NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: HOUSTON

ORG_NAME: RICE UNIVERSITY

PHR: PROJECT NARRATIVE In this proposal, we will create unnatural organisms able to biosynthesize noncanonical amino acid building blocks and use them for protein translation. The utility of these cells with 21 amino acid genetic code will be demonstrated by preparing novel bioactive molecules and cell sensors, thus providing a new design strategy for next-generation medicines.

PI_NAMEs: XIAO, HAN  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Amino Acids;Amino Acyl-tRNA Synthetases;Anabolism;Bioinformatics;Biological;biological systems;Cells;Chemicals;Collection;design;Development;Engineering;enzyme activity;Enzymes;Epigenetic Process;Eukaryotic Cell;Evaluation;Evolution;Exhibits;Generations;Genetic;Genetic Code;Goals;in vivo;inhibitor;interest;Ligase;Luciferases;Medicine;metabolic engineering;Monitor;natural product derivative;Natural Products;next generation;novel;Organism;Pathway interactions;Pharmaceutical Preparations;Post-Translational Protein Processing;programs;Property;Protein Biosynthesis;Protein Engineering;Proteins;Research;sensor;Site;Therapeutic;Time;tool;Transfer RNA;Transfer RNA Aminoacylation;Translations

PROJECT_TITLE: Engineering Proteins with Noncanonical Amino Acids


ADMINISTERING_IC: GM

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: OKLAHOMA CITY

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: Errors in the process of distributing chromosomes during cell division is the major cause of birth defects and contributes to tumor progression. The chromosomes are moved by microscopic cables. This project will explore how cells are able to attach chromosomes to these cables without errors, to assure that each daughter cell receives a correct chromosome set.

PI_NAMEs: DAWSON, DEAN S (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: addiction;Aneuploidy;Behavior;Biological Models;Biology;biophysical properties;Cell Cycle;Cell division;cell type;Cells;Centromere;chromosomal location;chromosome movement;Chromosome Segregation;Chromosomes;Congenital Abnormality;daughter cell;Emerging Technologies;Ensure;experimental study;Genetic Screening;Germ Cells;Goals;Infertility;insight;Kinetochores;Knowledge;Link;Mediating;Meiosis;Microscopic;Microtubules;Mitosis;Modeling;Optic Chiasm;Pathway interactions;Phosphotransferases;Play;Polyploid Cells;Positioning Attribute;Process;Prometaphase;Role;Saccharomycetales;segregation;Side;Somatic Cell;success;Testing;transmission process;Tumor Cell Line;tumor progression;Yeasts

PROJECT_TITLE: Centromere behaviors that promote proper chromosome segregation in meiosis and mitosis

STUDY_SECTION: MRAC

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: CHEMISTRY

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative. Numerous genetic diseases are caused by the misfolding of integral membrane proteins, which is a process that remains poorly understood. Based on our recent identification of various classes of biosynthetic defects, we propose a series of innovative experiments to determine how mutations cause these defects, how they impact membrane protein translation, and how they remodel membrane protein quality control. Our results will provide adaptable new experimental tools and novel insights into the molecular basis of disease.

PI_NAMEs: SCHLEBACH, JONATHAN PATRICK (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Adopted;Biological Process;Buffers;Calnexin;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Defect;Delta F508 mutation;Disease;Drug Targeting;Endoplasmic Reticulum;Equilibrium;Evolution;experimental study;fitness;Genetic Diseases;innovation;insight;Integral Membrane Protein;Ligand Binding;Link;mechanical force;Mediating;Membrane;Membrane Proteins;Molecular;Molecular Chaperones;Molecular Conformation;molecular recognition;Mutation;mutation screening;novel;Outcome;Pathway interactions;Process;Production;Protein Biosynthesis;protein complex;protein degradation;protein expression;protein misfolding;Proteins;Proteome;proteostasis;Quality Control;Regulation;Ribosomal Frameshifting;Role;secretory protein;Series;Shapes;Site;tool;Transcript;Translations;Variant;Voltage-Gated Potassium Channel

PROJECT_TITLE: Molecular Mechanisms of Membrane Protein Misfolding and Quality Control in Cellular Proteostasis

STUDY_SECTION: MRAE

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE The proposed research will determine the mechanistic causes of phenotypic variation within and between individuals that differ in their genotypes, sexes, or environments in which they live. These causes of phenotypic variation are important in human health and disease—including mental health and genetic disorders—but they are extremely challenging to study in humans and mammalian model systems. To address that challenge, the proposed research will use fly models where phenotypic variation can be measured at scale and genetic mechanisms can be dissected with powerful molecular tools.

PI_NAMEs: MEISEL, RICHARD P. (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Affect;Area;Bacterial Infections;Behavioral;Biological;Biological Models;comparative genomics;Disease;Drosophila genus;Drosophila melanogaster;Environment;Environmental Risk Factor;fly;functional genomics;Gene Expression;Genes;Genetic;Genetic Diseases;genetic resource;Genetic Variation;genome resource;Genomic approach;Genotype;Goals;Health;Heterogeneity;Human;human disease;Immune response;immunoregulation;Individual;Laboratories;Laboratory Study;Measures;Mental Health;model organism;Modeling;Molecular;Musca domestica;Organism;Phenotype;Physiological;Population;Research;sex;Sex Chromosomes;Sex Differences;sexual dimorphism;Testing;tool;trait;Variant;Work

PROJECT_TITLE: Genetic mechanisms of phenotypic variation within and amongst genotypes, environments, and sexes

STUDY_SECTION: MRAA

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


NIH_SPENDING_CATS: Cannabinoid Research;Natural Products

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: PROJECT NARRATIVE In the backdrop of growing recognition of lipids in the body and sparse knowledge of their biochemistry and function, herein, we propose to understand the mechanism of how membrane proteins metabolize lipids such as poly unsaturated fatty acids (PUFAs) and lipid-like xenobiotics and lead to the formation of novel lipid metabolites that are involved in immunomodulation.

PI_NAMEs: DAS, ADITI  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;Award;Binding;Biochemical;Biochemistry;Cannabinoids;Cell Culture Techniques;chemical synthesis;Cytochrome P450;Disease;Endocannabinoids;Enzymes;falls;Fluorescence Spectroscopy;Foundations;Funding;Goals;imaging platform;Immune System Diseases;immunoregulation;innovation;Institution;Knowledge;Laboratories;lipid metabolism;lipidomics;Lipids;Mammalian Cell;Mass Spectrum Analysis;Mediating;Membrane;Membrane Lipids;Membrane Proteins;Metabolism;Methodology;Mission;molecular dynamics;nanodisk;National Institute of General Medical Sciences;neuroinflammation;novel;Orphan;Paper;Pharmacology;Pharmacology Study;programs;protein expression;Publishing;receptor;Recombinants;Research;Research Proposals;Role;scaffold;symposium;systemic inflammatory response;Therapeutic;therapeutic development;tool;Translating;Unsaturated Fatty Acids;Work;Xenobiotics

PROJECT_TITLE: Biochemistry of membrane proteins involved in lipid and cannabinoid metabolism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MBBC-R (55)]


ED_INST_TYPE: SCHOOLS OF MEDICINE

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

ORG_CITY: WASHINGTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: HOWARD UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE Public Health Relevance: The proposed research project will expand our understanding of the genetic code, RNA modifications, and the control of gene expression in response to various stressors in a wide variety of bacteria. This new information will help us understand how bacteria evolve and adapt to harsh environments. This will assist us in preparing for emerging or re-emerging bacterial infections.

PI_NAMEs: THOMPSON, KARL M (contact)

PROJECT_TERMS: Address;Automobile Driving;Bacteria;Bacterial Infections;Bacterial Model;Bacterial Physiology;Biology;Cell Physiology;chemical addition;Clostridium difficile;Codon Nucleotides;cofactor;Data;Environment;epitranscriptomics;Escherichia coli;experimental study;Firmicutes;Gene Expression;Gene Expression Regulation;Gene Modified;Genetic Code;genetic regulatory protein;Genus Mycobacterium;Goals;Growth;Guanine + Cytosine Composition;Isomerism;Knowledge;Life;Messenger RNA;model organism;Modification;Molecular Chaperones;multiple omics;Mycobacterium smegmatis;novel;Nucleotides;Post-Transcriptional Regulation;Process;programs;Proteins;public health relevance;Regulation;Regulon;Research;Research Project Grants;response;Ribonucleases;Ribosomes;RNA;RNA immunoprecipitation sequencing;Role;Signal Transduction;Staphylococcus aureus;stressor;Testing;Transfer RNA;Work

PROJECT_TITLE: Epitranscriptomic and post-transcriptional regulation of the RNome in gram negative and firmicute bacteria


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

ORG_CITY: Chicago

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Cholesterol and its metabolites are the most prolific small molecules in the human body and play multifaceted roles in health and disease. Yet no current therapies can directly intercept cholesterol metabolite activities, in large part because we lack the tools to fully define their molecular functions. In this work, we will fashion precise chemical tools and technologies to profile cholesterol metabolites on an interactome-wide scale, creating druggable opportunities to target their activities in disease.

PI_NAMEs: ONDRUS, ALISON EVELYNN (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Address;Architecture;Chemicals;chemoproteomics;Cholesterol;Cholesterol Homeostasis;design;Disease;druggable target;Fluorescence Microscopy;Health;Human;Human body;human disease;Image;Immune System Diseases;Immunity;immunoregulation;innovation;Intercept;Ligands;Malignant Neoplasms;Membrane;Metabolite Interaction;Microscopy;Molecular;Nerve Degeneration;next generation;Oncogenic;Orphan;Play;Process;Proteins;Proteome;receptor;Role;Signal Transduction;small molecule;Specific qualifier value;Technology;tool;tumorigenic;Work

PROJECT_TITLE: Molecular tools for cholesterol metabolite signaling


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Networking and Information Technology R&D (NITRD)

ORG_CITY: SANTA CRUZ

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

ORG_STATE: CA

PHR: Project Narrative: This broad research program will investigate the origins, maintenance, and consequences of genetic variation. We will marshall a range of computational, statistical and experimental methods to study the origins of genetic novelty at the level of individual positions in the genome and genome structure itself. We will investigate molecular consequences and fitness effects that drive new variation to be lost or persist in natural populations.

PI_NAMEs: CORBETT-DETIG, RUSSELL  (contact)

PROJECT_TITLE: Origins, Functional, and Evolutionary Consequences of Genomic Variation


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

ORG_CITY: COLLEGE PARK

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: Development of the vertebrate embryo requires the production and distribution of broad types of molecules. This project uses uniquely sensitive technologies to understand how small molecules called metabolites contribute to the coordination of embryonic development.

