ORG_CITY: HANOVER

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: The degradation of long-lived organelles and large protein aggregates by selective autophagy is critical for organelle quality control and maintaining cellular homeostasis. When selective autophagy is dysfunctional, it cannot efficiently degrade these cytosolic components, and this can lead to human diseases, including cancer and neurodegenerative disease. We are studying the initiation mechanisms of selective autophagy to better understand how dysfunctions in this process may lead to a loss in the degradation of organelles.

PI_NAMEs: RAGUSA, MICHAEL JOSEPH (contact)

PROJECT_TERMS: Autophagocytosis;Autophagosome;Biochemical;Biological Models;Cell Physiology;Cellular biology;Compensation;Defect;Disease;Functional disorder;Homeostasis;human disease;Individual;Inflammatory;Integral Membrane Protein;knock-down;Lipid Biochemistry;Lysosomes;Malignant Neoplasms;Mammalian Cell;Membrane;Methods;Mitochondria;mitochondrial autophagy;Molecular;Mutagenesis;Neurodegenerative Disorders;novel;Organelles;pathogen;Play;prevent;Process;protein aggregation;Proteins;Quality Control;receptor;reconstitution;recruit;Role;structural biology;System;Vacuole;Vesicle;Work;Yeasts

PROJECT_TITLE: Dissecting the Molecular Mechanisms of Selective Autophagy

STUDY_SECTION: MRAB

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


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: HOUSTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: This grant works to improve methods for cryo electron microscopy and tomography, to image cells and molecules at subnanometer resolution, 100-1000x finer than the best optical microscopes. This method can directly visualize processes like viral infection or cancer at a cellular level with sufficient resolution to see molecular interactions. The methods developed here will help extend these methods to extract information about not only static structure, but motion and interactions between molecules at the same high resolutions.

PI_NAMEs: LUDTKE, STEVEN J (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: 3-Dimensional;Binding;Biological;Cells;cellular imaging;Computer software;Cryo-electron tomography;Cryoelectron Microscopy;Data;deep learning;Development;Dose;Electron Beam;electron tomography;Freezing;Gaussian model;Grant;Image;image processing;improved;Individual;interest;macromolecular assembly;macromolecule;method development;Methods;Microscope;Molecular;Molecular Conformation;Motion;nanometer resolution;Noise;Optics;Process;Resolution;Specimen;Structural Biologist;Structure;three dimensional structure;Time;Viral Cancer;Virus Diseases;Visible Radiation;Visualization;Work

PROJECT_TITLE: Support for CryoEM and CryoET Development in the Ludtke Lab

STUDY_SECTION: MRAE

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


ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project Narrative We study multiple aspects of mammalian nuclear cell biology related to human disease. One set of investigations uses biochemical and biophysical experiments to understand how proliferation marker protein Ki-67 protects chromosomes from DNA damage. Another set of experiments explores dynamic events in the nuclei of macrophages, evaluating formation of specific RNA and protein clusters when they are stimulated by inflammatory signals.

PI_NAMEs: KAUFMAN, PAUL D. (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Acute;Affect;Anti-Inflammatory Agents;Area;Arginine;Binding;Biochemical;Biology;Biophysics;C-terminal;cell injury;Cell Nucleolus;Cell Nucleus;Cell Physiology;cell type;Cellular biology;Charge;Chromatin;Chromosomes;Complex;Cryoelectron Microscopy;cytokine;Cytoprotection;Data;Defect;Dipeptides;DNA;DNA Damage;DNA strand break;Event;experimental study;Genome;genome-wide;genomic locus;Health;Heterochromatin;Human;human disease;Infectious Agent;Inflammatory;Innate Immune System;interest;Interferon Type II;Interleukin-4;Interphase;Investigation;Label;Leucine;Libraries;Lipopolysaccharides;Macrophage;Maps;Mitogen-Activated Protein Kinase Kinases;Mitosis;Mitotic;Mitotic Chromosome;mutant;Neoplasm Metastasis;Nuclear;Nucleic Acids;Nucleosomes;Nucleotides;p38 Mitogen Activated Protein Kinase;Pattern;Phosphorylation;Proliferation Marker;Property;protein biomarkers;Proteins;Research Project Grants;response;RNA;RNA Processing;RNA Splicing;Signal Transduction;Site;Speed;Structure;Surface;System;Testing;TP53 gene;tumor growth;Tumor Markers

PROJECT_TITLE: Cell Biology of Mammalian Nuclei

STUDY_SECTION: MRAC

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: COLLEGE STATION

ORG_DEPT: CHEMISTRY

ORG_NAME: TEXAS A&M UNIVERSITY

PHR: Project Narrative: Iron and copper are essential for human health but they can also damage cells and entire organs. Thus, understanding how these metals are imported into our bodies and cells, and how they move within cells, is highly significant. In this project we will characterize metal “trafficking” and regulation in cells and in the blood, with the ultimate aim of developing better treatments for metal- related diseases.

