ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative We request an administrative supplement to grant R35GM149355 for the purchase of an Isothermic Cryogenic Dry-Vapor Freezer to replace our current Isothermic Cryogenic Dry-Vapor Freezer which has broken down and is not repairable. The research proposed requires that we generate and store many cell lines and this equipment will be essential to achieve the research proposed in the parent grant.

PI_NAMEs: SMITH, SUSAN  (contact)

PROJECT_TERMS: Administrative Supplement;Aliquot;Cancer cell line;Cell Aging;cell growth;Cell Line;Cells;cohesion;cryogenics;Custom;Dryness;Equipment;Freezing;Goals;Grant;Human;Human Cell Line;Lentivirus;Measures;overexpression;parent grant;parent project;Proteins;Reproducibility;Research;Resolution;Sister Chromatid;System;telomere;vapor

PROJECT_TITLE: Mechanisms of Telomere Cohesion - Equipment Supplement

STUDY_SECTION: MRAA

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


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Machine Learning and Artificial Intelligence;Women's Health Research

ORG_CITY: STONY BROOK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_FIPS: US

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

ORG_STATE: NY

PHR: NARRATIVE: In response to NOT-GM-24-021, we apply for a supplement to our ongoing NIGMS award 5R01GM148970- 02, “DMS/NIGMS 1: Topological Study on Histological Images and Spatial Transcriptomics”. We propose to extend the parent award by integrating the developed methods with state-of-the-art deep learning methodology, in order to produce more powerful topology- and gene-informed feature representation for spatial transcriptomics data. The method will use topological features and gene features as guidance for contrastive learning and teacher-student consistency learning so that histology image patches are mapped into a powerful topology- and gene-informed features. We expect such features will demonstrate strong prediction power in downstream tasks.

PI_NAMEs: CHEN, CHAO  (contact);JOHNSON, TRAVIS STEELE;ZHANG, JIE

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Award;Chromosome Mapping;Data;deep learning;Ensure;Gene Expression;Genes;Goals;histological image;Histology;Image;Indiana;Learning;Malignant Breast Neoplasm;Malignant neoplasm of brain;Maps;Measures;Methodology;Methods;National Institute of General Medical Sciences;parent project;predictive modeling;preservation;response;Sampling;Slide;Spottings;Students;teacher;Testing;Training;transcriptomics;triple-negative invasive breast carcinoma;Universities


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: ITHACA

ORG_DEPT: CHEMISTRY

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative To assemble complex molecules rapidly, efficiently, and with predictable outcomes is among the most significant challenges in the discovery of new medicinal agents. This proposal addresses several major technological gaps in the field of organic synthesis, and its successful completion will speed the preparation of novel medicinal lead structures.

PI_NAMEs: LIN, SONG  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Electrochemistry as an enabling tool for reaction discovery

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: NARRATIVE We will develop new types of fluorescent proteins, reporters and optogenetic tools for imaging, detection and light-regulation of molecular processes and interactions in mammalian cells, tissues and model animals. These probes will emit or be activated in the near-infrared spectral range where tissue transparency is the highest and will use the heme-derived compound biliverdin, naturally available in mammalian tissues, as the chromophore. The planned genetically encoded near-infrared optical probes will allow non-invasive visualization, sensing and light-control of the biochemistry and physiology of cells, organs and whole organisms in normal and pathological conditions, as well as spectral multiplexing with optical reagents of the visible range.

PI_NAMEs: VERKHUSHA, VLADISLAV  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: absorption;Animal Model;Animals;Antigens;Biliverdine;Biochemistry;cell growth regulation;Cell Physiology;Cells;chromophore;Complement;Detection;Development;Engineering;Enzymes;Exhibits;Fluorescent Probes;Gene Delivery;Heme;Imaging Device;imaging probe;improved;in vivo;in vivo imaging;Knowledge;Light;light scattering;Lighting;Mammalian Cell;Mammals;Metabolism;Molecular;nanobodies;Near-infrared optical imaging;non-invasive imaging;novel;Optics;optogenetics;Organ;Pathologic;Performance;Photochemistry;Photoreceptors;Physiology;Phytochrome;Process;protein function;Proteins;Reagent;receptor;Regulation;Reporter;Signal Induction;spatiotemporal;Technology;Tissues;tool;Visualization;Whole Organism

PROJECT_TITLE: Near-infrared Fluorescent Probes and Optogenetic Tools


NIH_SPENDING_CATS: Bioengineering;Immunotherapy

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative This project will enhance our capability to invent therapeutics and subsequently prepare these medicines on large-scale. Inspired by Nature’s catalyst, we develop ideal, environmentally friendly, and powerful ways to transform simple building blocks (aldehydes, alkenes, and alkynes) into architectures relevant to medicine. Our expertise in molecular design and synthesis will also be applied to address challenges at the interface of chemical theory, fluorescent microscopy, and drug discovery.

PI_NAMEs: DONG, VY M (contact)

PROJECT_TERMS: Address;Aldehydes;Alkenes;Alkynes;Amines;Architecture;Biology;cancer immunotherapy;Carbon;Catalysis;catalyst;chemical reaction;chemical synthesis;Chemicals;Cobalt;Copper;cost;Coupling;cyclopropene;design;design and construction;diene;drug discovery;Environment;Equipment;experimental study;Friends;functional group;innovation;insight;invention;Medicine;Metals;Methodology;Methods;Microscopy;Modernization;Molecular;Molecular Probes;Nature;Nitrogen;NMR Spectroscopy;Organic Synthesis;parent project;Periodicity;Pharmaceutical Chemistry;Research;Research Project Summaries;Rhodium;Science;Styrenes;Theoretical Studies;theories;Therapeutic;tool;Training;Transition Elements;unsaturated bonds

PROJECT_TITLE: Innovative Tools for Chemical Synthesis: Metal-Hydride Catalysis,  Medicinal Motifs, and Molecular Probes

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


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: Nashville

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative We will use high-throughput mutagenesis to map which amino acids in the protein sequence are essential for function and which subset of these are involved in communicating the coupling of DNA binding and ATP hydrolysis in a DNA polymerase clamp loader, a member of the family of complex molecular machines called AAA+ ATPases. We will also use statistical models trained on genome sequences of clamp loaders from diverse organisms to infer the essential constraints on and between amino acids in clamp loaders and test these inferences in a biological context. The aims of this project represent a unified body of work to use new assay systems to understanding clamp loader and AAA+ mechanism, and to test the potential for engineering complex macromolecular machines using our sequence-based design.

PI_NAMEs: KURIYAN, JOHN  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Amino Acid Sequence;Amino Acids;ATP Hydrolysis;ATP phosphohydrolase;Bacteria;Bacteriophage T4;Base Sequence;Behavior Control;Binding;Biological;Biological Assay;cell behavior;Cells;Closure by clamp;Communication;Complex;Coupling;design;Diffuse;Disease;Dissociation;DNA;DNA Binding;DNA biosynthesis;DNA-Directed DNA Polymerase;Engineering;Equipment;Escherichia coli;Eukaryotic Cell;Evolution;Family;Family member;Genome;Goals;Human;Hydrolysis;insight;Macromolecular Complexes;Maps;Mechanics;member;Modeling;Molecular Machines;Mutagenesis;Mutation;Organism;Performance;Process;Property;protein complex;protein function;Proteins;Research;Set protein;Site;Slide;Speed;Statistical Models;System;Testing;three dimensional structure;Training;Transcriptional Regulation;transmission process;Virus

PROJECT_TITLE: Equipment Supplement for Mechanism and Evolutionary Design of DNA Polymerase Clamp Loaders


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Social Determinants of Health;Women's Health Research

ORG_CITY: WINSTON-SALEM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Significant gaps exist in our understanding of how a suboptimal in utero environment impacts aging processes and trajectories. We have developed a unique cohort of baboons exposed in utero to maternal overnutrition in order to determine how this suboptimal environment during fetal developmental impacts aging in adult offspring. The requested bridge funds will cover animal per diems of the cohort that are central to our U19 program, which is essential for the U19 renewal resubmission, with maintained support essential to guarantee that these animals are not assigned to other studies at the Southwest National Primate Research Center.

PI_NAMEs: CLARKE, GEOFFREY DAVID;COX, LAURA A (contact);HUBER, HILLARY FRIES;OLIVIER, MICHAEL ;ROSS, CORINNA NICOLE;SALMON, ADAM ;SHIVELY, CAROL A.

PROGRAM_OFFICER_NAME: COGLIATI, TIZIANA PAOLA

PROJECT_TERMS: Address;Adult Children;Affect;Age;age acceleration;age-related disease;Aging;aging process;Animal Nutrition;Animals;cohort;Development;Disparity population;effective therapy;Environment;Environmental Risk Factor;Exposure to;fetal;Fetal Development;Funding;Genetic;hallmarks of aging;Health;healthspan;healthy aging;Human;in utero;Individual;Measures;Metabolism;Molecular;neighborhood disadvantage;nonhuman primate;normal aging;novel;Overnutrition;Papio;Physiology;Pregnancy;prenatal exposure;Primates;Process;Program Development;programs;Public Health;Research;social factors;System;targeted treatment;therapy development;Uterus;western diet

PROJECT_TITLE: Womb to Tomb:  Developmental Programming and Aging Interactions in Primates


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Eczema / Atopic Dermatitis;Food Allergies;Nutrition;Pediatric;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: PEDIATRICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative A cohort of 2500 unselected mother-infant pairs enrolled prenatally and followed to 3 years of age with the primary outcomes of development of (1) food allergy and (2) moderate-severe eczema in the first year of life, and secondary outcomes of (3) recurrent wheeze in the first 3 years of life, (4) sensitization to foods in the first year of life, (5) any eczema in the first 6 months of life, and (6) food allergy at 3 years of life.

PI_NAMEs: BUNYAVANICH, SUPINDA ;SICHERER, SCOTT H;WOOD, ROBERT A (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: 3 year old;Affect;Allergic Disease;Atopic Dermatitis;Biological;Biological Assay;Biological Markers;biomarker identification;Birth;Categories;Child;Child Health;Chronic Disease;Clinical;cohort;cost;Development;Disease;Eczema;Enrollment;falls;Family;Food;Food Hypersensitivity;Future;Genetic;Goals;high risk;Incidence;Infant;Inflammation;Investigation;Life;Mothers;novel;Pathway interactions;Phenotype;predictive marker;predictive modeling;prenatal;Prevention;Prevention strategy;primary outcome;Process;Protocols documentation;Quality of life;Recurrence;Risk Factors;Role;Sampling;secondary outcome;skin barrier;Statistical Models;Systems Biology;Time;Wheezing

PROJECT_TITLE: New Horizons in the Prevention and Treatment of Food Allergy


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pain Research;Physical Activity;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE: Spanish-speaking Hispanics/Latinos adults experience significant disparities in pain treatment and outcomes relative to their English-speaking White counterparts. This diversity supplement will adapt the study design and materials of the parent grant to reflect the cultural needs and preferences of Spanish- speaking Hispanic/Latino adults with chronic pain. This will provide Dr. Giraldo-Santiago with the necessary training to advance her career development goals in qualitative methods and cultural adaptation of mind-body interventions.

