ORG_CITY: MISSOULA

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: Project Narrative This equipment supplement to R01GM148610: EmCAST: Stabilizing Proteins and Tuning Dynamics with High Precision and Accuracy will allow the replacement of an aging ThermoElectron Forma 435 Orbital Shaker that is no longer reliable and has significant down time. The proposed Eppendorf Innova 44R Incubator Shaker will replace lost capacity for protein expression in the PI’s lab and add new capabilities for protein expression at room temperature and below. This equipment is essential to produce protein variants for this project to further validate the ability of EmCAST to predict stabilizing mutations, technology which will be important for extending the shelf life of protein pharmaceuticals.

PI_NAMEs: BOWLER, BRUCE E (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TITLE: Equipment Supplement to R01GM148610 for an Eppendorf Innova 44R Incubator Shaker

STUDY_SECTION: MSFB

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


ADMINISTERING_IC: DE

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Dental, Oral, and Craniofacial Disease;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pregnancy;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: Newark

ORG_COUNTRY: UNITED STATES

ORG_DEPT: DENTISTRY

ORG_FIPS: US

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Programs that seek to improve the oral health of vulnerable pregnant women by increasing dental care utilization have had limited success. This prospective study will identify upstream factors that predict downstream dental care utilization during pregnancy and will evaluate how dental care utilization during pregnancy affects oral health during this important time.

PI_NAMEs: RUSSELL, STEFANIE L (contact)

PROGRAM_OFFICER_NAME: ELWOOD, WILLIAM N

PROJECT_TERMS: Address;Advocate;Affect;Biological Process;Birds;Clinical;Collaborations;college;Data;Dental;Dental Care;Dental caries;Dentistry;Dentists;design;Discipline of Nursing;Discipline of obstetrics;Disease;Doctor of Philosophy;Environment;Equation;ethnic minority;evidence based guidelines;experience;Female;First Pregnancy Trimester;Gender;Gingivitis;Goals;Guidelines;Gynecologic;Gynecology;Health;health related quality of life;healthy lifestyle;Hospitals;improved;Income;innovation;Investigation;Link;Low income;Measures;Medicaid;Medical;Modeling;Mouth Diseases;New York;Oral Examination;Oral health;Outcome;Participant;Pathway interactions;Patients;Periodontitis;Postpartum Period;Predictive Factor;Pregnancy;pregnant;Pregnant Women;prenatal;Prenatal care;Preventive;Preventive treatment;Process;programs;prospective;Prospective Studies;Psychologist;psychosocial;Psychosocial Factor;racial minority;Recommendation;recruit;Reporting;reproductive;Research;Risk;Scientist;Services;sex;social;Social Behavior;sociologist;Specific qualifier value;success;Surveys;Testing;theories;Therapeutic;therapy design;Third Pregnancy Trimester;Time;Tooth Loss;Universities;Woman

PROJECT_TITLE: Pathways to Oral Health Among Low-income Pregnant Urban Women


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Congenital Structural Anomalies;Neurosciences;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: CAMBRIDGE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: Narrative The project seeks to gain a quantitative understanding of how human stem cell organoids, which have been validated against fetal tissue using single cell and in situ sequencing, respond to and process signals to axially elongate, and how the stem cells in the elongating tailbud are maintained to sustain this elongation. To achieve this goal, the reproducible embryonic stem cell organoid system will be studied using a combination of microscopy, single cell sequencing, statistical inference, mathematical modeling, and molecular biology. In the longer term, a quantitative understanding of how the embryo sustains axial elongation will help better understand the mechanisms of developmental defects.

PI_NAMEs: RAMANATHAN, SHARAD  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Anterior;Automobile Driving;Cell Line;cell type;Cells;Defect;Development;developmental disease;Disease;dynamic system;Embryo;embryonic stem cell;Etiology;Event;experimental study;Feedback;Fetal Tissues;Future;gene regulatory network;Goals;Growth;Human;Human Development;human embryonic development;human stem cells;Image;in situ sequencing;In Vitro;Ligands;Maintenance;mathematical model;Measures;Microscopy;Modeling;Molecular Biology;morphogens;Musculoskeletal System;neural;Noise;novel;Organoids;Pattern;Pluripotent Stem Cells;prevent;Process;progenitor;receptor;Reporter;Reproducibility;Research;scoliosis;self-renewal;Signal Pathway;Signal Transduction;single cell sequencing;spatiotemporal;Spinal Cord;Spinal Dysraphism;stem cell organoids;stem cells;System;Tail;Tissues;transcription factor;Undifferentiated;Work

PROJECT_TITLE: Measuring and modeling the dynamics of patterning in human stem cells

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Aging;Bioengineering;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: BIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Proteins are long chains that must fold into specific three-dimensional structures to carry out their functions, which include digesting nutrients, making muscles contract, and enabling communication of neurons in the brain, among many others. Like long strands of yarn quickly become entangled if not organized into balls, proteins that fail to fold into their functional structures promptly tend to clump together into aggregates, which can be detrimental to cellular and organismal function and is associated with neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Our mechanistic studies will clarify how proteins fold into their functional structures and avoid aggregation, providing fundamental insights into disease mechanisms.

PI_NAMEs: HILSER, VINCENT J. (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: aging related disease;Alzheimer's Disease;attenuation;Bacteria;Binding;Biological;Biology;Biophysics;Brain;Cell Physiology;Cells;Codon Nucleotides;Communication;Complex;Contracts;Coupled;Cultured Cells;Cytosol;cytotoxic;defined contribution;Detection;detection method;Disease;Ensure;Eukaryota;Event;experimental study;Future;Geometry;Goals;In Vitro;in vivo;Individual;insight;laser tweezer;Length;Link;Malignant Neoplasms;Measurement;Measures;mechanical force;Mechanics;Molecular;Molecular Chaperones;Muscle;Neurodegenerative Disorders;Neurons;novel therapeutic intervention;Nutrient;optic tweezer;Outcome;overexpression;Parkinson Disease;Pathway interactions;Peptides;Peptidyltransferase;polypeptide;Process;Productivity;Property;protein aggregation;Protein Biosynthesis;protein folding;protein misfolding;Proteins;Proteome;proteostasis;reconstitution;Regulation;Resolution;ribosome profiling;Ribosomes;Role;Shapes;single molecule;Structure;Tertiary Protein Structure;three dimensional structure;Translations;Variant;Work;Yeasts

PROJECT_TITLE: Folding and Chaperone Interactions of Multi-domain Proteins


ED_INST_TYPE: SCHOOLS OF MEDICINE

ORG_CITY: STONY BROOK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

ORG_STATE: NY

PHR: Project Narrative Our work identified specific functions for individual sphingolipids, thus leading to their appreciation as ‘bioactive molecules’, and in the parent proposal we focus on key enzymes of sphingolipid metabolism with important functions in cancer, inflammation, and Alzheimer’s disease. In this administrative supplement, we are requesting the purchase of a QuantStudio 3 Real-Time PCR system in support of R35 GM118128. This instrument will accelerate our work on studying cell growth, cell death, migration, invasion, and colony formation for which colorimetric readouts are used for quantification and normalization.

PI_NAMEs: HANNUN, YUSUF AWNI (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Acceleration;Administrative Supplement;Alzheimer's Disease;biological adaptation to stress;Cell Death;cell growth;Cell Nucleus;Ceramides;Data;DNA Damage;Enzymes;Goals;human disease;Individual;Inflammation;instrument;Invaded;Lipids;Malignant Neoplasms;Mediating;Metabolism;migration;Nuclear;Parents;Pathway interactions;place fields;Protein phosphatase;Regulation;Research Proposals;response;Role;Solid;Sphingolipids;Sphingomyelinase;Stimulus;Structure;System;Therapeutic;Time;tool;Transducers;Work;Yeasts

PROJECT_TITLE: Administrative Supplement: Neutral Sphingomyelinases and Bioactive Ceramides.

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


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

ORG_CITY: NEW YORK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Public Narrative: This project will develop and apply novel genetic technology to understand blood cell biology. Our research will provide a new insight to understanding how blood cells are generated and regulated in mammals.

PI_NAMEs: DING, LEI ;YAZAWA, MASAYUKI  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Address;Biological;Blood Cells;Cell Differentiation process;Cell Proliferation;Cells;Cellular biology;DNA;Gene Expression;genetic manipulation;genetic technology;Genome engineering;Hematopoiesis;Hematopoietic stem cells;insight;Lighting;Mammals;Mediating;Molecular;Molecular Genetics;novel;nuclease;optogenetics;recombinase;Research;Resolution;spatiotemporal;stem cell biology;System;tool

PROJECT_TITLE: Confocal illumination system to apply optogenetic tools for hematopoietic stem cell biology with single cell resolution

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative This study will support the Center to Accelerate Population Research in Alzheimer’ (CAPRA) overarching goal to stimulate new, innovative, and high-quality population ADRD research and to increase accessibility of these resources for a broad spectrum of ADRD investigators. To support this goal, this supplement includes utilization of the NIA Data LINKAGE program to develop new Alzheimer’s disease and related dementias (ADRD) datasets linked to claims data in the Health & Retirement Study (HRS), the National Health and Aging Trends Study (NHATS), and through nursing home assessment data via the Minimum Dataset (MDS). Additionally, this study will test the rigor of a validated claims-based ADRD identification algorithm when applied across differently sampled national datasets where services are linked to claims.

PI_NAMEs: BYNUM, JULIE PW (contact)

PROGRAM_OFFICER_NAME: FAZIO, ELENA

PROJECT_TERMS: Acceleration;Address;Aging;Agreement;Algorithms;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Alzheimer's disease test;Applications Grants;beneficiary;clinical diagnosis;Cognitive;community based care;community based service;Contracts;County;Data;Data Linkages;data repository;Data Set;Data Sources;Databases;Dementia;Demography;Development;Diagnosis;Economics;Environment;experience;Foundations;Funding;Future;Geography;Goals;Grant;Health;Health and Retirement Study;health care delivery;Home;Individual;innovation;insight;Knowledge;Link;Location;Long-Term Care;longitudinal dataset;Medicaid;Medicare;Medicare claim;Mentors;Michigan;Nursing Homes;Observational Study;older adult;Participant;patient home care;performance tests;Persons;Population;Population Research;Population Study;programs;Public Health;Public Policy;Research;Research Methodology;Research Personnel;Resources;Sampling;Sampling Studies;Services;Site;Surveys;Testing;tool;trend;United States Dept. of Health and Human Services;Work

PROJECT_TITLE: Center to Accelerate Population Research in Alzheimer’s (CAPRA)


ORG_DEPT: CHEMISTRY

PHR: Project Narrative We seek to discover new principles for selective catalysis, and to apply those principles to the discovery of valuable organic reactions. The fruit of this effort will be new classes of small- molecule, chiral organic catalysts engineered to induce rate acceleration and stereoselectivity in a wide range of challenging transformations through networks of attractive non-covalent interactions. These catalysts form the basis for conceptually novel and efficient methods for the synthesis of chiral organic compounds of known or potential utility in public health.

