Protocols documentation;rational design;recruit;Recruitment Activity;Research;Research Personnel;Research Project Grants;Resources;Scientist;Senior Scientist;Series;Services;Skeletal Muscle;skills;skills training;small molecule;Speed;STEM field;Students;success;symposium;Therapeutic;Time;Tissue Engineering;Tissues;Training;Translating;Translational Research;translational therapeutics;Underrepresented Minority;Voice;web site;Western Europe;Work

PROJECT_TITLE: Administration and Enrichment


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

PROJECT_TERMS: Acceleration;Address;Adult;Aerobic;Age;Aging;Animal Model;Animals;Arthrogryposis;base;Biochemical;Biological Assay;Biopsy;Biopsy Specimen;Cancer Center;Cell Differentiation process;Cells;cellular engineering;Center for Translational Science Activities;Clinic;Clinical;clinical application;clinical investigation;Collaborations;commercialization;Communities;Complement;Computer software;Contractile Proteins;Contracture;Core Facility;Coupled;Cues;Development;Devices;directed differentiation;Disease;Distal;Educational workshop;effectiveness evaluation;Embryo;Engineering;Environment;Environmental Impact;Evaluation;experimental study;Faculty;fetal;Fibroblasts;Functional disorder;Funding;gene therapy;Generations;Genetic;Goals;graduate student;high throughput screening;Histologic;Human;human disease;human stem cell-derived;improved;indexing;Individual;induced pluripotent stem cell;Injury;insight;instrument;instrumentation;Interdisciplinary Study;investigator training;Ischemia;Kinetics;Measurement;Measures;Mechanics;meetings;Metabolic;Metabolism;Mission;Mitochondria;Modeling;Molecular;Molecular Target;Muscle;Muscle Cells;Muscle Development;Muscle Fibers;Muscle function;Muscular Dystrophies;muscular structure;Myofibrils;Myopathy;Nature;novel;novel therapeutic intervention;Operative Surgical Procedures;Organ;Organelles;Pathology;Pathway interactions;Pediatric Hospitals;Peripheral Blood Mononuclear Cell;personalized approach;Pharmaceutical Preparations;Pharmacologic Substance;Postdoctoral Fellow;preclinical study;Preparation;Property;Protein Analysis;Proteins;Proteomics;Protocols documentation;Rapid screening;recruit;regenerative cell;Rejuvenation;Relaxation;repaired;Research;research and development;Research Personnel;Resources;Sample Size;sarcopenia;Scientist;Services;Skeletal Muscle;skills;Skin;small molecule;Source;stem cell differentiation;stem cell model;stem cells;Structure;success;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Time;Tissue constructs;Tissue Engineering;Tissues;tool;Training;Urine;Work

PROJECT_TITLE: Mechanics and Devices


NIH_SPENDING_CATS: Bioengineering

PI_NAMEs: RAFTERY, DANIEL  (contact)

PROJECT_TERMS: acylcarnitine;Address;Amino Acids;Apoptosis;aqueous;Atrophic;base;Bile Acids;Biochemical;Biological;Biological Assay;Biology;biomarker discovery;Biopsy;Cardiolipins;Cell Physiology;Cells;Cellular Metabolic Process;Coenzymes;Collaborations;Complement;Consumption;Coupling;Data;Data Collection;Devices;Disease;Equilibrium;Experimental Designs;Fiber;Functional disorder;Genus Hippocampus;Goals;Health;Hemoglobin;Homeostasis;improved;in vivo;in vivo evaluation;Individual;insight;Institution;Ligaments;Link;lipidomics;Lipids;Magnetic Resonance;Mass Spectrum Analysis;Measurement;Measures;Mechanics;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;Monitor;mouse model;Mus;Muscle;muscle degeneration;Muscle Fibers;muscle metabolism;muscle physiology;Myoglobin;Myopathy;Optics;Oxidation-Reduction;Oxidative Phosphorylation;Oxidative Stress;Oxygen;Pathology;Pathway Analysis;Permeability;Phosphorylation;prevent;Production;Protein Biosynthesis;protein degradation;Reactive Oxygen Species;Research;Research Personnel;Respiration;Rest;Role;Sampling;Skeletal Muscle;Spectrum Analysis;Spirometry;Statistical Data Interpretation;Statistical Methods;Stress;System;Systems Biology;Tendon structure;Therapeutic;Therapeutic Intervention;tool;Training;Universities;Washington

PROJECT_TITLE: Metabolism Core


NIH_SPENDING_CATS: Aging;Bioengineering;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Sarcopenia

PI_NAMEs: DAVIS, JENNIFER MICHELLE (contact)

PROJECT_TERMS: Acceleration;Address;analytical tool;Animal Model;Area;base;Behavior;Binding;Bioinformatics;Biology;Biophysics;Cell model;Clinical Investigator;Code;Collaborations;Communities;complex data;Computer Models;computerized tools;computing resources;Data Analytics;Data Science;Data Set;design;Development;Disease;e-science;Education and Outreach;Educational Activities;Educational process of instructing;Educational workshop;Elements;Energy Supply;Engineering;experience;Experimental Designs;Experimental Models;Exposure to;Faculty;Familiarity;Functional disorder;Future;Generations;Goals;Human Resources;in silico;Inherited;insight;Intervention;Kinesiology;Knowledge;Laboratories;large datasets;Lead;Learning;Link;Machine Learning;machine vision;Markov Chains;Measures;Mechanics;Mediating;member;Metabolic;Metabolism;Mission;Mitochondria;Mitochondrial Proteins;Modeling;Molecular;Molecular Analysis;molecular dynamics;Movement;multi-scale modeling;Muscle;muscle aging;Muscle Development;Muscle function;muscle physiology;Muscle Proteins;muscular structure;Mutation;Myopathy;novel;novel therapeutic intervention;open source;Organism;Outcome;Pathologic;Periodicals;Phenotype;Physiological;Postdoctoral Fellow;Process;programs;Protein Engineering;Proteins;Reproducibility;Research;Research Personnel;Resources;Sarcomeres;sarcopenia;Services;Signal Transduction;simulation;Skeletal Muscle;skills;small molecule;Structure;Students;synergism;System;Techniques;theories;Therapeutic;therapeutic development;Time;tool;Training;Training and Education;Translational Research;Universities;Visualization;Visualization software;Washington;Work

PROJECT_TITLE: Quantitative Analysis Core


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD)

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Transcriptional regulation of gene expression plays a critical role in many cellular processes, but its fundamental mechanism is not fully understood. The main goal of the proposed research program is to develop statistical models and computational methods to predict functional transcriptional regulators from cross- platform multi-scale omics data and to study transcriptional factor binding activities in mammalian genomes. The anticipated outcome will provide useful tools to the biomedical research community and unique insights into understanding fundamental mechanisms of gene regulation in biological processes and human diseases.

PI_NAMEs: ZANG, CHONGZHI  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Big Data;Binding;Biological Process;Biomedical Research;Cell Physiology;cell type;Cells;Communities;Computer Models;computerized tools;Computing Methodologies;Data;Data Analyses;Disease;DNA;epigenomics;functional genomics;Gene Expression;Gene Expression Regulation;Genetic Transcription;Genome;genomic data;Genomics;Goals;human disease;improved;innovation;insight;mammalian genome;multimodality;novel;open source;Organism;Outcome;Performance;Play;Process;programs;Public Domains;recruit;Regulator Genes;Regulatory Element;Research;Role;Statistical Models;Structure;tool;transcription factor;Transcriptional Regulation;user-friendly

PROJECT_TITLE: Integrative computational models for functional epigenomics and transcriptional regulation


ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project Narrative Coordinated gene expression of the correct target genes is essential for all organisms and to prevent the formation of disease states from cancer to neurodegeneration. We will define the mechanisms by which pioneer transcription factors and long non-coding RNAs function together to coregulate genes across time and space in diverse cell types. By determining these new mechanisms for coordinated gene expression, we will inform efforts to correct misregulation of genes in disease contexts.