PI_NAMEs: NEMES, PETER  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Affect;Biological;Cell Differentiation process;Cells;Communication;Complex;Custom;Data;design;Development;Developmental Biology;Embryo;embryo cell;embryo stage 2;Embryonic Development;Folic Acid;Generations;Genes;Genetic Transcription;Germ Layers;Human Development;innovation;insight;Interdisciplinary Study;Knowledge;Laboratories;Mass Spectrum Analysis;Messenger RNA;Metabolic;Metabolism;metabolomics;Microscopy;Modeling;Molecular;Neural Tube Closure;next generation sequencing;Normal Cell;Pattern;Performance;Play;Post-Translational Protein Processing;Process;Production;programs;Proteins;Proteomics;Rana;Reaction;Reproducibility;Research;Resolution;Role;Scientist;small molecule;System;Tadpoles;Technology;Time;Tissues;tool;Transcript;transcriptomic profiling;Translations;vertebrate embryos;Vertebrates;Work;Xenopus;Xenopus laevis

PROJECT_TITLE: Sub-Cellular Mass Spectrometry Discoveries: Metabolic Encoding of the Embryonic Body Plan


NIH_SPENDING_CATS: Arthritis

ORG_CITY: LUBBOCK

ORG_NAME: TEXAS TECH UNIVERSITY

PHR: PROJECT NARRATIVE Membrane proteins are targeted by the majority of FDA approved drugs. Interactions like dimerization affect the way these proteins function and respond to drug binding, but have not been fully characterized for many important drug targets. This project uses an advanced fluorescence spectroscopy to probe membrane protein interactions in cells to determine how dimerization alters membrane protein structure and function.

PI_NAMEs: SMITH, ADAM W. (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Affect;Arthritis;Asthma;Binding;cancer therapy;Cell membrane;cell motility;Cell Surface Receptors;cell type;Cells;Chemicals;chemokine receptor;Color;Complex;Coupled;CXCR4 gene;dimer;Dimerization;Disease;drug development;Drug Targeting;Environment;Family;FDA approved;Fluorescence;Fluorescence Spectroscopy;G protein coupled receptor kinase;G-Protein-Coupled Receptors;GPR3 gene;Hematopoietic stem cells;Heterodimerization;Infiltration;innovation;insight;instrument;Kinetics;Ligand Binding;Ligands;Link;Malignant Neoplasms;Membrane Proteins;Methodology;migration;Nature;Outcome;Pharmaceutical Preparations;Physiologic pulse;Prevalence;Protein Family;protein function;protein structure;Psoriasis;receptor;Receptor Protein-Tyrosine Kinases;Research;research and development;Role;Signal Pathway;Signal Transduction;Spectrum Analysis;structural biology;Structure-Activity Relationship;targeted treatment;Thermodynamics;Translational Research;Tyrosine Kinase Inhibitor;Work

PROJECT_TITLE: Resolving the interaction network of cell surface receptors


ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS SAN ANTONIO

PHR: The research program is focused on the development of synthetic methods that enable access to medicinally important functionalized molecules by harnessing the unexplored reactivity of organosulfur compounds. The innovative methods will facilitate construction of biological probes and therapeutic agents, advancing drug discovery and contributing to the improvement of human health and well-being.

PI_NAMEs: LARIONOV, OLEG V (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: New organosulfur-based strategies for efficient construction of carbon-carbon and carbon-heteroatom bonds


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

ORG_CITY: BOSTON

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative Most human complex diseases are multigenic, but our understanding of how biological processes are controlled by complex gene regulatory interactions in healthy states and how the operations are disrupted in disease states is lacking. In the PI’s research program, a suite of computational systems biology algorithms will be developed to construct and model gene regulatory circuits of higher complexity to fill an important gap in our understanding of cellular state transitions and their abnormal behavior in disease. The research efforts will provide important new information on the causes of human diseases and will also generate publicly available computational tools for building mechanistic models from omics data relevant to human health and to numerous diseases.

PI_NAMEs: LU, MINGYANG  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;algorithm development;Algorithms;Automobile Driving;Basic Science;Behavior;Benchmarking;Biological Process;Biology;Cell Differentiation process;Chromosome Mapping;Clinical;Collaborations;Complex;computational suite;Computer Assisted;computerized tools;Computing Methodologies;Data;data resource;Data Set;design;Developmental Process;Disease;dynamic system;Epithelium;experimental study;Gene Expression;gene interaction;gene network;gene regulatory network;Genes;genomic data;Genomic medicine;Goals;Grain;Health;Human;human disease;in silico;in vivo;Intervention;Kinetics;knowledge integration;mathematical model;Mesenchymal;Methods;Modeling;models and simulation;new technology;next generation sequencing;operation;Patients;programs;reconstruction;Research;Risk;Signal Transduction;success;System;Systems Biology;Technology;Therapeutic Intervention;tumorigenesis;Uncertainty

PROJECT_TITLE: New Computational Systems Biology Methods for Modeling Gene Regulatory Circuits

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MRAF-C (01)]


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

ORG_STATE: NY

PHR: PROJECT NARRATIVE Cryptochrome (CRY) UV-A/blue light photoreceptors are found in humans and plants, where they regulate diverse processes like circadian rhythms, tumor suppression, metabolism, DNA repair, flowering, and growth. The proposed studies aim to determine the molecular mechanisms by which CRYs interpret light quality and quantity to regulate plant growth. Understanding the mechanisms of CRY and its associated signaling will lead to improved crop yields for human nutrition and the prevention and development of therapies for diseases linked to impaired CRY function like cancer, diabetes, and neuronal disorders.

PI_NAMEs: PEDMALE, VINCENT U (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TITLE: The Role of Cryptochromes in environmental regulation of growth


ORG_CITY: SAINT LOUIS

ORG_NAME: SAINT LOUIS UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The proposed research will deliver an entirely automated approach to accelerate and broaden access to various glycans needed for analytical and biomedical applications from simple renewable precursors. Machine-assisted synthesis ensures rigorous experimental design to obtain robust and unbiased results by significantly reducing variability, ensuring authentication of key chemical resources, and improving reproducibility of experiments. Completely automated synthesis will enhance transparency, simplify the implementation of our protocols in other, even non-specialized, labs thereby increasing the availability of glycans, and aid global efforts to develop automated technologies, carbohydrate-based therapeutics, diagnostics, and analytical tools.

PI_NAMEs: DEMCHENKO, ALEXEI V (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acceleration;analytical tool;Automation;Carbohydrates;chemical resource;chemical synthesis;Complex;Dedications;Development;diagnostic tool;Discipline;Ensure;Equipment;Experimental Designs;experimental study;glycosylation;High Pressure Liquid Chromatography;High School Student;Human Milk;improved;interest;Medicine;Methods;Monitor;Monosaccharides;Nature;Organism;pandemic disease;Polysaccharides;Procedures;Production;Productivity;Protocols documentation;Public Health;rapid growth;Reaction;Reaction Time;Reagent;Reproducibility;Research;research and development;Research Personnel;Scientist;Societies;Solid;Solvents;Specialist;sugar;System;Technology;Therapeutic;Training;user-friendly;Work

PROJECT_TITLE: Methods and technologies for chemical synthesis of glycans


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Machine Learning and Artificial Intelligence

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: This MIRA proposal will provide fundamental insight into how myosin motors perform such an amazing diversity of functions, from muscle contraction to hearing, using a combination of atomically-detailed computer simulations and biophysical experiments. This insight will enable us to interpret genetic variation and design new myosin variants and drug-like modulators of myosin function, thereby demonstrating our level of understanding and laying a foundation for the future development of new therapeutics.

PI_NAMEs: BOWMAN, GREGORY  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Accounting;Amaze;Amino Acid Sequence;beta-Myosin;Biological Process;Biology;Biophysics;Complex;Computer Simulation;design;Development;Disease;Drug Design;drug discovery;drug-like compound;experimental study;Family;Foundations;Future;Genetic Variation;Hearing;Heart Diseases;Heart failure;insight;Machine Learning;member;Motor;motor behavior;motor control;Muscle Contraction;Mutation;Myosin ATPase;Myosin S-1;novel therapeutics;Parasitic infection;Pharmaceutical Preparations;protein structure;Proteins;rational design;Series;simulation;Structure;success;Testing;tool;Variant;Work

PROJECT_TITLE: Understanding and controlling protein energy landscapes by combining simulations and experiments


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Biotechnology

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative DNA-encoded chemical libraries and DNA-encoded enzyme activity probes are new approaches to facilitate biomedical research by uitilizing the power of DNA analysis techniques. Advancing these techniques, particularly for medicinal chemistry applications, will provide useful tools for researchers for biological discovery and in the development of new therapeutics. 1

PI_NAMEs: KRUSEMARK, CASEY JOHN (contact)

PROJECT_TERMS: adenylyl cyclase 1;Affinity Chromatography;Agonist;Area;Binding;Binding Proteins;Biochemical;Biological;Biological Assay;Bioluminescence;Biomedical Research;Bromodomain;cancer therapy;Cells;Chemicals;Collection;Detection;Development;Disease;DNA;DNA amplification;DNA analysis;DNA Sequence;drug development;Drug resistance;Drug Targeting;Energy Transfer;enzyme activity;Family;G-Protein-Coupled Receptors;high throughput screening;Human;In Vitro;inhibitor;Link;Malignant Neoplasms;Membrane;Modality;novel;novel strategies;novel therapeutics;Opioid;Pain;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phosphotransferases;programs;protein purification;Protein Tyrosine Kinase;Proteins;Proteomics;receptor;Research;Research Personnel;Role;Sampling;Signal Pathway;small molecule libraries;Solid;Techniques;tool;Transcriptional Regulation;tumor;Tyrosine Kinase Inhibitor;Work

PROJECT_TITLE: Harnessing the In Vitro Selection for Activity-based Proteomics and Chemical Probe Development

STUDY_SECTION: MRAB

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


ORG_CITY: RICHARDSON

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: PROJECT NARRATIVE Chloride ions are required for essential functions in the human body, spanning electrolyte balance, acidosis, innate immunity, circadian rhythms, and even taste sensation. At the same time, dysregulated chloride levels have been linked to diseases such as cystic fibrosis, hearing loss, hypertension, kidney stones, osteopetrosis, and pain. We are engineering new technologies for imaging chloride in living systems to fundamentally understand how cells store and regulate chloride in homeostasis and signaling, paving the way ultimately to therapeutically control this anion for the betterment of human health.

PI_NAMEs: DODANI, SHEEL  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Acidosis;Address;Albers-Schonberg disease;Anions;Biological;Biological Process;Biosensor;Cell Line;Cells;Chloride Ion;Chlorides;Circadian Rhythms;Cystic Fibrosis;Democracy;design;Diet;Dimensions;Disease;Electrolyte Balance;Engineering;Esthesia;Genetic;Goals;Health;hearing impairment;Homeostasis;Human;Human body;Hypertension;Image;Imaging technology;improved;innovation;Kidney Calculi;Link;Malignant Neoplasms;Measures;Monitor;Myocardial dysfunction;Myotonia;Natural Immunity;Nervous System Disorder;new technology;Organism;Pain;Physiological;programs;Proteins;Regulation;Reproducibility;Research;Signal Transduction;Taste Perception;Technology;Therapeutic;therapeutic target;Time;user-friendly

PROJECT_TITLE: Fluorescent Biosensors to Illuminate Chloride Homeostasis and Signaling


NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: NARRATIVE Human cells employ several mechanisms to avoid genomic instability at repetitive sequences that can lead to genomic alterations and diseases. My laboratory is interested in unraveling these mechanisms and detect errors during processing of repetitive DNA or RNA sequences that could lead to genomic instability and cell dysfunction.