PI_NAMEs: JACOBSEN, ERIC N (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Development, Elucidation, and Application of New Principles in Stereoselective Catalysis


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: RICHMOND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative  The Hsp70/Hsp110 molecular chaperones play multiple essential roles in maintaining cellular protein homeostasis, a fundamental cellular process that is inevitably linked to many human diseases including fungal infections. In this proposal, we aim to understand the basic molecular mechanism of Hsp110s in the Hsp70/Hsp110 chaperone machinery in maintaining protein homeostasis using a unique chemical tool that we recently identified, and thereby provide crucial insights on how to target them for treating fungal infections.

PI_NAMEs: LIU, QINGLIAN  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;anti-fungal agents;Binding;Biological Process;Candida albicans;Cell Physiology;Cells;chaperone machinery;Chemicals;Complex;design;Distant;Endoplasmic Reticulum;Foundations;Future;Genetic;Growth;Guanine Nucleotide Exchange Factors;Homologous Gene;Human;human disease;In Vitro;in vivo;inhibitor;innovation;insight;Link;Molecular;Molecular Chaperones;Mycoses;Names;new therapeutic target;novel;Nucleotides;Pharmaceutical Chemistry;Play;prevent;Process;protein folding;Protein Import;Proteins;proteostasis;Role;Saccharomyces cerevisiae;Solid;Structure;Therapeutic;Time;tool;Toxic effect;Yeasts

PROJECT_TITLE: Structural and functional studies of Hsp70/Hsp110 molecular chaperones

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project Narrative It has become feasible for small research groups to sequence individual genomes and for larger groups to sequence tens of thousands of individuals. The parent proposal created a multi-institutional, cross disciplinary team to discover and validate disease causing splicing mutations in patients. This supplement will greatly extend our ability to develop more realistic models of splice site recognition as long read sequencing helps account for all the splicing decisions and crosstalk that occur in the processing of each pre-mRNA.

PI_NAMEs: FAIRBROTHER, WILLIAM G (contact)

PROJECT_TITLE: Discovering Splicing Defects in Human Genes


ORG_DEPT: BIOCHEMISTRY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Single-particle cryo-EM, a method of molecular structure research pioneered in the PI's lab, has been further developed with the inclusion of time-resolved techniques to allow capture and structure determination of short- lived states. A combination of standard and time-resolved techniques will be applied to elucidate processes in protein biosynthesis with fundamental significance to public health. In addition, a novel method of data analysis aiming at characterization of the dynamic behavior of molecules will be applied to large datasets of important membrane-associated molecules: rotary ATPase and Cystic fibrosis trans-membrane conductance regulator.

PI_NAMEs: FRANK, JOACHIM  (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: ATP phosphohydrolase;Behavior;Biological;Collaborations;Cryoelectron Microscopy;Cystic Fibrosis Transmembrane Conductance Regulator;Data Analyses;Dimensions;Encephalomyocarditis virus;Escherichia coli;Free Energy;Image;Kinetics;large datasets;Length;Liquid substance;macromolecular assembly;macromolecule;Maps;Membrane;Methods;Microfluidic Microchips;millisecond;Molecular Conformation;Molecular Structure;novel;particle;Preparation;Procedures;Process;Protein Biosynthesis;Public Health;Quality Control;Reaction;Recycling;Research;Resolution;Ribosomes;Sampling;Specialist;Structure;Techniques;Time;Translation Initiation;Translation Process;Translational Regulation;Translations;Virus;Visualization;Yeasts

PROJECT_TITLE: Structural Studies of Macromolecular Assemblies Using Cryo-EM


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative Protein-protein and protein-RNA interactions are vital for numerous biological processes, from cellular signaling to gene regulation, and their misregulation has been associated with a variety of diseases. Selective modulation of these interactions would, therefore, facilitate the discovery of candidate therapeutic agents for a broad range of diseases. The proposed research describes approaches for developing synthetic protein mimics for targeting chosen biomolecular complexes.

PI_NAMEs: ARORA, PARAMJIT S (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Acceleration;Administrative Supplement;Binding;Biological;Biological Process;Biology;Chemistry;Complex;Development;Disease;Double-Stranded RNA;Engineering;Epitopes;Event;Foundations;Funding;Gene Expression Regulation;Grant;inhibitor;Inosine Diphosphate;instrument;instrumentation;Ligands;Mediating;Membrane Proteins;Messenger RNA;Molecular;molecular size;National Institute of General Medical Sciences;Nucleic Acids;parent grant;peptidomimetics;Procedures;protein complex;Protein Inhibition;protein protein interaction;Proteins;rational design;receptor;Research;RNA;RNA-Protein Interaction;scaffold;Signal Pathway;Signal Transduction;small molecule;Structure;synthetic protein;System;Technology;Tertiary Protein Structure;Therapeutic;Therapeutic Agents;therapeutic candidate;Therapeutic Intervention;therapeutic target;Time;Work

PROJECT_TITLE: Biomolecular Recognition with Synthetic Protein Mimics


ADMINISTERING_IC: EB

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE This study aims to perform the first investigation of non-invasive, non-thermal, mechanical high-intensity focused ultrasound (histotripsy) ablation using an ultra-high rate treatment method with ultrasound- and robotic-guidance to rapidly, precisely, and completely ablate entire soft tissue sarcomas (STS). Canine STS share biologic similarities with human STS, and clinical research in pet dogs with STS offers a unique opportunity to accelerate treatment advances for humans, while also improving treatments for canine STS. The results of this study are expected to transform histotripsy practice through efficient ablation of large tumors and open up new pathways for its rational deployment in other cancers that will uniformly improve canine and human health.

PI_NAMEs: KLAHN, SHAWNA  (contact)

PROGRAM_OFFICER_NAME: KING, RANDY LEE

PROJECT_TERMS: Ablation;Acceleration;Acoustics;Address;Affect;aggressive therapy;Anatomy;Animals;Behavior;Biological;Blood Vessels;cancer clinical trial;Canis familiaris;chemotherapy;Clinical;clinical implementation;clinical outcome measures;Clinical Research;clinical translation;Clinical Trials;clinically relevant;Combined Modality Therapy;Controlled Study;Data;Dermal;Development;Device or Instrument Development;Diagnosis;Dose;effective therapy;Effectiveness;effectiveness evaluation;Evaluation;Excision;Family suidae;Feedback;Focused Ultrasound Therapy;Frequencies;functional improvement;functional outcomes;Goals;Health;heat injury;Histologic;Histology;Human;Image;Image Analysis;image guided;improved;in vivo;in vivo evaluation;innovation;insight;interdisciplinary collaboration;Investigation;Life;Local Therapy;Location;Malignant Neoplasms;Mechanics;Mesenchymal;Methods;Modeling;Morbidity - disease rate;Nerve;non-invasive system;novel;Operative Surgical Procedures;Outcome;Pathology;Pathway interactions;patient population;patient safety;Patient-Focused Outcomes;Patients;Phase;Physiologic pulse;Positioning Attribute;pre-clinical;Preparation;preservation;prevent;Process;prototype;Quality of life;Radiation therapy;real-time images;Recurrent tumor;research clinical testing;Resected;response;Retreatment;Risk;Robotics;Safety;safety and feasibility;Soft tissue sarcoma;Structure;System;Techniques;Technology;Testing;Time;tissue phantom;Tissues;Transducers;Translational Research;treatment optimization;treatment strategy;tumor;tumor ablation;tumor heterogeneity;tumor progression;Tumor Subtype;Tumor Volume;Ultrasonic Therapy;ultrasound;years of life lost

PROJECT_TITLE: Ultrasound-guided robotic histotripsy array system for non-invasive precise and complete ablation of soft tissue sarcoma

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


ORG_CITY: ARLINGTON

ORG_NAME: UNIVERSITY OF TEXAS ARLINGTON

ORG_STATE: TX

PHR: Project Narrative The mitochondrial unfolded protein response mediates mitochondrial recovery during stress while also promoting an innate immune response to promote host survival during pathogen infection. The discoveries we will make in this proposal not only have implications to our fundamental understanding of host-pathogen interactions, but also bear clinical relevance in an era of antibiotic resistance and need for alternative therapeutic strategies.

PI_NAMEs: PELLEGRINO, MARK WATSON (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Animals;Anti-Bacterial Agents;Antibiotic Resistance;antibiotic resistant infections;antimicrobial;Bacterial Antibiotic Resistance;Bacterial Infections;Caenorhabditis elegans;Cell Physiology;Cell Survival;Clinical;clinically relevant;Coupling;Defense Mechanisms;detection of nutrient;Diet;Drug Metabolic Detoxication;Environment;fighting;Functional disorder;Genetic;Genetic Transcription;Host Defense Mechanism;Immune system;Infection;Innate Immune Response;insight;Intervention;Intuition;Lead;Mediating;Metabolic;Metabolism;microbial;Mitochondria;mouse model;multitask;Natural Immunity;pathogen;pathogenic microbe;Play;Predisposition;Proteins;proteostasis;Reactive Oxygen Species;Recovery;Regulation;residence;response;Role;Signal Pathway;Stress;Therapeutic

PROJECT_TITLE: Mechanisms of host protection during infection via the mitochondrial unfolded protein response


PHR: The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is known for its fundamental roles in remodeling cellular membranes to enable membrane protein degradation, HIV budding, and cell division. The work in this proposal builds on and extends our discovery that ESCRTs also stabilize and repair membranes throughout the endolysosomal network. Insight into how this machinery maintains compartmental membrane integrity has important implications for understanding inflammatory responses, pathogen invasion, and mechanisms underlying necrotic cell death.

PI_NAMEs: HANSON, PHYLLIS I (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TITLE: ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

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

ORG_CITY: GREENSBORO

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: NORTH CAROLINA AGRI & TECH ST UNIV

ORG_STATE: NC

PHR: PROJECT NARRATIVE. Meprin metalloproteases have been implicated in the pathophysiology of chronic kidney injury induced by diabetes and neurodegenerative disease (e.g. Alzheimer’s disease). The proposed parent project will determine; (1) how single nucleotide polymorphisms (SNPs) in the meprin genes impact interaction between the meprin enzymes and their substrates, (2) how cleavage of meprin substrates influence signaling pathways involved in disease progression, and (3) the potential use of meprins and meprin cleavage products in early diagnosis of tissue injury. This knowledge is important in developing therapeutic targets and diagnostic tools for diseases such as chronic kidney injury and Alzheimer’s disease. The requested funding for purchase of a high-resolution fluorescent microscope will facilitate microscopic analysis of kidney and brain tissue and acquisition of publication quality images.