PI_NAMEs: GREENBERG, JONATHAN ;VRANCEANU, ANA-MARIA  (contact)

PROGRAM_OFFICER_NAME: MURRAY, PETER DANIEL

PROJECT_TERMS: actigraphy;Address;Adult;Area;Benchmarking;career;career development;Career Mobility;chronic musculoskeletal pain;chronic pain;chronic pain patient;Classification;Clinical;Clinical Trials;community clinic;cost;Data;disability;Disparity;efficacy clinical trial;efficacy trial;emotional functioning;Enrollment;Ensure;ethnic minority;ethnic minority population;Ethnic Origin;Expectancy;experience;Feedback;fitbit;follow-up;Funding;Future;Geography;Goals;Grant;Health;heuristics;Hispanic;Hispanic Populations;implementation protocol;improved;improved outcome;innovation;Interdisciplinary Study;International;Intervention;Latino;Latino Population;Linguistics;Measurement;Measures;Mentors;Mentorship;Methodology;Methods;Mind-Body Intervention;mind/body;Modeling;multi-site trial;multimodality;National Center for Complementary and Integrative Health;Non-Malignant;novel;Outcome;Outcomes Research;Pain;Pain Clinics;Pain management;Pain Measurement;pain outcome;parent grant;Parents;Participant;patient oriented;Patient Self-Report;Patients;Performance;Persons;Physical assessment;Physical Function;Population;preference;Preparation;Procedures;programs;Protocols documentation;Psychological reinforcement;Puerto Rican;Qualitative Methods;Race;racial minority;racial minority population;Randomized;randomized, clinical trials;Recommendation;recruit;research data dissemination;Research Design;Research Personnel;Research Project Grants;Sampling;satisfaction;sedentary;Single-Blind Study;Site;skills;Social Work;Spanish;success;Surveys;Testing;Time;Training;underserved community;United States;Walking;walking program;whole health;Work

PROJECT_TITLE: Improving multimodal physical function in adults with heterogeneous chronic pain; Multi-site feasibility RCT (Diversity Supplement)


ADMINISTERING_IC: CA

FUNDING_MECHANISM: OTHERS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PI_NAMEs: DAVIDSON, SHAWN MICHAEL (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Adipose tissue;Affect;Alanine;bioinformatics tool;Biological;Biological Assay;Body Weight decreased;Cachexia;Cancer Cachexia;Cancer Model;Cancer Patient;Cells;Complex;Cryopreservation;Cryoultramicrotomy;Data;Development;Drosophila genus;effective therapy;Fatty acid glycerol esters;fly;food consumption;Gene Expression;Genetically Engineered Mouse;Glucose;Glutamine;Human;improved;Infusion procedures;insight;Isotopes;Leucine;Liver;Maps;mass spectrometric imaging;Mass Spectrum Analysis;mathematical model;Measurement;Metabolic;Metabolic Pathway;metabolic profile;Metabolism;metabolomics;Methods;Modeling;Molecular;molecular pathology;mouse model;multiple omics;Mus;Muscle;muscle form;new therapeutic target;Normal tissue morphology;novel;Nutrient;Nutritional Support;Organ;Outcome;Patient-Focused Outcomes;Pattern;Population;preservation;Process;Quality of life;Resolution;Sampling;Signal Transduction;Slide;Spatial Distribution;spatial integration;Specificity;Specimen;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;stable isotope;Survival Rate;Syndrome;targeted cancer therapy;targeted treatment;Techniques;Technology;Therapeutic;tissue preparation;Tissue Sample;Tissues;TP53 gene;Tracer;Transcript;transcriptomics;tumor;tumor progression;Tumor Tissue;Universities;Visualization;Visualization software;Work

PROJECT_TITLE: CANCAN - Spatially resolved metabolic measurements in cells and organs during cancer cachexia


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Lymphatic Research;Lymphedema;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Contact PD/PI: Thomas, Susan Napier PROJECT NARRATIVE The lymphatic vasculature provides crucial functions for the maintenance of homeostasis in a variety of tissues and organs by providing the primary route through which immune cells, large proteins, lipids, and interstitial fluid are returned to the blood circulation. This proposed work seeks to utilize drug delivery strategies to 1) enhance lymphatic pumping via pharmacologic modulation of ion channels within the lymphatic muscle of the intact vasculature and 2) reduce the local inflammation through targeted immunomodulator delivery locally and to the lymph node downstream of the site of lymphedema. Findings from this work will lead to a new class of therapeutic strategies for regional enhancement of lymphatic pump function and reducing inflammation in lymphedema. Project Narrative Page 7

PI_NAMEs: DIXON, JAMES BRANDON;THOMAS, SUSAN NAPIER (contact)

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: Acute;Animals;biocompatible polymer;Biodistribution;Blood;Blood Circulation;Blood Vessels;Breast Cancer survivor;Calcineurin;Calcineurin inhibitor;Calcium Channel Agonists;cancer therapy;Cells;channel blockers;Chronic;chronic pain;Complex;controlled release;design;Developed Countries;Diagnosis;Disease;Disease Progression;Dose;draining lymph node;Drug Delivery Systems;Drug Formulations;Drug Targeting;Drug Utilization;expectation;Failure;Fatigue;Fibrosis;fluorescence imaging;Functional disorder;Genetic Models;Health Care Costs;Homeostasis;Human;human disease;imaging capabilities;Immune;immune modulating agents;immunodeficiency;Immunomodulators;improved;In Situ;in vivo;Incidence;Infection;Inflammation;Inflammatory;inhibitor;Injections;insight;Intercellular Fluid;Ion Channel;L-Type Calcium Channels;Life;Life Expectancy;Ligation;Limb structure;Lipids;Liquid substance;Longevity;Lymph;lymph nodes;Lymphatic;lymphatic circulation;lymphatic drainage;Lymphatic function;lymphatic pump;Lymphatic System;lymphatic vasculature;lymphatic vessel;Lymphedema;Maintenance;Malignant Breast Neoplasm;Mastectomy;Measures;Mental Depression;Methods;Micelles;Microsurgery;Modeling;Molecular;mouse model;Mus;Muscle;Near-infrared optical imaging;novel;novel therapeutics;Operative Surgical Procedures;Organ;Outcome;Pathogenesis;Pathologic;Pathological anxiety;Pathology;Patient Compliance;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Phenotype;Philosophy;Physiology;Population;Population Dynamics;Populations at Risk;Potassium Channel;Potassium Channel Blockers;Pre-Clinical Model;pressure;Prevalence;prevent;programs;Proteins;Pump;Rattus;reduce symptoms;Research;Rodent Model;Route;Sentinel Lymph Node Biopsy;Sheep;sheep model;Signal Transduction;Site;Skin;Spleen;Surgical Models;Survivors;Swelling;synergism;Syringes;System;Technology;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Tissues;Tracer;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;Transgenes;Transplantation;Vascularization;Work

PROJECT_TITLE: LYMPHEDEMA THERAPY VIA LYMPHATIC TARGETED DRUG DELIVERY


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Aging;Clinical Research;HIV/AIDS

ORG_DEPT: MISCELLANEOUS

PHR: PROJECT NARRATIVE People with human immunodeficiency virus (HIV) are at increased risk of age- related disease and complications such as frailty. The proposed research aim 3 determine the association of novel SHBG glycans with frailty among men with HIV. This work will inform efforts to find new therapeutic targets for frailty via the improvement of alterations in the hypothalamic-pituitary-gonadal axis in men with HIV.

PI_NAMEs: PENA DIAS, JENNY  (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: age related;age-related disease;Aging;Anabolic Agents;Award;Biochemical;Biological Markers;Biostatistical Methods;career;Data;design;Digestion;Epidemiology;epidemiology study;experience;falls;frailty;Globulins;glycoproteomics;Goals;Gonadal Steroid Hormones;high risk;HIV;Hospitalization;hypothalamic pituitary gonadal axis;Immunoprecipitation;improved;Inflammation;Inflammatory;insight;Intervention;Laboratories;liquid chromatography mass spectrometry;Measurement;men;Mentors;Modification;mortality;new therapeutic target;novel;novel strategies;Outcome;Performance;Persons;Plasma Proteins;Polysaccharides;prevent;Research;Research Personnel;Risk;systemic inflammatory response;Techniques;Testosterone;Work

PROJECT_TITLE: Alteration in the hypothalamic-pituitary-gonadal axis and frailty in aging men with HIV

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_DEPT: PHYSIOLOGY

PHR: Project Narrative Blood pressure is lower in females than it is in males. We discovered that a receptor called OLFR558 is responsible for this sex difference. In this proposal, we will work to understand how OLFR558 affects blood pressure, how it acts differently in males versus females, and whether OLFR558 also plays a role in hypertension.

PI_NAMEs: PLUZNICK, JENNIFER L (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Affect;Angiotensin II;Animal Model;arteriole;Attenuated;Blood Pressure;blood pressure elevation;Blood Vessels;Budgets;cell type;Cells;Diastolic blood pressure;DOCA;experimental study;Female;Four Core Genotypes;genotypic sex;Human;Hypertension;Incidence;Infusion procedures;Inherited;insight;Kidney;Knock-out;knockout animal;Knockout Mice;LoxP-flanked allele;male;Mediating;Modeling;Mus;olfactory receptor;Peripheral;Phenotype;Premenopause;receptor;Renin;Reporting;response;Role;sex;Sex Differences;Signal Transduction;Sodium Chloride;Telemetry;Testing;Tissues;Wild Type Mouse;women versus men;Work

PROJECT_TITLE: Sex Differences in Blood Pressure and Olfactory Receptor 558 (OLFR558)


NIH_SPENDING_CATS: Genetics

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Proteins catalyze most of the reactions on which life depends, so it is of no surprise that there are many links between the dysregulation of protein synthesis and disease progression. An understanding of the mechanism and regulation of human protein synthesis will help us better understand the progression of many diseases and provide novel drug targets.

PI_NAMEs: FRASER, CHRISTOPHER S (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Biological Assay;Cells;crosslink;Disease;Disease Progression;Event;Fluorescence;genome-wide analysis;Hour;Human;Immunoprecipitation;Initiator Codon;innovation;Kinetics;Knowledge;Life;Link;Messenger RNA;model building;Modeling;Monitor;new therapeutic target;Pathway interactions;Peptide Initiation Factors;Physiological;Post-Translational Protein Processing;programs;Protein Biosynthesis;Proteins;Reaction;reconstitution;recruit;Regulation;response;ribosome profiling;Ribosomes;single molecule;Site;Stimulus;Sucrose;System;Testing;Thermodynamics;Time;Translating;translation assay;Translations

PROJECT_TITLE: The mechanisms of mRNA recruitment to the human ribosome


NIH_SPENDING_CATS: Digestive Diseases;Liver Disease;Patient Safety

ORG_CITY: BUFFALO

ORG_NAME: HAUPTMAN-WOODWARD MEDICAL RESEARCH INST

PHR: Project Narrative  The proposed research is relevant to public health because it focuses on functional and mechanistic studies of a transport protein – OATP1B1 that is involved in the uptake of various endogenous molecules and drugs into hepatocytes, which is the first step in the process of drug processing in the liver. Due to the promiscuity of OATP1B1, various co-administered drugs could compete with each other, resulting in elevated plasma levels of the drugs, and risking adverse side effects. Also, some cancers overexpress OATP1B1 and it is the conduit through which anti-cancer medications or hormones that promote the growth of the cancers enter the cells. Thus, deciphering the structure and mechanism of OATP1B1 would advance our understanding of these processes, and aid in drug design that minimizes drug-drug interactions, which is relevant to the NIH’s mission.