PI_NAMEs: GERHARDT, JEANNINE  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Adopted;Apoptosis;BRCA1 gene;Cell Death;Cell Physiology;Cell Proliferation;Cells;Chromosome Fragility;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Repair;DNA Repair Pathway;DNA replication fork;DNA Sequence;DNA Sequence Alteration;Functional disorder;Generations;Genetic Transcription;Genome;Genomic Instability;Genomics;Goals;Human;interest;Knowledge;Laboratories;Messenger RNA;Molecular;Mutation;Myopathy;Nervous System Disorder;Nuclear;Oocytes;Organism;Outcome Study;Ovarian Diseases;Pathway interactions;polypeptide;prevent;Process;programs;protein expression;Proteins;repaired;Repetitive Sequence;Research;RNA;RNA Sequences;Structure;Translation Initiation;Translations;Travel

PROJECT_TITLE: Repetitive sequences causing genomic instability and cell dysfunction


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Bioengineering;Nutrition

ORG_CITY: BERKELEY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project narrative Metabolic syndrome caused by dysregulation of metabolic pathways is implicated in the pathophysiology of many common diseases including cardiovascular disease, diabetes, cancer, and infectious diseases. The goal of this project is to better understand the regulation of metabolic homeostasis using a combination of mathematical modeling and experimental approaches in live cells. A better understanding of metabolic homeostasis has the potential to lead to novel therapies for common diseases associated with metabolic syndrome.

PI_NAMEs: TITOV, DENIS VASILIEVICH (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;Allosteric Regulation;Anabolism;Cardiovascular Diseases;Cell Line;Cells;Citric Acid Cycle;Communicable Diseases;conflict resolution;CRISPR/Cas technology;Diabetes Mellitus;Disease;Engineering;enzyme activity;Enzymes;experience;experimental study;Fluorescence;Functional disorder;Glycolysis;Goals;Homeostasis;In Vitro;Individual;Kinetics;Knowledge;Malignant Neoplasms;mathematical model;Measures;Metabolic;metabolic abnormality assessment;Metabolic Pathway;Metabolic syndrome;Metabolism;Mitochondria;Modeling;non-alcoholic fatty liver disease;novel therapeutics;Oxidative Phosphorylation;Pathway interactions;Pentosephosphate Pathway;Positioning Attribute;predictive modeling;Production;Property;Proteins;Reaction;reconstitution;Regulation;Research;Respiration;Role;sensor;Structure;Testing;Thermodynamics;tool

PROJECT_TITLE: Toward a quantitative understanding of metabolic homeostasis


NIH_SPENDING_CATS: Biotechnology;Contraception/Reproduction;Genetics;Human Genome;Infertility;Women's Health Research

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: PROJECT NARRATIVE Accurate chromosome segregation and repair of DNA breaks during sperm and egg development are essential for preventing infertility, miscarriages, birth defects, and cancer. Developing sperm and eggs accomplish this through specific exchanges of DNA, called recombination events. The proposed research will reveal the mechanisms of these recombination events to increase understanding of fundamental processes critical to human health.

PI_NAMEs: LIBUDA, DIANA ELIZABETH (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Affect;Age;Biological Assay;Biological Models;Caenorhabditis elegans;Cell division;Cell Physiology;Chromosome Segregation;Chromosome Structures;Chromosomes;Congenital Abnormality;Cytology;Development;DNA;DNA Double Strand Break;DNA Repair;egg;Ensure;Event;Genetic;Genetic Recombination;Genetic Variation;Genome;genome integrity;genome sequencing;Genome Stability;genomic locus;Germ Cells;Goals;Haploidy;Health;Human;in vivo;Infertility;Knowledge;Ligase;Malignant Neoplasms;Meiosis;Meiotic Prophase I;Meiotic Recombination;Modeling;Molecular Profiling;Oogenesis;Outcome;Pathway interactions;preference;prevent;Process;programs;Proteins;Publishing;repaired;Research;sex;Sister Chromatid;sperm cell;Spontaneous abortion;Testing;whole genome;Work

PROJECT_TITLE: Recombination pathway and partner choices during meiosis


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative The goal of my research is to deepen our fundamental molecular level understanding of all aspects of the function of K+ and Na+ channels and biomembranes using molecular dynamics (MD) simulations based on atomic models. Malfunction of ion channels have a broad impact on human health, including neurological disorders, epilepsy, heart arrhythmia, immune response, and cellular secretion. The fundamental knowledge gained by the proposed studies promises new insight that will support the development of molecular therapies targeting these channels.

PI_NAMEs: ROUX, BENOIT  (contact)

PROJECT_TERMS: Affect;Arrhythmia;Back;Biological;Biology;Cell secretion;Charge;Complex;Comprehension;Computer software;Cryoelectron Microscopy;Development;driving force;Electronics;Electrostatics;Environment;Epilepsy;Goals;Health;Human;Immune response;insight;Integration Host Factors;Ion Channel;Ions;Knowledge;Lipids;machine learning algorithm;Mediating;Membrane;Modeling;Molecular;Molecular Conformation;molecular dynamics;molecular targeted therapies;mutant;Nervous System Disorder;Permeability;Phosphatidylglycerols;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylserines;Phospholipids;physical model;Play;Potassium;Potassium Channel;Process;programs;Regulation;Research;Role;Sampling;Side;Signal Transduction;simulation;small molecule;Sodium;Structure;System;voltage;X-Ray Crystallography

PROJECT_TITLE: Molecular dynamics studies of K+ and Na+ channels and biomembranes based on a polarizable force field


NIH_SPENDING_CATS: Aging;Genetics;Nutrition;Osteoporosis

ORG_CITY: ITHACA

ORG_NAME: BOYCE THOMPSON INST FOR PLANT RESEARCH

PHR: Project Narrative The physiological changes associated with aging and metabolism underlie increases in the incidence of many diseases, including, diabetes, cancer, neurological disorders, heart disease, and osteoporosis. In nematodes, several different classes of small molecules have been shown to significantly retard the effects of ageing and modulate fat metabolism. The proposed study aims to investigate the biological mechanisms through which these and other endogenous compounds modulate lifespan, development, and metabolism in nematodes, which will contribute to our understanding metabolic dysfunction and age-related decline in humans.

PI_NAMEs: SCHROEDER, FRANK CLEMENS (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Acceleration;age effect;age related decline;Aging;Agonist;Agriculture;Anabolism;Architecture;Area;Bacteria;Behavior;Biological;Biological Assay;Biological Process;Biology;Biomedical Research;Caenorhabditis elegans;chemical genetics;Complement;Development;Diabetes Mellitus;dietary;Disease;Ecology;Endocrine;Family;Future;Genetic;Genetic Screening;Genomics;Germ Lines;Glucosides;Goals;Heart Diseases;Homologous Gene;Human;Incidence;interest;Investigation;Knowledge;life history;life span;lipid metabolism;male;Malignant Neoplasms;Mammals;Medicine;Metabolic dysfunction;Metabolism;metabolome;metabolomics;Methodology;model organism;mutant;Nematoda;Nervous System Disorder;Neurotransmitters;Nuclear Receptors;Nucleosides;Orthologous Gene;Osteoporosis;Pathway interactions;Perception;Phenotype;Physiological;Physiology;PPAR alpha;Research;Resistance;Role;Sampling;Serotonin;Signal Pathway;Signal Transduction;Signaling Molecule;small molecule;Steroid Receptors;Stress;transcriptomics;Work

PROJECT_TITLE: Small Molecule Signaling in Caenorhabditis elegans


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Project Narrative The synthetic strategies developed in this project will help pave the way to invent new drug discovery approaches. From our screening efforts, we anticipate finding small-molecule inhibitors and probes that may have the potential to be further developed into new drug candidates to treat bacterial and viral infection as well as cancer.

PI_NAMEs: SHARPLESS, KARL BARRY (contact)

PROJECT_TERMS: Amines;Bacterial Infections;Binding Proteins;Biological;Chemical Structure;Chemicals;Chemistry;Development;drug candidate;drug discovery;Family;Fluorides;Fluorine;Goals;In Vitro;in vivo;inhibitor;invention;Isotopes;lead optimization;Libraries;Lipid Binding;Malignant Neoplasms;novel therapeutics;Pharmaceutical Preparations;Phenols;Phosphorus;Positron-Emission Tomography;radiotracer;Reaction;screening;small molecule;small molecule inhibitor;small molecule libraries;Sulfur;Virus Diseases

PROJECT_TITLE: Sulfur(VI) Fluoride Exchange (SuFEx): new developments and biological applications


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative Humans show remarkable variation in response to the same infectious agents. Yet, our understanding of the genetic and evolutionary determinants of this variation is still at an early stage. This project will study the impact of genetic variation and natural selection to population variation in the gene expression response of immune cells to live pathogens and other immune stimuli.

PI_NAMEs: BARREIRO, LUIS BRUNO (contact)

PROJECT_TERMS: Address;Africa;Autoimmune Diseases;Biology;Cells;Chronic;Communicable Diseases;Complex;Disease;Environment;Epigenetic Process;Evolution;Gene Expression;Genes;Genetic;Genetic Drift;Genetic Transcription;genetic variant;Genetic Variation;Genomics;Host Defense;Human;Human Genome;human migration;Immune;Immune response;Immune system;Immunity;Individual Differences;infancy;Infection;Infectious Agent;Inflammatory;Modernization;Molecular;Natural Selections;pathogen;Pathogenicity;Phenotype;Play;Population;Predisposition;pressure;programs;Research;response;Role;Shapes;Stimulus;trait;Variant

PROJECT_TITLE: Characterizing the genetic and evolutionary determinants of population variation in transcriptional responses to pathogens


ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE/PUBLIC HEALTH RELEVANCE The PEGASUS-2 research program applies precision medicine discovery to improve the effectiveness and safety of drugs administered for common acute conditions. This integrated systems biology approach utilizes multi-omic methods to untangle the biology of drug effectiveness and safety in acute care settings decreasing health care costs and improving patient care.