PI_NAMEs: ONGERI, ELIMELDA MOIGE (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Actins;Administrative Supplement;Alzheimer's Disease;Amyloid beta-Protein Precursor;Anti-Inflammatory Agents;Area;Award;biomarker development;brain tissue;brush border membrane;cancer cell;CCL2 gene;Chronic;Complex;Computer software;Coupled;Cyclic AMP-Dependent Protein Kinases;cytokine;Cytoskeletal Proteins;Dementia;Diabetes Mellitus;Diabetic Nephropathy;diagnostic development;diagnostic tool;Disease;Disease Progression;E-Cadherin;Early Diagnosis;Endothelial Cells;Enzymes;Equipment;equipment acquisition;Extracellular Matrix;Extracellular Matrix Proteins;Fibrosis;fluorescence microscope;Functional disorder;Funding;Genes;Genetic Predisposition to Disease;Goals;Hypoxia;IL18 gene;Image;Imaging technology;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Injury to Kidney;insight;Interleukin-1 beta;Interleukin-6;Kidney;Kidney Diseases;Knockout Mice;Knowledge;Leukocytes;Macrophage;Malignant Neoplasms;Measures;Mediating;Mediator;Mentors;Meprin;meprin alpha;Metabolism;Metalloproteases;Microscopic;microscopic imaging;Minority Groups;Molecular;Molecular Biology;monocyte;mouse model;Nerve Degeneration;Neurodegenerative Disorders;occludin;Organ;Osteosarcoma;parent project;Physiological;podocyte;programs;protein expression;Protein Isoforms;Protein Kinase C;Proteins;Proteomics;Proximal Kidney Tubules;Publications;Pulmonary Fibrosis;Renal Carcinoma;Research;Research Support;Resolution;response;Severities;Signal Pathway;Signal Transduction;Signaling Protein;Single Nucleotide Polymorphism;Skin;Small Intestines;Stains;Therapeutic;therapeutic target;Tight Junctions;tissue injury;tool;Transcend;translational study;TREM2 gene;Underrepresented Minority;villin

PROJECT_TITLE: Administrative Supplement for Imaging Equipment Purchase


NIH_SPENDING_CATS: Muscular Dystrophy;Myotonic Dystrophy;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: NARRATIVE Regulation of the cellular signaling pathways that control the actin cytoskeleton is essential in development and homeostasis. This application focuses on the LIM domain kinases, enzymes which are key regulators of the actin cytoskeleton, and their upstream kinases, the MRCKs. We aim to delineate the atomic-level mechanism of LIMK and MRCK control, to understand how the dual specificity kinases can phosphorylate a range of substrates, and how the LIMKs are recruited to the MRCKs.

PI_NAMEs: BOGGON, TITUS JONATHON (contact);TURK, BENJAMIN E

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: actin depolymerizing factor;Actins;Adaptor Signaling Protein;Architecture;Area;Binding;Binding Proteins;Biochemical;Biophysics;CDC42 gene;cell growth regulation;Cells;Cellular Morphology;cofilin;Complex;Coupled;Cues;Cytoskeleton;Data;Development;Enzymes;Eukaryotic Cell;extracellular;Family;Guanosine Triphosphate Phosphohydrolases;Homeostasis;Laboratories;LIM Domain;LIM Domain Kinase 1;LIMK1 gene;Mediating;Microfilaments;Modeling;Molecular;molecular dynamics;Movement;Myotonic Dystrophy;p21 activated kinase;Phosphorylation;Phosphotransferases;Process;Protein Kinase;Proteins;recruit;Regulation;rho GTP-Binding Proteins;Signal Pathway;Signal Transduction;Specificity;Surface;upstream kinase;X-Ray Crystallography

PROJECT_TITLE: LIM domain kinases: regulation and substrate recognition


NIH_SPENDING_CATS: Brain Disorders;Neurosciences

PHR: Project Narrative Human GABAB receptor and human calcium-sensing receptor are dimeric G protein-coupled receptors that mediate key biological phenomena including neurotransmission and Ca2+ homeostasis. Here we address the fundamental questions of how these receptors are activated by extracellular stimuli and how their functions are regulated. Defects in the signaling activities of these receptors are associated with disorders of the brain, bone and mineral metabolism, and our work will inform about the disease mechanisms and assist the design of novel therapeutic agents.

PI_NAMEs: FAN, QING R (contact)

PROJECT_TERMS: addiction;Address;Anxiety;Behavior Disorders;Biological Phenomena;Blood;Bone Diseases;Brain Diseases;Calcium-Sensing Receptors;Central Nervous System;Cognitive;Coupling;Defect;design;Development;dimer;Disease;Epilepsy;extracellular;Extracellular Domain;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;GTP-Binding Proteins;Homeostasis;Human;Hypercalcemia;Length;Life;Ligand Binding;Ligands;Mediating;Membrane;Metabolism;Minerals;Molecular;neurotransmission;novel therapeutics;Proteins;receptor;Receptor Activation;receptor function;Research;Signal Transduction;spasticity;Stimulus;Structural Models;Structure;synaptic inhibition;System;Therapeutic Agents;Transmembrane Domain;Work

PROJECT_TITLE: Molecular mechanism of dimeric G protein-coupled receptor signaling


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

ORG_CITY: WOODS HOLE

ORG_NAME: MARINE BIOLOGICAL LABORATORY

PHR: With this supplemental request, we are seeking to acquire a benchtop instrument for analysis of interactions between proteins, nucleic acids and small molecules that would enhance our access to the new technology.

PI_NAMEs: ARKHIPOVA, IRINA  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Affect;Biological Assay;Enzymes;Equipment;Eukaryota;Horizontal Gene Transfer;In Vitro;innovation;instrument;laboratory equipment;Monitor;monomer;new technology;Nucleic Acids;protein complex;Proteins;response;Reverse Transcriptase Inhibitors;RNA;RNA Binding;RNA-Directed DNA Polymerase;RNA-Protein Interaction;small molecule;Source;Surface Plasmon Resonance;System;Tail;Technology

PROJECT_TITLE: Horizontal gene transfer as the source of evolutionary innovation in eukaryotes


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

PHR: Heritable changes that can last for multiple generations without changing DNA sequence have been reported in many organisms, including humans. By focusing on the regulatory architectures that promote or prevent gene silencing in the nematode C. elegans, we will gain broadly applicable insights regardless of the molecules that mediate similar regulatory interactions in other systems. These insights will improve the diagnosis and treatment of hereditary diseases, especially those with an epigenetic origin in previous generations.

PI_NAMEs: JOSE, ANTONY MERLIN (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Architecture;Caenorhabditis elegans;Chemicals;chromatin modification;Cytoplasmic Granules;Diagnosis;Disease;DNA Methylation;DNA Sequence;Double-Stranded RNA;Epigenetic Process;Gene Expression;Gene Silencing;Generations;Genes;Germ Lines;Goals;Hereditary Disease;Heredity;Heritability;Human;improved;insight;Mediating;Modeling;Modification;Nematoda;Organism;Phase;piRNA;Predisposition;prevent;Proteins;psychological trauma;Regulation;Reporting;Resolution;response;RNA;RNA Binding;RNA Interference;RNA Stability;Small RNA;Starvation;Stressful Event;System;Transgenic Model

PROJECT_TITLE: Transgenerational gene silencing

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative  The central objective of this proposal is to develop a technological platform that harnesses light energy and biocatalysis to synthesize molecules of significant relevance to human life. We envision doing this by establishing cyanobacterial endosymbionts within yeasts cells, such that the endosymbiotic cyanobacteria provide ATP and assimilated carbon (generated from photosynthesis) to the yeast cells, which utilize it to produce biologically important natural products. The above endosymbiotic platform will allow us to couple the remarkable biosynthetic and biocatalytic potential of yeast to the photosynthetic ability of cyanobacteria to develop a sustainable and simple bioproduction platform to produce key precursors of FDA approved compounds, Artemisinin and Taxol.

PI_NAMEs: MEHTA, ANGAD  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Harnessing light and model endosymbiosis to produce natural products

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Rare Diseases;Tuberculosis

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Granulomas drive the course of pulmonary tuberculosis disease and treatment, but we lack detailed understanding of how granuloma features interact with immune function and the bacterial pathogen. In this project, we will develop and utilize a geospatial information system for tuberculosis granulomas to provide new insights into granulomas during disease and treatment.

PI_NAMEs: ALDRIDGE, BREE BEARDSLEY;RENGARAJAN, JYOTHI  (contact)

PROGRAM_OFFICER_NAME: EICHELBERG, KATRIN

PROJECT_TERMS: Activities of Daily Living;Affect;Animals;Antibiotic Therapy;Antigens;antimicrobial;Architecture;Bacteria;Bacterial Physiology;Cell Physiology;cell type;Cells;Clinical;Communication;Computational Biology;Computer Analysis;Computer Models;Containment;Data;design;Development;Disease;Disease Outcome;Drug Tolerance;Enzymes;Formalin;Gene Expression;Geographic Information Systems;Granuloma;Growth;Human;imaging modality;Immune;immune function;Immunofluorescence Immunologic;Immunology;immunopathology;Immunophenotyping;In Situ;Individual;Infection;Information Systems;inhibitor;insight;Investigation;Lesion;Lung;Macaca;Macaca mulatta;Macrophage;Maps;Metabolic;Modeling;multidisciplinary;Mycobacterium tuberculosis;nonhuman primate;novel;novel therapeutics;pathogen;Pathogenesis;pathogenic bacteria;Pathologic;Periodicity;permissiveness;PET/CT scan;Pharmaceutical Preparations;Physiological;Physiology;Predisposition;Procedures;pulmonary granuloma;Pulmonary Tuberculosis;response;scaffold;single-cell RNA sequencing;Stress;Structure of parenchyma of lung;Systems Biology;T cell response;T-Lymphocyte;Techniques;Technology;Testing;Therapeutic;tissue fixing;Tissues;tool;transcriptomics;Treatment Protocols;Tryptophan;Tryptophan 2,3 Dioxygenase;Tuberculosis;tuberculosis granuloma;tumor-immune system interactions;virtual

PROJECT_TITLE: Deep spatial immune profiling of granulomas and M. tuberculosis adaptation to disease and treatment


ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE Bacterial genes acquired through horizontal transfer are silenced by small histone-like proteins and by the transcription termination factor Rho. Expression of these genes, which are required for bacterial survival under some conditions, depends on accessory proteins that relieve silencing. In this project, we will investigate mechanisms by which Escherichia coli cell envelope biogenesis genes are silenced and activated by RfaH.

PI_NAMEs: ARTSIMOVITCH, IRINA  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Address;Antibiotics;Bacteria;Bacterial Genes;Binding;Biochemical;Biochemistry;Biogenesis;biological adaptation to stress;Biology;cell envelope;Cells;Chromatin;Communities;Complex;Coupling;Data;DNA;DNA-Binding Proteins;DNA-Directed RNA Polymerase;Elongation Factor;Ensure;Environment;Enzymes;Escherichia coli;Exclusion;experimental study;Family;Filament;Food;Funding;Gene Expression;Gene Expression Regulation;gene repression;Gene Silencing;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Growth;Habitats;Heterochromatin;Histones;Homologous Gene;Hyperactivity;In Vitro;in vivo;in vivo evaluation;insight;Interdisciplinary Study;Life;Maintenance;Mediating;Molecular;Molecular Chaperones;Molecular Conformation;Molecular Genetics;Nature;Nucleoproteins;Nutrient;Operon;paralogous gene;Phylogenetic Analysis;Positioning Attribute;Productivity;promoter;Proteins;Proteomics;Regulation;repaired;Research Personnel;rho;Rho Factor;RNA;RNA chemical synthesis;Source;Stress;Structure;termination factor;tool;Transcription Elongation;Transcription Initiation;transcription termination;Translating;Translations;Travel;Virulence Factors;Work

PROJECT_TITLE: Cellular factors maintaining and reversing silencing of bacterial chromatin


ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative The proposed research will elucidate the basic molecular mechanisms underlying cilia dependent vertebrate Hedgehog pathway, an essential cell-signaling pathway required for embryonic development and adult tissue homeostasis. The fundamental knowledge gained through this work is expected to aid research that is aimed at development of therapeutic agents to combat birth defects and human cancers linked to errors in this pathway.