PI_NAMEs: LINDAHL, PAUL A. (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Apoproteins;Binding;biological systems;Blood;cell injury;Cells;Cellular biology;Chemicals;Chromatography;Citrates;Client;Complex;Copper;Coupled;Custom;Cytosol;Dangerousness;Differential Equation;Disease;genetic strain;Health;Homeostasis;Human;improved;innovation;Ions;Iron;Iron Overload;Kinetics;Life;Liquid Chromatography;Mammalian Cell;mass spectrometer;mathematical model;Metabolic;metal complex;Metallothionein;Metals;Methods;Mitochondria;model design;molecular mass;Mossbauer Spectroscopy;Mus;novel;Nutrient;Organ;Organelles;Paper;Peer Review;Plasma;Property;Publishing;Refrigeration;Regulation;Role;Spectrometry, Mass, Electrospray Ionization;System;tool;trafficking;Transition Elements;United States National Institutes of Health;Yeasts

PROJECT_TITLE: Iron Trafficking and Regulation in Biological Systems


NIH_SPENDING_CATS: Infectious Diseases;Machine Learning and Artificial Intelligence

PHR: Project Narrative Drug resistance is a major problem limiting therapy options for millions of people in both infectious diseases and cancer. My research aims to understand the molecular mechanisms by which mutations in a drug target confer resistance. With this understanding, we can devise better strategies for designing drugs that would be robust and avoid resistance.

PI_NAMEs: SCHIFFER, CELIA A. (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Active Sites;Bacterial Infections;Communicable Diseases;Complex;Computational Technique;Coupled;Disease;Distal;Drug Design;Drug resistance;drug resistance development;Drug Targeting;Effectiveness;Enzymes;Evolution;Foundations;functional group;Future;Goals;HIV-1 protease;inhibitor;insight;Laboratories;Machine Learning;machine learning algorithm;Malignant Neoplasms;Modern Medicine;Molecular;molecular dynamics;Mutation;Mycoses;novel strategies;Peptide Hydrolases;Persons;Pharmaceutical Preparations;Predisposition;pressure;Research;Resistance;resistance mutation;Structure;System;tool;Variant;Viral;Virus;Virus Diseases

PROJECT_TITLE: Defining and Avoiding Molecular Mechanisms of Drug Resistance


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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

ORG_CITY: LOS ANGELES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative: The PI proposes to develop an intelligent ultrafast bioimaging program which could open a new area of investigation and lead to a series of fundamental scientific discoveries.

PI_NAMEs: GAO, LIANG  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TITLE: Ultrafast bioimaging


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: PHILADELPHIA

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Project narrative. Replicative stress and cellular exposure to genotoxic agents can lead to double-strand breaks (DSBs) which are the most lethal DNA lesions. To significantly advance our basic knowledge of some of the most intriguing and important areas of DSB repair (DSBR), the Pomerantz lab proposes to continue to address: i. whether RNA directly contributes to DSBR; how DSBR proteins are structurally and chemically regulated, and; whether undiscovered DSBR pathways exist and contribute to genome instability/integrity.

PI_NAMEs: POMERANTZ, RICHARD T (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Address;Area;Basic Science;Biotechnology;cancer cell;Cell Proliferation;Cell Survival;Cells;Chemicals;Chemistry;CRISPR/Cas technology;Development;DNA Damage;DNA lesion;DNA Repair;Double Strand Break Repair;Exhibits;Exposure to;Genome engineering;genome integrity;Genomic Instability;Human;inhibitor;Knowledge;Malignant Neoplasms;Mediating;Molecular;Mutagens;Nobel Prize;Nonhomologous DNA End Joining;novel;Pathway interactions;Poly Adenosine Diphosphate Ribose;Polymerase;precision medicine;Proteins;Recording of previous events;Regulation;repaired;response;RNA;RNA-Directed DNA Polymerase;Science;Stress;Tumor Suppression