PI_NAMEs: MONTE, ANDREW ALBERT (contact)

PROJECT_TERMS: Accident and Emergency department;Acute;acute care;analytical method;Award;biobank;Biological Specimen Banks;Biology;Cardiovascular Diseases;Clinical;Data;data integration;Drug Targeting;Effectiveness;Electronic Health Record;Emergency Medicine;Emergency Situation;epigenomics;Funding;Future;Genetic;Genetic Polymorphism;Health Care Costs;improved;Link;Machine Learning;medication safety;Metabolic;metabolomics;Methods;Modeling;multiple omics;Nausea;Pain;Patient Care;Patients;Pharmaceutical Preparations;Pharmacogenomics;Pharmacotherapy;phenotypic data;polygenic risk score;precision medicine;programs;prospective test;Proteomics;public health relevance;Research;Research Personnel;Safety;Site;success;Systems Biology;Therapeutic

PROJECT_TITLE: Personalizing EmerGency/Acute therapeuticS Utilizing Systems biology (PEGASUS-2)


NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Women's Health Research

ORG_CITY: LAS CRUCES

ORG_NAME: NEW MEXICO STATE UNIVERSITY LAS CRUCES

ORG_STATE: NM

PHR: Project Narrative This application focuses on addressing challenges in the general research field of quantitative single cell analysis. We plan to advance time-resolved flow cytometry as a quantitative tool to study a range of biomedical applications with examples that include metabolic models of the dynamic changes in cellular respiration as well as the quantification of exosomes and micro vesicles. Our long-term goal is to support high-throughput cell screening and support pre-clinical and biomedical experiments.

PI_NAMEs: HOUSTON, JESSICA PEREA (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TITLE: Advanced approaches for biomedical measurements using time-resolved and micro-flow cytometry


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative The cells in our body are not just blobs, rather they are complex machines with detailed internal geometries essential for their proper function. Abnormal cell structure is seen in many diseases, and is one of the main methods used to diagnose different types of cancer by examining cells in the microscope. We do not understand how the molecules of life combine to create the complicated shapes and structures seen inside cells, and this is the problem that I am trying to solve.

PI_NAMEs: MARSHALL, WALLACE  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Abnormal Cell;Address;Biological Models;cancer type;Cell Physiology;cell type;Cells;Cellular biology;Cellular Structures;Complex;Development;Diagnosis;Disease;Engineering;Flagella;Genetic;Genomics;Geometry;Human body;Image Analysis;interdisciplinary approach;Learning;Length;Life;Link;mathematical model;Methods;Microscope;Microscopy;model organism;Molecular Biology;Morphogenesis;nanomachine;Natural regeneration;Organelles;Organism;Physics;Physiological;Regulation;Shapes;Structure;tool;Work

PROJECT_TITLE: Origins of Cell Geometry


ORG_CITY: STANFORD

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE: The goal of our lab is to uncover the basic principles of gene and chromatin regulation that govern single-cell dynamic responses, distill them into predictive mathematical models, and use this information to build effective and reliable tools for genetic and epigenetic control of endogenous and synthetic genes in human cells. Using high-throughput synthetic biology and single-cell methods, we will systematically measure and model the mechanisms and dynamic capabilities of different gene regulatory components: human and viral transcription factors and chromatin regulators, and their associated DNA elements (enhancers, promoters, and insulators). These measurements, models, and tools are essential for understanding how gene regulation and epigenetic mechanisms contribute to cellular decisions such as cell differentiation, immune response, and cancer progression, and they will enable safer and more efficient genetic, epigenetic, and cellular therapies.

PI_NAMEs: BINTU, LACRAMIOARA  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;Aging;Architecture;Binding;Biological Process;Biophysics;Catalogs;Cell Differentiation process;Cell Therapy;cell type;Cells;Chromatin;Development;Disease;DNA;Elements;Enhancers;Environment;epigenetic memory;Epigenetic Process;epigenetic therapy;Flow Cytometry;Fluorescence Microscopy;Gene Expression;Gene Expression Regulation;Gene Silencing;gene therapy;Genes;Genetic;genetic corepressor;genetic regulatory protein;Goals;Heterogeneity;Human;Human Genome;Immune response;Immune System Diseases;mathematical model;Measurement;Measures;Methods;Modeling;Play;Population;Process;promoter;Proteins;Regulation;Regulatory Element;response;Role;Side;Signal Transduction;single cell analysis;synthetic biology;Synthetic Genes;Time;tool;transcription factor;tumor progression;Viral;Viral Genes;Viral Proteins;Virus Diseases;Work

PROJECT_TITLE: Single-cell analysis and synthetic control of mammalian chromatin dynamics and gene regulation


ED_INST_TYPE: GRADUATE SCHOOLS

PHR: PROJECT NARRATIVE Epithelia are the core cell type of animals, forming protective barriers that also shape most tissues during development. This project will study underinvestigated mechanisms by which extracellular matrix sculpts organs, defects in which can cause congenital malformations. It will also study how damaged epithelial barriers signal to other organs to help the animal respond systemically to injury, including through the Tumor Necrosis Factor signaling pathway.

PI_NAMEs: BILDER, DAVID  (contact)

PROJECT_TERMS: Address;Adult;Animals;antimicrobial;Architecture;Basement membrane;Biochemical;Biology;cell type;Chronic;Collaborations;Communication;Congenital Abnormality;Defect;Development;Disease;Distant;Drosophila genus;empowerment;epithelial injury;Epithelium;experimental study;Extracellular Matrix;Foundations;Funding;Genetic;Goals;Health;Homeostasis;Image;Immune response;Inflammation;Injury;Investigation;Knowledge;Laboratories;mechanical properties;Mechanics;Mediating;Morphogenesis;Movement;multidisciplinary;National Institute of General Medical Sciences;Normal tissue morphology;Organ;Pathology;Pathway interactions;Pattern;Phylogeny;programs;Research;Resistance;response;Shapes;Signal Pathway;Signal Transduction;Signaling Molecule;Sterility;Techniques;tissue repair;Tissues;TNF gene;transmission process;Work;wound response

PROJECT_TITLE: Epithelial biology: morphogenesis and damage signaling


NIH_SPENDING_CATS: Neurosciences;Sleep Research

ORG_CITY: DAVIS

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The circadian clock controls most aspects of human life and health. Based on our studies during the past 13 years, we believe that temperature preference rhythm in Drosophila is an innovative model for understanding fundamental regulatory mechanisms of body temperature rhythms in mammals. Our studies will expand the current understanding of mammalian body temperature rhythm, sleep disorders, and general sleep-associated issues, such as jet lag or the sleep disturbances common to night-shift workers.

PI_NAMEs: HAMADA, FUMIKA  (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Body Temperature;Calcitonin Receptor;circadian pacemaker;Circadian Rhythms;Disease;Drosophila genus;Environment;Exhibits;fly;Foundations;Genes;Goals;Health;Homeostasis;Homologous Gene;Human;Human body;innovation;insight;Jet Lag Syndrome;Knowledge;Life;Link;Mammals;Metabolism;Modeling;Molecular;Motor Activity;neural circuit;neuromechanism;Neuropeptide Receptor;Outcome;Output;Pacemakers;Pathway interactions;Pattern;Physiology;preference;Process;Receptor Signaling;Research;shift work;Sleep;Sleep Disorders;Sleep disturbances;sleep regulation;Temperature;Time;Wakefulness

PROJECT_TITLE: Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

STUDY_SECTION: MRAD

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


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

PHR: Automated docking is a workhorse for rational drug design, however, applying these methods to peptides has remained challenging, thus impeding the rational designing of peptide-based therapeutic approaches. We have been at the forefront of the development peptide-docking docking methods with our state-of-the-art physics- based docking engine, AutoDock CrankPep (ADCP), which can successfully dock linear and cyclic peptides with up to 20 standard amino acids, and we have established that AlphaFold2 multimer and ADCP can be combined to achieve higher docking success rates. We will further develop ADCP to support more therapeutic peptides; synergistically combine it with AlphaFold2 multimer; and explore the use of these protein-peptide docking methods for approaching peptide-peptide docking, yielding docking tools that will impact the research of many computational and medicinal chemists and biologist, contribute to our understanding of biological processes, and significantly advance biomedical research.

PI_NAMEs: SANNER, MICHEL F. (contact)

PROJECT_TERMS: Amino Acids;Benchmarking;Binding;Biological;Biological Process;biological systems;Biology;Biomedical Research;Brain Injuries;Cell Physiology;Chemicals;Collaborations;Communities;Computer software;Computing Methodologies;Cyclic Peptides;Cyclization;Data;Data Set;deep learning;design;Development;Docking;Drug Design;frontier;in silico;Medicine;Methods;novel;Open Reading Frames;open source;peptide drug;Peptides;Physics;Play;polypeptide;pre-clinical;prevent;Production;programs;Proteins;rational design;Research;Research Support;Role;small molecule;software development;Software Tools;stroke patient;structural biology;Structure;success;Therapeutic;tool;translational applications;translational impact;vaccine development;Work

PROJECT_TITLE: Structure-based in-silico prediction of peptide interactions.


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: DURHAM

ORG_NAME: DURHAM VA MEDICAL CENTER

ORG_STATE: NC

PHR: Colorectal cancer (CRC) is prevented through screening for colon cancer precursors and continued preventive exams over time. Risk stratification is a personalized medicine approach that identifies individuals at high risk and low risk and provides the right amount of CRC prevention through determining the timing and frequency of colonoscopy. In order to achieve risk stratification for CRC prevention we need models that incorporate the history of CRC screening and results for each Veteran, as well as incorporate other factors, like genetic risk factors. The goal of this project is to build statistical and computational methods, databases, and specimen biorepositories using the VA medical record that follow Veterans over time to support research into building tools that include polyp genetic information for better CRC risk stratification.

PI_NAMEs: HAUSER, ELIZABETH R (contact)

PROJECT_TERMS: age effect;Algorithms;analytical tool;Big Data;biobank;Biological;Biological Specimen Banks;Biometry;Cancer Etiology;cancer risk;Catalogs;Cessation of life;Clinical;Clinical Data;clinical practice;clinical risk;cohort;colon cancer screening;Colonic Adenoma;Colonoscopy;Colorectal Cancer;colorectal cancer prevention;colorectal cancer progression;colorectal cancer risk;colorectal cancer screening;Colorectal Neoplasms;Computational Biology;computerized tools;Computing Methodologies;cooperative study;Data;data integration;data quality;data resource;Data Science;Data Scientist;Data Set;data tools;Databases;design;Development;Disease;Evaluation of Risk Factors;Excision;experience;Exposure to;follow-up;Frequencies;Future;Genetic;genetic analysis;genetic information;Genetic Markers;Genetic Models;Genetic Risk;genetic risk factor;genomic biomarker;genomic data;Genomics;Goals;Grant;Guidelines;Healthcare Systems;high risk;high risk population;Histopathology;Human Genetics;improved;Incidence;Individual;Joints;Libraries;Longitudinal cohort;Longitudinal Studies;Medical Records;military veteran;Modality;Modeling;mortality;mortality risk;Mutation;novel;Pathology;personalized medicine;phenomics;Phenotype;Pilot Projects;polygenic risk score;Polyps;Precancerous Polyp;prevent;Prevention;Preventive;prognostic;programs;progression risk;prospective;Recording of previous events;Research;Research Personnel;research study;Research Support;Resources;Risk;Risk Assessment;Risk Factors;risk prediction;risk prediction model;risk stratification;Safety;Sampling;screening;Somatic Mutation;Specimen;Statistical Methods;Statistical Models;Testing;Time;tissue resource;Tissues;tool;tv watching;United States;Universities;Veterans;Work

PROJECT_TITLE: Building Data Science Tools for Genetic Models of Colorectal Cancer Progression and Risk


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Dementia is a serious issue for Veterans, particularly given the increasing age of Veterans in VA. We will use data from the Million Veteran Program (MVP), one of the world’s largest biobanks, to examine the genetic underpinnings of dementia risk in Veterans. This includes genome-wide association studies of MVP participants of multiple ancestry groups. We will also use new methods to increase the accuracy of dementia genetic risk scores in African American and Hispanic populations, reducing a possible source of health disparities. In addition, we will look for genetic variants that interact with combat related exposures and health problems that occur often in Veterans to increase risk of dementia. Finally, we will refine our algorithms for identifying cases of dementia in the VA electronic medical record, which will increase our power to detect genetic associations. All of this will represent a leap forward in what is known about the genetic architecture of dementia, and in African American and Hispanic Veterans in particular.