PI_NAMEs: PAZ, AVIV  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Affect;anti-cancer;Binding Sites;Biochemical;Biological Assay;Carrier Proteins;Cell membrane;Cells;Cellular Assay;Chemistry;Coupled;Cryoelectron Microscopy;Data;Data Reporting;Docking;Drug Design;Drug Interactions;Drug Prescriptions;Epitopes;Exhibits;Goals;Growth;Hepatic;Hepatocyte;Hormones;Human;Image;innovation;insight;Ion Transport;Knowledge;Life;Ligand Binding;Ligands;Literature;Liver;Malignant Neoplasms;Membrane;Membrane Transport Proteins;Methodology;Microscopic;Mission;Molecular Conformation;Motion;novel;overexpression;Pharmaceutical Preparations;Plasma;Play;Process;Property;Protein Isoforms;protein purification;protein reconstitution;protein structure;Proteins;proteoliposomes;Protocols documentation;Public Health;Reproducibility;Research;Role;side effect;simulation;Specificity;structural determinants;Structure;United States National Institutes of Health;uptake;voltage;Xenobiotics

PROJECT_TITLE: Structure meets function for OATP1B1, a transporter involved in the uptake of endogenous and xenobiotic materials and drugs


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics

ORG_CITY: HANOVER

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: Project Narrative: The funded project will determine the regulatory mechanisms of chromosome segregation during meiosis. These studies are relevant to public health because errors in chromosome segregation can cause trisomy conditions, infertility, and miscarriage. I am requesting a Nikon Ti2E microscope system to undertake the experiments in the funded grant.

PI_NAMEs: LACEFIELD, SONI  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Affect;Cell Cycle;Cell Cycle Regulation;Cell Division Process;Cells;Chromosome Arm;Chromosome Segregation;Chromosomes;Data;Development;Diploid Cells;DNA biosynthesis;Down's Syndrome;Engineering;Ensure;Event;experimental study;Funding;Germ Cells;Grant;Haploidy;Image;Imaging technology;Infertility;innovation;Investigation;Kinetochores;Location;Meiosis;Microscope;Microtubules;model organism;Monitor;novel;Phosphotransferases;Positioning Attribute;prevent;Process;Production;Protein phosphatase;Proteins;Public Health;Regulation;Research;Saccharomyces cerevisiae;Saccharomycetales;Spontaneous abortion;System;Testing;tool;Trisomy

PROJECT_TITLE: Timing and regulation of meiotic commitment


ORG_CITY: SAINT LOUIS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative:  Relevance to public health: Zinc is an essential nutrient that is critical for human health, since zinc deficiency and excess both cause a wide range of health problems. This research will determine how animals protect themselves against excess zinc by storing zinc in lysosomes, and how lysosomes are remodeled to accommodate zinc storage. These studies address novel aspects of the basic biology of lysosomes, which may be informative for lysosomal storage diseases in humans. Insights into mechanisms of zinc homeostasis may suggest new strategies for treating diseases caused by abnormal zinc metabolism.

PI_NAMEs: KORNFELD, KERRY  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TITLE: Lysosome remodeling mediates high zinc homeostasis

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed research is relevant to human health because the development of selective chemical reactions will enable the synthesis of new pharmaceutical agents and tools to study biological systems. Specifically, the proposed research will lead to the development of sustainable, environmentally enzyme-mediated reactions. Ultimately, this work will also lead to fundamental discoveries that will be applied to human health.

PI_NAMEs: NARAYAN, ALISON  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Administrative Supplement;Amino Acids;Area;Benchmarking;Biochemical Reaction;bioinformatics tool;Biological;biological systems;catalyst;chemical function;chemical reaction;Chemicals;Communities;Complex;Computer Models;Derivation procedure;design;Development;Environment;Enzymes;equipment acquisition;functional group;Goals;Grant;Health;Human;Hydroxylation;Mediating;Methods;Modernization;National Institute of General Medical Sciences;Natural Products;Nucleotides;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Protein Family;Proteins;Reaction;Reagent;Research;Site;small molecule;Sustainable Development;tool;Work

PROJECT_TITLE: Expanding the synthetic utility of enzymes-Administrative Supplement for Equipment Purchases


ORG_CITY: CHAMPAIGN

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PROJECT NARRATIVE  Phosphoinositides (PIPs) are minor components of the eukaryotic membrane but major regulators of cellular functions. One of the cellular processes regulated by PIPs is autophagy, a process essential for a broad range of cellular functions and tissue development, and dysregulated in many human diseases. The proposed studies based on our recent discoveries will uncover novel mechanisms of PIP regulation of autophagy and potentially reveal new therapeutic targets.

PI_NAMEs: CHEN, JIE  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Animal Model;Autophagocytosis;Autophagosome;Biochemical;Biogenesis;Biophysics;Cell Physiology;Cells;Cellular biology;Complex;Data;detection assay;Development;Ensure;Family;FRAP1 gene;Grant;Guanine Nucleotide Exchange Factors;Human;human disease;in vivo;inhibitor;Injury;late endosome;Link;Lipids;Lysosomes;Mammalian Cell;Mediating;Membrane;Minor;mouse model;muscle regeneration;Nervous System Disorder;new therapeutic target;novel;Outcome;PH Domain;Phosphatidylinositols;Phosphorylation;Physiological;Play;Process;Protein Kinase C;Proteins;Regulation;Role;Signal Transduction;single molecule;Skeletal Muscle;Tissues

PROJECT_TITLE: Phosphoinositide signaling in autophagy

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ORG_CITY: BINGHAMTON

ORG_NAME: STATE UNIVERSITY OF NY,BINGHAMTON

PHR: Project Narrative: Experimental insight into the mechanism of organic reactions is critical for the rational design of new and improved methodologies for the synthesis of medicinally relevant organic molecules. This proposal addresses this integral need by utilizing experimental and computational approaches to understand reaction mechanisms in two emerging areas of catalysis where new reaction discovery has far outpaced mechanistic understanding – (a) the conversion of abundant carbon-hydrogen bonds to valuable new carbon- carbon bonds commonly known as C-H functionalization; and (b) methodologies that combine nickel and photocatalysts to forge valuable new carbon-carbon or carbon-heteroatom bonds from inexpensive precursors.

PI_NAMEs: VETTICATT, MATHEW J (contact)

PROJECT_TITLE: Mechanistic Studies at the Frontiers of Catalysis


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Climate-Related Exposures and Conditions;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Physical Injury - Accidents and Adverse Effects;Post-Traumatic Stress Disorder (PTSD);Social Determinants of Health;Substance Misuse;Suicide;Violence Research

ORG_CITY: NEW YORK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The United States faces a critical challenge with climate change and worsening mental and behavioral health outcomes, with over 4 million deaths from suicide, assault, and psychoactive drug use in the last four decades, constituting 5% of all deaths. Disparities persist across sociodemographic group; climate-related stressors, particularly tropical cyclones, significantly influence mental health, potentially leading to anxiety, PTSD, intimate partner violence, and drug use behaviors. This project aims to characterize long-term trends and disparities in these deaths, assess the short-term impact of tropical cyclones, and evaluate the long-term effects of recurrent tropical cyclone exposure, leveraging robust data and advanced statistical methods to inform public health strategies and prioritize mental health resources for vulnerable communities.

PI_NAMEs: PARKS, ROBBIE M (contact)

PROGRAM_OFFICER_NAME: BOYLES, ABEE

PROJECT_TERMS: Acute;Address;Age disparity;age group;Air Pollution;Alcohol consumption;Anxiety;Anxiety Disorders;assault;behavioral health;Biological;Cause of Death;Cessation of life;Climate;climate change;climate-related health;Communities;Conflict (Psychology);County;Data;Data Sources;Death Rate;Death Records;Deaths of despair;Disasters;Disparity;Drug usage;drug use behavior;economic impact;Environmental Epidemiology;Environmental Exposure;Environmental Health;Ethnic Origin;experience;Face;Firearms;Frequencies;graduate student;Grant;Health Planning;Health Priorities;Health Resources;Hurricane;improved;Income;indexing;Individual;Inflammation;Injury;intimate partner violence;Knowledge;Link;Long-Term Effects;Longitudinal trends;Low income;Mediating;Mental Depression;Mental Health;Mental Health Associations;Methodology;Methods;Modeling;Modification;Moods;mortality;neuropsychiatry;Opioid;Outcome;Oxidative Stress;Parents;perceived stress;Persons;Population;Population Growth;Post-Traumatic Stress Disorders;Prevention;Property;Psyche structure;psychological distress;Psychotropic Drugs;Public Health;Qualifying;Race;Readiness;Records;Recurrence;Research;Resources;response;Severities;sex;skills;Sleeplessness;Social stratification;social vulnerability;sociodemographic group;sociodemographic variables;socioeconomics;spatiotemporal;Statistical Methods;Stress;stressor;student training;substance misuse;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide prevention;Surgeon;System;Time;Training;Trauma;trend;United States;United States National Center for Health Statistics;United States National Institutes of Health;Universities;Violence;vulnerable community;Vulnerable Populations;Water;Work;young adult

PROJECT_TITLE: Disparities in Deaths of Despair and Violence and Tropical Cyclones in the United States


NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Headaches;Lymphatic Research;Migraine;Nutrition;Obesity;Osteoporosis;Pain Research

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: NARRATIVE: This project uses powerful biochemistry, pharmacology, and structural biology techniques to reveal how calcitonin family peptide hormones bind to their receptors on the surface of cells and develop novel tools for studying the receptors. The hormones regulate bone remodeling, vascular tone, blood glucose, and food intake and the receptors are drug targets for diseases including osteoporosis, migraine headache, cardiovascular disorders, and diabetes and obesity. Our studies will facilitate the development of therapeutics targeting these receptors and reveal concepts that are broadly relevant for several areas of human health and disease because the receptors are members of the large GPCR family that regulates most aspects of physiology.