PI_NAMEs: LARSCHAN, ERICA NICOLE (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: 3-Dimensional;Binding;Biochemical;Biological Process;Cell Differentiation process;cell type;Cells;Chromatin;Chromatin Loop;Complex;Dimerization;Disease;Distant;DNA;Dosage Compensation (Genetics);Drosophila genus;Elements;Enhancers;gene correction;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genome;Goals;Link;male;Malignant Neoplasms;Mediating;Nerve Degeneration;Organism;prevent;Process;promoter;recruit;Regulation;Regulatory Element;Specificity;System;Time;transcription factor;Untranslated RNA;X Chromosome

PROJECT_TITLE: Coregulation of genes by pioneer transcription factors and noncoding RNAs


ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Project Narrative While it is clear that small molecules are central to orchestrating all cellular processes, we know relatively little about the functions of many metabolites. To address this gap in our knowledge, this proposal aims to explore protein-metabolite interaction networks to identify and functionally characterize regulatory metabolite-protein pairings. The results of this research will inform our understanding of how organisms exploit metabolites to regulate cellular functions; the long-term outcome of the proposed research will lead to innovation in the form of small molecule-based strategies aimed at improving plant and animal health /resilience.

PI_NAMEs: SKIRYCZ, ALEKSANDRA  (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;Animals;Arabidopsis;Biochemical;Biology;Caenorhabditis elegans;Carbon;Cell Physiology;Complex;Computing Methodologies;Data;Data Set;Dipeptides;Dissection;Environment;Enzyme Interaction;Enzymes;Escherichia coli;experimental study;Foundations;Fractionation;Goals;Gram-Negative Bacteria;Health;improved;innovation;interest;Knowledge;Lead;Ligands;Mass Spectrum Analysis;Metabolic;Metabolism;Metabolite Interaction;model organism;Mouse-ear Cress;Nematoda;novel;Organism;Outcome;Plants;Process;programs;protein complex;protein metabolite;Proteins;Regulation;Research;resilience;Role;Saccharomyces cerevisiae;Saccharomycetales;small molecule;Solid;Validation;Work;Yeasts

PROJECT_TITLE: Protein-metabolite interaction networks for functional characterization of metabolites.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-H (56)]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: NORMAN

ORG_NAME: UNIVERSITY OF OKLAHOMA

ORG_STATE: OK

PHR: Project Narrative This project aims to develop quantum-mechanics-based multiscale computational methods to quickly and accurately model enzymatic reactions and biomedical imaging probes. It will lead to reliable and efficient computational tools for use by the general scientific community. It will facilitate the study of enzymatic reaction mechanisms and the computer-aided design of new bioimaging probes.

PI_NAMEs: SHAO, YIHAN  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Active Learning;Address;Alkanes;BCAR1 gene;Biochemical Reaction;bioimaging;biomedical imaging;Catalysis;Chorismate Mutase;chromophore;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;Computer software;Computer-Aided Design;computerized tools;Computing Methodologies;design;DNA;electronic structure;Electronics;Environment;Enzymatic Biochemistry;Enzyme Tests;Enzymes;flexibility;Free Energy;Funding;Generations;Halogens;imaging probe;Learning;Machine Learning;Mechanics;method development;Methodology;Methods;Modeling;Modification;Molecular;Molecular Conformation;molecular dynamics;molecular mechanics;multi-scale modeling;Multiscale Mechanics;photoacoustic imaging;Physics;Protocols documentation;Quantum Mechanics;Reaction;Signal Transduction;simulation;Solvents;System;Technology;Time;tool;Training

PROJECT_TITLE: Multiscale Modeling of Enzymatic Reactions and Bioimaging Probes


ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: NARRATIVE Bacteria make a number of flagella inserted in a particular pattern according to their species. Here we propose to study how flagellar number is controlled in response to environmental stimuli and how flagella are positioned in space and time during cell growth. Our work contributes to the understanding of bacterial self-organization and the regulation of flagella and other virulence-associated nanomachines.

PI_NAMEs: KEARNS, DANIEL B (contact)

PROJECT_TITLE: Swarming motility and the regulation of flagellar biosynthesis in Bacillus subtilis


NIH_SPENDING_CATS: Congenital Structural Anomalies;Infant Mortality;Pediatric;Rare Diseases;Spina Bifida

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Narrative Neural tube defects (spina bifida and anencephaly, for example) constitute the second-most common class of birth defects, resulting in significant suffering and monetary costs: ~$1 billion total in hospitalization costs for all US patients annually. This proposal seeks to understand mechanisms of apical constriction, a change in cell shape that contributes to successful neural tube closure, using C. elegans as a model for efficient investigation of cellular and molecular mechanisms. The long-term goal of the work is to understand fundamental mechanisms that can lay a foundation for future diagnosis and prevention of neural tube defects.

PI_NAMEs: GOLDSTEIN, ROBERT P (contact)

PROJECT_TERMS: Actins;Address;Anencephaly and spina bifida X linked;Animals;Apical;Architecture;Basic Science;Biological;Biological Models;Caenorhabditis elegans;Cell Shape;Cells;Cellular biology;Complex;Congenital Abnormality;constriction;Development;Developmental Biology;Diagnosis;Event;Financial cost;Foundations;Future;gastrulation;Goals;Hospital Costs;improved;in vivo;innovation;insight;Investigation;Laboratories;Modeling;Molecular;Morphogenesis;Motor Activity;motor control;Neural tube;Neural Tube Closure;Neural Tube Defects;novel;Patients;Pattern;polarized cell;Prevention;Research;Shapes;tool;transmission process;Vertebrates;Work

PROJECT_TITLE: C. elegans Gastrulation: a Model for Understanding Apical Constriction Mechanisms


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Chronic Pain;Genetics;Neurodegenerative;Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Substance Misuse

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative: The epidemic of chronic pain and opioid overdose in the US demands the identification of new and effective alternative therapies. This high-risk, high-reward application will elucidate the unknown function of an understudied potassium channel regulatory protein, LRRC55, in pain, and explore if targeting LRRC55 can be a novel pain management strategy.

PI_NAMEs: CHEN, YONG ;YANG, HUANGHE  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Adverse effects;Affect;Alternative Therapies;Analgesics;Animals;behavior test;Behavioral Assay;Biology;Calcium-Activated Potassium Channel;cell type;Cells;chronic constriction injury;chronic pain;chronic pain management;clinical application;combat;Complex;constriction;Darkness;Data;Drug or chemical Tissue Distribution;Drug Targeting;druggable target;effective therapy;Electrophysiology (science);Epidemic;Epilepsy;Exhibits;experimental study;Foundations;Freund's Adjuvant;Functional disorder;Future;Genes;genetic regulatory protein;high reward;high risk;Hyperalgesia;improved;In Situ Hybridization;Inflammatory;inflammatory pain;inhibitor;Injury;Intrathecal Injections;Ion Channel;knock-down;Knock-out;Knowledge;large-conductance calcium-activated potassium channels;Leucine-Rich Repeat;leucine-rich repeat protein;Link;mechanical allodynia;Mechanics;Mediating;Methods;Movement Disorders;multicatalytic endopeptidase complex;Mus;nerve injury;Nervous System;Nervous System Disorder;Nervous System Physiology;Neurons;new therapeutic target;non-opioid analgesic;novel;Opioid;Opioid Analgesics;opioid epidemic;opioid misuse;opioid overdose;Organ;Overdose;Pain;pain behavior;Pain management;pain model;pain perception;pain sensation;pain signal;painful neuropathy;pandemic disease;Pathologic;Pathway interactions;Phenotype;Pilot Projects;Potassium Channel;prevent;Proteins;Public Health;Quantitative Reverse Transcriptase PCR;Research;Research Personnel;Role;sciatic nerve injury;sex;side effect;Site;Small Interfering RNA;Solid;Specificity;Spinal Cord;Spinal Ganglia;success;Surveys;Testing;Therapeutic;therapeutic target;Transcript;Translating;Translational Research;transmission process;Up-Regulation

PROJECT_TITLE: Exploring the unknown function of LRRC55 in pain

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 DPI-7 (03)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

PHR: NARRATIVE Long noncoding RNAs (lncRNAs) play critical roles in health and homeostasis by regulating gene expression, but their mechanisms of action are poorly defined. Our research will determine how lncRNAs and proteins interact to achieve specific gene regulatory outcomes and will develop new ways to predict the presence of regulatory function in lncRNAs. We expect our work to reveal new and conserved mechanisms of gene regulation as well as disease etiologies and therapeutic opportunities in many settings.