PI_NAMEs: LOGUE, MARK W (contact)

PROJECT_TERMS: Address;African;African American;African ancestry;Age;Age-associated memory impairment;agent orange;Aging;Algorithms;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;Benchmarking;biobank;Blood Vessels;Clinical;Cognitive;cognitive testing;cohort;Cohort Studies;combat;combat trauma;Complex;Computerized Medical Record;Craniocerebral Trauma;Data;Dementia;dementia risk;Development;Diabetes Mellitus;Diagnosis;disorder risk;Disparity;Early Diagnosis;effective therapy;Environment;Environmental Exposure;Environmental Risk Factor;follow-up;gene environment interaction;Genes;Genetic;genetic analysis;genetic architecture;genetic association;Genetic Diseases;Genetic Risk;genetic risk factor;genetic variant;Genome;genome wide association study;genome-wide;Genomics;Genotype;Health;health disparity;Hispanic;Hispanic ancestry;Hispanic Populations;human old age (65+);Impaired cognition;improved;Individual;International Classification of Disease Codes;Knowledge;Late Onset Alzheimer Disease;Link;Machine Learning;machine learning method;Medical Records;Methods;mild cognitive impairment;Military Personnel;Not Hispanic or Latino;Participant;Pathology;Patient Self-Report;Patients;Performance;Phenotype;phenotyping algorithm;polygenic risk score;Population;Post-Traumatic Stress Disorders;Prevalence;programs;Proxy;Psychopathology;Reporting;Research Priority;Risk;Risk Factors;risk prediction;risk variant;Sensitivity and Specificity;Source;symptomatology;Techniques;Toxin;Trauma;Traumatic Brain Injury;Variant;Vascular Dementia;Veterans;Work

PROJECT_TITLE: Early Cognitive Impairment as a function of Alzheimer's Disease and Trauma


PHR: Gulf War Illness (GWI) is a chronic, debilitating illness suffered by Veterans of the 1990-1991 Gulf War. Veterans suffering from GWI are often subject to years of medical uncertainty as they make their way through multiple clinics to try to diagnose and ultimately treat their chronic symptoms, if possible. Complicating this medical journey is the absence of biomarkers that can be used to diagnose the conditions and that might provide clues as to treatments and etiology. We will use the Gulf War Era Cohort and Biorepository to test metabolomic biomarkers and combine metabolomics data with genetic variation to identify pathways important in Gulf War Veterans Illnesses. Our results hold promise for rapid incorporation of findings into biomarker discovery and validation and ultimately treatment studies and clinical trials.

PROJECT_TERMS: Affect;affective disturbance;analytical tool;Award;biobank;Biological;Biological Assay;Biological Markers;biological systems;biomarker discovery;biomarker identification;biomarker validation;Biomedical Technology;Blood;Characteristics;Chronic;Clinic;Clinical Trials;cohort;Communities;comorbidity;Complement;Complex;Data;data integration;data repository;Data Set;Databases;design;Development;Diagnosis;Disease;Distress;DNA Modification Process;effective therapy;epidemiology study;Epigenetic Process;Etiology;Exanthema;experience;experimental study;Fatigue;gastrointestinal;Genes;Genetic;Genetic Markers;genetic variant;Genetic Variation;Genome;genome wide association study;genome-wide;Genomics;Genotype;Goals;Gulf War;Gulf War veteran;Headache;Health;immune function;Individual;Inflammation;instrument;Laboratories;Life;Lipids;liquid chromatography mass spectrometry;Machine Learning;machine learning method;Measures;Medical;medical complication;Metabolic;Metabolic Pathway;metabolome;metabolomics;Methods;Methylation;mitochondrial dysfunction;Modernization;Molecular;Neurocognitive;Pain;Participant;Pathway interactions;Patients;Persian Gulf;Persian Gulf Syndrome;persistent symptom;Phenotype;Physiological;Preparation;programs;Quality Control;Research;research and development;Research Personnel;Research Project Grants;Research Proposals;Resources;response;Sample Size;Science;small molecule;Subgroup;Surveys;symptom cluster;Symptoms;Systems Biology;Techniques;Testing;Therapeutic Research;Therapeutic Trials;Tissues;Treatment Efficacy;Uncertainty;Validation;Veterans;Work

PROJECT_TITLE: Integrating genomics and metabolomics data to identify molecular characteristics of Gulf War Veterans' illnesses


ORG_CITY: NORTHPORT

ORG_NAME: NORTHPORT VA MEDICAL CENTER

PHR: Military personnel are at an increased risk of developing blood cell mutations due to their exposure to various environmental hazards. The goal of this proposal is to understand how hematopoietic mutation promotes cardiovascular diseases. The findings from the proposed studies will improve our treatment of two of the most important human health threats, cancer and heart disease.

PI_NAMEs: ZHAN, HUICHUN  (contact)

PROJECT_TERMS: Acceleration;Adhesions;Adult;Affect;Age;Aorta;beta-Galactosidase;Binding;Blood Cells;Blood Vessels;Cardiac;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Physiology;cardiovascular risk factor;Cardiovascular system;CDKN2A gene;Cell Adhesion Molecules;Cell Aging;Cell Cycle;Cell Line;Cell Physiology;cell type;Coronary artery;Development;Diet;Disease;E-Selectin;Echocardiography;Endothelial Cells;endothelial dysfunction;Endothelium;Environmental Hazards;Event;experimental study;Exposure to;Functional disorder;Genes;Genetic;Goals;Harvest;Health;Heart;Heart Diseases;Heart failure;Hematopoiesis;Hematopoietic;hematopoietic stem cell expansion;Hematopoietic stem cells;Hemostatic function;High Fat Diet;Hospitalization;Human;human disease;human model;improved;In Vitro;in vivo;Incidence;Individual;Induced Mutation;induced pluripotent stem cell;inhibitor;insight;JAK2 gene;knock-down;Knock-out;Leukocytes;Lung;Malignant Neoplasms;Measures;Mediating;Methods;Military Personnel;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;MPL gene;Mus;mutant;Mutation;Myeloproliferative disease;Older Population;Pathology;Patients;Persons;Phenotype;Phosphotransferases;Play;premature;Production;Proteins;receptor;Reporting;Risk;Risk Factors;Role;senescence;Signal Transduction;Site;Small Interfering RNA;stem;stem cells;Testing;thrombogenesis;Thrombopoietin;Thrombosis;Time;Toxic Environmental Substances;Transgenic Organisms;Vascular Diseases;Vascular Endothelial Cell;Vascular Endothelium;Venous;Veterans;Work

PROJECT_TITLE: Endothelial dysfunction in clonal hematopoiesis and its contribution to cardiovascular complications


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Regenerative Medicine;Sarcopenia;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT NARRATIVE Sarcopenia, the age-dependent loss of skeletal muscle mass and strength, is a major public-health problem that affects the elderly, leading to loss of mobility, long-term care institutionalization, and diminished quality of life. Muscle stem cells (MuSCs) are key drivers of muscle regeneration, and MuSC subpopulations exhibit considerable heterogeneity in their regenerative capacity, especially with aging. Here we will develop novel strategies to isolate, characterize and overcome the defects in the dysfunctional aged MuSC subset and the aged stem cell niche, informing potential therapeutics to improve skeletal muscle regeneration in the elderly.

PI_NAMEs: BLAU, HELEN M (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: 3' Untranslated Regions;Affect;age related;age related decline;age-related muscle loss;aged;Aging;aging related;American;Architecture;Biological Assay;Blocking Antibodies;CD36 Antigens;CD47 gene;Cell Count;Cell Physiology;Cell surface;Cells;Censuses;Cyclic AMP;Cytometry;Data;data integration;Defect;Detection;Dimensions;Elderly;Exhibits;falls;frailty;Functional disorder;Generations;Goals;Heterogeneity;Homeostasis;Impairment;improved;in vivo;in vivo evaluation;Incidence;indexing;Injury;innovation;insight;Institutionalization;Investigation;Kinetics;Knowledge;Lead;Long-Term Care;Maps;Measurement;Molecular;Morbidity - disease rate;Movement;Mus;Muscle;muscle aging;muscle form;Muscle function;muscle progenitor cell;muscle regeneration;muscle repair;muscle strength;Muscular Atrophy;Natural regeneration;neutralizing antibody;novel;novel strategies;novel therapeutic intervention;novel therapeutics;old mice;Outcome;p38 Mitogen Activated Protein Kinase;paracrine;Phenotype;Polyadenylation;Population;Population Heterogeneity;Post-Transcriptional Regulation;posttranscriptional;prevent;Proliferating;prospective;Proteins;PTPNS1 gene;Public Health;Quality of life;receptor;regeneration model;regenerative;Regenerative capacity;Regenerative response;Research;resilience;Resolution;sarcopenia;self-renewal;Series;Signal Transduction;single cell technology;single-cell RNA sequencing;Skeletal Muscle;skeletal muscle wasting;stem cell aging;stem cell expansion;stem cell function;stem cell niche;stem cell population;Surface;Technology;Therapeutic;Therapeutic Intervention;Thrombospondin 1;Tissue imaging;Tissues;tool;Transcript;transcriptome sequencing;Up-Regulation

PROJECT_TITLE: Control of Muscle Stem Cells to Enhance Regeneration

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: Project Narrative  Alzheimer’s disease (AD) is the leading cause of late-onset dementia affecting a large population of our aging society, yet we still do not have an effective way to treat this devastating disease. Towards this, the goal of this project is to understand the molecular etiology of AD by studying a strong genetic risk factor TREM2 which modulates microglial functions and immune responses in the brain. In vivo mouse models and in vitro iPSC cellular models will be used to collectively address the dynamic effects of TREM2-mediated molecular pathways to both inform disease mechanisms and suggest treatment strategies.