PI_NAMEs: SUBRAMANIAN, RADHIKA  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Adult;Basal cell carcinoma;base;Binding;Biochemical;Biological;Biological Assay;Biology;Cell Physiology;Cells;Cilia;combat;Complex;Congenital Abnormality;Craniofacial Abnormalities;Cytoplasm;Data;developmental disease;Embryonic Development;Erinaceidae;experience;gene repression;Goals;hedgehog signal transduction;Homeostasis;Human;imaging modality;Knowledge;Link;Location;malformation;Malignant Neoplasms;Mediating;Medulloblastoma;Microtubules;Molecular;Mutation;Newborn Infant;Nuclear Import;Organelles;Pathway interactions;Property;protein complex;Protein Dynamics;protein protein interaction;Proteins;Reaction;real-time images;reconstitution;Research;Resolution;Series;Signal Pathway;Signal Transduction;Signal Transduction Pathway;single molecule;skeletal;smoothened signaling pathway;therapeutic development;Tissues;transcription factor;tumor;Work

PROJECT_TITLE: Protein dynamics underlying cilium-dependent Hedgehog signaling

STUDY_SECTION: NCSD

STUDY_SECTION_NAME: Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section[NCSD]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Liver Disease;Microbiome;Nutrition;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: HONOLULU

ORG_NAME: UNIVERSITY OF HAWAII AT MANOA

ORG_STATE: HI

PHR: PROJECT NARRATIVE Obesity-associated non-alcoholic fatty liver disease (NAFLD) is now the primary cause of liver cancer and the driver of the increase in this lethal disease. While certain gut bacteria have been implicated in NAFLD or NAFLD-induced liver fibrosis, longitudinal studies are needed to provide evidence for the temporal relationship. We will identify the kinds of gut bacteria and their metabolic pathways that are associated with increase in liver fat, more extensive liver stiffness, and increase in blood biomarker-based liver fibrosis over time in a prospective multiethnic study of underrepresented Asian Americans and Native Hawaiians, and Whites.

PI_NAMEs: HULLAR, MEREDITH ;LAMPE, JOHANNA W;LIM, UNHEE  (contact)

PROGRAM_OFFICER_NAME: LAI, GABRIEL Y

PROJECT_TERMS: 16S ribosomal RNA sequencing;Address;Affect;aged;Asian Americans;Bacteria;Bile Acids;Biological Markers;biomarker panel;Blood;blood-based biomarker;Cancer Burden;carbohydrate metabolism;chronic liver disease;Clinic;cohort;Diet;Dietary Factors;Dietary Practices;Disease;Disease Progression;dysbiosis;elastography;Endotoxins;Ethnic Population;Etiology;Fatty acid glycerol esters;Fibrosis;follow up assessment;follow-up;Fusobacterium;gut bacteria;gut microbiome;gut microbiota;high risk population;Image;Intervention;Investigation;Japanese American;Laboratories;lipopolysaccharide-binding protein;Liver;Liver Fibrosis;liver stiffness;longitudinal design;Longitudinal Studies;Magnetic Resonance Imaging;Malignant neoplasm of liver;Measures;Mediating;Mediation;Metabolic Pathway;metagenomic sequencing;Methods;microbial;multi-ethnic;Native Hawaiian;non-alcoholic fatty liver disease;novel;Obesity;older adult;Participant;Pathway interactions;Phenotype;population based;prevent;prospective;Race;racial population;stool sample;Time;trend

PROJECT_TITLE: Longitudinal Study of Early NAFLD Progression and the Gut Microbiome in Asian Americans, Native Hawaiians and Whites

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE Project Narrative DNA damage arising from oxidative stress promotes multiple human diseases, and the primary cellular defense against this oxidative DNA damage is the multi-protein base excision repair (BER) pathway. The overarching goal of this proposal is to understand the molecular mechanisms of each BER factor both individually and within larger multi-protein/DNA complexes using naked duplex DNA and nucleosomes. We will employ elegant biophysical approaches to elucidate inherent BER complexities, while providing both a foundation for interpreting the biological response and the subsequent development of rational therapeutic treatments towards enhancing human health.

PI_NAMEs: FREUDENTHAL, BRET D (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Award;Base Excision Repairs;Biological;biophysical techniques;Cell model;Cells;Chromatin;Complex;Cryoelectron Microscopy;Dangerousness;Development;DNA;DNA Damage;DNA Repair;DNA Repair Gene;DNA Structure;DNA-Directed DNA Polymerase;Drug Combinations;Drug Design;Enzyme Kinetics;Enzymes;Foundations;Genome Stability;Goals;Hand;Health;Human;human disease;Individual;interdisciplinary approach;Malignant Neoplasms;Methodology;Microscopy;Modification;Molecular;molecular dynamics;Multiprotein Complexes;Mutagenesis;novel therapeutics;Nucleosomes;oxidative DNA damage;Oxidative Stress;Pathway interactions;Positioning Attribute;Proteins;Repair Complex;repair enzyme;repaired;response;Role;Scientific Advances and Accomplishments;single molecule;Telomerase;telomere;Therapeutic;therapeutic development;United States National Institutes of Health;X-Ray Crystallography

PROJECT_TITLE: Supplement to NIH Award 2 R35GM128562-06


NIH_SPENDING_CATS: Bioengineering;Genetics;Machine Learning and Artificial Intelligence

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE RNA molecules play fundamental roles in transmitting and regulating genetic information in all living systems, including disease-causing bacteria, RNA viruses like HIV and SARS-CoV-2, tumor cells, and our own brains and bodies. New potentially life-saving therapies and vaccines that target or repurpose these RNAs are being hindered by our imperfect understanding of how RNAs fold into intricate 3D structures. Our research addresses these gaps through computational tools, most recently through deep learning neural networks. Training predictive models and making inferences with these neural networks requires heavy use of graphics processing units (GPU), at a scale that could not be envisioned at the time of our original proposal but now appears necessary for us to carry out the proposed research.

PI_NAMEs: DAS, RHIJU  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: 2019-nCoV;3-Dimensional;Address;Adoption;Anti-Bacterial Agents;Bacteria;Behavior;Biochemical;Biological;Biomedical Engineering;Biophysics;blind;Brain;Chemicals;Communities;Complex;computerized tools;Crystallography;deep neural network;design;Development;Disabling;Disease;Engineering;experimental study;genetic information;Heterogeneity;HIV;Life;Medical;Methods;Modeling;Modification;Molecular Conformation;molecular modeling;Mutation;neoplastic cell;neural network;novel;Organism;Phylogenetic Analysis;Play;predictive modeling;prospective;Proteins;Regulation;Research;RNA;RNA Folding;RNA Viruses;Role;Software Tools;structural biology;Structure;success;Technology;Testing;therapeutic genome editing;three dimensional structure;Time;tool;Training;transmission process;tumor;Untranslated RNA;Vaccines;Viral;Work

PROJECT_TITLE: Modeling and design of complex RNA structures

STUDY_SECTION: MRAB

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


ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Narrative Pyroptosis is a highly inflammatory form of cell death mediated by the gasdermin family members, and is implicated in infections and autoimmune or autoinflammatory disorders. This proposal will leverage our expertise in structural and biochemical studies of gasdermins and inflammatory caspases to investigate the post- translational regulation of gasdermins by proteases, ubiquitin ligases, palmitoyltransferases, and other enzymes. Better understanding of the mechanisms of gasdermin regulation is highly significant, which may stimulate the development of novel therapeutics that target pyroptosis and inflammation.

PI_NAMEs: XIAO, TSAN SAM (contact)

PROJECT_TERMS: Autoimmune Diseases;autoinflammatory diseases;Biochemical;Biology;Caspase;Cell Death;cytokine;Development;Enzymes;Family member;IL18 gene;Immune signaling;Infection;Inflammasome;Inflammation;Inflammatory;insight;Knowledge;Mediating;microbial;Modification;Molecular;new therapeutic target;Pathologic;Pathway interactions;Peptide Hydrolases;Physiological;Post-Translational Protein Processing;Post-Translational Regulation;programs;Regulation;Research;Signal Pathway;Structure;ubiquitin ligase;Ubiquitination

PROJECT_TITLE: Regulation of gasdermins through protease processing and other post-translational modifications.


ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project narrative. This is an application for the Administrative Supplement to the currently active R01 GM141546- 02 entitled “Role of retinoid oxidoreductase complex in controlling the embryonic development”. The Administrative Supplement will allow us to purchase a new BioTek Cytation C10 Confocal Imaging Reader that will greatly facilitate and advance our workflow. This instrument will enhance our ability to acquire, process and analyze imaging data and support success and continuation of our studies.

PI_NAMEs: BELIAEVA, OLGA V (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TITLE: Role Of Retinoid Oxidoreductase Complex In Controlling The Embryonic Development


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Nutrition

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Chemoenzymatic construction of synthetic human milk oligosaccharide (HMO) glycome Efficient and innovative methods will be developed and related enzymes will be identified for target-oriented chemoenzymatic synthesis of human milk oligosaccharides (HMOs) in a systematic manner. The resulting compounds are important standards for analysis, probes to identify HMO-binding proteins, and reagents to explore the multifaceted applications of HMOs as infant formula additives, potential nutraceuticals and therapeutics. The chemoenzymatic synthetic process is programmable, can be adapted for automation, and readily scalable for large-scale production of HMOs in the future.

PI_NAMEs: CHEN, XI  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Atlases;Automation;Binding Proteins;Breastfed infant;Carbohydrates;Chemicals;cost effective;design;Discipline of Nursing;Disease;Economics;Engineering;Enzymes;Escherichia coli;Fermentation;Fucose;Future;glycosylation;glycosyltransferase;Health;Human Milk;human milk oligosaccharides;improved;In Situ;Individual;Infant formula;Infection;innovation;Isomerism;Lactation;Lactose;large scale production;Libraries;Life;Maps;method development;Methods;Milk;Monosaccharides;nucleoside triphosphate;nursing mothers;Nutraceutical;Polysaccharides;Process;Production;Reagent;Role;Route;scale up;Sialic Acids;sialylation;Site;Source;Speed;Structure;Substrate Specificity;sugar nucleotide;Therapeutic;tool;user-friendly;Vertebral column

PROJECT_TITLE: Supplement:Chemoenzymatic construction of synthetic human milk oligosaccharide (HMO) glycome

STUDY_SECTION: SBCA

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


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative The properly regulated expression of protein-coding genes transcribed by RNA polymerase II (RNAPII) is essential for normal growth and development; disturbances in this regulation are hallmarks of cancer and other diseases. Both the transcription cycle of RNAPII and the cell division cycle are governed by the opposing actions of cyclin-dependent kinases (CDKs) and protein phosphatases, which have emerged as potential targets in cancer therapy. Comprehensive models of how CDKs and phosphatases work together during the transcription cycle, and how this coordination is disrupted in cancer cells, are needed both to deepen understanding of normal gene regulation and to guide efforts to target the RNAPII machinery therapeutically.