PI_NAMEs: PIOSZAK, AUGEN A (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: adrenomedullin;adrenomedullin receptor;Affect;Affinity;Agonist;amylin receptor;antagonist;Area;base;Binding;Biochemical;Biochemistry;Biological Assay;Biological Models;Blood;Blood Glucose;Blood Vessels;Bone remodeling;Calcitonin;Calcitonin Gene-Related Peptide;Calcitonin Receptor;calcitonin receptor-like receptor;Calcitonin-Gene Related Peptide Receptor;Cardiovascular Diseases;Cardiovascular system;Cell surface;Complex;Coupling;Cyclic AMP;Diabetes Mellitus;Disease;drug development;Drug Receptors;Drug Targeting;Eating;Exhibits;Extracellular Domain;Family;Food Intake Regulation;Funding;G-Protein-Coupled Receptors;GTP-Binding Proteins;Health;Heterodimerization;Hormone Receptor;Hormones;Human;in vivo;islet amyloid polypeptide;Kinetics;Ligand Binding;Lymphatic System;lymphatic vasculature;member;Membrane Proteins;Methods;Migraine;Molecular;molecular dynamics;novel;Obesity;Osteoporosis;Outcome;Pathway interactions;peptide hormone;Peptides;pharmacologic;Pharmacology;Physiology;Ramp;RAMP1;receptor;receptor-activity-modifying protein;Regulation;Resolution;response;Signal Transduction;structural biology;Techniques;Tertiary Protein Structure;Therapeutic;therapeutic development;therapeutic target;tool;Variant;X-Ray Crystallography

PROJECT_TITLE: RAMP-altered class B GPCR hormone binding and signaling

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative High levels of cellular reactive oxygen species (ROS) are associated with macromolecular damage and the pathology of a wide-range of neurogenerative disorders and aging. At physiological levels, ROS play a central role in signaling through post-translational modifications, which serve to limit or cope with the potential damage associated with cellular ROS. Our work focuses on the identification and mechanistic characterization of ROS-based signaling pathways that help to manage ROS within healthy cells, to ultimately determine what changes in redox signaling are associated with the loss in ROS homeostasis associated with disease.

PI_NAMEs: SEVIER, CAROLYN S (contact)

PROJECT_TERMS: Aging;Area;Award;biological adaptation to stress;cell injury;Cell Physiology;Cells;coping;Coupled;Cysteine;Development;Disease;Endoplasmic Reticulum;endoplasmic reticulum stress;Event;experience;Goals;Homeostasis;Human Resources;Individual;insight;Knowledge;Methionine;methionine sulfoxide reductase;Molecular;Molecular Chaperones;Outcome;oxidation;Oxidation-Reduction;Pathology;Pathway interactions;Physiological;Play;Post-Translational Protein Processing;Predisposition;programs;Proteins;Reactive Oxygen Species;Research;Resolution;Role;Signal Pathway;Signal Transduction;Source;therapeutically effective;Work

PROJECT_TITLE: Molecular mechanisms of cellular redox signaling


NIH_SPENDING_CATS: Nutrition

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Molecular and Cellular Mechanisms of Copper-Dependent Nutrient Signaling and Metabolism PROJECT NARRATIVE The transition metal copper (Cu), which is acquired as a dietary nutrient, contributes to the balance between cell proliferation and cell death that is essential for life. An emerging paradigm in nutrient sensing and protein regulation, termed metalloallostery, whereby protein activity is controlled by Cu at non-catalytic sites has expanded the contribution of Cu to signaling events and enabled therapeutic exploitation of Cu-dependent disease associated cellular processes. This proposal will build on this new and clinically relevant signaling paradigm by delineating molecular and cellular mechanisms that underlie Cu-dependent adaptations to nutrient scarcity that are critical for sustaining energy balance for survival under physiological conditions and in diseases settings.

PI_NAMEs: BRADY, DONITA C (contact)

PROJECT_TERMS: Amino Acids;Applications Grants;Area;Autophagocytosis;Binding;Biogenesis;Biology;Carbohydrates;Cell Death;Cell Physiology;Cell Proliferation;clinically relevant;cofactor;Copper;detection of nutrient;Development;dietary;Disease;energy balance;Ensure;Enzymes;Equilibrium;Event;flexibility;Homeostasis;Knowledge;Life;lipid metabolism;Lipids;MAP2K1 gene;Mediating;Mediator;Metabolic;Metabolism;Mitochondria;Molecular;novel;Nutrient;Oxidation-Reduction;Oxygen;Phenotype;phosphoric diester hydrolase;Phosphotransferases;Physiological;Physiology;Protein Kinase;Proteins;Recycling;Regulation;Research;Signal Pathway;Signal Transduction;Signaling Molecule;Site;Stress;Therapeutic;therapeutic target;Transition Elements


ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Despite the success of cancer immunotherapy as a therapeutic modality, the majority of cancer patients do not benefit from this treatment. Studies of the mechanisms of response and resistance to immune checkpoint inhibitors in the tumors and blood of treated cancer patients and in murine models will provide insights that will guide the design of new combinatorial therapies. By understanding the precise immune cells that can be induced to kill tumor cells, we ultimately seek to translate our findings to develop more effective immunotherapies tailored to drive these cells.

PI_NAMEs: FONG, LAWRENCE  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Advanced Malignant Neoplasm;anti-tumor immune response;Antigens;Antitumor Response;Basic Science;bench to bedside;Blood;cancer immunotherapy;Cancer Patient;cancer therapy;CD4 Positive T Lymphocytes;cell type;Cells;Clinical;Clinical Trials;Clone Cells;Combination immunotherapy;combinatorial;cytotoxic;design;experience;functional plasticity;Future;Goals;high dimensionality;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immunosuppression;Immunotherapy;insight;interest;Knock-out;Maps;Mediating;Modality;mouse model;multidisciplinary;Neoadjuvant Therapy;neoplastic cell;novel;Operative Surgical Procedures;Pathway interactions;Patients;Pharmaceutical Preparations;Positioning Attribute;Proteomics;Research;Resected;Resistance;response;single cell genomics;single-cell RNA sequencing;success;T cell receptor repertoire sequencing;T-Lymphocyte;Therapeutic;Translating;Translational Research;tumor

PROJECT_TITLE: Determinants of response to cancer immunotherapy


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Machine Learning and Artificial Intelligence;Precision Medicine

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE The goal of this research program is to develop computational methods that enhance the role of metabolomics in systems biology approaches for biomarker discovery. Specifically, statistical, network-based, and deep learning methods will be developed for ranking putative metabolite IDs and selection of metabolite biomarker candidates. The performance of the proposed methods for metabolite identification and biomarker selection will be evaluated by comparing them with other tools and through experimental methods including: (1) comparing the fragmentation patterns of unknown analytes against those from reference compounds; and (2) targeted quantitative analysis of selected analytes.

PI_NAMEs: RESSOM, HABTOM W (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Address;Administrative Supplement;Biological;Biological databases;biomarker discovery;biomarker selection;candidate marker;candidate selection;computerized tools;Computing Methodologies;computing resources;Coupled;Data;deep learning;Disease;glycoproteomics;Goals;high throughput analysis;innovation;instrument;Libraries;Liquid Chromatography;Mass Fragmentography;mass spectrometer;Mass Spectrum Analysis;metabolomics;Methods;multiple omics;Network-based;parent project;Pattern;Performance;phosphoproteomics;Play;programs;Proteomics;Research;Resolution;Resources;Role;Sampling;small molecule;System;Systems Biology;Time;tool;Validation

PROJECT_TITLE: Systems Metabolomics for Biomarker Discovery


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: HOUSTON

ORG_DEPT: GENETICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PI_NAMEs: BOERWINKLE, ERIC A.;DOHENY, KIMBERLY F;GIBBS, RICHARD A (contact)

PROGRAM_OFFICER_NAME: DUTKA, TARA

PROJECT_TERMS: Achievement;Address;All of Us Research Program;biobank;Biological Assay;Calibration;candidate validation;Clinical;cohesion;college;cost;cost effective;Data;Data Analyses;data management;data resource;design;Development;Disease;DNA;DNA Methylation;DNA sequencing;Effectiveness;Ensure;experience;Generations;Genetic;Genome;genome analysis;genomic variation;Genomics;Genotype;Goals;Health;health data;Hereditary Disease;Hispanic Populations;human genome sequencing;Individual;Infrastructure;Institutional Review Boards;Knowledge;Leadership;Literature;Measurement;Medicine;meetings;Mental disorders;Mental Health;metabolomics;Metadata;Methylation;multiple omics;Participant;Pathogenicity;Pathway interactions;Penetrance;Phase;Pilot Projects;Production;programs;Proteins;Proteomics;Protocols documentation;Public Health Schools;Publications;Readiness;Reporting;Research;Research Personnel;Resources;RNA;Role;Sampling;Scanning;Secure;sequencing platform;Series;Site;Speed;success;synergism;Texas;tool;United States National Institutes of Health;Universities;Update;usability;Variant;Vision;whole genome;Work;working group

PROJECT_TITLE: All of Us at the Baylor-Hopkins Clinical Genome Center


NIH_SPENDING_CATS: Bioengineering;Neurosciences

PHR: Project Narrative The objective of this Equipment Supplement is to purchase a benchtop fluorescence activated cell sorter to accelerate the objectives of the parent Maximizing Investigators’ Research Award (MIRA). The goal of the MIRA is to elucidate the role olfactory receptors (ORs) expressed outside the olfactory tissue play in human health and assess their potential as therapeutic targets. Olfactory receptors are a subtype of transmembrane proteins called G-protein coupled receptors (GPCRs), which are an important therapeutic target. As part of the proposed research, we also work towards understanding how GPCR signaling pathways talk to one another and the consequences of this crosstalk for human health, with the goal of enabling the development of new therapies.

PI_NAMEs: PERALTA-YAHYA, PAMELA  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Acceleration;Architecture;Area;Award;Behavior;Binding;Cell Physiology;Cells;Color;combinatorial;Deposition;Development;Educational process of instructing;Engineering;Equipment;Event;fluorescence activated cell sorter device;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Genetic;Goals;Health;Human;Integral Membrane Protein;Ligands;machine learning algorithm;next generation;novel therapeutics;olfactory receptor;overexpression;Parents;Phenotype;Play;Process;Receptor Activation;Research;Research Personnel;Role;sensor;Signal Pathway;Sorting;Speed;Therapeutic;therapeutic target;Tissues;tool;training data;treatment response;Work

PROJECT_TITLE: Equipment Supplement: Olfactory receptor-based sensors for biomedical applications


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE Sociality is an essential component of animal behavior, and its deficits are closely associated with mental illnesses in humans, such as autism spectrum disorder. We previously discovered that the enzyme topoisomerase II alpha (Top2a) senses environmental toxicants and regulate social behavior through an epigenetic mechanism, but how does this pathway affect different cell types of the brain and what are the downstream targets of this pathway remain poorly understood. This diversity supplement aims to support an eligible postdoctoral researcher to answer these questions using cutting edge single-cell multimodal omics (transcriptomics and epigenomics) approaches.