PI_NAMEs: CALABRESE, JOSEPH MAURO (contact)

PROJECT_TERMS: Angelman Syndrome;Autoimmunity;biological systems;Biology;cell type;Data;Disease;epigenetic regulation;Etiology;Gene Expression;Gene Expression Regulation;gene repression;Gene Silencing;Genes;Genetic Diseases;Genetic Transcription;Genome;Health;Homeostasis;Human;insight;Introns;Link;Malignant Neoplasms;mammalian genome;Mediating;Organism;Outcome;Phenotype;Play;Process;programs;Proteins;Repression;Research;Rett Syndrome;RNA;RNA analysis;RNA Processing;RNA Sequences;RNA Splicing;RNA-Binding Proteins;RNA-Protein Interaction;Role;Structure;Therapeutic;Time;Transcriptional Regulation;transcriptome;Untranslated RNA;Variant;Work;X Chromosome;X Inactivation

PROJECT_TITLE: Mechanisms of gene regulation by long noncoding RNAs


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Embryonic - Non-Human

PHR: PROJECT NARRATIVE Enhancers are short non-coding DNA sequences that act to drive transcription of their target genes, often at long genomic distances and in a highly tissue-specific manner. The goal of the proposed research is to understand fundamental principles of long-range gene regulation by enhancers. This knowledge is important to identify new types of therapeutic strategies for human disease and for realizing the promise of precision medicine.

PI_NAMEs: WYSOCKA, JOANNA  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TITLE: Uncovering fundamentals of gene regulation by enhancers


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Genetics;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases;Spinal Muscular Atrophy

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: PROJECT NARRATIVE RNA binding proteins control the processing of RNA, often in a cell-specific or tissue-specific manner, as evidenced by the disease Spinal Muscular Atrophy wherein mutation of a ubiquitously-expressed RNA binding protein (SMN-1) causes cell-specific defects in motor neurons. We aim to use the genetic and molecular strengths of the nematode C. elegans to dissect the reasons why broadly-expressed RNA binding proteins have tissue-specific effects, and moreover to investigate new and emerging types of RNA regulation controlled at the tissue-specific level.

PI_NAMEs: NORRIS, ADAM  (contact)

PROJECT_TERMS: Alternative Splicing;Amino Acids;Caenorhabditis elegans;Cells;circular RNA;Code;Defect;Disease;Exons;experimental study;frontotemporal lobar dementia amyotrophic lateral sclerosis;functional outcomes;Genetic;Genetic Transcription;human disease;Individual;interest;Length;Messenger RNA;Modality;Modeling;Molecular;motor neuron degeneration;Motor Neurons;Mutation;Nematoda;novel;Nucleotides;Outcome;Phenotype;Physiological;Process;Regulation;RNA;RNA Degradation;RNA Processing;RNA Splicing;RNA Stability;RNA-Binding Proteins;Role;SMN1 gene;Spinal Diseases;Spinal Muscular Atrophy;Tissues;transcription factor

PROJECT_TITLE: Dissecting RNA regulation in single cells and tissues


ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: Narrative Protein post-translational modifications mediate myriad of cellular events, and unregulated protein modifications are widely associated with disease states. The program aims to develop chemical approaches to characterizing the enzymes governing three protein modifications, acetylation, methylation, and phosphorylation, which will lead to a greater understanding of disease formation and development of new treatments.

PI_NAMEs: PFLUM, MARY KAY H (contact)

PROGRAM_OFFICER_NAME: HARTON, MARIE DEBORAHGAYNELLE

PROJECT_TERMS: Acetylation;Address;analog;Biological;Biomedical Research;Cells;Cellular biology;Chemicals;Collaborations;Complex;Development;Disease;Drug Design;drug development;Enzymes;Epigenetic Process;epigenetic regulation;Event;Funding;Genetic Transcription;HDAC1 gene;HDAC6 gene;Histone Deacetylase;Histones;innovation;Label;Link;Malignant Neoplasms;Mediating;Methods;Methylation;Molecular;Multiprotein Complexes;mutant;National Institute of General Medical Sciences;Pharmacotherapy;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Play;Post-Translational Protein Processing;programs;Protein Acetylation;protein function;Protein Isoforms;Protein Methylation;Proteins;Reaction;Role;System;targeted treatment;tool;Transcriptional Regulation;Work

PROJECT_TITLE: Chemical Approaches to Study Protein Post-translational Modifications


NIH_SPENDING_CATS: Bioengineering;Genetics;Networking and Information Technology R&D (NITRD)

ORG_CITY: COLLEGE STATION

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: TEXAS ENGINEERING EXPERIMENT STATION

ORG_STATE: TX

PHR: Project Narrative The formation of biomolecular condensates is emerging as a unifying mechanism underlying the formation of many membraneless organelles that perform essential biological functions, such as transcription, genome organization, stress response, and DNA repair. Aberrant phase separation has also been linked to diseases such as a number of sarcomas and neurodegenerative diseases, e.g. ALS, Alzheimers, and FTD. Thus, generating a molecular framework of phase-separated assemblies is vital to a mechanistic understanding of their function and dysfunction.

PI_NAMEs: MITTAL, JEETAIN  (contact)

PROJECT_TERMS: Alzheimer's Disease;Amino Acid Sequence;Belief;Biological;biological adaptation to stress;Biological Process;Biology;cancer drug resistance;Cell Physiology;Chromatin;Collaborations;Computer Models;Computing Methodologies;Disease;DNA Damage;DNA Repair;Family;Functional disorder;Fusion Oncogene Proteins;Future;Gene Expression;Genetic Transcription;Genome;Heterochromatin;heterochromatin-specific nonhistone chromosomal protein HP-1;in silico;in vivo;innovation;interest;Knowledge;Link;Membrane;Methods;Microscopy;Modeling;Molecular;multi-scale modeling;Names;Neurodegenerative Disorders;Organelles;Pathologic;Phase;Physical condensation;Polyhomeotic;predictive modeling;Process;Proteins;reconstitution;Regulation;Rheology;RNA-Binding Proteins;Role;Sarcoma;Satellite RNA;Site;System;Techniques;Translating;Work

PROJECT_TITLE: Multiscale Computational Models to Investigate the Role of Phase Separation in Biology


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative The new imaging methods that will result from the proposed research are relevant to public health because they provide fundamental information that enables the efficient and sustainable preparation of compounds for drug discovery. The fundamental insight from these studies is relevant to NIGMS’s mission because the increased accessibility of these pharmaceutical candidates lays the foundation for advances in disease treatment.

PI_NAMEs: BLUM, SUZANNE A. (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: analytical tool;aqueous;Area;Behavior;Carbon;Catalysis;catalyst;Chemicals;Chemistry;cold temperature;Coupling;Data;Development;Disease;drug discovery;drug synthesis;drug-like compound;Emulsions;experimental study;Fluorescence;fluorescence lifetime imaging;Fluorescence Microscopy;Foundations;human disease;Image;imaging agent;Imaging Device;imaging modality;innovation;insight;Laboratories;Lead;Ligands;Mass Spectrum Analysis;Measures;Metals;method development;Methods;microscopic imaging;Mission;Modeling;Modernization;multidisciplinary;National Institute of General Medical Sciences;next generation;NMR Spectroscopy;novel therapeutics;Organic Chemistry;Organic Synthesis;Pharmacologic Substance;Powder dose form;Preparation;Process;Production;Public Health;Publications;Reaction;Reagent;Recycling;Research;Route;success;Surface;surfactant;System;Techniques;Therapeutic;Therapeutic Agents;Transition Elements;Water

PROJECT_TITLE: Understanding Mechanisms of Organic Reactions and Processes through Imaging


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: The outcomes of this research will contribute to advancing our understanding of many human diseases that are associated with impaired autophagy and the cellular response to energy stress. These diseases include cancer, diabetes, neurodegeneration, and age-related pathologies.

PI_NAMEs: KIM, DO-HYUNG  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Address;Age related pathologies;Amino Acids;Apoptosis;Area;Autophagocytosis;Cell Energetics;cell growth;Cell Survival;Cells;coping;Diabetes Mellitus;Disease;Endoplasmic Reticulum;Energy Supply;FRAP1 gene;Growth;human disease;Impairment;improved;insight;Knowledge;Learning;Location;Malignant Neoplasms;Mammalian Cell;Metabolism;Mitochondria;mitochondrial autophagy;mitochondrial dysfunction;Nerve Degeneration;Nutrient;Outcome Study;Outcomes Research;Pathway interactions;Phosphotransferases;Play;Post-Translational Protein Processing;Protein Biosynthesis;Protein Kinase;Regulation;Research;response;restraint;Role;sensor;Signal Transduction;single molecule;Stress

PROJECT_TITLE: Mechanisms of autophagy and mTOR signaling


NIH_SPENDING_CATS: Natural Products

PHR: Project Narrative Organic molecules containing oxygen and nitrogen are ubiquitous in biomedical research and in the treatment of a range of human ailments including mental health conditions, conditions associated with inflammation, cancer and diabetes as well as cardiovascular, infectious and neurodegenerative diseases. This project is centered on the development of efficient, catalytic and selective methods for carbon–oxygen, carbon–nitrogen and carbon– carbon bond formation, useful in the efficient construction and structural optimization of bioactive organic molecules. This project includes applications of the developed chemical methods to the synthesis of select natural products, drugs, and derivatives thereof to enable their structural assignments, mechanism of action and metabolism studies.