PI_NAMEs: FISHER, ROBERT P (contact)

PROJECT_TERMS: Binding;cancer cell;cancer therapy;Cell Cycle;Cell Cycle Regulation;Cell division;Cells;Chromatin;Code;Collaborations;Complex;Coupling;Cyclin-Dependent Kinases;Disease;Dissection;Drug Targeting;Elongation Factor;Ensure;Event;Family;Gene Expression;Gene Expression Regulation;Genetic Transcription;genome editing;genome-wide;Genomics;Goals;Growth and Development function;Human;Link;Malignant Neoplasms;member;Messenger RNA;Modeling;Mutation;Pathway interactions;Phase;phosphatase-1 kinase;Phosphoric Monoester Hydrolases;Phosphorylation;promoter;Protein Dephosphorylation;protein expression;Protein phosphatase;Protein Phosphatase 2A Regulatory Subunit PR53;recruit;Regulation;response;RNA Polymerase II;Role;Signal Transduction;Site;small molecule;Specificity;Substrate Specificity;Testing;Therapeutic;transcription factor TFIIH;Transcriptional Regulation;Work

PROJECT_TITLE: Cyclin-dependent kinase control of cell-division and transcription cycles


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Pancreatic Cancer;Rare Diseases

ORG_CITY: OMAHA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE This application requests supplemental funds for purchasing a CFX Opus 96 Real-Time PCR System. The equipment is intended to be used for the genotyping and phenotyping studies proposed in the R01 research project titled “PR55-alpha controlled PP2A in the regulation of the Hippo/YAP pathway” to facilitate the achievement of the goals of this project. The equipment would also benefit the University of Nebraska Medical Center research community.

PI_NAMEs: YAN, YING  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Achievement;Anchorage-Independent Growth;Automobile Driving;cancer initiation;Catalytic Domain;Cell Separation;Cells;Communities;Complex;Critical Pathways;CUL1 gene;Cytoplasm;Data;Development;Disease;DNA analysis;Equipment;experimental study;F-Box Proteins;Family;Funding;Gene Expression Profiling;Genes;Genotype;Goals;Human;improved;innovation;knock-down;Knowledge acquisition;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Medical center;Messenger RNA;mouse model;Mus;Nebraska;Neoplasm Metastasis;new therapeutic target;novel;Oncogenic;pancreatic cancer cells;Pathway interactions;Patients;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Productivity;Protein Kinase;Protein phosphatase;Protein Phosphatase 2A Regulatory Subunit PR53;Proteins;Real-Time Systems;Regulation;Request for Applications;Research;Research Project Grants;Retinal blind spot;RNA analysis;Role;Sampling;scaffold;Signal Transduction;Source;Specimen;Standardization;Substrate Specificity;success;Survival Rate;System;targeted treatment;Testing;Time;Tissues;TP53 gene;tumor progression;Tumor Suppression;tumorigenesis;Tumorigenicity;ubiquitin-protein ligase;Universities;Work

PROJECT_TITLE: CFX Opus 96 Real-Time PCR System for precision genotyping and phenotyping

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Narrative Protein allostery is a fundamental phenomenon in which ligand binding at one site affects substrate activity or ligand binding at a second, distal site of the protein. Allostery is a primary mode of regulation for enzymes and other proteins that drive signal transduction and metabolism, and it is now being used in some drug development efforts, even though the mechanisms of allostery are not well understood. The work in this project will characterize dynamics and allosteric communication pathways for the homodimeric enzymes chorismate mutase and thymidylate synthase, and for engineered optogenetic conformational switch proteins.

PI_NAMEs: LEE, ANDREW L (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Address;Affect;Allosteric Regulation;Antineoplastic Agents;Area;Attention;base;Behavior;Binding Sites;Biochemistry;Biology;biophysical analysis;biophysical techniques;Calorimetry;Catalysis;chemical conjugate;Chemistry;Chorismate Mutase;Communication;dimer;Distal;drug development;drug discovery;Engineering;Enzymes;Escherichia coli;Exhibits;falls;flexibility;Fluorouracil;Foundations;Goals;Guanosine Triphosphate Phosphohydrolases;Human;improved;interest;Investigation;Label;Laboratories;Ligand Binding;Ligands;Metabolism;Molecular Conformation;molecular dynamics;Movement;Nature;NMR Spectroscopy;optogenetics;Pathway interactions;Property;Protein Engineering;protein function;Proteins;Protomer;Regulation;Relaxation;Role;Signal Transduction;Signaling Protein;Site;small molecule;Structure;System;Technology;Thymidylate Synthase;Work;X-Ray Crystallography;Yeasts

PROJECT_TITLE: Mechanisms and dynamics of allosteric function in proteins


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative We aim to develop new technology to quantitatively analyze thousands of proteins in a single experiment, which will be widely beneficial to studying biological systems in health and diseases. We will apply these techniques to study how proteins partition between the nucleus and cytoplasm and to measure how proteins are degraded. This study will provide us with insight into how healthy and diseased cells control their protein abundance levels and determine protein subcellular localization.

PI_NAMEs: WÜHR, MARTIN  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Active Biological Transport;Address;Behavior;Biochemical;biological systems;Biology;Cell Nucleus;Cells;cost;Cytoplasm;Data;data quality;Democracy;Development;Diffusion;Disease;Embryo;experimental study;Genes;Genetic Transcription;Goals;Health;Human Genome Project;improved;insight;interest;mass spectrometer;Measurement;Measures;Methods;Modeling;new technology;Nuclear Pore;Organism;Property;protein degradation;protein expression;Proteins;Proteome;Proteomics;Regulation;Research;Shotguns;System;Techniques;Technology;Time;Translations;zygote

PROJECT_TITLE: Development of New Proteomics Technology and its Application to Study Cellular Organization


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

ORG_CITY: PHILADELPHIA

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: Narrative Our research aims to develop advanced machine-learning tools to analyze molecular sequences, providing new insights into the evolution of genomes and organisms. By comparing these innovative methods with traditional approaches and emerging deep learning methods, we will develop approaches to understand the genetic basis of traits and reconstruct the tree of life. To achieve this, we are assembling powerful and dedicated computing equipment with GPU acceleration to run complex analyses that will push the boundaries of current scientific knowledge.

PI_NAMEs: KUMAR, SUDHIR  (contact)

PROJECT_TERMS: Acceleration;Address;Benchmarking;Big Data Methods;Biological;comparative;Complex Analysis;computer infrastructure;Computer Systems;computing resources;Data Set;Dedications;deep learning;deep learning model;design;Development;Echolocation;Ensure;Equipment;Evolution;experience;Genes;Genetic;Genetic Models;Genome;Genomics;High Performance Computing;improved;innovation;insight;Institution;Knowledge;Learning;learning strategy;Life;Machine Learning;machine learning method;Maintenance;Mammals;Memory;Methods;Modeling;Molecular;Molecular Analysis;Molecular Evolution;Organism;parent grant;Parents;Photosynthesis;Phylogenetic Analysis;Poaceae;Probability;programs;Proteins;Research;Resources;Running;Sequence Alignment;Set protein;Site;System;tool;Training;trait;Trees

PROJECT_TITLE: Methods For Evolutionary Genomics Analysis


ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative A number of viruses like hepatitis B virus (HPB), herpes simplex virus-1 (HSV-1) and Thogoto virus (THOV) target the general transcription factor TFIIB to regulate expression of viral-specific genes during pathogenicity. TFIIB has also been implicated in neurodegenerative disorder, spinocerebellar ataxia, and cardiac hypertrophy. With a view to understand functioning of TFIIB in a cell, our focus in this grant proposal is elucidation of the overall role of TFIIB in transcriptional regulation in the cell.

PI_NAMEs: ANSARI, ATHAR IMTIAZ (contact)

PROJECT_TERMS: Administrative Supplement;Affinity;Applications Grants;Binding;Cell Proliferation;Cells;Centrifugation;chromatin protein;Complex;Development;Disease;Equipment;Eukaryota;experimental study;Genes;Genetic Transcription;genome-wide;global run on sequencing;Grant;Heart Hypertrophy;Hepatitis B Virus;Herpesvirus 1;Investigation;Laboratories;Manuals;Mass Spectrum Analysis;Mediating;Molecular;Molecular Sieve Chromatography;mutant;Neurodegenerative Disorders;novel;Pathogenicity;Play;Prevalence;Process;promoter;protein protein interaction;protein purification;recruit;Refrigeration;repaired;RNA purification;Role;Speed;Spinocerebellar Ataxias;System;termination factor;Thogoto virus;transcription factor;Transcription Factor TFIIB;Transcription Initiation;transcription termination;Transcriptional Regulation;Viral;Virus;Yeasts

PROJECT_TITLE: A new paradigm of general transcription factor TFIIB functionality in termination and promoter directionality


NIH_SPENDING_CATS: Cancer;Genetics;Human Genome

ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because proper control of chromosome segregation is necessary to prevent aneuploidy and genomic instability, which contribute to the development and progression of tumors and trisomy syndromes. Furthermore, determining the mechanisms and regulation of kinesin motor proteins is directly related to understanding how alterations in the functions of these proteins disrupt development and contribute to congenital disorders and cancer.

PI_NAMEs: STUMPFF, JASON K (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Administrative Supplement;Aneuploidy;Biological;Biophysics;cell type;Cells;Chromosome Arm;chromosome missegregation;Chromosome Segregation;Chromosome Structures;Congenital Disorders;crosslink;Development;Ensure;Equipment;Funding;Generations;genome integrity;Genomic Instability;interdisciplinary approach;Kinesin;Knowledge;Lead;Length;live cell imaging;Malignant Neoplasms;Mechanics;micronucleus;Microscope;Microtubules;Mitosis;Mitotic Chromosome;Mitotic spindle;Molecular;Molecular Motors;Motor;Movement;Mutagenesis;neoplastic cell;Play;preservation;prevent;protein function;Proteins;Public Health;Regulation;Research;Role;single molecule;Slide;Structure;Syndrome;System;Tissues;Trisomy;tumor progression;Whole Organism

PROJECT_TITLE: Equipment Supplement - NOT-GM-24-021 (PI: J. Stumpff)


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Aging;Brain Disorders;Genetics;Human Genome;Neurodegenerative;Neurosciences;Parkinson's Disease;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: ROCHESTER

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Public Health Relevance Statement: Project Narrative Due to the lack of model systems, it has been difficult to study complex gene-environment interactions in Parkinson's disease. Using a combination of Drosophila genetics and patient-derived induced pluripotent stem cells, we can develop a model that can be utilized to identify and study the mechanisms of interaction among GWAS candidate genes, environmental factors, and α-synuclein. This K99/R00 proposal aims to characterize a novel interaction among LRRK2, rotenone, and α-synuclein, study the mechanism of the interaction, and subsequently validate this novel multiplex system, which can be used to study these previously unknown interactions among environmental and genetic factors and is a step towards personalized medicine.