PROJECT_TITLE: Novel Mechanisms and Regulation of Mammalian Double-Strand Break Repair

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


NIH_SPENDING_CATS: Aging;Genetics

ORG_NAME: RICE UNIVERSITY

PHR: PROJECT NARRATIVE Mitochondria undergo constant surveillance, integrating a variety of signals into a cohesive feedback program that coordinates with the nucleus to ensure prompt homeostatic rebalancing critical for optimal mitochondrial function and cellular health. My lab has been instrumental in studying mitochondrial surveillance, with a particular focus on the ESRE network and its interactions with other protective mechanisms. Identifying the relationship between mitochondrial damage and changes in lipid homeostasis, propagation of the ESRE-activating signal to the nucleus, and how changes in RNA metabolism are coordinated to ensure a prompt response will help identify methods to promote improved health across the human lifespan.

PI_NAMEs: KIRIENKO, NATASHA  (contact)

PROJECT_TERMS: Acute;Aging;alcohol exposure;alcohol response;Apoptosis;Binding;Biochemical;Biochemical Process;Bioenergetics;Biological;biological adaptation to stress;Cardiovascular Diseases;Cell Death;Cell Nucleus;Cells;Chronic Disease;Ensure;extend lifespan;Feedback;gene conservation;Gene Expression;Genes;Genetic;Health;Homeostasis;Human;improved;interest;life span;Lipids;Malignant Neoplasms;MED15;Mediator;Metabolic Diseases;Methods;Mitochondria;Mitochondrial Proteins;Neurodegenerative Disorders;Nucleotides;Organelles;overexpression;Pathway interactions;Play;Production;programs;promoter;Protein Import;Proteins;proteostasis;Reactive Oxygen Species;Regulation;response;Response Elements;RNA metabolism;Role;Signal Transduction;Small Nucleolar Ribonucleoproteins;Stress;Techniques;transcription factor;Translating;Up-Regulation

PROJECT_TITLE: Regulation of mitochondrial surveillance

STUDY_SECTION: MRAD

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


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

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative  The Durrant lab aims to advance pharmaceutical and basic-science research by developing leading-edge computational techniques for designing and optimizing bioactive small molecules. Our tools characterize drug- gable binding pockets on the surfaces of disease-implicated proteins, predict pocket flexibility, suggest small- molecule ligands, and propose chemical additions to improve binding. Building on our previous research, we will continue to develop and apply innovative computational technologies, with an expanded focus on accuracy through machine learning, accessibility, and broad adoption.

PI_NAMEs: DURRANT, JACOB D (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TITLE: Developing and Applying Accessible Computational Technologies for the Design of Small-Molecule Ligands


ORG_DEPT: GENETICS

PHR: PUBLIC HEALTH RELEVANCE Regulated cell death is a critical feature of normal development and a healthy response to environmental or chemical stresses. Failures to control cell death correctly can cause serious diseases, such as neurodegeneration and cancer. The goal of this research program is to gain a comprehensive understanding of the mechanisms that control regulated cell death, how these mechanisms go awry in diseased cells, and the most effective strategies for targeting regulated cell death therapeutically.

PI_NAMEs: LEE, MICHAEL JUNGHO (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Apoptosis;Apoptotic;Bioinformatics;cancer cell;Cell Death;Cells;Cessation of life;Chemicals;Combination Drug Therapy;computerized tools;Decision Making;Development;Disease;Failure;Gene Expression;Genetic;Genetic Screening;Goals;improved;insight;Malignant Neoplasms;mathematical model;Methods;Necrosis;Nerve Degeneration;Normal Cell;Outcome;Pathway interactions;Pharmacotherapy;Phenotype;Process;programs;public health relevance;Regulation;Regulator Genes;Regulatory Pathway;Research;response;Rupture;Signal Transduction;Stress;System;Therapeutic;Translating;transmission process;Variant;Vision;Work

PROJECT_TITLE: Systems and Network-level Regulation of Cell Death


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: Boulder

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE Transposable elements make up over 50% of the human genome and there is growing evidence that the reactivation of these sequences plays an important role in many human diseases including cancer and autoimmunity. This proposal will integrate genomic analysis and immunological approaches to advance our understanding of how these elements impact cellular function in health and disease.