PI_NAMEs: CHEMLER, SHERRY R (contact)

PROJECT_TERMS: Aerobic;Alkenes;Amines;analog;bioactive natural products;Biochemical;Biological;Biology;Biomedical Research;Carbon;Cardiovascular Diseases;Chemicals;Chemistry;Communicable Diseases;Complex;Copper;Development;Diabetes Mellitus;Disease;drug discovery;drug synthesis;enantiomer;Engineering;Ethers;Human;Inflammation;insight;invention;Malignant Neoplasms;Maps;Mental Health;metabolic abnormality assessment;Methods;Natural Products;Natural Selections;Neurodegenerative Disorders;Nitrogen;Oxygen;Pharmaceutical Preparations;Pharmacologic Substance;pi bond;Process;Production;Reaction;Research;Resources;Route;Sampling;small molecule;Structure;Technology;Therapeutic Agents;Time;wasting

PROJECT_TITLE: New Methods for Nitrogen and Oxygen Heterocycle Synthesis


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Biotechnology;Natural Products

ORG_CITY: BERKELEY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Public Health Relevance Statement: The proposed research is relevant to public health because it studies the biosynthetic mechanisms of unique functionalities in natural products that serve as biological warheads and are also useful for numerous chemical biology applications. A detailed mechanistic understanding is thus of both biomedical and biotechnological importance to target or adapt these biosynthetic pathways in a wide endeavor to promote human health.

PI_NAMEs: ZHANG, WENJUN  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Alkenes;Alkynes;Anabolism;Area;Biochemical;Bioinformatics;Bioinorganic Chemistry;Biological;Biology;Biophysics;Biotechnology;Chemicals;Chemistry;computational chemistry;Engineering;Enzymatic Biochemistry;enzyme mechanism;Enzymes;functional group;Genetic;Goals;Health;Human;human disease;Image;insight;interdisciplinary approach;Logic;Microbiology;Molecular;Natural Products;Nature;novel;Organic Synthesis;Parents;Pathway interactions;pharmacophore;physical property;programs;Property;Protein Engineering;Public Health;public health relevance;reconstitution;Research;small molecule;structural biology;Structure;System;uptake;Visualization

PROJECT_TITLE: Biosynthesis of Unusual Bio-Orthogonal Functionalities in Natural Products


NIH_SPENDING_CATS: Genetics;Prevention

ORG_CITY: ANN ARBOR

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project narrative There are tens of millions of human genetic variants in protein coding genes, most of which are so rare in the population that for any given variant, little to nothing can be said about its impact upon gene function and disease risk. We develop methods to experimentally test many thousands of variants, but to date this approach is generally limited to genes affecting cell growth in culture, which is poor proxy for the mechanism by which many genetic disorders act. Here we develop and apply models to make entire classes of human disease genes newly accessible to these methods, improving our understanding of how those genes function, and proactively mapping which of their variants can cause disease.

PI_NAMEs: KITZMAN, JACOB OTTO (contact)

PROJECT_TERMS: Address;Affect;Alleles;biobank;Calibration;cancer risk;Case Study;Catalogs;cell growth;Clinical;clinically actionable;Code;Data;Disease;disorder risk;DNA;DNA Damage;Equity;gene function;gene repair;Genes;Genetic Diseases;genetic testing;genetic variant;Genetic Variation;genomic data;Genotype;health record;Human;human disease;Human Genetics;Immunologic Deficiency Syndromes;improved;Individual;Inherited;Knowledge;Link;Malignant Neoplasms;Maps;Medical Genetics;Methods;Mismatch Repair;Modeling;Neurodevelopmental Disorder;Noise;Pathogenicity;Pathway interactions;Penetrance;Population;Proteins;Proxy;response;Structure;Sum;Syndrome;Testing;trait;Variant

PROJECT_TITLE: Expanding the Reach of Massively Parallel Variant Effect Screens


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

PHR: The export of mRNA from the nucleus to the cytoplasm is an essential step of gene expression in eukaryotic cells and thus fundamental for all cellular functions. This mRNA export process is often targeted by viruses to suppress host gene expression and facilitate viral replication. The proposed work will provide significant insights into the mechanisms and regulation of mRNA export in health and during viral infections.

PI_NAMEs: REN, YI  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: 2019-nCoV;Architecture;ATP phosphohydrolase;Biochemical;Cell Nucleus;Cell Physiology;Complex;Cytoplasm;Disease;Eukaryotic Cell;Foundations;Gene Expression;Genetic Transcription;Grant;Health;Influenza A virus;insight;Knowledge;Link;Malignant Neoplasms;messenger ribonucleoprotein;Messenger RNA;Molecular;mRNA Export;Nervous System Disorder;novel therapeutics;Nuclear;Nuclear Accidents;Nuclear Export;particle;Pathologic;Pathway interactions;Physiological;Process;Proteins;receptor;Regulation;Research;Solid;spatiotemporal;Testing;Transcript;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Mechanisms and Regulation of Nuclear mRNA Export


NIH_SPENDING_CATS: Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative An adult human being has approximately 100,000 billion cells comprised of more than 200 cell types, which all originate from a single cell—a fertilized egg. Therefore, a fundamental question to understanding any complex living organism is how cells become different while faithfully maintaining the same genetic material. In this application we plan to systematically study how epigenetic information is established and partitioned into daughter cells in development, homeostasis and regeneration, which will have broad impaction on stem cell biology, developmental biology, chromatin biology, and regenerative medicine.

PI_NAMEs: CHEN, XIN  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Adult;Biological Process;Biology;cell behavior;Cell Differentiation process;Cell division;cell type;Cells;Chromatin;Communities;Complex;daughter cell;Degenerative Disorder;Development;Developmental Biology;Diabetes Mellitus;Disease;DNA Sequence;Drosophila genus;epigenetic memory;Epigenetic Process;epigenetic regulation;Failure;Gene Expression;gene function;Genetic Materials;genomic locus;Germ Lines;germline stem cells;Histones;Homeostasis;in vivo;Infertility;Inherited;insight;Intestines;male;Malignant Neoplasms;Meiosis;Methods;Mitosis;Muscular Dystrophies;Natural regeneration;neuroblast;Neurodegenerative Disorders;Organism;Play;Regenerative Medicine;Role;segregation;self-renewal;Series;stem cell biology;stem cells;System;Therapeutic;tool;zygote

PROJECT_TITLE: Study epigenetic inheritance during development, homeostasis and regeneration


ED_INST_TYPE: OVERALL MEDICAL

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE We propose to investigate the mechanisms by which methylarginine marks function as docking sites for effector proteins by identifying new effectors and characterizing known effectors in-depth, to better understand the signal transduction pathways that are regulated by arginine methylation.

PI_NAMEs: BEDFORD, MARK T. (contact)

PROJECT_TERMS: Address;Arginine;Aromatic Amino Acids;Biological;Deposition;DNA Damage;Docking;Goals;Knowledge;Lysine;Mammals;Methylation;Mus;novel;Phosphotransferases;Post-Translational Protein Processing;Protein Array;Protein-Arginine N-Methyltransferase;Proteins;Proteomics;Reader;recruit;response;Role;Series;Signal Transduction;Signal Transduction Pathway;Site;Work

PROJECT_TITLE: A Functional Analysis of Arginine Methylation


ORG_CITY: BOSTON

ORG_DEPT: PHYSICS

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative This line of study will use novel all-atom models to perform simulations of ribosomes from various organisms. One goal is to determine which interactions govern the dynamics, which can provide insights into ribosome- related diseases. In addition, by comparing bacterial and human ribosome dynamics, we aim to identify novel strategies for antibiotic design.