PI_NAMEs: ZHAO, NA  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: 3-Dimensional;Abeta clearance;abeta deposition;abeta toxicity;Address;Affect;Aging;aging brain;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;amyloid formation;amyloid pathology;Apolipoprotein E;Behavior;Biochemical;Biological Models;Brain;Cell Line;Cell model;cell type;Cells;Cerebrum;Cognitive;CRISPR/Cas technology;Dementia;density;Deposition;Development;Disease;Disease Progression;Electrophysiology (science);Etiology;Future;Gene Delivery;gene editing technology;Genes;genetic risk factor;genomic locus;Goals;histopathological examination;Human;human induced pluripotent stem cells;human model;human old age (65+);Image;Immune;Immune response;In Vitro;in vivo;in vivo Model;induced pluripotent stem cell;Inflammatory Response;Injury;innovation;Knock-in;Knock-out;Knowledge;loss of function;Mediating;Messenger RNA;Metabolism;Methods;Microdialysis;Microglia;middle age;Modeling;Molecular;Molecular Profiling;Molecular Target;Morphology;mouse model;Mus;Mutation;Nerve Degeneration;Neurons;novel;Organoids;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Phagocytosis;pharmacologic;Population;Process;rare variant;risk variant;RNA Splicing;Role;Senile Plaques;single-cell RNA sequencing;Societies;stem cell model;Synapses;System;tau Proteins;Tauopathies;Techniques;Technology;Testing;Toxic effect;transcriptome sequencing;treatment strategy;TREM2 gene;two photon microscopy;two-photon;Validation;Variant

PROJECT_TITLE: TREM2-mediated microglial dynamic function in Alzheimer disease

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Mental Health;Nanotechnology;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative The proposed research is relevant to public health because the 3D bioprinted stem cell platform developed here will permit a new degree of precision and sophistication towards in vitro modeling of brain development. This approach will enable modelling the dynamic architecture and physiology of the developing human brain, which is imperative for understanding neurodevelopmental disorders. Our work will accelerate the design and application of technologies for manipulating complex, multicellular human stem cell models with robotic level precision.

PI_NAMEs: SERPOOSHAN, VAHID ;SLOAN, STEVEN A (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: 3-Dimensional;Acceleration;Achievement;Address;Architecture;Bathing;Behavior;Benchmarking;Biocompatible Materials;bioink;Biological;Biological Assay;Biological Models;Biomechanics;Biomedical Engineering;bioprinting;Brain;brain parenchyma;brain tissue;cell behavior;Cell Differentiation process;Cell Survival;Cells;Complex;cost;cranium;Cues;Custom;design;Development;Diffusion;Disease;Distress;Dorsal;Electrophysiology (science);Elements;Emotional;Encapsulated;Environment;extracellular;Extracellular Matrix;Financial Hardship;Generations;Geometry;Glycoproteins;Glycosaminoglycans;Goals;Health;Histologic;Histology;Human;human induced pluripotent stem cells;human model;human stem cells;hydrogel scaffold;Image;In Vitro;in vitro Model;Individual;innovation;Kinetics;Laboratories;Leadership;Light;matrigel;Measurement;Measures;meter;Methods;Modeling;Molecular;morphogens;nano;nanoparticle;Nanotechnology;Nature;nervous system development;Nervous System Disorder;Nervous System Physiology;neural;neural circuit;neural model;neurodevelopment;Neurodevelopmental Disorder;Neurons;Neurosciences;novel;Organoids;Output;Pattern;photoactivation;physical property;Physiological;Physiology;prevent;Printing;Proliferating;Property;Proteins;Proteoglycan;Protocols documentation;Public Health;Reagent;Reproducibility;Research;Resolution;Robotics;Role;scaffold;Scheme;Shapes;SHH gene;Signal Transduction;Signaling Molecule;single-cell RNA sequencing;skills;small molecule;smoothened signaling pathway;spatial integration;spatiotemporal;stem cell fate;stem cell model;stem cells;success;synergism;System;Technology;Testing;Tissue constructs;Tissue Engineering;Tissues;tool;Work

PROJECT_TITLE: Leveraging 3D bioprinted organoid constructs to pattern and model human brain development

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences

ORG_DEPT: PSYCHIATRY

PHR: Project Narrative In this proposal, we describe experiments aimed at understanding the distributed circuits that generate adaptive avoidance behavior, and how they may become disrupted in states of increased anxiety. Understanding these circuits is the first step in the generation of novel, targeted, circuit based therapeutics for the treatment of mood and anxiety-related disorders.

PI_NAMEs: KHEIRBEK, MAZEN A (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Adaptive Behaviors;Adopted;Adult;American;Amygdaloid structure;anatomical tracing;Anatomy;Anxiety;Anxiety Disorders;anxiety-like behavior;anxiety-related behavior;anxiety-related disorders;Area;Arousal;avoidance behavior;Axon;Beds;Behavior;Behavior assessment;Behavior Control;Behavioral;behavioral response;biological adaptation to stress;Biological Assay;Cell Nucleus;cell type;Classification;Complex;Conflict (Psychology);Data;Detection;Electrophysiology (science);Emotional;emotional behavior;experimental study;Financial Hardship;Fright;Functional disorder;Functional Imaging;Funding;Gene Expression Profiling;Generations;Goals;Hippocampus;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Image;innovation;Lateral;Learning;maladaptive behavior;Maps;Mediating;microendoscope;Moods;Mus;nerve supply;neural circuit;Neurons;neurophysiology;neuroregulation;novel;Optics;optogenetics;Organizational Productivity;Output;Population;Property;Publishing;Resolution;Role;Shapes;Slice;Stimulus;Stress;Structure;Structure of paraventricular nucleus of thalamus;Testing;Thalamic structure;Therapeutic;tool;treatment of anxiety disorders;Work

PROJECT_TITLE: Hippocampal modulation of subcortical circuits in the control of emotional behavior

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Genetics;Lung;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: NEUROSCIENCES

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Breathing disorders, ranging from sleep apneas to respiratory failure, which is the leading cause of death in Amyotrophic Lateral Sclerosis (ALS), are caused by disruptions in the connections between the neurons and muscles that control breathing. This proposal aims to understand the genetic and molecular mechanisms that control the development and maintenance of respiratory neurons, in an attempt to identify novel therapeutic targets for respiratory dysfunction.

PI_NAMEs: PHILIPPIDOU, POLYXENI  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Address;Adult;Air Movements;alternative treatment;Amyotrophic Lateral Sclerosis;Automobile Driving;axon guidance;Behavior;Behavioral Assay;Binding Sites;Biological Assay;Birth;body position;Brain Stem;Breathing;Cause of Death;Cells;Cervical spinal cord structure;ChIP-seq;cofactor;Collagen;coping;CRISPR/Cas technology;Defect;Development;developmental disease;Disease;Electrophysiology (science);Embryo;Enhancers;Excision;Exhibits;Frequencies;Genes;Genetic;genetic approach;Genetic Diseases;Genetic Models;Genetic Transcription;Goals;High-Throughput Nucleotide Sequencing;Homeobox Genes;HOX protein;improved;in vivo;insight;Interneurons;Lead;Life;Limb structure;Lung;Maintenance;Mammals;Maps;Mediating;Membrane;Metabolic;Methodology;Methods;Molecular;Motor;Motor Activity;motor behavior;motor neuron development;Motor Neuron Disease;Motor Neurons;Movement;Mus;Muscle;Muscular Dystrophies;Mutant Strains Mice;nerve supply;neural circuit;neural network;Neurodegenerative Disorders;Neurons;new therapeutic target;Pathway interactions;Pattern;Perinatal mortality demographics;Plethysmography;Predisposition;programs;promoter;protein function;Proteins;Regulatory Element;Repression;Respiration Disorders;respiratory;Respiratory Diaphragm;Respiratory Failure;Respiratory physiology;Rett Syndrome;Role;Sleep Apnea Syndromes;Specific qualifier value;Spinal;Spinal Cord;Spinal cord injury;Sudden infant death syndrome;Synapses;Testing;transcription factor;transcription factor Oct-6;transcriptome sequencing;Transgenic Mice;Vertebrates

PROJECT_TITLE: Genetic Control of Phrenic Motor Neuron Development and Maintenance

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Asthma;Biotechnology;Health Effects of Indoor Air Pollution;Lung;Prevention

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: NARRATIVE We have discovered an E3 ubiquitin ligase, Cul5, that becomes activated following T cell receptor stimulation and then functions in T cells to limit their differentiation into pathogenic Th2 and Th2/17 cells. Cul5 thus prevents the development of asthma following allergen exposure. We now propose studies that will reveal the biology and mechanistic underpinnings of how this ligase functions in T cells. These studies will provide molecular insight into how Th2/17 cells develop and drive pathology, and will aid the rational design of therapies that target this pathway.

PI_NAMEs: OLIVER, PAULA MARIA (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Acute;Affect;Airway Disease;airway remodeling;Allergens;allergic airway disease;American;Antigens;Asthma;asthma model;asthmatic patient;Binding;Biochemical;Bioinformatics;Biological;Biological Products;Biology;Cell Count;Cell Differentiation process;Cell Physiology;Cell secretion;Cell Survival;Cells;Cellular biology;Cessation of life;Chronic;chronic inflammatory disease;Clinic;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Complex;Cullin Proteins;cytokine;Cytoprotection;Data;Development;Disease;Eosinophilia;Etiology;Extrinsic asthma;Fibrosis;Foundations;Glycylglycine;Goals;Goblet Cells;Hyperplasia;In Vitro;in vivo;Individual;Inflammation;Inflammatory;insight;Interleukin-9;Ligase;Mass Spectrum Analysis;mast cell;Mediating;Methods;Modeling;Molecular;Mouse Strains;Mus;novel;novel therapeutic intervention;Pathogenicity;Pathology;Pathway interactions;Patients;Predisposition;prevent;Production;Proteins;Proteomics;Pulmonary Inflammation;Pyroglyphidae;rational design;receptor;recruit;Reporter;response;Role;screening;Severities;Severity of illness;Signal Pathway;small molecule;success;T cell differentiation;T-Cell Receptor;T-Lymphocyte;targeted treatment;Th2 Cells;Therapeutic;therapy development;tool;transcriptome sequencing;Ubiquitin;ubiquitin ligase;ubiquitin-protein ligase

PROJECT_TITLE: A Cul5 E3 ubiquitin ligase complex that prevents allergic asthma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)R]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Kidney Disease;Rare Diseases

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Mutations in the INF2 gene cause kidney disease in humans. Many different changes in this gene cause the filtering units of the kidney, the glomeruli, to function improperly. A better understanding of how defects in this gene cause human disease will have significant and direct implications for understanding both rare and common forms of kidney disease.