PI_NAMEs: CHUONG, EDWARD BO-YI (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Area;Autoimmunity;Bioinformatics;Biological Process;cancer cell;Cell Physiology;Cells;Complex;CRISPR screen;Development;Disease;DNA;DNA Transposable Elements;Elements;Epigenetic Process;epigenome;epigenomics;Evolution;experimental study;follow-up;functional genomics;gene regulatory network;Genes;Genetic Transcription;Genome;Genomics;Graph;Health;human disease;Human Genome;Immune;Immune response;Immunity;Immunologics;Individual;Malignant Neoplasms;Maps;Mediating;multiple omics;pan-genome;Parasites;Pathogenesis;Pathologic;Play;Population;Positioning Attribute;Protein Isoforms;Research;response;Role;Shapes;Signal Transduction;Technology;transcriptome;transcriptome sequencing;Variant;Work

PROJECT_TITLE: Transposon-mediated rewiring of gene regulatory networks


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Human Genome;Infertility;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Defects in the key developmental process where germline stem cells switch to entry into meiotic prophase and gametogenesis can result in the formation of aneuploid progeny and infertility. Since ethical and practical issues limit studies in humans, research in model organisms is essential. This work will complete the regulatory network and delineate processes governing this essential step in germline development, informing on how the switch is executed in other animals, including humans.

PI_NAMEs: SCHEDL, TIM  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Aneuploidy;Animals;base;Basic Science;Behavior;Caenorhabditis elegans;Cells;Chromosome Pairing;Chromosomes;Congenital Abnormality;Defect;Development;Developmental Process;Ethics;Fertility;Gametogenesis;Genetic;Genetic Models;genome-wide;Genomics;Germ Cells;Germ Lines;germline stem cells;Goals;Health;Human;in vivo;Infertility;Investigation;Knowledge;Meiosis;Mitotic Cell Cycle;model organism;Molecular;mutant;novel;Organism;Pathway interactions;Post-Transcriptional Regulation;Process;programs;Prophase;protein degradation;Proteins;Proteomics;Repression;Research;Route;stem cell fate;stem cell self renewal;stem cells;System;transcriptomics;ubiquitin-protein ligase;Work

PROJECT_TITLE: Control of germline stem cells and the switch to meiotic development in C. elegans


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: Public Health Relevance Statement Mitochondrial dysfunction is known to cause more than 200 named disorders, and is associated with aging, neurodegeneration, cardiovascular disease, and diabetes mellitus. Mitochondrial DNA degradation is an important, but poorly understood process. The application seeks to decipher the chemical and molecular basis of mtDNA degradation, which is important for understanding mitochondrial genomic maintenance and developing new therapeutics for mitochondrial diseases.

PI_NAMEs: ZHAO, LINLIN  (contact)

PROJECT_TERMS: Acceleration;Address;Aging;Area;Biochemical;Bioenergetics;Biology;Cardiovascular Diseases;Cells;Cellular Assay;Characteristics;Chemicals;Diabetes Mellitus;Disease;DNA Biochemistry;DNA lesion;DNA Repair;Drug Targeting;Enzymatic Biochemistry;Etiology;Eukaryota;Genome;Genomics;Goals;Hispanic-serving Institution;Immune System Diseases;Inflammatory;insight;Kinetics;Knowledge;Laboratories;Maintenance;Mass Spectrum Analysis;Metabolism;Methods;Minority;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;Mitochondrial DNA depletion syndromes;mitochondrial dysfunction;Molecular;mtTF1 transcription factor;Names;Natural Immunity;Nerve Degeneration;novel therapeutics;Outcome;Oxidative Phosphorylation;Pathology;Play;Process;Productivity;Property;Protein Biochemistry;Protein Subunits;Proteins;Proteomics;public health relevance;Research;Ribosomal RNA;Role;Signal Transduction;Site;Small Interfering RNA;System;Therapeutic;Transfer RNA

PROJECT_TITLE: Chemical and Molecular Mechanisms of Mitochondrial DNA Degradation


ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative:  The efficient and modular synthesis of small organic molecules is critical to the pharmaceutical industry. Thus, development of new methods that access difficult to prepare structural motifs or improve efficiency of synthetic sequences are significant and contemporary research objectives in organic chemistry. The primary expected outcomes of our program of research are the introduction of new and unique alkene functionalization reactions that will facilitate the synthesis of a wide range of molecules that are challenging to prepare through alternative methods.