PI_NAMEs: WHITFORD, PAUL CHARLES (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: antibiotic design;Antibiotic Resistance;Antibiotics;Bacteria;Bacterial Infections;Biochemical;candidate identification;Cells;Collaborations;combat;Cryoelectron Microscopy;design;Development;Disease;experimental group;experimental study;Face;Functional disorder;Goals;Human;human disease;insight;Investigation;Kinetics;Laboratories;laboratory experiment;Life;Methods;Mitochondria;Modeling;Molecular;Molecular Conformation;Motion;next generation;novel;novel strategies;Nuclear Magnetic Resonance;Organism;Protein Biosynthesis;Proteins;Ribosomes;Role;side effect;simulation;single molecule;small molecule;structural biology;targeted treatment;Techniques;Therapeutic;therapeutically effective;Time;Translations;Work

PROJECT_TITLE: Elucidating the mechanisms that enable translation in bacterial and eukaryotic ribosomes


NIH_SPENDING_CATS: Bioengineering;Networking and Information Technology R&D (NITRD)

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE In order to carry out processes essential for life, molecular complexes are in constant motion in the cell. Although our understanding of the structural dynamics and heterogeneity of molecules has increased dramatically in recent years, researchers currently lack tools to readily create dynamic molecular models. Taking advantage of our decades of experience creating visualizations and developing software, we propose to launch a free and open-source suite of tools that will enable molecular biologists to create, share, and annotate animated three-dimensional models of molecules.

PI_NAMEs: IWASA, JANET  (contact)

PROJECT_TERMS: 3-Dimensional;Adopted;animation;Archives;Case Series;Case Study;Cells;Communities;Complex;Computational Biology;Computer software;experience;Goals;Heterogeneity;insight;Life;Methods;Modality;Modeling;Molecular;Molecular Conformation;molecular dynamics;molecular modeling;Motion;open source;open source tool;Process;Publishing;Research;Research Personnel;Series;single molecule;software development;structural biology;success;System;Techniques;Testing;three-dimensional modeling;tool;Training;Visualization;Visualization software

PROJECT_TITLE: New Tools for Visualizing Dynamic Molecular Complexes


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease

ORG_CITY: PORTLAND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative: Voltage gated K+ channels (Kv) play important roles in human physiology and mutations in Kv channels can cause diseases such as epilepsies and cardiac arrhythmias. In this proposal, we use a multidisciplinary approach that combines unnatural amino acid mutagenesis with structural and functional studies to investigate the mechanisms of voltage gating and C-type inactivation that regulate the flux of K+ through Kv channels. Understanding the mechanisms of voltage gating and C-type inactivation is essential for the development of therapeutics that target Kv channels.

PI_NAMEs: VALIYAVEETIL, FRANCIS  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Arrhythmia;Binding;Binding Sites;Cardiac;Cells;Cellular Membrane;Cyclic Nucleotides;Disease;Endocrine;Epilepsy;Generations;Grant;Human;insight;interdisciplinary approach;Investigation;Ion Channel;Ions;Methods;Modification;Molecular Conformation;Muscle;Mutagenesis;Mutation;neurotransmission;Physiological;Physiology;Play;Post-Translational Protein Processing;Process;programs;Proteins;Research;Role;Side;Structure;therapeutic development;therapeutic target;unnatural amino acids;Vertebral column;voltage;Voltage-Gated Potassium Channel

PROJECT_TITLE: Structure-function studies on Ion channels


NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Epigenetic processes provide a layer of regulation that is above the genetic sequence and are essential to understand health and disease. In model organisms, such as yeast and flies, noncoding RNAs play important role in regulating the flow of epigenetic information, but their contribution to these processes in mammals remains poorly understood at a mechanistic level. We will leverage our expertise in RNA biochemistry, functional genomics, and mass spectrometry to identify and characterize RNAs that shape transitions in epigenetic states that accompany the differentiation from embryonic stem cells to neurons.

PI_NAMEs: BONASIO, ROBERTO  (contact)

PROJECT_TERMS: Acute;Ants;Binding Sites;Biochemical;Biochemistry;Biological Models;Biotechnology;Cell Differentiation process;Cells;Chemicals;Chromatin;design;directed differentiation;Disease;embryonic stem cell;Engineering;epigenetic memory;Epigenetic Process;Event;extracellular vesicles;fly;follow-up;Foundations;functional genomics;gene repression;Genetic;genome-wide;Goals;Health;Knock-out;Laboratory Study;Mammalian Cell;Mammals;Maps;Mass Spectrum Analysis;Mediating;Medicine;Methods;model organism;Modification;Molecular;Mouse Embryonic Stem Cells;mutant;mutation screening;Neurons;Pathway interactions;Play;Polycomb;Process;protein complex;Proteins;Proteome;recruit;Regulation;Research;RNA;RNA Binding;RNA Biochemistry;RNA-Protein Interaction;Role;Shapes;System;Technology;Untranslated RNA;Work;Yeasts

PROJECT_TITLE: Revealing the RNA foundations of chromatin-based epigenetics


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative The goal of the proposed research is to create new directions for catalytic regioselective dicarbofunctionalization of unactivated alkenes. We will develop these processes through photoredox and transition metal catalysis by intercepting carbon-centered radical and alkylmetal intermediates, formed upon the addition of alkyl sources to alkenes, with different organo-reagents. This research program will invent new methods for rapidly constructing complex molecular motifs present in pharmaceuticals, bioactive molecules and drug targets, and will make significant impacts on the biomedical mission of the NIH.

PI_NAMEs: GIRI, RAMESH  (contact)

PROJECT_TITLE: New Directions in Alkene Difunctionalization Reactions


PHR: Project Narrative Almost all the cells in the human body have clocks and disruption of clocks have been linked to many human diseases including diabetes, obesity, and neurodegenerative diseases. By employing novel cell biological approaches our goal is to reveal spatiotemporal mechanisms controlling circadian rhythms. This work will lead to a deeper understanding of how clocks are regulated at the subcellular level in vivo and impact our ability to treat diseases resulting from circadian dysfunction.

PI_NAMEs: YADLAPALLI, SWATHI  (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Architecture;Behavior;Biochemical;Biological;Biological Assay;Biological Models;Cell Nucleus;Cells;circadian;Circadian Dysregulation;circadian pacemaker;circadian regulation;Circadian Rhythms;Clock protein;Complex;Cytoplasm;Development;Diabetes Mellitus;Disease;Drosophila genus;Engineering;Event;functional genomics;Gene Expression;Gene Expression Regulation;Gene Structure;Genes;Genetic;Genetic Screening;Genetic Transcription;Genome;Goals;Hour;Human body;human disease;Human Pathology;Image;Immunity;in vivo;insight;Label;Laboratories;Learning;Link;Malignant Neoplasms;Memory;Messenger RNA;Metabolism;Methods;Molecular;Neurodegenerative Disorders;Neurons;novel;novel therapeutic intervention;Nuclear;Obesity;Organism;Phase;Physical condensation;Physiology;Post-Transcriptional Regulation;Proteins;Proteomics;Repression;Research;Resolution;Role;Sleep Wake Cycle;spatiotemporal;Time;tool;Work

PROJECT_TITLE: Spatiotemporal mechanisms controlling circadian rhythms


PHR: PROJECT NARRATIVE Biology and Biochemistry of the Microtubule Cytoskeleton The microtubule cytoskeleton is essential for a wide range of biological processes in all eukaryotic cells. The functions of microtubules are facilitated by microtubule-associated proteins (MAPs) and molecular motors that organize microtubules in three-dimensional space or use them as tracks for intracellular trafficking, and are extended by a constellation of tubulin post-translational modifications that act to regulate MAP/motor protein-MT interactions. We work to establish how the cellular system of MAPs, motor proteins, and tubulin PTMs organize MTs to drive essential cellular processes such as mitosis.

PI_NAMEs: OHI, RYOMA  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: 3-Dimensional;Address;Affinity;Binding;Binding Proteins;Biochemical;Biochemistry;Biological;Biological Process;Biology;Cell Physiology;Cellular biology;Cytoplasm;Cytoskeleton;Dynein ATPase;Eukaryotic Cell;Higher Order Chromatin Structure;In Vitro;inhibitor;insight;Kinesin;Kinetochores;Knowledge;Microtubule-Associated Proteins;Microtubules;Mitosis;Mitotic spindle;Molecular Motors;Motor;Neurons;Output;Pathway interactions;Play;Polymers;Post-Translational Protein Processing;Process;Property;Proteins;reconstitution;Research;Research Proposals;screening;Stress;Subcellular structure;System;trafficking;Tubulin;Work;Writing


ORG_CITY: CHESTNUT HILL

ORG_NAME: BOSTON COLLEGE

PHR: Project Narrative Catalytic reactions provide access to otherwise inaccessible compounds, and do so with minimal energy expenditure and waste generation. We will develop new strategies, catalysts, and methods for efficient and cost-effective preparation of otherwise difficult-to- access bioactive molecules that are likely to be critical to drug development.