PI_NAMEs: GENG, YIJIE  (contact)

PROGRAM_OFFICER_NAME: LAWLER, CINDY P

PROJECT_TERMS: Affect;Animal Behavior;autism spectrum disorder;Behavioral;Brain;Career Mobility;cell type;Cells;Chromatin;Collaborations;Complex;Computer Analysis;Development;DNA topoisomerase II alpha;Eligibility Determination;environmental toxicology;Enzymes;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;Etiology;Goals;Grant;Human;insight;Knock-out;Knowledge;Maps;Mental disorders;Mentors;Methods;Molecular;multimodality;Mus;Neurodevelopmental Disorder;novel;Parents;Pathway interactions;Postdoctoral Fellow;Regulatory Element;Research;Research Personnel;risk variant;Role;screening;skills;social;Social Behavior;Technology;Toxic effect;Toxic Environmental Substances;toxicant;Toxicology;transcriptome;transcriptomics;Zebrafish

PROJECT_TITLE: A systematic study of the environmental etiology of autism spectrum disorder using high-throughput behavioral screening


ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative GPCR-mediated signaling pathways play a key role in all physiological systems as well as pathophysiological conditions including cancer, immune disorders, cardiovascular diseases, metabolic disorders (e.g. obesity, diabetes), pain and addiction. Over 30% of all prescription drugs on the market act via these receptors. The structural biology study of the human GPCR family will result in developing a deeper and thorough understanding of molecular mechanisms of ligand recognition and receptor function, which should translate into development of more efficient therapeutics with diminished side effects.

PI_NAMEs: CHEREZOV, VADIM  (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Acceleration;addiction;beta-arrestin;Binding Sites;Biochemical;Biophysics;Cardiovascular Diseases;Cell membrane;Complex;Computers;Data;design;Development;Diabetes Mellitus;Drug Prescriptions;Drug Targeting;experimental study;Family;G-Protein-Coupled Receptors;Goals;GTP-Binding Proteins;Human;Human Genome;Immune System Diseases;improved;insight;Laboratories;Ligands;Malignant Neoplasms;Marketing;Membrane;Membrane Proteins;Metabolic Diseases;Modeling;Molecular;Molecular Mechanisms of Action;novel;novel therapeutics;Obesity;Pain;Physiological;Play;programs;Proteins;receptor;receptor function;receptor-mediated signaling;Research;Resolution;side effect;Signal Pathway;Signal Transduction;Specificity;structural biology;Structure;System;technology development;Therapeutic;three dimensional structure;tool;Translating;transmission process

PROJECT_TITLE: Structural Biology Of G Protein-Coupled Receptors


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE These studies in jawless vertebrates will yield insight into the basic evolutionary and functional principles by which the T cell arm of the adaptive immune system contributes to the discrimination of non-self and the maintenance of healthy self. A newly recognized family of variable lymphocyte receptors that are part of the T cell-associated system will be characterized.

PI_NAMEs: COOPER, MAX DALE (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Adaptive Immune System;adaptive immunity;Address;Administrative Supplement;arm;B-Lymphocytes;Cell Physiology;Cell Separation;Cells;Cellular biology;Characteristics;Complex;CRISPR/Cas technology;Cytoplasmic Tail;Development;Discrimination;Distant;Family;feeding;Gene Expression Profile;Genes;Genome;Genomics;Hagfish;Immunoglobulin Domain;Immunoglobulins;innovation;insight;Integral Membrane Protein;Investigation;ITAM;Jaw;Lampreys;Larva;Lasers;Leucine-Rich Repeat;leucine-rich repeat protein;Lymphocyte;Lymphocyte Subset;Maintenance;Mass Spectrum Analysis;Mediating;Microscope;Monoclonal Antibodies;Mutate;Names;Nature;novel;Orthologous Gene;Petromyzon marinus;Phosphotransferases;Phylogenetic Analysis;Phylogeny;Proteins;receptor;receptor expression;Receptor Signaling;Signal Transduction;Signaling Molecule;single-cell RNA sequencing;src Homology Region 2 Domain;Structure;Surveys;System;T cell differentiation;T-Cell Receptor;T-Lymphocyte;Tissues;Transcript;Vertebrates;ZAP-70 Gene;γδ T cells

PROJECT_TITLE: T Cell Differentiation and Diversification in Jawless Vertebrates: Administrative Supplement for purchase of Laser Capture Microscope

STUDY_SECTION: MRAC

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Genetics;Microbiome

ORG_DEPT: VETERINARY SCIENCES

PHR: Project Narrative Functional metagenomic screening of stool samples for novel bacterial steroidogenic enzymes necessitates a dedicated analytical instrument to allow the throughput our project requires. This instrument should be able to separate steroid isomers and determine mass and generate daughter ions that serve as “fingerprints” to assist in identification. ThermoFisher Vanquish Flex UHPLC coupled with VWD & IR, and TSQ Fortis Plus electrospray ionization (ESI) Triple Quadrupole MS will provide the platform we need to complete the parent project.

PI_NAMEs: RIDLON, JASON MICHAEL (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;Adrenal Cortex Hormones;Affect;Amino Acid Sequence;Anaerobic Bacteria;Androgens;Androstenedione;Bacteria;bacterial metabolism;bile acid metabolism;biobank;Biochemical;Biochemical Reaction;Bioinformatics;Clostridium;Collection;college;Colon Carcinoma;Communities;Consumption;cost;Coupled;Custom;Cytochrome P450;Daughter;Dedications;dehydroxylation;Disease;DNA;Electrospray Ionization;Enzymes;Equipment;Escherichia coli;expression vector;Feces;Fingerprint;Funding;Gene Cluster;gene discovery;Genes;Goals;gut bacteria;gut microbiome;Health;Homologous Gene;host-associated microbial communities;Human;Human Microbiome;Hydrocortisone;Illinois;immune function;Institution;instrument;Ions;Isomerism;Journals;Ketones;Ketosteroids;Knowledge;Laboratories;Libraries;Ligation;liquid chromatography mass spectrometry;Malignant neoplasm of prostate;Manuscripts;Maps;Metabolic Biotransformation;Metabolism;metabolomics;Metagenomics;Methodology;microbial;microbiome;Mixed Function Oxygenases;National Institute of General Medical Sciences;Nature;novel;Organism;Oxygen;parent project;Parents;Pathway interactions;Phylogenetic Analysis;prevent;Process;Progesterone;protein folding;Protein Isoforms;Reaction;Reproductive Physiology;Sampling;screening;Solvents;Standardization;stereochemistry;Stereoisomer;steroid metabolism;Steroids;stool sample;System;Testosterone;therapeutic target;Time;transcriptome sequencing;Transketolase;United States National Institutes of Health;urinary;Urine

PROJECT_TITLE: Gut bacterial metabolism of the side-chain of corticosteroids

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative from the Parent Award Cell-adhesion receptors are key molecules for cellular communication and have emerging functions in numerous cellular processes. The research proposed in this application will yield key insights into fundamental molecular mechanisms that underlie the function of two poorly understood families of cell-adhesion receptors in multicellular organisms (namely the 33 adhesion G Protein-Coupled Receptors (aGPCRs) and the four teneurins). This research will provide critical knowledge into the molecular mechanisms of intercellular communication, and since many aGPCRs and teneurins are found mutated in neurological disorders and cancers, this research is expected to provide crucial clues for the development of novel strategies to understand and treat these disorders.

PI_NAMEs: ARAC-OZKAN, DEMET  (contact)

PROJECT_TERMS: adhesion receptor;Adhesions;Biochemical;Biological Assay;Biophysics;brain malformation;Cell Adhesion;Cell Physiology;Cell Surface Receptors;Communication;Communities;Complex;Development;developmental disease;Disease;Eukaryota;Evolution;extracellular;Family;FDA approved;Future;G-Protein-Coupled Receptors;Genetic study;Goals;Heart;human disease;insight;intercellular communication;interdisciplinary approach;Knowledge;Ligands;Link;Malignant Neoplasms;malignant neurologic neoplasms;Mediating;Molecular;Mutagenesis;Mutate;Nature;nervous system development;Nervous System Disorder;novel strategies;Organism;parent project;Pharmaceutical Preparations;Physiological;programs;Protein Engineering;receptor;receptor function;Research;Role;Signal Transduction;Skeletal system;Structure;success;Testing;Therapeutic;three dimensional structure;tool;Work

PROJECT_TITLE: Structural and Functional Studies of Cell-Adhesion Receptors


NIH_SPENDING_CATS: Natural Products

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: Narrative Equipment supplement – same as the parent grant

PI_NAMEs: STOLTZ, BRIAN M (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: bioactive natural products;driving force;Equipment;Organic Chemistry;parent grant

PROJECT_TITLE: The Synthesis of Bioactive Natural Products as a Driving Force for Discovery in Organic Chemistry


NIH_SPENDING_CATS: Charcot-Marie-Tooth Disease;Genetics;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Rare Diseases

ORG_DEPT: PSYCHIATRY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative The Integrated Stress Response (ISR) signaling pathway helps cells adapt to various conditions of stress, and abnormal ISR signaling is associated with various metabolic and neurodegenerative diseases. This pathway simultaneously activates gene transcription and suppresses general mRNA translation. Here, we propose to determine how stress-responsive transcripts bypass mRNA translation blocks associated with ISR, and determine their significance in stress adaptation and disease manifestation.

PI_NAMEs: RYOO, HYUNG D (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Address;Amino Acyl-tRNA Synthetases;biological adaptation to stress;Bypass;Cells;Cellular Stress;Charcot-Marie-Tooth Disease;Disease;DNA Sequence Alteration;Drosophila genus;Equipment;Gene Expression;Genes;Genetic;Genetic Screening;Genetic Transcription;Goals;Heterozygote;human disease;interest;Mediating;Messenger RNA;Metabolic Diseases;Modeling;mRNA Translation;Mutation;Neurodegenerative Disorders;novel therapeutic intervention;Organism;Pathway interactions;Peptide Initiation Factors;Phosphotransferases;Physiological;Process;programs;Regulation;Research;Ribosomes;ribosomopathy;Signal Pathway;Stress;Stress Response Signaling;Testing;tool;Transcript;Translational Repression;Translations

PROJECT_TITLE: Translational control of stress response signaling - Equipment Supplement


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);HIV/AIDS;Harm Reduction for Substance Misuse;Health Services;Infectious Diseases;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Prevention;Social Determinants of Health;Substance Misuse;Substance Misuse Prevention;Wound Healing and Care

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative The supplement proposed the addition of wound care services provided by a trained nurse to a novel mobile, integrated PrEP intervention (Check It) that delivers on-site PrEP, peer navigation, and point of care drug checking. Check It aims to both increasing engagement of people who inject drugs (PWID) in the PrEP continuum and to reduce overdose. Adding wound care services is urgently needed given the prevalence among this population, driven by xylazine’s presence in the drug supply. Xylazine causes wounds that are significantly associated with elevated HIV risk among this vulnerable population. Check It is being evaluated by a longitudinal study (SCOPE) of PWID (N=500) that is collecting baseline and 18-month follow up data in four high drug-use areas zone where Check It will provide services.