PI_NAMEs: SARKAR, SOUVARISH  (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: Actins;Adult;Age;alpha synuclein;Astrocytes;Atlases;Automobile Driving;Autopsy;Award;Biochemical;Biological Assay;Biological Models;Brain;Caffeine;Candidate Disease Gene;career development;Cells;Cerebrospinal Fluid;chemokine;Coculture Techniques;comparative;Complex;cytokine;Data;Development;Disease;disorder risk;dopaminergic neuron;Drosophila genus;Drug Targeting;druggable target;Environment;Environmental Health;Environmental Risk Factor;Epidemiology;epidemiology study;Etiology;experimental study;Exposure to;fly;Fostering;Future;gene environment interaction;Gene Modified;Genes;Genetic;genetic risk factor;genome wide association study;Goals;Growth;Head;Human;in vivo;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inflammation;Inflammatory;Inhalation;Institution;Interleukin-1 beta;Knock-out;knowledge base;Laboratories;Lead;loss of function;LRRK2 gene;Mediating;Mentors;Methods;Modeling;Molecular;mouse model;mutant;Mutation;National Institute of Environmental Health Sciences;Nerve Degeneration;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurons;neurotoxicity;neurotoxicology;Neurotoxins;Nicotine;novel;Outcome;Paraquat;Parents;Parkinson Disease;Pathogenesis;Pathology;Pathway interactions;patient derived induced pluripotent stem cells;Patients;personalized medicine;Pesticides;pharmacologic;Phase;Phosphotransferases;Play;pluripotent stem cell differentiation;Population;Positioning Attribute;precision drugs;Proteomics;public health relevance;purine metabolism;Research;Research Personnel;Risk;Rodent Model;Role;Rotenone;Scientist;Series;skills;stem cell model;superresolution microscopy;System;Techniques;Time;TNF gene;tool;Toxic effect;Toxicology;Training;transcriptome sequencing;Tyrosine 3-Monooxygenase;Urate

PROJECT_TITLE: An in vivo multiplex model to study gene-environment interaction in Parkinson's Disease

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative from the Parent Award Potassium channels are membrane proteins that catalyze the transfer of K+ ions down an electrochemical gradient with high efficiency and selectivity. Understanding of voltage-dependent K+ channel structure and function relates directly to health and disease. Their function has been associated with such basic cellular functions as the regulation of electrical activity, signal transduction and osmotic balance. K+ channels are members of the voltage-dependent channel superfamily, which include explicitly voltage-activated channels (Na+, Ca2+, and a large number of K+ channels), as well as voltage-independent channels (i.e., the inward rectifiers and the cyclic nucleotide activated channels). The sub-family of non-domain swapped K+ channels include a great deal of functional diversity, including depolarization activated (EAG, hERG), hyperpolarization-activated (KAT1, HCN), and dual voltage and Ca2+ activation (BK). In higher organisms, dysfunctions associated to these channels may lead to uncontrolled periods of electrical hyperexcitability, like epileptic episodes and cardiac arrhythmias. Not surprisingly, voltage-dependent channels are also the target of many therapeutic agents.

PI_NAMEs: PEROZO, EDUARDO A (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Arrhythmia;Attention;base;Biochemical;Cell Physiology;Charge;Ciona intestinalis;Computer Models;Computing Methodologies;Coupling;Cyclic Nucleotides;Disease;Electrophysiology (science);Epilepsy;Equilibrium;Event;Functional disorder;Goals;Health;Human;improved;Ion Channel Gating;Ions;member;Membrane;Membrane Potentials;Membrane Proteins;Methanococcus;Molecular;Molecular Conformation;Motion;Movement;Myotonia;Organism;Osmosis;parent project;Phosphoric Monoester Hydrolases;Potassium Channel;Protons;Regulation;Resolution;response;sensor;Series;Signal Transduction;Site;Slide;Spin Labels;Structure;System;Techniques;Testing;Therapeutic Agents;voltage;X-Ray Crystallography

PROJECT_TITLE: Structural Basis of Coupling and Dynamics in K+ Channels


ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Climate-Related Exposures and Conditions;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Patient Safety;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

PHR: PROJECT NARRATIVE The island of Puerto Rico has experienced 3 major back-to-back public health emergencies over the past 3 years: Hurricane Maria, a swarm of earthquakes, and the COVID-19 pandemic. This study will use three different but complementary sources of quantitative and qualitative data to study the impact of these public health emergencies on the preparedness, response, recovery and resiliency, as well as patient health care experiences and utilization, among general hospitals and community clinics across the island.

PI_NAMEs: CHAVEZ, LIGIA M.;ORTEGA, ALEXANDER N (contact)

PROGRAM_OFFICER_NAME: PATEL, ANURADHA DIPAK

PROJECT_TERMS: Accident and Emergency department;Adult;Affect;analytical method;Asthma;Back;barrier to care;burden of illness;burnout;Businesses;care systems;Caring;Cellular Phone;Chronic Care;Clinic;Clinics and Hospitals;cohort;Communicable Diseases;Communities;community clinic;Community Health;COVID-19;COVID-19 pandemic;Data;design;Diabetes Mellitus;Dialysis procedure;Disasters;Earthquakes;Electricity;Elements;Emergency Situation;Environmental Hazards;Epidemic;Equipment;Event;experience;Floods;follow-up;Frequencies;Funding;General Hospitals;Government;Health;health care availability;health care delivery;health care disparity;Health care facility;health care service;health care service utilization;health disparity;health disparity populations;Health Personnel;Health Policy;Health Services Accessibility;Health system;Healthcare;Healthcare Systems;Homelessness;Hospitals;Hurricane;informant;Infrastructure;insurance claims;Insurance Coverage;Interview;Island;Left;Literature;Long-Term Effects;Measures;Medicaid;Medical;medical supply;Methods;Minority Groups;Modeling;Natural Disasters;novel coronavirus;Occupations;Operative Surgical Procedures;Out-Migrations;Ownership;pandemic disease;patient-level barriers;Patients;Pharmaceutical Preparations;Pharmacy facility;Phase;Poverty;Preventive care;Privatization;Provider;public health emergency;Publishing;Puerto Rican;Puerto Rico;Quality of Care;Readiness;Recommendation;Recovery;Research;resilience;Resources;response;Risk Management;Rural;Sampling;Series;Services;Source;Stress;Surveys;System;Time;trend;Unemployment;Uninsured;Water

PROJECT_TITLE: Provider Experiences with Puerto Rico Medicaid Following Multiple Disasters


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: Project Narrative for the SEAL (Stopping Eczema and ALlergy) Study Food allergy (FA) is an Epidemic among children throughout the world. The overall objective of our current SEAL (Stopping Eczema and Allergy) study is to prevent allergy by enhancing the skin barrier with proactive skin care utilizing the combination of skin emollient early in life with topical anti-inflammatory agents as required to decrease epicutaneous allergen sensitization and FA. The effectiveness of this prevention strategy will be monitored by novel measures of skin barrier function and the emergence of protective immune responses in infants and young children benefiting from our novel preventative approach.

PI_NAMEs: LACK, GIDEON ;LEUNG, DONALD YM;NADEAU, KARI C. (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Allergens;allergic response;Allergy to peanuts;Anti-Inflammatory Agents;Atopic Dermatitis;atopy;Child;Clinical;Clinical Research;cohort;commensal bacteria;comparison control;Country;Dryness;Eczema;Emollients;Epidemic;Epithelium;food allergen;food consumption;Food Hypersensitivity;high risk infant;Hypersensitivity;Immune response;improved;Incidence;infancy;Infant;Intervention Trial;Learning;Life;Measures;Monitor;novel;oral tolerance;Parents;patient retention;Prevalence;prevent;Prevention;prevention effectiveness;Prevention strategy;prospective;Randomized;recruit;Research;Severities;Skin;skin barrier;Skin Care;Steroids;Testing;treatment group;trial design

PROJECT_TITLE: Admin Supp UK - SEAL (Stopping Atopic dermatitis and ALlergy) Study: Prevent allergy by enhancing the skin barrier


NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: NARRATIVE (from the funded grant application) This project explores the structural-molecular basis of communication between enzymes catalyzing consecutive chemical reactions in praline metabolism, These enzymes are increasing recognized for their roles in cancer and the virulence of pathogens, and mutations in praline metabolic genes cause numerous hereditary diseases, Understanding how the activities of praline metabolic enzymes are coordinated enriches our understanding of complex enzyme mechanisms and the multifaceted roles of praline metabolism in human health and disease.

PI_NAMEs: BECKER, DONALD F;TANNER, JOHN J (contact)

PROJECT_TERMS: 3-Dimensional;Active Sites;Aging;Applications Grants;Architecture;Bacteria;bacterial fitness;Biochemistry;Catabolism;Cell Culture Techniques;Cells;Cellular Structures;Centrifugation;chemical reaction;Communication;Complex;Cryoelectron Microscopy;Crystallography;Disease;electron density;Ensure;Enzyme Kinetics;enzyme mechanism;Enzymes;Equipment;Escherichia coli;Escherichia coli Proteins;Evolution;experimental study;Faculty;Failure;Flavins;flexibility;Floor;forgetting;Funding;Genes;Glutamates;Goals;Health;Hereditary Disease;Human;instrument;Kinetics;Knowledge;Length;Life;Ligand Binding;Ligands;Liquid substance;Malignant Neoplasms;Manuals;Measurement;Mediating;Metabolic;Metabolism;Modeling;Molecular;Molecular Conformation;Multienzyme Complexes;mutant;Mutation;Nature;Nitrogen;novel;Output;oxidation;Oxidation-Reduction;parent project;pathogen;Pathogenesis;Pathway interactions;Performance;Physiological;Production;Proline;Protein Conformation;protein protein interaction;protein purification;Proteins;Reaction;Recombinant Proteins;Refrigeration;Research;Research Personnel;Resolution;Roentgen Rays;Role;Running;sensor;Signal Transduction;Site;Site-Directed Mutagenesis;Sonication;Speed;structural biology;Structure;success;System;Time;Transcription Repressor;Variant;Virulence;Work;X-Ray Crystallography

PROJECT_TITLE: Substrate Channeling and Communication in Proline Metabolic Enzymes


ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE Human and animal organ size and shape are precisely controlled by a patterning process during embryonic development and individual growth. Our current knowledge about this patterning process is still limited. The outcome of this project will demonstrate a previously less recognized patterning mechanism by ion channel- mediated bioelectricity, and this knowledge could be used for developing preventive and therapeutic interventions for human congenital diseases in the future.