PI_NAMEs: HOVEYDA, AMIR H (contact)

PROJECT_TERMS: 3-Dimensional;Alkenes;analog;Area;bioactive natural products;Biological;catalyst;chemical synthesis;Complex;Contracts;cost effective;cyclic compound;design;Development;Disease;drug development;Energy Metabolism;experience;functional group;Funding;Generations;innovation;Investigation;Isomerism;Methods;novel therapeutics;Periodicity;Pharmaceutical Preparations;Polycyclic Compounds;Preparation;Process;programs;Reaction;response;Shapes;Structure;United States National Institutes of Health;wasting

PROJECT_TITLE: New Catalysts, Strategies and Methods for Stereoselective Chemical Synthesis


NIH_SPENDING_CATS: Neurosciences

PHR: Project Narrative: Cytokinesis and the septin cytoskeleton play essential roles in cell proliferation and differentiation and are required for the survival of all organisms. Defects in cytokinesis or septins cause lethality or serious diseases including cancer, infertility, and neurodegenerative diseases. Thus, mechanistic study of cytokinesis and the septin cytoskeleton is important not only for understanding basic biology but also for developing new strategies to treat human diseases.

PI_NAMEs: BI, ERFEI  (contact)

PROJECT_TERMS: Actomyosin;Address;Alzheimer's Disease;Architecture;Bacterial Infections;Basic Science;Biochemical;Biology;cell behavior;Cell Cycle;Cell Differentiation process;cell motility;Cell Physiology;Cell Proliferation;Cells;cilium biogenesis;constriction;Cytokinesis;Cytoskeleton;Data;Defect;Dendritic Spines;Diffusion;Disease;Event;Evolution;Fission Yeast;Genetic;hereditary neuropathy;Higher Order Chromatin Structure;human disease;Imaging technology;Infertility;insight;Life;Malignant Neoplasms;Mammalian Cell;Molecular;Morphogenesis;Myosin Type II;Neurodegenerative Disorders;Organism;Parkinson Disease;Platinum;Play;Protein Isoforms;Public Health;Publishing;Role;Saccharomycetales;scaffold;Site;Spermiogenesis;Stereotyped Behavior;superresolution microscopy;Testing;Vesicle;Yeast Model System

PROJECT_TITLE: Cytokinesis and the Septin Cytoskeleton

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-S (55)]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: This proposal is concerned with conserved signaling systems that convey information between cells, tissues, and organs during animal development. This work on the simple model system C. elegans will provide fundamental knowledge that is relevant to human biology and health, because aberrations in the same conserved signaling systems that regulate development in this model and indeed, in all animals, can cause congenital developmental disorders and cancer in people. Understanding these processes and the genes and genetic interactions that mediate them is critical for precision medicine and the development of diagnostic and therapeutic tools for human disease.

PI_NAMEs: GREENWALD, IVA S (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Animals;Area;Biological Models;Biosensor;Caenorhabditis elegans;Cancer Etiology;Cell Communication;Cell Fate Control;Cells;clinically relevant;Communication;Congenital Abnormality;CRISPR/Cas technology;Development;developmental disease;diagnostic development;Disease;Ensure;Event;Feedback;Funding;Genes;Genetic;genetic analysis;Genome engineering;Goals;Health;Human;Human Biology;Human Development;human disease;Image;insight;Integral Membrane Protein;Investigation;Knowledge;Lateral;Ligands;Logic;Malignant Neoplasms;Mediating;Methods;model organism;Modeling;notch protein;novel strategies;Organ;Outcome;Pathway interactions;Persons;Physiological;Population;precision medicine;precursor cell;Process;protein function;receptor;Regulation;reproductive development;Resolution;Signal Pathway;Signal Transduction;Specific qualifier value;System;Systems Development;Therapeutic;Time;Tissues;tool;transcriptomic profiling;Uterus;Visualization;Work

PROJECT_TITLE: Regulatory Circuitry and Mechanisms Controlling Cell Fate in C. elegans


ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative G protein-coupled receptors are important drug targets that can exhibit preference for signal transduction pathways, a phenomenon known as biased signaling. To design pathway-selective drugs, mechanistic understanding at the molecular level is required to identify structural motifs that govern biased signaling. Using chemical and structural biology approaches, this project focuses on uncovering these structural motifs by employing structure-based mutagenesis, biased ligands, and in vitro assay platforms to identify common mechanisms of ligand bias at key receptor targets. 1

PI_NAMEs: MCCORVY, JOHN D (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Agonist;beta-arrestin;Binding;Biology;Cell Communication;Cells;Chemicals;design;Dissociation;Drug Targeting;Exhibits;G-Protein-Coupled Receptors;Generations;GTP-Binding Proteins;high throughput screening;in vitro Assay;Integral Membrane Protein;Kinetics;Laboratories;Ligands;Measures;Molecular;Movement;Mutagenesis;Pathway interactions;Pharmaceutical Preparations;preference;Process;Production;receptor;recruit;Research Personnel;Second Messenger Systems;side effect;Signal Pathway;Signal Transduction;Signal Transduction Pathway;structural biology;Structure;Structure-Activity Relationship;targeted treatment;Therapeutic

PROJECT_TITLE: Molecular Mechanisms of G protein-coupled Receptor Biased Signaling


NIH_SPENDING_CATS: Complementary and Integrative Health;Natural Products

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Natural products offer unmatched chemical and structural diversity compared to any other small molecule families and remain the best sources of drugs and drug leads, but most gene clusters encoding natural product biosynthesis are silent when the microorganisms are cultured under standard laboratory conditions. This proposal aims to discover new natural products by mining actinobacterial genomes, develop enabling technologies to produce them in enough quantities for structural elucidation and biological evaluation, and study their biosynthetic machineries to inspire new chemistry, biology, and medicine. The long-term goal of our research program is to understand at a molecular level how microorganisms synthesize complex natural products and to exploit this knowledge to discover novel natural products and engineer their analogues for drug discovery.

PI_NAMEs: SHEN, BEN  (contact)

PROJECT_TITLE: Mining Actinobacterial Genomes for Natural Product Discovery and Biosynthesis


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_DEPT: VETERINARY SCIENCES

PHR: Project Narrative Abnormalities in meiosis are leading causes of infertility, pregnancy loss, and birth defects (trisomy and monosomy) in humans. A number of key meiosis factors will be investigated in this project. Completion of this project will provide important insights into the etiology of infertility, birth defects, and sex chromosome anomalies.

PI_NAMEs: WANG, PEIJING JEREMY (contact)

PROJECT_TERMS: Biochemical;Biological;Cells;Chromosome abnormality;Chromosome Pairing;Chromosomes;Congenital Abnormality;Coupled;Defect;DNA Double Strand Break;Etiology;Eukaryota;Evolution;F Factor;Genetic;Genetic Recombination;Genetic Variation;Genome;genome integrity;Genomics;Germ Cells;Haploidy;Human;Infertility;innovation;insight;Knowledge;Maintenance;Meiosis;Meiotic Recombination;Molecular;Monosomy;novel;Organism;Play;Ploidies;Population;Pregnancy loss;prevent;Process;Proteins;Proteomics;Regulation;Role;segregation;sex;sex chromosome aneuploidy;Sex Chromosomes;Trisomy

PROJECT_TITLE: Molecular Mechanism and Regulation of Meiosis


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative More than 30% of approved pharmaceutical drugs on the market targets G protein coupled receptors that regulates various cellular and physiological functions. Understanding mechanisms controlling receptor function under normal and pathological conditions will help to further develop or improve therapies for various diseases that receptors' functions are dysregulated.

PI_NAMEs: IRANNEJAD, ROSHANAK  (contact)

PROJECT_TERMS: Architecture;Biogenic Amines;Cell membrane;Cell surface;Cells;Clinical;Cues;Disease;Drug usage;Endosomes;Environment;Event;Functional disorder;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Goals;Golgi Apparatus;GTP-Binding Proteins;Hormones;improved;Investigation;Knowledge;Ligands;Lipids;Location;Marketing;Mediating;Membrane;Molecular;novel;Organelles;Outcome;Pathologic;Peptide Initiation Factors;Peptides;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacology;Physiological;Physiology;programs;Proteins;receptor;Receptor Activation;receptor function;receptor internalization;Receptor Signaling;recruit;Research;response;Signal Transduction;Site;Therapeutic;tool;Visualization;Work

PROJECT_TITLE: Investigation of a Newly Discovered Organelle-Based Signaling Paradigm


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_NAME: WISTAR INSTITUTE

PHR: PROJECT NARRATIVE Most mammalian genes express alternative cleavage and polyadenylation (APA) isoforms with different coding sequences (CDS) and/or 3’ untranslated regions (3’UTRs). Our research goal is to elucidate molecular mechanisms of APA regulation and cellular consequences of APA isoform expression under various physiological and pathological conditions.