PI_NAMEs: SHERMAN, SUSAN G. (contact)

PROGRAM_OFFICER_NAME: JENKINS, RICHARD A

PROJECT_TERMS: Address;adverse outcome;AIDS prevention;Amputation;Animals;Area;Bacteremia;Baltimore;Care given by nurses;care systems;Caring;Cessation of life;Cities;Communities;condoms;Continuity of Patient Care;cost;Counseling;Data;Drug usage;Effectiveness of Interventions;Enrollment;experience;Exposure to;Fentanyl;follow-up;Fourier Transform;Frequencies;General Population;Goals;Health;health care delivery;health care settings;Heroin;high risk;HIV;HIV Infections;HIV risk;Hospitalization;illicit opioid;incremental cost-effectiveness;Infection;Infectious Skin Diseases;Infective endocarditis;Injecting drug user;Injections;Intervention;Interview;Longitudinal cohort study;Longitudinal Studies;Maintenance;Marketing;Maryland;Measures;medically necessary care;meetings;member;Needle Sharing;Needle-Exchange Programs;novel;Nurses;nursing administration;opioid user;Outcome;Overdose;overdose death;overdose prevention;Overdose reduction;parent grant;Parents;Participant;peer;peer support;Penetration;Persons;Pharmaceutical Preparations;point of care;Population;pre-exposure prophylaxis;Prevalence;prevent;preventive intervention;primary outcome;programs;Puerto Rico;recruit;Reporting;Research;Risk;Risk Behaviors;risk perception;Risk Reduction;Sampling;scale up;service delivery;Service delivery model;Services;Site;social stigma;Soft Tissue Infections;Specialist;Sterile coverings;substance use;Surveillance Program;Testing;Time;Training;Tranquilizing Agents;Transportation;uptake;Urine;Vulnerable Populations;wound;wound care;wound cleaning;wound treatment;Xylazine

PROJECT_TITLE: Impact of a novel HIV peer navigationand overdose prevention intervention on engagement in the HIV prevention and treatment cascade.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(02)-M]


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;Sleep Research

ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Alzheimer’s disease is a pressing healthcare issue for our healthcare system and the more than five million patients and families affected by the disease. This research will help understand how changes in the circadian clock contribute to worsening neuronal function, contributing to our understanding of the disease’s cause and potentially uncovering new strategies for prevention or treatment.

PI_NAMEs: GAMBLE, KAREN L;ROBERSON, ERIK D (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Ablation;Affect;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Animal Model;Area;Behavioral;Bioinformatics;bioinformatics pipeline;Cell Physiology;Cells;circadian;Circadian Dysregulation;circadian pacemaker;circadian regulation;Circadian Rhythms;Clinical;comparison group;Data;dentate gyrus;design;designer receptors exclusively activated by designer drugs;Development;Disease;Diurnal Rhythm;Electrophysiology (science);epileptiform;Event;excitatory neuron;Exhibits;experimental study;Family;fighting;Functional disorder;Gene Expression;Genes;Genetic;Genetic Transcription;Healthcare;Healthcare Systems;Hippocampus;Human;human model;Impaired cognition;Impairment;inhibitory neuron;innovation;insight;Interneurons;Intervention;Investigation;Knock-in;Knowledge Portal;Ligands;LoxP-flanked allele;Mediating;Membrane;Molecular;molecular clock;mouse model;Mus;neural;neuroimaging;neuronal excitability;Neurons;neurophysiology;Parvalbumins;patch clamp;Pathogenesis;Pathology;Patients;Pattern;Periodicity;pharmacologic;Phase;Physiology;postsynaptic;Predisposition;Prevention strategy;Property;Prosencephalon;Regulation;Research;response;Seizures;single molecule;Slice;tau Proteins;Testing;Time;tool;transcriptome sequencing;transcriptomics;translating ribosome affinity purification and RNA-sequencing;Variant;Wild Type Mouse

PROJECT_TITLE: Circadian changes in network excitability and Alzheimer disease pathogenesis


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Patient Safety;Prevention

ORG_NAME: ALLIANCE NCTN FOUNDATION

PHR: PROJECT NARRATIVE The Alliance NCI Community Oncology Research Program (NCORP) Research Base conducts research in cancer prevention, cancer symptom control, and cancer care delivery with a special emphasis on minority, underserved, and older patients and with a strong commitment to building collegial relationships with NCORP Community sites and Minority/Underserved Community sites. The Alliance NCORP seeks to continue its mission into the next grant cycle of generating practice-changing research that directly and favorably impacts the lives of cancer patients and those at risk for cancer.

PI_NAMEs: GALANIS, EVANTHIA ;HAHN, OLWEN ;PASKETT, ELECTRA D. (contact)

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: Academic Medical Centers;Address;Advocate;Area;base;Blood;cancer care;cancer clinical trial;Cancer Patient;cancer prevention;cancer risk;cancer therapy;care delivery;chemotherapy;Clinical;Clinical Oncology;Clinical Research;Clinical Trials;Collaborations;Collection;Committee Membership;Communities;Community Clinical Oncology Program;data sharing;Databases;Diagnosis;Funding;Grant;Human;innovation;Intervention;Malignant Neoplasms;Manuscripts;Mentorship;Metastatic malignant neoplasm to brain;Metastatic Neoplasm to the Bone;Minority;Mission;National Clinical Trials Network;Nausea and Vomiting;older patient;Oncology;Parents;Patient Outcomes Assessments;Patients;premalignant;Prevention;programs;Publishing;Quality of life;repository;Research;Research Personnel;Risk;Site;skeletal-related events;Source;Symptoms;Tissue Sample;Training;translational oncology;Translational Research;treatment trial;Tumor Tissue;underserved community;United States;Work

PROJECT_TITLE: Alliance NCORP Research Base - BIQSFP GY11 Supplements


ORG_NAME: UNIVERSITY OF HOUSTON

PHR: Project narrative  RNA editing of transposable elements within cellular RNAs by the ADAR1 enzyme helps the cell distinguish between self and non-self RNAs. The Z-RNA binding domain of ADAR1 plays a role in that process, which remains uncharacterized. Our goal is to structurally, dynamically and geographically (across transcriptomes) characterize the formation of Z-RNA and their recognition by ADAR1, with repercussions on better understanding cancer and certain auto- immune diseases.

PI_NAMEs: VICENS, QUENTIN  (contact);VOGELI, BEAT ROLF

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Adenosine;adenosine deaminase;Adopted;Adoption;Affect;Alu Elements;Autoimmune;Autoimmune Diseases;Base Sequence;Binding;Binding Sites;Biological Process;Biophysics;Brain Diseases;Cells;Contracts;Cytoplasm;Cytosine;Disease;DNA Transposable Elements;dsRNA adenosine deaminase;Enzymes;Event;Gene Expression Regulation;Geography;Goals;Guanosine;Human;Immune response;Immune system;in vivo;Infection;Infectious Agent;Innate Immune Response;Inosine;Interferons;Joints;Knowledge;Lead;Left;Malignant Neoplasms;Mediating;Methods;Molecular Conformation;molecular recognition;mutant;Names;Nervous System Disorder;next generation sequencing;Nuclear;plasma protein Z;Play;Point Mutation;Population;Prevalence;Process;Protein Isoforms;Proteins;pseudotoxoplasmosis syndrome;Publishing;Regulation;response;restraint;RNA;RNA Binding;RNA Conformation;RNA Editing;RNA Recognition Motif;RNA Viruses;Role;Sampling;Site;Specificity;Structure;Techniques;three dimensional structure;transcriptome;transcriptome sequencing;tumor;tumor progression;Work;Z-Form DNA

PROJECT_TITLE: Molecular recognition by ADAR1 of Z-RNA within transcriptomes

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Health Services;Pediatric;Prevention

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative The delivery of survivorship care for young adults (ages 18-39) with cancer is often fragmented and poorly coordinated, resulting in suboptimal care and leaving these young adult survivors with persistent unmet needs. This supplement will leverage a fully enrolled clinical trial evaluating a psychosocial intervention to improve quality of life outcomes for young adults with cancer to examine how early survivorship care aligns with the National Standards for Cancer Survivorship Care and identify barriers and facilitators to obtaining high-quality care. Results will inform future interventions tailored to the needs of young adults with cancer to enhance survivorship care and quality of life outcomes.

PI_NAMEs: DEVINE, KATIE A (contact)

PROGRAM_OFFICER_NAME: SMITH, ASHLEY

PROJECT_TERMS: Abnormal coordination;Address;Administrative Supplement;Aftercare;Age;age group;cancer care;cancer risk;Cancer Survivor;Cancer Survivorship;cancer survivorship care;cancer therapy;care coordination;care systems;career;Caring;clinical trial enrollment;Communication;Comprehensive Cancer Center;Data;Developmental Process;Distress;Education;Educational Intervention;efficacy evaluation;Emotional;Enrollment;experience;Financial Hardship;follow-up;Future;Goals;health related quality of life;Health system;Healthcare;Healthcare Systems;help-seeking behavior;improved;Incidence;Individual;interest;Intervention;Interview;Literature;Malignant Neoplasms;Mediating;Methods;Monitor;National Cancer Institute;Newly Diagnosed;novel;Oncology;Outcome;parent project;Parents;participant enrollment;Patients;Perception;Population;Primary Care;Problem Solving;Process;Provider;psychosocial;psychosocial outcome;Quality of Care;Quality of life;Reporting;Research;response;Sampling;Services;sex;skills;skills training;social;stressor;Suggestion;Supportive care;Surveys;Survival Rate;Survivors;survivorship;therapy development;Time;treatment effect;Treatment/Psychosocial Effects;United States;United States Department of Veterans Affairs;Variant;Well in self;Work;young adult

PROJECT_TITLE: Bright IDEAS-Young Adults: Problem-Solving Skills Training to Reduce Distress among Young Adults with Cancer


PHR: Project narrative Cutting edge technology is critical for productivity and reliability of scientific research, which is the principal way to find new diagnostic and treatment tools to fight human diseases.

PI_NAMEs: SVITKINA, TATYANA  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;Administrative Supplement;Cytoskeleton;Equipment;fighting;Fluorescence Microscopy;Funding;Goals;human disease;Image;novel diagnostics;parent grant;Productivity;Research;Structure;System;Technology;tool;ultra high resolution

PROJECT_TITLE: Structure and functions of the actin cytoskeleton


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

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

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

PI_NAMEs: GOLDSTEIN, ROBERT P (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

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

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


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: NARRATIVE RNA decay is critical for proper cellular functions and homeostasis. In this proposal, we exploit novel RNA sequencing methods to develop a mechanistic understanding of a conserved biological mechanism of co- translational mRNA decay known as “ribothrypsis”. Deciphering the biology of ribothrypsis will enhance our understanding of how gene dysregulation underlies human diseases, paving the way to the development of new RNA-based diagnostics.