PI_NAMEs: ZHANG, GUANGJUN  (contact)

PROJECT_TITLE: Roles of ion-channel mediated bioelectricity in developmental patterning

STUDY_SECTION: MRAC

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


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Public health relevance Our studies will generate new mechanistic concepts and principles in understanding how cytosolic double- stranded DNA sensing pathways are activated and regulated at the molecular level. New insights and robust assays arising from our research will also aid in the development of therapies targeting various human inflammatory diseases involving these sensors.

PI_NAMEs: SOHN, JUNGSAN  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Active Sites;Autoantigens;Biochemical;Biological Assay;Cells;cofactor;Coupled;Cytosol;Dimerization;Disease;ds-DNA;Electron Microscopy;Foundations;Host Defense;Human;human disease;Inflammatory;Innate Immune System;insight;Invaded;Link;Measurement;mechanical force;Metals;Methods;Molecular;novel therapeutic intervention;Nucleotides;pathogen;Pathway interactions;Periodicity;Phase;programs;public health relevance;Radiation induced damage;Regulation;Research;Role;sensor;Signal Pathway;Signal Transduction;single molecule;Stigmatization;targeted treatment;Testing;therapy development;X-Ray Crystallography

PROJECT_TITLE: Mechanistic Studies of cytosolic double-stranded DNA sensing pathways.


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Health Services;Nutrition;Obesity;Prevention

ORG_CITY: MADISON

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Log2Lose is a clinical trial that seeks to evaluate whether people lose more weight when they receive small financial incentives for weekly weight loss or diet logging. Study software collects and analyzes weight data from a cellular-connected scale and dietary data from a smartphone dietary application (‘app’). Algorithms analyze these data to determine if participants meet the criteria to receive an incentive. Participants receive a text message about whether they earned an incentive, and, if so, receive payment on a debit card.

PI_NAMEs: CADMUSBERTRAM, LISA ANNE (contact);VOILS, CORRINE IONE

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Address;Adult;Algorithms;Award;Behavioral;Body Weight decreased;Cellular Phone;Clinical;Clinical Trials;clinically significant;cohort;Communities;Computer software;cost;cost effective;cost effectiveness;cost-effectiveness ratio;Data;design;Diet;dietary;Educational process of instructing;evidence base;experience;extrinsic motivation;financial incentive;four-arm study;Goals;Health;Health behavior and outcomes;improved;Incentives;Individual;Intervention;intervention cost;intervention effect;Intervention Trial;Interview;intrinsic motivation;Joints;Maintenance;male;Manuscripts;Measures;Mediating;men;Monitor;Obesity;Outcome;Paper;parent grant;Participant;Patients;payment;Persons;Phase;Population;Prevalence;primary endpoint;Process;program costs;Program Effectiveness;programs;Publications;Quality of life;Randomized;recruit;Role;Single-Blind Study;Site;skills;Technology;Testing;Text Messaging;Time;Weight;weight loss intervention;weight loss program;weight maintenance;Weight maintenance regimen;Writing

PROJECT_TITLE: Log2Lose: Incenting weight loss and dietary self-monitoring in real-time to improve weight management

STUDY_SECTION: CLTR

STUDY_SECTION_NAME: Clinical Trials Review Study Section[CLTR(MA)]


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: MINEOLA

ORG_NAME: NEW YORK UNIVERSITY D/B/A NYU LONG ISLAND SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE This diversity supplement request for Mr. Christian Pacheco aims to provide mentorship, training, and research experience via parent study, titled Biogenesis and Catabolism of Atherogenic Lipoproteins (P01 HL160470-01A1 5700) and Core 2: Human Tissues, Lipidomics, and Proteomics Core led by Dr. Jose O. Aleman.

PI_NAMEs: HUSSAIN, M MAHMOOD (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Accounting;Adipose tissue;Admission activity;analytical method;analytical tool;Apolipoproteins B;Atherosclerosis;bariatric surgery;Basic Science;Biogenesis;Bioinformatics;Biology;Biometry;Biostatistics Core;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;career development;Catabolism;Centrifugation;Ceramides;Clinical;clinical practice;clinical risk;Collaborations;Communication;Communities;Compensation;cost effectiveness;Data;Data Analyses;Data Analytics;data curation;data format;Data Set;Data Sources;Diabetes Mellitus;Equation;experience;Exposure to;Frequencies;Future;Goals;Human;human tissue;improved;Individual;Institution;instrumentation;interest;Knowledge;Laboratories;lectures;Libraries;lipidomics;Lipids;Lipoproteins;Liver;Macrophage;Measurement;medical schools;meetings;member;Mentors;Mentorship;metabolomics;Methods;Modeling;Molecular;Molecular Sieve Chromatography;Mus;New York;novel;Obesity;Outcome;parent grant;Parents;particle;Pathway Analysis;Pharmacotherapy;Physicians;Plasma;Population;population health;Procedures;Process;programs;Proteins;Proteomics;Regulation;Research;Research Design;Research Personnel;Risk Marker;Role;Sampling;Series;Services;Standardization;Supervision;Systems Biology;Technology;Testing;tool;Training;Translational Research;Triglycerides;Ultracentrifugation;Work

PROJECT_TITLE: Analytical Integration of Lipoprotein Lipidomics

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP(JA)]


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Metal–protein interactions are essential for the function of at least one-third to one-half of all proteins in cells. The incorrect binding of a metal to a protein, however, can lead to harmful effects on the cell, including toxicity. This proposal requests resources for the purchase of liquid chromatography instrumentation for protein purification to support NIH-funded research in an R01 grant (GM145035- 01A1) to identify the protein targets of metal stress and elucidate molecular mechanisms that lead to toxicity. The outcomes will advance our understanding of how proteins across the proteome respond to exposure to excess levels of biologically relevant Zn and Cu, with important implications for developing pharmacological agents to leverage metal stress against microbial pathogens and cancer.

PI_NAMEs: FITZGERALD, MICHAEL C;FRANZ, KATHERINE J. (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Address;Affect;Binding;Biophysics;cancer cell;Cell Physiology;Cells;equipment acquisition;Escherichia coli;experience;Exposure to;fast protein liquid chromatography;Funding;Grant;Human;instrument;instrumentation;Laboratories;Link;Liquid Chromatography;Malignant Neoplasms;Mass Spectrum Analysis;Metals;Methodological Studies;Methods;Molecular;non-Native;Outcome;parent grant;pathogenic microbe;pharmacologic;Physiologic pulse;protein purification;Proteins;Proteolysis;Proteome;Proteomics;Publishing;Request for Proposals;Research;Resources;spectroscopic survey;Stress;success;System;Toxic effect;United States National Institutes of Health

PROJECT_TITLE: Elucidating the Molecular Basis of Cellular Metal Stress by using Mass Spectrometry-Based Proteomic Methods


ORG_DEPT: GENETICS

PHR: PROJECT NARRATIVE Eukaryotes sense nutrients via the TARGET OF RAPAMYCIN (TOR) signaling hub to coordinate healthy growth and development; because of its central role in biology, dysregulation of TOR signaling causes or contributes to a broad range of human diseases, including cancers, age-related health decline, and metabolic disorders. Developing focused therapeutics that target disease-causing TOR signaling pathways without hampering healthy TOR-dependent growth and development will require a deep mechanistic and evolutionary understanding of the TOR signaling network. This project will take an innovative approach by elucidating how TOR senses amino acids in plant cells through an aminoacyl tRNA synthetase, illuminating how tRNA synthetases gain noncanonical roles in cells and contributing fresh perspective to ongoing debates about the relative roles and contributions of proposed mammalian amino acid sensors for TOR.

PI_NAMEs: BRUNKARD, JACOB O (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: age related;Amino Acids;Amino Acyl-tRNA Synthetases;Biochemical;Biological Assay;Biology;Biomedical Research;Cells;Complex;Cues;detection of nutrient;Disease;Eukaryota;Genetic;Goals;Growth;Growth and Development function;Health;Homeostasis;Human;human disease;improved;innovation;life span;Malignant Neoplasms;Maps;Mediating;Metabolic;Metabolic Diseases;Metabolism;Modeling;Molecular;Morbidity - disease rate;mortality;Mutate;novel;Nutrient availability;Pathway interactions;Physiological;Plants;Protein Kinase;Regulation;Reporting;Role;sensor;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Sirolimus;System;Therapeutic;therapeutic target;Translations;United States;Work

PROJECT_TITLE: A tRNA synthetase is an amino acid sensor for TOR in plants

STUDY_SECTION: CSRS

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY

ORG_STATE: TX

PHR: PROJECT NARRATIVE  The major goal of the current application is to understand functions of posttranslational lysine modifications in the regulation of chromatin, polyubiquitination functions, and cyclic GMP-AMP synthase. The project is relevant to public health and the NIH’s mission in promoting health and combating diseases because it will reveal the molecular basis of chromatin and cyclic GMP-AMP synthase regulation by posttranslational lysine modifications and assist in the identification of therapeutics that target chromatin and cyclic GMP-AMP synthase modifications.

PI_NAMEs: LIU, WENSHE RAY (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Academia;Address;Amber;Amino Acids;Amino Acyl-tRNA Synthetases;Binding;Biological;biological research;Biology;Cells;Charge;Chemicals;Chromatin;Codon Nucleotides;Complex;Cryoelectron Microscopy;Cyclic GMP;Disease;ds-DNA;Engineering;Enzymes;Epigenetic Process;Eukaryotic Cell;Genetic;Goals;Half-Life;HDAC1 gene;Health Promotion;Histones;Human;Industry;Innate Immune Response;KDM1A gene;Lysine;Mass Spectrum Analysis;Methods;Mission;Modification;Molecular;Mutagenesis;mutant;novel;Nucleosomes;pathogen;Polyubiquitination;Post-Translational Regulation;Prokaryotic Cells;Protein Biosynthesis;Protein Isoforms;Proteins;Proteomics;Public Health;pyrrolysine;reconstitution;Regulation;Research;Role;sensor;Site;System;Techniques;therapeutic target;tool;Ubiquitin;Ubiquitin Like Proteins;United States National Institutes of Health

PROJECT_TITLE: Use of the Noncanonical Amino Acid Mutagenesis Technique in Combination with Other Approaches to Study Functions of Posttranslational Lysine Modifications in Proteins


ADMINISTERING_IC: CA

ED_INST_TYPE: HOSPITALS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: OVERALL – PROJECT NARRATIVE Improved understanding of the biology and heterogeneity of precursor lesions, including the interactions that these lesions harbor with the surrounding microenvironment, are a prerequisite for improving outcomes in pancreatic cancer, the third most common cause of cancer related deaths. The TriState Pancreatic Adenocarcinoma TBEL (Tri-PACT) Center brings together a collaborative group of investigators from three institutions who will use credentialed animal models and patient-derived materials to pursue three highly interdependent projects on basic and translational research in pancreatic cancer precursor lesions.