PI_NAMEs: TIAN, BIN  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Untranslated Regions;Address;Affect;Autophagocytosis;Cell Differentiation process;Cell Proliferation;cell type;Cells;Cellular Stress;Code;Computational Biology;functional genomics;Gene Expression;Gene Expression Regulation;Genes;Goals;Growth;interdisciplinary approach;Messenger RNA;Metabolic;Metabolism;Molecular;Molecular Biology;Pathologic;Physiological;Polyadenylation;Protein Isoforms;Proteins;Regulation;Research;Role;Secretory Cell;Site;transcription termination

PROJECT_TITLE: Regulation of gene expression by alternative polyadenylation


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Project Narrative: The design and synthesis of new medicines requires access to a diverse array of chiral building blocks. This proposal describes mechanistic analysis and engineering of enzymes that can synthesize such molecules by overcoming classical limitations to forging carbon-carbon bonds. This research will yield generalizable insights into enzyme activity and advance our understanding of how to rapidly engineer new enzymes for the construction of medicines and diagnostics.

PI_NAMEs: BULLER, ANDREW  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Engineering promiscuous enzymes for synthesis of biological building blocks


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Data Science;Genetics;Heart Disease;Machine Learning and Artificial Intelligence;Muscular Dystrophy;Myotonic Dystrophy;Networking and Information Technology R&D (NITRD);Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PALO ALTO

ORG_NAME: GREENSTONE BIOSCIENCES, INC.

PHR: PROJECT NARRATIVE  The ability to use in vitro cellular data for efficacy assessment will create drug development opportunities for rare diseases that were previously considered too challenging due to the small number of patients. This proposal will aim to establish “clinical trial in a dish” using induced pluripotent stem cells (iPSCs) that capture patient- specific genetic diversity as a tool for evaluating clinical trial readiness to accelerate, de-risk, and streamline drug discovery for rare diseases. We will also combine artificial intelligence and machine learning to identify safe and effective compounds to test in iPSC models and validate in mouse models to demonstrate the effectiveness of iPSCs in determining clinical trial readiness of a candidate drug.

PI_NAMEs: PANG, PAUL  (contact)

PROGRAM_OFFICER_NAME: CHEN, ALICE

PROJECT_TERMS: 3' Untranslated Regions;Acceleration;Adult;Affect;Affinity;Alternative Splicing;Animal Model;Arrhythmia;Artificial Intelligence;Binding;Biological Process;Biological Sciences;Body System;Cardiac;Cardiology;Cardiovascular system;Cause of Death;Cell Line;Cell model;Cell Survival;Chemicals;Clinical;clinical trial in a dish;clinical trial readiness;Clinical Trials;college;CUG repeat;Custom;Cytosine;Data;Defect;Development;Disease;disease phenotype;Docking;Dose;drug candidate;drug development;drug discovery;drug efficacy;Drug Kinetics;Effectiveness;efficacy evaluation;Electrocardiogram;Female;Fibrosis;General Population;generative artificial intelligence;Genes;Genetic Transcription;Genetic Variation;Guanine;Heart;human induced pluripotent stem cells;Implantable Defibrillators;improved;In Vitro;in vitro Model;in vivo;Individual;induced pluripotent stem cell;induced pluripotent stem cell technology;Machine Learning;machine learning pipeline;male;medication safety;Medicine;Mendelian disorder;Molecular;molecular dynamics;mouse model;Mus;Muscular Dystrophies;Myotonic Dystrophy;Myotonic dystrophy type 1;novel;novel therapeutics;Organoids;Outcome;Pathogenicity;Patient Recruitments;patient stratification;Patients;Pharmaceutical Preparations;Pharmacological Treatment;Phenotype;Pre-Clinical Model;prevent;professor;Quality Control;Rare Diseases;Respiratory Failure;response;Risk;RNA;RNA Splicing;RNA-Binding Proteins;Safety;safety assessment;Senior Scientist;Site;Specificity;standard of care;stem cell model;stem cell organoids;Structure;sudden cardiac death;Syndrome;Systemic disease;Testing;Thymine;tool;Training;transcriptome sequencing;Universities;Validation;virtual

PROJECT_TITLE: AI/ML and iPSC-Derived Organoids for Myotonic Dystrophy Drug Discovery

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 RD-3 (02)]


NIH_SPENDING_CATS: Genetics

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE RNA and DNA form stable structures that must be transiently disrupted in many essential cellular processes. All human cells have proteins that promote disruptions or changes to RNA and DNA structures, and defects in these proteins are linked to many diseases including cancer. We are striving to understand how these proteins function to gain insight into why malfunctions in them lead to diseases and to improve treatments.

PI_NAMEs: RUSSELL, RICK  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Acceleration;Affinity;Area;Base Pairing;Basic Science;Cations;Cell Physiology;Cells;Chimeric Proteins;Clustered Regularly Interspaced Short Palindromic Repeats;combat;crosslink;Defect;design;Disease;Disulfides;DNA;DNA Structure;Electrostatics;Enzymes;Genetic Diseases;Goals;Guide RNA;helicase;Human;improved;insight;Lead;Life;link protein;Malignant Neoplasms;Measures;Mediating;Molecular;Molecular Chaperones;Nature;Nucleic Acids;Nucleosomes;Polyamines;Property;protein function;Proteins;Research;RNA;RNA Folding;RNA Helicase;RNA Probes;Specificity;Structure;Tail;Testing;tool;Variant;Work

PROJECT_TITLE: Mechanisms and Specificity of Proteins that Manipulate DNA and RNA Structure


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Cells, organs and organisms are to a great extent susceptible to osmotic stress caused by unbalanced water content or dehydration, with hyperosmotic stress having been linked to several human diseases. This research program will make use of a powerful unbiased genetic screen and time-resolved signal transduction analyses to dissect molecular and cellular mechanisms mediating hyperosmotic and dehydration stress sensing and signal transduction. This research will leverage an easily manipulated and highly developed model system to develop an in-depth understanding of eukaryotic osmotic stress response mechanisms.

PI_NAMEs: SCHROEDER, JULIAN I (contact)

PROJECT_TITLE: Osmotic Stress Sensing and Signal Transduction in Arabidopsis


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE The cellular genome is compacted in the basic repeating assembly called chromatin, the anomalous regulation of which is characteristic of many diseases and cancers. Viruses hijack and manipulate host cells, including cellular chromatin, to exploit cellular resources and produce viral progeny. In this proposal, we will employ multiple nuclear-replicating viruses to identify commonly used chromatin vulnerabilities that will allow us to pinpoint new targets for the development of innovative therapies for cancer, inflammation, and viral diseases.

PI_NAMEs: AVGOUSTI, DAPHNE CHRISTINA (contact)

PROJECT_TERMS: 3-Dimensional;Adenovirus Protein;Adenoviruses;Area;Biological Process;biological systems;Biology;cancer therapy;Cell Cycle;Cell Nucleus;Cells;Characteristics;Chromatin;chromosome conformation capture;Chromosomes;Cytomegalovirus;Development;Disease;dynamic system;Electron Microscopy;Environment;Funding;Genetic Transcription;Genome;Herpes Simplex Infections;Herpesviridae;Heterochromatin;Histones;Human;Immunofluorescence Microscopy;Inflammation;Innovative Therapy;Malignant Neoplasms;marginalization;Measurement;Methodology;Methods;Molecular Biology;Nuclear;pathogen;Positioning Attribute;Regulation;Resolution;Resources;RNA Splicing;Structure;System;Techniques;Technology;Testing;TP53 gene;Viral;Virus;Virus Assembly;Virus Diseases;virus host interaction;Virus Replication

PROJECT_TITLE: Investigating chromatin mechanisms using viral systems


NIH_SPENDING_CATS: Genetics;Hematology;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative The ends of telomeres, the DNA-protein complexes that cap our linear chromosomes, are maintained by telomerase that synthesizes the G-strand and CST–Polymeraseα-Primase that synthesizes the C-strand. Telomerase is a highly regulated determinant of aging, stem cell renewal, and tumorigenesis, and mutations in telomerase and telomere binding or associated proteins can lead to aplastic anemia, dyskeratosis congenita, pulmonary fibrosis, myelodysplastic syndromes, Coats plus syndrome, and other telomere biology disorders. We propose to use an integrative structural and molecular biology approach to investigate their mechanisms of action and regulation of telomere synthesis, which should reveal the structural basis of mutations leading to disease and for drug targeting.