PI_NAMEs: IBRAHIM, FADIA FAYEZ (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Biological;Biology;Cell Physiology;Development;Diagnostic;endonuclease;Eukaryota;Event;Gene Expression;Gene Expression Regulation;Genes;Goals;Homeostasis;Human;human disease;insight;Length;Mediating;Messenger RNA;Methods;Modeling;Modification;Molecular;mRNA Decay;Names;next generation sequencing;novel;Phase;post-doctoral training;Post-Transcriptional Regulation;recruit;Regulation;Ribosomes;RNA;RNA Decay;Role;transcriptome;transcriptome sequencing;Translating;Translations;Yeasts

PROJECT_TITLE: Mechanism for post-transcriptional gene regulation by Ribothrypsis


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Narrative The research proposes to use dynamic nuclear polarization (DNP) to improve the sensitivity in magic angle spinning NMR experiments which will lead to molecular structures with higher precision. In particular, we propose to apply high frequency DNP to familial amyloid systems whose structure we will determine and to high resolution multidimensional 17O experiments. We will develop instrumentation for the experiments, and new time domain methods for more rapid data acquisition the research will have a profound impact on structural biology, medical imaging and solution NMR.

PI_NAMEs: GRIFFIN, ROBERT GUY (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Amplifiers;Amyloid;Amyloid Proteins;Arctic mutation;Biological Models;biological systems;Biophysics;Circulation;data acquisition;design;Development;Diamond;Dimensions;Early Onset Alzheimer Disease;experimental study;Frequencies;Helium;improved;instrument;instrumentation;Isotope Labeling;Label;Lasers;Magic;Medical Imaging;Methodology;Methods;Molecular Structure;mutant;North America;Nuclear;Nuclear Magnetic Resonance;Peptides;Physiologic pulse;Procedures;Proteins;Research;Resolution;Series;Solid;Stretching;structural biology;Structure;System;Techniques;Temperature;Time;Translating

PROJECT_TITLE: High Field DNP and EPR in Biological Systems

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

PHR: PROJECT NARRATIVE Calcium-mediated signaling through inositol 1,4,5-triphosphate receptors (IP3Rs) is essential for the regulation of numerous physiological processes. Deregulation of IP3Rs leads to pathological changes in calcium signaling and is implicated in the pathogenesis of diverse diseases including cancer, neurodegenerative, autoimmune, and metabolic diseases. The goal of the proposed study is to elucidate the molecular mechanism of IP3R activity and regulation paving the road for development of novel therapeutic agents to control IP3R activity in the diseased state.

PI_NAMEs: KARAKAS, ERKAN  (contact)

PROJECT_TERMS: Affinity;Apoptosis;Autoimmune Diseases;Binding;Binding Sites;Biological Assay;Calcium;Calcium Signaling;Cell division;cell type;Cryoelectron Microscopy;Cytoplasm;Data;Development;Disease;Distant;Endoplasmic Reticulum;Fluorescence;Gene Expression;Goals;Growth Factor;Hormones;Image;Inositol;insight;Ion Channel Gating;ITPR1 gene;Learning;Ligands;Malignant Neoplasms;Mediating;Membrane;Memory;Metabolic;Metabolic Diseases;Mitochondria;Molecular;Motility;mutant;Neurodegenerative Disorders;Neurotransmitters;novel;novel therapeutic intervention;novel therapeutics;Pathogenesis;Pathologic;Peptides;pharmacologic;Physiological Processes;Property;protein aminoacid sequence;Publishing;receptor;Receptor Inhibition;Regulation;Research;Signal Transduction;Site;small molecule;structural determinants;Structure;Synaptic Transmission;Testing;Therapeutic Agents;tool;trafficking;tripolyphosphate;X-Ray Crystallography

PROJECT_TITLE: Structure and function of inositol triphosphate receptors

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Genetics;Human Genome;Microbiome;Natural Products

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: Natural products continue to be the most valuable source of drug leads, however, the traditional process of discovering natural products is exceedingly inefficient. This project will accelerate the discovery process by combining the power of genome-mining and reactivity-based screening to rapidly locate novel structures of basic scientific and biomedical interest.

PI_NAMEs: MITCHELL, DOUGLAS ALAN (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acceleration;Algorithms;Anabolism;Animals;Bacteria;Bacterial natural products;Big Data;Bioinformatics;Biological;Biology;Chemicals;Classification;Data;Development;Drug Kinetics;Emerging Technologies;Enzymes;Gene Structure;Genetic;Genome;genomic data;Genomics;Geography;human disease;improved;innovation;interest;Invertebrates;Knowledge;Length;Life;Macrolides;Metabolic;metagenome;Metagenomics;microbial;microbiome;microbiome sequencing;Mining;Modernization;Molecular;Molecular Probes;Molecular Structure;Natural product discovery;Natural Products;Natural Products Chemistry;Natural Source;novel;Pathway interactions;Pharmaceutical Preparations;Polyenes;Process;Resources;screening;Shapes;Soil;Source;Streptomyces;Structure;symbiont;synthetic biology;Taxonomy;tool;Toxic effect;user-friendly

PROJECT_TITLE: Genomics Accelerated Natural Product Discovery


ORG_CITY: LUBBOCK

ORG_NAME: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER

PHR: Project narrative Because K+ selective ion channels are essential regulators of cell excitability, their dysfunction underlies a myriad of human pathological conditions that make them excellent targets for drugs to treat very diverse diseases, such as: LQT syndrome, arrhythmia, epilepsy, autoimmune diseases and diabetes. It follows that understanding the function-structure correlations of K+ channels at atomic resolution will pave the road to develop highly-specific therapeutic drugs to correct channelopathies. The central tenet of this grant application is how the structure determine the function of ion channel and how this relationship is influenced by the cell membrane lipid composition.

PI_NAMEs: CUELLO, LUIS GONZALO (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Achievement;Affinity;Alkali Metals;Applications Grants;Arrhythmia;Autoimmune Diabetes;Autoimmune Diseases;Behavior;Binding Sites;Calorimetry;Cell membrane;Cells;Consumption;Coupling;design;Development;Disease;Disulfides;Drug Targeting;Electrophysiology (science);Engineering;Epilepsy;Escherichia coli;Eukaryotic Cell;Functional disorder;Funding;Human;Individual;Ion Channel;Ions;Lipid Bilayers;Lipids;Measures;Membrane Lipids;Metal Ion Binding;Methodology;Molecular Conformation;novel;novel therapeutics;overexpression;Pathologic;Pharmaceutical Preparations;Phospholipids;Physiological;Physiology;Potassium Channel;Regulation;Resolution;scaffold;Structure;Syndrome;Therapeutic;Thermodynamics;Thick;Time;Titrations;United States National Institutes of Health;Work

PROJECT_TITLE: A comprehensive thermodynamic and structural characterization of ion channel function and its regulation by the lipid bilayer composition.


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;Human Genome;Mental Health;Mental Illness;Neurodegenerative;Neurosciences

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Approximately 65% of Alzheimer's disease (AD) patients experience neuropsychiatric symptoms (NPS), which are associated with accelerated disease progression, greater functional impairment, higher caregiver burden, and earlier institutionalization. Current treatments for these NPS have limited efficacy and high rates of adverse side effects, highlighting the urgent need for safe, effective treatments. To nominate potential therapeutic targets, we propose to investigate the genetic and molecular basis of NPS in AD.

PI_NAMEs: WINGO, ALIZA PHAM (contact);WINGO, THOMAS SPURGEON

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Acceleration;Accounting;Address;Affect;Agitation;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Anxiety;Autopsy;Biological Process;Bipolar Disorder;Black Box;Brain;brain tissue;Caregiver Burden;Caregivers;causal variant;Characteristics;comorbidity;Data;debilitating symptom;Delusions;Dementia;differential expression;Disease Progression;Disinhibition;Drug Targeting;effective therapy;Environment;experience;Functional impairment;Future;Genes;Genetic;Genetic Risk;genetic variant;Genets;genome wide association study;genome-wide;Genotype;Hallucinations;Heritability;Human;Individual;insight;Institutionalization;Knowledge;Major Depressive Disorder;Measures;Mediator;Medical;Mendelian randomization;Mental Depression;Mental disorders;mild cognitive impairment;Modeling;Molecular;mortality;multiple omics;neuropsychiatric symptom;new therapeutic target;novel;Participant;Pathogenesis;Pathway Analysis;Pathway interactions;Pharmaceutical Preparations;Phenotype;Plasma;pleiotropism;potential biomarker;Prefrontal Cortex;protein expression;Proteins;Proteome;Proteomics;Public Health;Publishing;risk variant;Role;Schizophrenia;side effect;Signal Transduction;Sleep disturbances;Testing;Therapeutic Studies;therapeutic target;Transcript;transcriptome;transcriptomics;Translating;United States;variant detection;Work

PROJECT_TITLE: The brain multi-omic approach to identify key molecular drivers of neuropsychiatric symptoms in Alzheimer's dementia

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Biotechnology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LA JOLLA

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative We request funding to purchase a qPCR machine, a cell culture incubator, and a cryostat, for the purpose of studying the molecular mechanisms underlying SSC development and expansion. These studies lay the foundation for the goal of developing SSC therapy for treating human male infertility, a condition affecting >200 million men world-wide.

PI_NAMEs: TAN, KUN ;WILKINSON, MILES FROME (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: activin A;Adult;Affect;Cell Culture Techniques;Cells;cryostat;Dedications;Equipment;experimental study;Foundations;Frequencies;Funding;Generations;Genetic Markers;Germ Cells;Goals;Grant;Human;human male;Immunofluorescence Immunologic;In Vitro;in vivo;Incubators;Label;Male Infertility;Measures;Mediating;men;Modeling;Molecular;mouse model;Mouse Strains;Mus;novel;parent grant;Pathway interactions;precursor cell;protein biomarkers;Proto-Oncogene Proteins c-akt;Regulation;RNA Decay;Role;self renewing cell;self-renewal;Spermatogenesis;Stem Cell Development;stem cell therapy;stem cells;TAL1 gene;Temperature;Testing;Testis;transcription factor;Transgenic Mice;United States National Institutes of Health

PROJECT_TITLE: Spermatogonial Stem Cell Establishment and Regulation

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


NIH_SPENDING_CATS: Cancer;Genetics;Human Genome

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Principal Investigator: Wu, Xiaohua Investigating DNA double-strand break repair mechanisms in mammalian cells Project Narrative  Gross chromosomal rearrangement (GCR) is a hallmark of cancer cells, and DNA double- strand breaks (DSBs) are a major source of GCR. Given that microhomology sequences are often present at chromosomal rearrangement junctions in cancer, and repetitive sequences constitute about half of the human genome, it is important to understand the mechanisms underlying microhomology-mediated end joining and recombination at repetitive sequences. Our research in this proposal will create new knowledge and insight on DSB repair mechanisms in mammalian cells and shed light on how genome instability is induced upon DNA damage and during the oncogenic process.