PI_NAMEs: HIGGS, HENRY N;POLLAK, MARTIN R. (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: Acceleration;Acetylation;Actins;Behavior;Binding;Binding Proteins;Biochemical;Biological;Biology;C-terminal;Calcium;Cells;Charcot-Marie-Tooth Disease;Complement;Complex;constriction;Defect;depolymerization;Disease;disease-causing mutation;Disinhibition;Endoplasmic Reticulum;Event;Exhibits;Family member;Focal and Segmental Glomerulosclerosis;formin-2;Functional disorder;gain of function;Genes;genetic regulatory protein;Genetically Engineered Mouse;Goals;Golgi Apparatus;Grant;Human;human disease;in vivo;Inherited;Kidney;Kidney Diseases;Knockout Mice;Lead;loss of function;Mediating;Mitochondria;Molecular;Monomeric GTP-Binding Proteins;mouse model;Mus;mutant;Mutation;N-terminal;Organelles;Persons;Phenotype;Play;podocyte;Point Mutation;polymerization;Polymers;protein complex;Protein Isoforms;Protein Region;Proteins;Regulation;RNA Splicing;Role;segregation;Site;stressor;Testing;Therapeutic;Time;Variant

PROJECT_TITLE: Biological Mechanism of INF2-mediated FSGS

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Cystic Fibrosis;Infectious Diseases;Lung;Pediatric;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: This K24 renewal award provides salary support for Dr. Hauser to spend 33% of his time mentoring MD fellows and junior faculty and expanding his patient-oriented research program. Patient-oriented research will focus on the bacterial pathogen Pseudomonas aeruginosa and will provide an ideal vehicle for the training of junior clinician investigators.

PI_NAMEs: HAUSER, ALAN R (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acute Pneumonia;Acute respiratory infection;Age;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Award;Bacteria;Biological Markers;biomarker identification;Bronchoalveolar Lavage;Categories;Cessation of life;Child;children with cystic fibrosis;Chronic;chronic infection;Clinical;Clinical Data;Clinical Trials;collaborative environment;Complication;Cystic Fibrosis;cystic fibrosis patients;Death Rate;Deterioration;Development;Disease;Doctor of Philosophy;Faculty;Failure;Fostering;Funding;Genes;Genetic;Genetic Diseases;Genetic Transcription;Genome;Genomics;Goals;Human;improved;Individual;Infection;Infection Control;Institution;Integration Host Factors;Intensive Care Units;Learning;Life;Link;Lung;Lung infections;Lung Transplantation;Mechanical ventilation;Mentors;Metabolic;Methodology;Microbiological Techniques;Mid-Career Clinical Scientist Award (K24);Monitor;Morbidity - disease rate;mortality;mouse model;Multicenter Studies;neutrophil;Outcome;Pathogenesis;pathogenic bacteria;Patient Care;patient oriented;patient oriented research;Patients;Pattern;Physicians;Play;Pneumonia;Population;Process;prognostic;programs;prospective;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pseudomonas Infections;pulmonary function;Randomized;Regimen;Research;Research Personnel;Resources;respiratory;Respiratory Tract Infections;Role;Sampling;Scientist;Severities;skills;Specimen;Systems Biology;Techniques;Testing;Time;Training;trait;United States National Institutes of Health;Universities;ventilator-associated pneumonia;Wages;Work

PROJECT_TITLE: Patient-Oriented Research on Pseudomonas aeruginosa

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Hearing Loss;Neurosciences;Prevention;Tobacco

ORG_CITY: IRVINE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Nicotine enhances auditory and cognitive functions because it mimics the brain’s system for “paying attention” to important sounds amid distractions (for example, understanding speech in a noisy environment). In part, nicotine does this by activating inhibitory neurons in the auditory cortex. Since age-related hearing deficits result in part from the loss of inhibitory neurons, this project will determine, in humans and mice, whether nicotine’s effects can compensate for reduced inhibition in aging and thereby restore auditory function.

PI_NAMEs: METHERATE, RAJU  (contact);RAZAK, KHALEEL A;SILVER, MICHAEL A;ZENG, FAN-GANG

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: absorption;Accounting;Acoustics;Acute;Address;Adult;Affect;Age;age effect;age related;age related changes;age related decline;Aging;aging related;Area;Attention;Auditory;Auditory area;Auditory Perception;auditory processing;Behavior;Behavioral;Biological Markers;biomarker identification;Brain;Brain imaging;Cells;Chronic;Clinical;Cognitive;Cognitive deficits;cognitive enhancement;cognitive function;Compensation;density;Detection;Development;Disease;distraction;drug candidate;Drug Combinations;drug development;Drug Kinetics;Drug Targeting;effective therapy;Elderly;Electroencephalography;Electrophysiology (science);Environment;Exercise;Frequencies;Functional Magnetic Resonance Imaging;functional magnetic resonance imaging/electroencephalography;FVB Mouse;Goals;Hearing;Hearing Aids;hearing impairment;Human;Hypertension;Image;Impaired cognition;Impairment;improved;In Vitro;in vivo;inhibitory neuron;Interneurons;Measures;Mental Depression;modifiable risk;Mus;neural;Nicotine;nicotine exposure;nicotine use;Nicotinic Receptors;Noise;non-smoker;Normal Range;novel;Oral;Outcome;Outcome Measure;Perception;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacological Treatment;Pharmacotherapy;Physiological;Physiology;Population;preclinical development;Presbycusis;Property;Psychoacoustics;Quality of life;receptive field;reduce symptoms;Reporting;Rest;Risk;Risk Factors;Route;Sensory;Slice;Smoking;smoking cessation;Social isolation;sound;species difference;Speech;Speech Perception;Stimulus;System;Techniques;Testing;Therapeutic;Tobacco;Topical application;Training;Translations

PROJECT_TITLE: Using nicotine to reverse age-related auditory processing deficits

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Mental Health;Neurosciences

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: Project Narrative Habits have a remarkable level of control over our everyday behavior, and they can be helpful (e.g., routine exercise) or detrimental (e.g., compulsive eating) to one’s well-being. Animal research has revealed specific brain areas that govern habit formation, allowing for further investigation to resolve finely timed neural mechanisms related to the acquisition and expression of habits. The project proposed here is pertinent to NIH’s mission that relates to developing necessary knowledge and insight about the precise neural mechanisms underlying how habits are controlled, how habits can be contextualized as arising from a network of brain areas, and how adulterations of normal habit signaling might contribute to obsessive-compulsive disorder, Tourette syndrome, and compulsive eating.

PI_NAMEs: AMAYA, KENNETH  (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Address;Amygdaloid structure;Animal Experimentation;Animals;Area;base;Basic Science;Behavior;Behavioral;behavioral phenotyping;behavioral response;Binge Eating;Brain;career;Cell Nucleus;cell type;Characteristics;Chronic;Code;Communication;Complex;Compulsive Behavior;Consultations;Corpus striatum structure;Data;Decision Making;design;Desire for food;Development;Disease;Electrophysiology (science);exercise regimen;Exhibits;expectation;experience;experimental study;Fellowship;flexibility;Food;Future;Gilles de la Tourette syndrome;Goals;Habits;Human;in vivo;in vivo calcium imaging;Individual;insight;interest;Investigation;Knowledge;Learning;Location;Mammals;Mental Health;Methodology;Methods;Mission;Motivation;neural;neural correlate;neuromechanism;neuronal patterning;Neurons;novel;Obsessive-Compulsive Disorder;Outcome;pars compacta;Pattern;Performance;Personal Satisfaction;Phase;Phenotype;Physiological;Postdoctoral Fellow;Prefrontal Cortex;Problem Solving;Process;psychologic;Rattus;Research;Research Personnel;response;Rewards;Rodent;Route;Running;Series;Signal Transduction;Stimulus;Structure;Substantia nigra structure;Techniques;Testing;Training;Translating;United States National Institutes of Health;Work

PROJECT_TITLE: Differential routing of valence information through the basolateral amygdala


ED_INST_TYPE: SCHOOLS OF OSTEOPATHIC MEDICINE

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

ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative Enzymes called cytidine deaminases are essential for living organisms to regulate nucleotide homeostasis, protect against viral infections, and drive mutations at specific parts of their genome. In this proposal, we will study the mechanism and biological function of a unique cytidine deaminase and its inhibitor that we have discovered in the bacterial pathogen Vibrio cholerae.

PI_NAMEs: NEIDITCH, MATTHEW B;WATERS, CHRISTOPHER M (contact)

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: Address;Bacteria;Bacterial Genome;Bacterial Physiology;Bacteriophages;Binding;Biochemical;Biochemistry;Bioinformatics;Biological;Biological Process;Biology;biotypes;Cells;Cellular biology;Cessation of life;clinically relevant;Collaborations;Cyclic GMP;Cytidine Deaminase;Defense Mechanisms;deoxycytidine deaminase;Discipline;Dissection;Enterobacter cloacae;Enzymes;Escherichia coli;Eukaryota;Evolution;experience;experimental study;Filament;Gene Expression;gene function;Genes;Genetic;Genetic study;Genome;Genomic Islands;Homeostasis;In Vitro;Infection;inhibitor;Island;Life;Microscopy;mutant;Mutation;N-terminal;Names;novel;Nucleic Acids;Nucleotides;Organism;Orthologous Gene;overexpression;pandemic disease;pathogenic bacteria;Peptides;Phosphotransferases;Physiology;Play;prevent;Productivity;Protein Biochemistry;protein complex;Proteins;Proteobacteria;Publications;Recording of previous events;Regulation;Research;Role;Signal Transduction;small molecule;structural biology;Structural Protein;Structure;System;Tertiary Protein Structure;Testing;tool;Toxic effect;Trans-Activators;Trees;Untranslated RNA;Vibrio;Vibrio cholerae;Viral;virtual;Virus Diseases;Water

PROJECT_TITLE: The contribution of novel cytidine deaminase regulatory systems to bacterial evolution

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


ORG_CITY: MINNEAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Public Health Relevance Surgical removal of the pancreas with autologous transplantation of the islets (“TPIAT”) relieves the severe unrelenting pain that can result from chronic pancreatitis. The islet autotransplantation portion of the procedure reduces the need for insulin therapy early after the surgery, but little is known about the long-term diabetes outcomes in patients who have had a TPIAT. In this study, we will evaluate how well islets function 5- 20 years after an islet autotransplant, what factors and hormones are important in regulating blood glucose [preventing high and low blood glucose], and whether diabetes complications are reduced by having functioning islets.

PI_NAMEs: BELLIN, MELENA D. (contact)

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TERMS: acute pancreatitis;Alpha Cell;Anatomy;Autologous Transplantation;Beta Cell;Blinded;Blood Glucose;C-Peptide;Cell Physiology;Cellular Stress;Chronic;chronic pancreatitis;Clinical;clinical care;clinically significant;Closure by clamp;cohort;Complex;Complications of Diabetes Mellitus;Continuous Glucose Monitor;counterregulation;Cross-Sectional Studies;Data;diabetes management;Diabetes Mellitus;Diabetic Ketoacidosis;Diabetic Retinopathy;Disabling;Dose;duodenectomy;Early treatment;endoplasmic reticulum stress;Enrollment;Event;Excision;Face;Functional disorder;Fund Raising;Future;Glucagon;glucagon-like peptide 1;glycemic control;Glycosylated hemoglobin A;Goals;graft function;Hormonal;Hormones;Hospitalization;Hypoglycemia;Impairment;improved;incretin hormone;Insulin;insulin secretion;Insurance;Intractable Pain;islet;Islets of Langerhans Transplantation;Kidney Diseases;L Cells;macrovascular disease;Measurement;Measures;Mediating;Medicaid;Medical;Medicare;Microvascular Dysfunction;Neuropathy;Operative Surgical Procedures;Opioid;Outcome;Pain;pain relief;Pancreas;Participant;patient subsets;Patients;Physicians;Population;Postoperative Period;preservation;prevent;Procedures;Production;Proinsulin;Protocols documentation;public health relevance;Quality of life;reconstruction;recruit;Recurrence;Regulation;Reporting;Research;response;Retinal Diseases;Risk;Risk Reduction;Severities;Source;Testing;Time;Total Pancreatectomy

PROJECT_TITLE: Long-Term Islet Function and Impact after Total Pancreatectomy with Islet Autotransplant (LIFT)

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Available influenza vaccines are insufficient to prevent infections, and alternate strategies are needed. A large proportion of influenza infections are acquired at home. This proposal involves dedicated mentoring of junior investigators in influenza transmission and its prevention, as well as effective execution of studies of factors that can be potentially modified to mitigate the risk of influenza transmission in households.