PI_NAMEs: FEIGON, JULI  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Affect;Aging;Aplastic Anemia;Binding;Biochemistry;Biology;Chromosomes;Coats plus syndrome;Complex;Cryoelectron Microscopy;Disease;DNA;DNA polymerase alpha-primase;DNA Primase;Drug Targeting;ds-DNA;Dyskeratosis Congenita;Dysmyelopoietic Syndromes;Goals;Health;Human;In Situ;Molecular Biology;Mutation;NMR Spectroscopy;Organism;particle;Polymerase;protein complex;Proteins;Pulmonary Fibrosis;recruit;Regulation;Research;RNA-Directed DNA Polymerase;stem cell division;structural biology;Structure;Telomerase;telomere;Tetrahymena;Tetrahymena thermophila;TNFRSF5 gene;tumorigenesis;Visualization

PROJECT_TITLE: Structural biology of telomerase and telomeres


ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Cells in the human body link to one another via protein complexes that respond to mechanical force in order to maintain tissue integrity, and to remodel tissues during embryonic development. We will determine how key proteins in cellular adhesion complexes and the cytoskeleton respond to force, and how their molecular behavior contributes to processes that shape living tissues. This study will significantly advance our understanding of the molecular events that drive cancer metastasis, in which the loss of cell-cell contacts is a key step, as well as the causes of cardiomyopathies and skin diseases in which cells lose their mechanical integrity.

PI_NAMEs: DUNN, ALEXANDER R (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actomyosin;Adherens Junction;Adhesions;afadin;alpha catenin;Area;Back;Behavior;Biochemical;Biological Assay;Biophysics;Cardiomyopathies;Cell Adhesion;Cell Physiology;Cells;Complex;Congenital Abnormality;Cytoskeleton;Data;Development;Disease;Drosophila genus;embryo tissue;Embryonic Development;Epithelium;Event;Exhibits;Funding;Genetic;Goals;Heart Diseases;Human body;imaging approach;Individual;Intercellular Junctions;Lead;Link;Malignant Neoplasms;mechanical force;mechanical load;Mechanics;Mediating;Molecular;molecular assembly/self assembly;molecular scale;Motion;Neoplasm Metastasis;planar cell polarity;polarized cell;Process;protein complex;protein protein interaction;Proteins;quantitative imaging;Shapes;Side;Signal Transduction;single molecule;skin disorder;Source;Structure;Tertiary Protein Structure;Testing;Tight Junctions;tissue repair;Tissues;Work;wound healing

PROJECT_TITLE: Molecular mechanisms underlying force transduction at cellular adhesion complexes


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Project narrative Fruit flies are a powerful model for evolutionary studies because many species exist whose genomes have been fully sequenced and can be analyzed using experimental genetics. This study will use evolutionary genetic methods to investigate why different fruit fly species cannot form viable progeny, how correct transmission of their chromosomes can sometimes go awry, and how different genetic systems may be used to form males and females. The results of this study will reveal processes that are relevant for understanding how animals evolve.

PI_NAMEs: BARBASH, DANIEL A (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TITLE: Evolutionary Genetics of Drosophila


NIH_SPENDING_CATS: Bioengineering;Immunotherapy;Machine Learning and Artificial Intelligence;Nanotechnology

ORG_CITY: Auburn

ORG_NAME: AUBURN UNIVERSITY AT AUBURN

ORG_STATE: AL

PHR: Our project aims to develop cutting-edge technologies for analyzing the immune system. We will use nanomaterial-based sensors and advanced computer algorithms to measure key immune proteins and track how immune cells behave and communicate. This project will provide critical insights into the immune system and help improve the diagnosis and treatment of immune-related diseases. Our goal is to make these new technologies widely available to researchers and clinicians, enabling better patient care and outcomes.

PI_NAMEs: CHEN, PENGYU  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: 3-Dimensional;Achievement;Autoimmune Diseases;Behavior;Biosensing Techniques;cell behavior;Cell Communication;Cells;clinical application;Communication;Computational algorithm;cytokine;Detection;Diagnosis;Diagnostic;Disease;effective therapy;empowerment;Encapsulated;Engineering;fundamental research;Goals;Hydrogels;Hypersensitivity;Immune;Immune response;Immune system;Immune System Diseases;Immunoassay;Immunologic Monitoring;immunological status;immunomodulatory therapies;Immunotherapy;improved;In Situ;in vitro Model;Individual;Infection;innovation;insight;Machine Learning;Malignant Neoplasms;Maps;Measures;Methods;Monitor;nanomaterials;nanoplasmonic;Nature;new technology;next generation;Patient Care;Patient-Focused Outcomes;Patients;Performance;Physiological;plasmonics;point of care;Proteins;Research Personnel;Resolution;sensor;Serum;Signal Transduction;spatiotemporal;Techniques;Technology;Time;Transplantation;Vision;Whole Blood

PROJECT_TITLE: Machine Learning-Assisted Integrated Optofluidic Nanoplasmonic Biosensing for Precision Immune Profiling and Monitoring


ORG_CITY: BERKELEY

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Calcium (Ca) is a ubiquitous second messenger in all eukaryotes ranging from budding yeast, plants, to human. Defects in Ca signaling cause numerous human diseases including Alzheimer’s disease, heart failure, metabolic diseases, immune disorders, neurodegenerative diseases, and cancer. Proposed research will contribute to the understanding of the basic conceptual framework of calcium signaling mechanisms highly relevant to human health.

PI_NAMEs: LUAN, SHENG  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Alzheimer's Disease;Animals;Arabidopsis;axon guidance;Biochemical;Calcium;Calcium Channel;Calcium ion;Calcium Signaling;Carrier Proteins;Cell Communication;Cell Death;cell growth;Cell Surface Receptors;Cells;Cellular biology;Cues;cyclic-nucleotide gated ion channels;Defect;Electrophysiology (science);Eukaryota;Family;Female;Fertilization;gene product;Genes;Genetic;Germ Cells;Goals;Growth;Health;Heart failure;Human;human disease;Hyphae;Immune response;Immune System Diseases;Laboratory Study;Language;male;Malignant Neoplasms;mechanotransduction;Mediating;Medical;Metabolic Diseases;Methods;Molecular;Natural Immunity;Neurodegenerative Disorders;Organ;pathogenic bacteria;Pathway interactions;Physiological;Plant Model;Plants;polarized cell;Pollen Tube;Procedures;Process;programs;reconstitution;Reproduction;Research;response;Saccharomycetales;Second Messenger Systems;Signal Pathway;Signal Transduction;Specificity;Structure-Activity Relationship;tool;Translating

PROJECT_TITLE: Calcium encoding mechanisms in a model plant


ADMINISTERING_IC: OH

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE World Trade Center (WTC) site destruction caused an intense particulate matter (PM) exposure. Since PM is responsible for a high percentage of cardiorespiratory disease/death we propose to investigate the development of WTC-PM induced cardiorespiratory and vascular dysfunction (WTC-CaRVD) in the FDNY cohort. Our proposal will identify biologically plausible therapeutic targets of oxidative stress and clinical phenotypes of WTC- CaRVD; which falls squarely within the purview of the James Zadroga 9/11 Health & Compensation Act.

PI_NAMEs: NOLAN, ANNA  (contact)

PROJECT_TITLE: World Trade Center Particulate Matter Induced Cardiorespiratory and Vascular Dysfunction:  a MultiOmic Approach


ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Common sleep disorders like obstructive sleep apnea (OSA) may represent risk factors for cognitive decline. We have found a very high prevalence of OSA in the World Trade Center responder population, and the present work will evaluate the impact of OSA on early markers of Alzheimer 's Disease using plasma biomarkers, PET/MR and cognition using a visual-spatial memory test. This study has the potential to identify the mechanisms by which sleep disruption contributes to Alzheimer's Disease neurodegeneration and guide therapeutic interventions in the future in the aging WTC responder population.

PI_NAMEs: AYAPPA, INDU A (contact)

PROJECT_TITLE: Role of Sleep Apnea in Cognition and Alzheimer's Disease Biomarkers in WTC Responders