PI_NAMEs: WU, XIAOHUA  (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Address;Biological;cancer cell;cancer genetics;Chromosomal Breaks;Chromosomal Rearrangement;coping;DNA Damage;DNA Double Strand Break;Double Strand Break Repair;Equilibrium;Genetic Diseases;Genetic Recombination;Genomic Instability;human disease;Human Genome;insight;Knowledge;Malignant Neoplasms;Mammalian Cell;Mediating;Oncogenic;Other Genetics;Pathway interactions;prevent;Principal Investigator;Process;repaired;Repetitive Sequence;Reporter;Research;Role;Sequence Homology;Source;Stress;System;Variant


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Diabetes;Health Services;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Palliative Care;Patient Safety;Precision Medicine;Primary Health Care

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE People with Alzheimer’s Disease, related dementias, and diabetes have a notably higher risk of hypoglycemia and adverse events, including hospitalization and death. This project’s goal is to increase awareness of hypoglycemic risks and shared decisions about treatment options among patients with ADRD-DM, caregivers, and primary care clinicians. To that end, I will design an assistive information technology leveraging continuous glucose monitoring and evaluate its impact on care.

PI_NAMEs: SAVOY, APRIL  (contact)

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Active Learning;Adverse event;adverse event risk;Aging;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;American;Awareness;Behavior Therapy;Behavioral Model;care delivery;caregiver education;Caregivers;Caring;Cellular Phone;Cessation of life;Clinical;Clinical Trials;Cognitive;collaborative care;collaboratory;Coma;Communities;Community Services;comorbidity;Comprehension;Computers;Continuous Glucose Monitor;Cultural Backgrounds;Data;Decision Making;dementia care;design;Detection;detection method;detector;Development;diabetes management;Diabetes Mellitus;Diagnostic;Effectiveness;Engineering;Event;experience;Funding;Future;Glucose;Goals;Guidelines;Health;Health system;Healthcare;high risk;Hospitalization;Human;human old age (65+);Hypoglycemia;Ideal 1;Impaired cognition;implementation science;improved;Incidence;Indiana;information display;Information Technology;innovative technologies;insight;interdisciplinary approach;iterative design;K-Series Research Career Programs;Knowledge;knowledge base;learning strategy;member;Mentored Research Scientist Development Award;Mentors;Mentorship;Modeling;monitoring device;multidisciplinary;National Institute on Aging;novel;Observational Study;older adult;Outcome;Participant;participant interview;Patient Selection;Patients;Perception;personalized care;Persons;Pharmaceutical Preparations;pilot trial;Population;Positioning Attribute;Pragmatic clinical trial;prevent;primary care clinician;Process;Prognosis;prototype;psychosocial;Quality of life;Recommendation;recruit;Reporting;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resources;Risk;risk mitigation;satisfaction;Scientist;Serious Adverse Event;shared decision making;skills;socioeconomics;Specialist;Technology;theories;Training;Underrepresented Minority;United States National Institutes of Health;Universities;usability;user centered design;wearable device;wireless transmission;women faculty;Work

PROJECT_TITLE: Enhancing shared decision-making to prompt and guide individualized care for people with Alzheimer's Disease and Diabetes


NIH_SPENDING_CATS: Bioengineering;Complementary and Integrative Health;Natural Products

ORG_CITY: ATLANTA

ORG_DEPT: DERMATOLOGY

ORG_NAME: EMORY UNIVERSITY

PHR: NARRATIVE Regardless of the biological source (bacterial, fungal, plant, animal, or engineered organism), natural product scientists face a common bottleneck: structure elucidation of compounds found in complex mixtures. Here, we propose development and optimization of a micro-crystal electron diffraction platform technology for high- throughput compound identification with nanogram quantities of analytes found in natural mixtures.

PI_NAMEs: NELSON, HOSEA MARTIN;QUAVE, CASSANDRA LEAH (contact)

PROGRAM_OFFICER_NAME: STILL, PATRICK COLBY

PROJECT_TERMS: Acceleration;analytical method;Animals;Bioinformatics;Biological;Chemicals;Collection;Complementary Health;Complex;Complex Mixtures;Cryoelectron Microscopy;Development;electron diffraction;Engineering;Face;Health;high throughput technology;Human;improved;Integrative Medicine;interest;Intervention;marine organism;mind/body;Modality;Molds;nano;Natural product discovery;Natural Products;NMR Spectroscopy;novel;Nuclear Magnetic Resonance;Organism;pharmacologic;physical property;Plants;Property;Reporting;Research;Roentgen Rays;Science;Scientist;signature molecule;small molecule libraries;solid state;Source;Speed;stereochemistry;Structure;submicron;technology platform;Validation;X-Ray Crystallography

PROJECT_TITLE: Development and validation of a high-throughput MicroED-driven platform technology for natural product discovery


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PUBLIC NARRATIVE Ribosomes are large cellular complexes that synthesize proteins. In addition, ribosomes regulate bacterial stress responses, and human neurodevelopment and synaptic plasticity. Dysregulation of these processes leads to disease. Understanding how ribosomes control gene expression requires high-resolution characterization of ribosome movements and interactions. We will use biochemical and cryo-EM methods to address the mechanisms of translation regulation, which may pave the way to development of therapeutics against bacterial and genetic diseases.

PI_NAMEs: KOROSTELEV, ANDREI  (contact)

PROJECT_TERMS: Address;Amyotrophic Lateral Sclerosis;Antibiotics;Bacteria;Bacterial Infections;Biochemical;biological adaptation to stress;Brain;Cell Nucleus;Cellular Stress;Complex;Cryoelectron Microscopy;Disease;Environment;Eukaryota;Gene Expression;Genetic;Genetic Diseases;Genetic Transcription;Human;In Vitro;Learning;memory consolidation;Messenger RNA;Methods;Molecular;Movement;Nervous System Disorder;neurodevelopment;Neuronal Plasticity;Neurons;Nonsense Codon;novel;Pathway interactions;Positioning Attribute;premature;Process;Protein Biosynthesis;Proteins;Proteome;Resolution;Ribosomal Interaction;Ribosomes;Stress;Synapses;Synaptic plasticity;therapeutic development;Time;Transcriptional Regulation;translation factor;Translational Regulation;Translations;Visualization

PROJECT_TITLE: Translational Control: Discovery and Mechanisms


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: STANFORD

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative (Public Health Relevance) All cells in an organism share the same DNA but express different genes including variations of gene sequence at the level of RNA (isoforms) in a highly controlled manner that allows complex multicellular organisms to develop. Why RNA isoforms exist and how they are regulated and function is a foundational and unsolved problem in biology with broad implications for predicting and treating diseases. This proposal will continue experimental and computational research towards discovering new aspects of how and why RNA isoforms exist and how they can be used to predict and provide therapeutic targets for treating disease.

PI_NAMEs: SALZMAN, JULIA  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Splice Site;Address;Affinity;Algorithms;Alternative Splicing;Animals;Archives;Atlases;Back;Base Pairing;Binding;Binding Proteins;Biochemical;Biochemical Pathway;Biogenesis;Biological;Biological Markers;Biology;blind;Blinded;candidate identification;Cell Culture Techniques;cell type;Cells;Chromatin;chromatin modification;Chromosome Mapping;circular RNA;Collaborations;Complex;Coupled;CRKL gene;crosslink;Data;Data Analyses;data mining;Data Set;deep learning;Defect;Detection;Development;digital;Disease;disease diagnostic;DNA;DNA Binding;DNA Insertion Elements;DNA Sequence;Drug Targeting;Elements;Engineering;Epigenetic Process;Eukaryota;Evolution;Exons;Experimental Genetics;experimental study;Funding;Gene Expression;Generations;Genes;Genetic;Genetic Diseases;Genetic Polymorphism;Genetic Transcription;genetic variant;Genome;genome-wide;genome-wide analysis;genomic predictors;Genomics;Goals;Human;human disease;Immune;Immunoprecipitation;Individual;insertion/deletion mutation;insight;Introns;Intuition;Joints;Knock-out;Knowledge;Lasso;Lead;Libraries;Linear Models;Lung;Maps;Measurement;Measures;Methods;Mining;Modeling;Mouse Lemur;mRNA Precursor;mutant;Noise;novel;Nucleic Acids;Organism;Outcome;Output;Pathogenicity;Pathway interactions;Pattern;Point Mutation;Population;precision medicine;predicting response;Preparation;pressure;prevent;Process;Processed Genes;Production;programs;promoter;Protein Isoforms;Proteins;public health relevance;Regulation;Reporting;Research;response;Ribosomes;RNA;RNA analysis;RNA Binding;RNA metabolism;RNA Sequences;RNA Splicing;RNA-Protein Interaction;Role;Salvelinus;Signal Transduction;single-cell RNA sequencing;Small Interfering RNA;Small Nuclear RNA;Small Nucleolar RNA;Small RNA;Spliceosomes;Statistical Data Interpretation;Statistical Methods;Statistical Models;Stretching;Structure;System;Technology;Testing;therapeutic target;Time;Tissues;Transcriptional Regulation;transcriptome sequencing;Untranslated RNA;Validation;Variant;Work

PROJECT_TITLE: Computational- and experimental- driven discovery of splicing regulation and circRNA function


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: NEW YORK

ORG_DEPT: CHEMISTRY

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: PUBLIC HEALTH RELEVANCE STATEMENT (PROJECT NARRATIVE) The essential task of synthesizing all the proteins encoded in an organism’s DNA is executed solely by the ribosome and its associated translation machinery (TM). Using a powerful combination of fluorophore-labeled biological components and experimental approaches unique to the applicant’s and their collaborators’ laboratories, this proposal aims to elucidate aspects of the process through which the TM executes and controls protein synthesis that have thus far remained difficult or impossible to investigate. Because the bacterial TM is the target of many clinically relevant small-molecule antibiotics and dysregulation of the human TM plays a causal role in several human diseases, including numerous viral infections and cancers, the results of these studies are expected to identify new targets and strategies for the development of next-generation antibiotics and small- molecule therapeutics for treating viral infections, cancers, and other human diseases.

PI_NAMEs: GONZALEZ, RUBEN L (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Antibiotics;Bacteria;Biochemical;Biological;clinically relevant;Complex;Development;DNA;Ensure;Eukaryota;flexibility;Fluorescence;fluorescence microscope;fluorophore;Gene Expression;Human;human disease;In Vitro;Initiator Codon;Investigation;Label;Laboratories;Life;Link;Location;Malignant Neoplasms;Messenger RNA;Modeling;Molecular Conformation;mutation correction;next generation;Nucleotides;Organism;Peptide Initiation Factors;Physiological;Play;Process;Production;Protein Biosynthesis;Proteins;public health relevance;Rest;Ribosomal Frameshifting;Ribosomal Proteins;Ribosomes;Role;single molecule;small molecule;small molecule therapeutics;Structure;System;Techniques;Translating;Translation Initiation;Translational Research;Translations;Viral Cancer;Virus Diseases;Yeasts

PROJECT_TITLE: An advanced single-molecule fluorescence microscope for investigation of translation at physiological relevant concentrations