PI_NAMEs: MAITRA, ANIRBAN  (contact);PASCA DI MAGLIANO, MARINA

PROGRAM_OFFICER_NAME: BERA, TAPAN K

PROJECT_TERMS: 3-Dimensional;Accounting;Age;Animal Model;Architecture;Basic Science;Biology;Cancer Biology;Cancer Center;Cancer Etiology;cancer genomics;Cessation of life;Collaborations;Communication;Computational Biology;Credentialing;Cues;cytokine;Data Analyses;data analysis pipeline;data harmonization;Data Science;data sharing;Dependence;dimensional analysis;Disease;Disease Progression;Distant;Early Diagnosis;endoplasmic reticulum stress;Epithelium;Event;Excision;Fibroblasts;Genetic;Genetic Engineering;Genome;Goals;Heterogeneity;high dimensionality;Histologic;Histology;Human;Immune;improved;improved outcome;In Situ;Individual;Institution;Interleukins;KRAS2 gene;Lesion;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Mediator;member;Metabolic;Michigan;Mitochondria;Modeling;Molecular;molecular pathology;mortality;Mucinous Neoplasm;Mus;Mutation;Neoplasms;Oncology;Operative Surgical Procedures;Organ;Pancreas;Pancreatic Adenocarcinoma;Pancreatic cystic neoplasia;Pancreatic Ductal Adenocarcinoma;Pancreatic Intraepithelial Neoplasia;pancreatic neoplasm;Papillary;paracrine;Pathogenesis;Pathway interactions;Patients;Play;Pre-Clinical Model;premalignant;Process;programs;prototype;Quality Control;reconstruction;Research;Research Personnel;Resolution;Resource Sharing;response;Role;Seminal;Signal Transduction;Site;Specificity;Survival Rate;Technology;Testing;Tissues;tool;transcriptomics;Translational Research;translational study;tumor heterogeneity;tumor metabolism;tumor microenvironment;tumor progression;ubiquitin-protein ligase;United States;Universities;Validation

PROJECT_TITLE: Effects of Tissue Block Age on Reliability and Accuracy of In situ Transcriptomics Across Organ Sites using Xenium Technology


NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: NARRATIVE Title: Investigating and improving performance of polygenic scores for cardiometabolic traits in Samoan adults Project Period: 2024-09-01 – 2026-08-31 The clinical utility of polygenic scores (PGSs) in individuals of Pacific Islander ancestry is unknown due to a paucity of Pacific Islanders participating in studies of PGSs. Therefore, the primary focus of this supplement is to provide the first ever examination of existing and development of PGSs of cardiometabolic traits in Pacific Islanders. This project will provide the first ever characterization of the portability of existing PGSs for Polynesian populations which will inform clinical interpretation of these PGSs among individuals with Polynesian ancestry.

PI_NAMEs: MINSTER, RYAN LEE (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: Adult;Biological Markers;Cardiometabolic Disease;cardiometabolism;Clinical;clinical practice;Development;disorder prevention;disorder risk;Face;Genetic;Genomics;Health;health disparity;health disparity populations;health equity;improved;Individual;Knowledge;Measures;Pacific Islander;Pacific Islands;Performance;Polynesian;Population;portability;Publishing;Research;Samoan;trait;Translating;Variant


ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: *The current equipment supplement request will not modify the original scope of funded research. Chemical damage to DNA is a major source of replication stress that can induce genome instability and drive the progression of cancer and ageing. This proposal investigates the mechanisms that enable the cellular DNA replication machinery to tolerate and repair DNA damage. Insights generated by this work may therefore inform the development of interventions that modulate replication stress to treat cancer and genetic diseases.

PI_NAMEs: SEMLOW, DANIEL  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Aging;Bacteria;Biochemical;Biochemistry;Bone marrow failure;Bypass;cancer cell;cancer predisposition;CDC45L gene;Cell Physiology;Cells;Cellular biology;Chemical Agents;Chemical Structure;Chemicals;chemotherapy;Chromatin;Chromosomal Rearrangement;chromosome missegregation;Cisplatin;clinically relevant;Coupled;crosslink;Data;Deoxyribonucleases;Disease Progression;Disparate;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA glycosylase;DNA Interstrand Cross-Link Repair;DNA Interstrand Crosslinking;DNA lesion;DNA Repair;DNA Repair Disorder;DNA replication fork;DNA-protein crosslink;egg;Ensure;Environment;Equipment;Event;Exhibits;experimental study;Exposure to;Fanconi Anemia pathway;Fanconi's Anemia;flexibility;Funding;gene product;Genetic Diseases;Genome;Genome Stability;genome-wide;Genomic Instability;genomic locus;gut bacteria;helicase;homologous recombination;Human;Human Genome;Induced Mutation;Inflammatory;insight;interest;Lesion;Link;Malignant Neoplasms;Maps;MCM2 gene;Mechlorethamine;Metabolism;Methods;microbiome;Molecular;Molecular Biology;Mutagens;Mutation;Natural regeneration;NEIL3 gene;novel;nuclease;Nucleotides;Outcome;Pathway interactions;Peptide Hydrolases;physical property;Physiological;preference;prevent;Process;programs;Proteins;Rana;recruit;repaired;replication stress;Research;Resolution;response;Role;S phase;Shapes;Single-Stranded DNA;Site;Source;Structure;Surgical incisions;Symptoms;Syndrome;Therapeutic;Therapeutic Intervention;therapy development;Time;Toxin;tumor progression;Work;Xenopus

PROJECT_TITLE: Supplement: Emerging Mechanisms of Replication-coupled DNA Repair


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The proposed studies will investigate the regulation of ferroptosis, a unique non-apoptotic cell death mechanism. This knowledge will enhance our understanding of this fundamental biological process. This research is relevant to public health because it may help identify new ways to manipulate ferroptosis to treat disease.

PI_NAMEs: DIXON, SCOTT  (contact)

PROJECT_TERMS: Address;Biochemical;Biological Process;Biology;biomarker identification;cancer therapy;Cell Death;Cell Death Process;Cell membrane;Cells;Chemicals;Coenzyme A Ligases;Complex;Cystine;Data;deprivation;Development;Disease;Endoplasmic Reticulum;Enzymes;Family member;functional genomics;Genes;Genetic;Genetic Screening;genome-wide;Genomics;Goals;Health;Human;Imaging Device;imaging modality;Imaging Techniques;improved;In Vitro;in vivo;innovation;insight;Iron;Knowledge;Lipid Peroxides;lipidomics;Lipids;Membrane;Metabolic;Mitochondria;Molecular;molecular marker;Morphology;Nerve Degeneration;novel;Pathology;Pharmaceutical Preparations;Phospholipids;Process;Production;Public Health;Regulation;Reperfusion Injury;Research;response;Role;Shapes;Signal Transduction;small molecule inhibitor;Stimulus;Technology;Testing;tool;Toxic effect;transcriptome sequencing;Transmission Electron Microscopy;tumor;Tumor Suppression

PROJECT_TITLE: Characterizing the Regulation of Ferroptosis


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Narrative The goal of this project is to provide cutting-edge training opportunities and to advance mechanisms of voltage- gated sodium, potassium and calcium channels through our use chemical biological approaches.

PI_NAMEs: AHERN, CHRISTOPHER A (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Adopted;Amplifiers;Arrhythmia;Binding;Binding Sites;Biological;Biology;Calcium Channel;Cardiac;Cations;Cell membrane;Cells;chemical binding;Chemicals;Chemistry;Clinical;Dissection;Environment;Epilepsy;Event;experimental study;extracellular;fighting;Foundations;Goals;Heart failure;Heart Rate;Human;Hypertension;Individual;innovation;Ion Channel;Ion Channel Gating;Ions;Light;Link;Long QT Syndrome;Mammalian Cell;Medicine;Membrane;Methods;Modification;Molecular;Muscle;Muscle Contraction;Neurons;Pain management;Pathway interactions;Peptides;Perception;Pharmaceutical Preparations;Phenylalanine;Phosphorylation;Physiological;Potassium Channel;potassium ion;Process;programs;Protein Conformation;protein structure;Proteins;Research;Resolution;response;Second Messenger Systems;sensor;Shapes;Signal Transduction;Site;skeletal;Sodium Channel;Speed;Therapeutic;training opportunity;Tyrosine;Vertebral column;voltage;voltage gated channel;Voltage-Gated Potassium Channel

PROJECT_TITLE: Chemical biology of voltage-gated cation channels


ORG_CITY: MIDDLETOWN

ORG_NAME: WESLEYAN UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative A number of biochemical processes have promise as antibiotic targets, but efforts towards those goals are hampered in part by a dearth of information regarding their molecular and biochemical details. This proposal will illuminate how bacteria respond and adapt to changes within their environments at a detailed structural and mechanistic level. The findings from these studies will inform future drug discovery effortsto target specific strains of bacteria.

PI_NAMEs: FISHER, ORIANA S (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Antibiotic Resistance;Antibiotics;Bacillus subtilis;Bacteria;Binding;Biochemical;Biochemical Process;Biochemistry;biological adaptation to stress;Biological Models;computer studies;Copper;design;Development;drug discovery;Environment;Enzymes;Exhibits;Family;Family member;Future;Goals;Investigation;Kinetics;Microbiology;Molecular;novel;novel therapeutics;Organism;Pathogenicity;Pathway interactions;Phosphotransferases;Phylogeny;Physiological;preference;Process;Proteins;Public Health;Research;small molecule inhibitor;Specificity;structural biology;Substrate Specificity;tool;Transcription Repressor;Transcriptional Regulation;Transition Elements;uptake;Variant

PROJECT_TITLE: Structural and functional basis of bacterial transcriptional regulation


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: MINNEAPOLIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative: Public Health Relevance Section  A combined chemical and genetics-based approach is being developed for the discovery of highly domain selective bromodomain inhibitor molecules for the epigenetic proteins BRD4 and BPTF. Inhibiting transcription factor function mediated by epigenetic proteins is a powerful but challenging approach for controlling disease. Our newly developed chemical probes and structural biology approaches described here will help establish distinct molecular mechanisms used by bromodomain-containing proteins for transcriptional regulation and for ultimately treating disease.

PI_NAMEs: POMERANTZ, WILLIAM CHARLES KRAUSE (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Address;Affinity;Autophagocytosis;Biology;biophysical techniques;Bromodomain;Cells;Chemicals;Chromatin;Complex;Development;Disease;disorder control;DNA;drug discovery;Drug Targeting;Epigenetic Process;epigenetic therapy;epigenome;Fluorine;Gene Expression Regulation;Genetic;Genetic Transcription;Goals;Health;Human;improved;Inflammation;inhibitor;innovation;Lead;Ligand Binding;Malignant Neoplasms;Mediating;Methodology;Methods;millisecond;Molecular;molecular assembly/self assembly;Nature;next generation;novel;Nucleosomes;Nylons;Pharmaceutical Preparations;programs;Protein Isoforms;protein protein interaction;Proteins;public health relevance;Rapid screening;Reader;Research;Role;small molecule;structural biology;Tertiary Protein Structure;tool;transcription factor;Transcriptional Regulation;tumor progression

PROJECT_TITLE: Chemical Probe Development for Epigenetic Complexes Enabled by Protein-Observed 19F NMR