PI_NAMEs: GRIJALVA, CARLOS G (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: Academic Medical Centers;Accident and Emergency department;Acute respiratory infection;Aerosols;Animals;Anti-viral Agents;associated symptom;Attenuated;Calibration;career;Cessation of life;Child;Clinic;Cohort Studies;cold temperature;Communities;Data;Day Care;Dedications;design;Development;Diagnostic tests;Disease;disease transmission;disorder prevention;economic cost;Effectiveness;Electronics;Enrollment;Environment;Evaluation;Faculty;Family;flu transmission;follow-up;Foundations;Funding;Genetic;health care settings;Health Policy;Home;Hospitalization;Hospitals;Household;Human;Humidity;improved;indexing;Infection;Infection prevention;Influenza;influenza epidemic;influenza infection;Influenza prevention;influenza surveillance;influenza virus vaccine;influenzavirus;instrument;Intervention;Laboratories;Life Style;Link;Measures;member;Mentors;Methods;mid-career faculty;Modeling;Modernization;modifiable risk;Molecular;Molecular Diagnostic Techniques;Morbidity - disease rate;mortality;National Institute of Allergy and Infectious Disease;Natural History;novel;older adult;patient oriented research;Patients;Pattern;Pharmacoepidemiology;Population;Postdoctoral Fellow;Predisposition;prevent;Prevention;Prevention strategy;preventive intervention;Process;prospective;Publications;Recommendation;Research;Research Personnel;Research Priority;Research Project Grants;respiratory;Reverse Transcriptase Polymerase Chain Reaction;Risk;Risk Factors;risk mitigation;Role;sample collection;seasonal influenza;Seasons;Serology;Severities;Severity of illness;skills;Social Interaction;Strategic Planning;Study models;Symptoms;Techniques;Temperature;Testing;therapy design;Time;Training;transmission process;universal influenza vaccine;Vaccination;vaccine effectiveness;Vaccines;virus genetics;Virus Shedding;Visit

PROJECT_TITLE: Mentoring in transmission of influenza and strategies for prevention


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Duchenne/ Becker Muscular Dystrophy;Genetics;Muscular Dystrophy;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative In Duchenne Muscular Dystrophy (DMD) the repeated cycles of muscle damage and repair lead to stem cell dysfunction but current therapies do not target muscle stem cells. The studies proposed here will assess the importance of telomere biology in the progression of muscular dystrophy, using new genetic mouse models that target the stem cell compartment. Our research is aiming to investigate the molecular mechanism of telomere dysfunction in skeletal muscle dystrophy.

PI_NAMEs: MOURKIOTI, FOTEINI  (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: Ablation;Adrenal Cortex Hormones;Age;Apoptosis;Binding;Biology;Breeding;Bypass;Cell Compartmentation;Cell Count;cellular imaging;Childhood;Creatine Kinase;Cytokinesis;Data;Defect;Disease Progression;DNA Binding;DNA Damage;DNA-Binding Proteins;Duchenne muscular dystrophy;Environment;Etiology;Event;exhaustion;Functional disorder;Genes;Genetic;Genetic Transcription;Histology;Human;Imaging Techniques;in vivo;injured;innovation;Knock-out;Knockout Mice;Lead;Length;Link;Methods;Molecular;Monitor;mouse model;Mus;Muscle;muscle degeneration;muscle hypertrophy;muscle progenitor cell;muscle regeneration;Muscle satellite cell;Muscular Dystrophies;Mutation;Myopathy;Natural regeneration;Necrosis;novel;Outcome;Patients;prevent;Proteins;Regulation;repaired;Reporter;Research;response to injury;Role;Scheme;senescence;Serum;Signal Pathway;Signal Transduction;Skeletal Muscle;stem cell proliferation;stem cells;telomere;Telomere Shortening;Testing;Time;Tissues;two photon microscopy;XRCC5 gene

PROJECT_TITLE: Molecular mechanisms of telomere function in muscle stem cells


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE Programmed retrotransposon activation likely promotes animal development. Our proposed studies aim to understand during development how retrotransposon activity is regulated and what is the molecular function and long-term impact of their activity to the hosts. This research will have the potential to provide new insights on controlling retrotransposons and on harnessing their developmental roles to improve human health.

PI_NAMEs: ZHANG, ZHAO  (contact)

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: Address;Adult;Animals;anti-microbial peptide;Anti-viral Response;Area;Automobile Driving;Biological;Biological Metamorphosis;Biomedical Research;cancer cell;Cells;combat;Data;Development;Disease;DNA Damage;DNA Sequence Alteration;Drosophila genus;Ensure;env Gene Products;Epigenetic Process;Event;fly;Future;Genetic;genetic element;Genetic Transcription;Goals;Grant;Gypsies;Health;Human;human disease;Human Genome;Immune;Immune system;Immunity;immunogenicity;improved;Infection;Inflammation;innate immune pathways;Innate Immune System;insight;Invaded;Laboratories;Learning;Length;Letters;Life Cycle Stages;Malignant Neoplasms;Messenger RNA;Modeling;Modification;Molecular;Monitor;Natural Immunity;Neurodegenerative Disorders;novel;pathogen;Pathologic;Pathology;Physiological;Physiology;prevent;Process;Production;programs;Regulation;Research;Resolution;Retrotransposon;RNA Splicing;Role;Scheme;Shapes;Signal Transduction;spatiotemporal;System;Technology;Testing;tissue regeneration;Tissues;tool;transcriptomics;Viral;virology;Virus;Virus Diseases

PROJECT_TITLE: Regulation, function, and impact of developmental retrotransposon activation

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Microbiome;Prevention

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative Clostridioides difficile causes severe infections of the colon, infections that commonly arise after use of antibiotics that destroy healthy populations of microbes which prevent infection. Our proposed studies are defining the specific microbes that provide this protection, and their mechanisms of action. This knowledge will be used to help create more defined, effective and safe therapies for this disease.

PI_NAMEs: BRY, LYNN  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Amino Acids;Antibiotics;Bile Acids;bile salts;biological adaptation to stress;Biological Markers;Biomass;Butyrates;Carbohydrates;Carbon;Clindamycin;Clostridium;Clostridium bifermentans;Clostridium difficile;Coenzyme A;Colon;Complex;Disease;Environment;Etiology;fecal transplantation;Fermentation;Free Association;Gene Deletion;Genes;Genetic;Germ-Free;Germination;Glycine;Growth;Health Care Costs;Human;human microbiota;Hydro-Lyases;Hydrolase;In Vitro;in vivo;Individual;Infection;Infection prevention;Intervention Studies;Knowledge;Leucine;Mediating;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Microbe;microbiota;Morbidity - disease rate;mortality;Mus;mutant;Nutrient;Oral;Outcome;Oxidants;Oxidoreductase;pathogen;Pathway interactions;Patients;Population;prevent;Production;programs;Proline;Pseudomembranous Colitis;Reproduction spores;resident commensals;Resources;Source;System;Testing;Tissues;Toxic Megacolon;Toxin;transcriptomics;Virulence;Virulent;Weight Gain

PROJECT_TITLE: Commensal control of C. difficile virulence

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention;Women's Health Research

ORG_CITY: ROOTSTOWN

ORG_NAME: NORTHEAST OHIO MEDICAL UNIVERSITY

PHR: PROJECT NARRATIVE Alzheimer’s disease is the most common cause of dementia, with women being disproportionally affected, and the biology underpinning this disparity is not well understood. The proposed research is relevant to public health because it focuses on understanding the developmental processes that elicit sex-specific inflammatory processes for sexually dimorphic onset and progression of Alzheimer’s disease. Thus, the proposed research is relevant to the part of the NIH’s mission that pertains to understanding the genetic and biological factors associated with aging and age-related diseases.

PI_NAMEs: REED, ERIN G (contact)

PROJECT_TERMS: Address;Affect;Age;age-related disease;aging related;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid;Biochemical;Biological Factors;Biology;Brain;brain cell;Breeding;Cell Differentiation process;Cells;combat;Complement;Dementia;Deposition;Development;Developmental Process;Disease;Disease Outcome;Disease Progression;Disparity;Estradiol;extracellular;Feminization;Four Core Genotypes;Gene Expression;Genetic;Germ Cells;glial activation;Goals;Gonadal Hormones;Gonadal Steroid Hormones;Health;Hormonal;Hormones;Immune;immune activation;Incidence;Indomethacin;Inflammation;Inflammatory;inflammatory milieu;Inflammatory Response;innovation;insight;Knowledge;Longevity;Masculine;Measures;Mediating;Mediator;Methodology;Methods;Microglia;Mission;Modeling;Molecular;Morphology;mouse model;Mus;Neonatal;Nerve Degeneration;Neuroanatomy;neurochemistry;Neurodegenerative Disorders;Neurofibrillary Tangles;neurofilament;neuroinflammation;Neurons;novel;novel therapeutic intervention;Nuclear Receptors;Onset of illness;Outcome;Play;Prevalence;Prevention;Prevention strategy;Probability;Process;Proteins;PTPRC gene;Public Health;receptor function;reduce symptoms;Research;Role;Severity of illness;sex;Sex Chromosomes;Sex Differences;sexual dimorphism;Signal Transduction;Specific qualifier value;success;Techniques;Testing;therapeutically effective;therapy development;treatment strategy;United States National Institutes of Health;Woman

PROJECT_TITLE: The developmental effects of sex chromosomes and hormones specify microglial inflammation in Alzheimer's diseaes

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ADMINISTERING_IC: FD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE To inform regulatory decision making, manufacturers and researchers seek to quantify the properties of the emissions generated by e-cigarettes, cigars, and heated tobacco products. A Universal Smoking Machine Adaptor that works reliably with existing smoking machines and the newer tobacco products would be ideal. This project will determine the feasibility of such an adaptor, then design, validate, manufacture and support its use in the tobacco science community.

PI_NAMEs: BRINKMAN, MARIELLE CAVANAUGH (contact);WAGENER, THEODORE LEE

PROGRAM_OFFICER_NAME: WAKEFIELD, CHRISTI

PROJECT_TITLE: Smoking Machine Adaptor Design Project for ENDS, Cigars, and Heated Tobacco Products (UC2)