PI_NAMEs: BROWN, MICHAEL KEVIN (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Methods and Strategies for Chemical Synthesis


NIH_SPENDING_CATS: Microbiome

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE The gut microbiota are known to influence normal physiology and transitions to disease, but the roles played by specific microbial proteins in these complex molecular processes remain poorly understood. Through this project, we will examine the structures and functions of diverse gut microbial enzymes, modulate their activities with targeted small molecules, and pinpoint their roles in human disease.

PI_NAMEs: REDINBO, MATTHEW R (contact)

PROJECT_TERMS: Amino Acids;Animal Model;antepartum depression;Beta-glucuronidase;Bile Acids;bile salts;Biochemistry;Biology;Chemicals;Clinical;Clostridium difficile;Complex;Development;Disease;Dopamine;Enzyme Inhibitor Drugs;Enzymes;Estrogens;experience;gut microbiome;gut microbiota;Heart Diseases;Human;human disease;Hydrolase;Indican;Indoles;Infection;inhibitor;Kidney Diseases;microbial;microbiota;Molecular;mouse model;multiple omics;Neurotransmitters;novel;novel diagnostics;novel therapeutics;Pathway interactions;Physiology;Play;Pregnant Women;Process;programs;Protein Family;Proteins;Recurrence;Research;Role;Sampling;Serotonin;small molecule;Source;steroid hormone;Structure;tool;Toxin;Tryptophanase;Uremia

PROJECT_TITLE: Gut Microbial Enzymes and Human Disease

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE During recovery of consciousness after general anesthesia, common clinical problems occur such as delirium and delayed awakening. There are no available treatments for these problems because the mechanisms underlying recovery of consciousness after general anesthesia are unknown. The goals of this MIRA proposal are to understand how cognition recovers after general anesthesia in rodents, and to test whether recovery of cognition may be accelerated by activating specific neural circuits involved in memory, attention, and arousal.

PI_NAMEs: SOLT, KEN  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Absence of pain sensation;Acceleration;Amnesia;Anesthesia procedures;Anesthetics;Arousal;Attention;Brain;Cell Nucleus;Clinical;Cognition;Cognitive;cognitive recovery;cognitive testing;common treatment;Conscious;Delirium;Estrous Cycle;Female;General Anesthesia;General anesthetic drugs;genetic manipulation;Goals;Grant;insight;Knowledge;Medicine;Memory;neural circuit;novel strategies;Operative Surgical Procedures;programs;Rattus;Recovery;Research;Rodent;Sex Differences;Testing;touchscreen;Unconscious State

PROJECT_TITLE: Anesthesia and Consciousness


PHR: Project Narrative  Organic compounds containing halogen or pseudohalogen substituents are used to combat many diseases of central importance to the mission of the NIH, but current methods for their preparation are often inefficient, poorly selective, or limited in scope. This proposal outlines the development of halogenases to correct these problems and enable late stage functionalization of biologically active compounds via halogenation and other atom transfer reactions.

PI_NAMEs: LEWIS, JARED C (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Address;Agrochemicals;alpha ketoglutarate;Azides;Binding;Biological;Catalysis;catalyst;combat;Coupling;design;Development;Directed Molecular Evolution;Disease;Electrons;Engineering;Enzymes;Evolution;experience;Flavins;halogenation;Halogens;improved;Methods;Mission;natural product inspired;Natural Products;non-Native;Oxidoreductase;Pharmacologic Substance;physical property;Preparation;Process;Reaction;Reporting;Site;small molecule;System;United States National Institutes of Health

PROJECT_TITLE: Engineering Halogenases for Small Molecule Functionalization and Enantioselective Catalysis


ORG_CITY: Newark

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: Narrative The ubiquitin proteasome system is currently underexploited for therapeutic interventions despite a vast number of proteins and complexes associated with this vital system. Our understanding of ubiquitin signaling mechanisms as mediated by the many forms of ubiquitin modifications is still lacking. Chemical tools are central to the efforts in unraveling the complex pathways and mechanisms in ubiquitin signaling and they also provide new ways of exploiting the ubiquitin pathway enzymes for drug development, thus achieving therapeutic benefit in treating human diseases such as neurodegeneration and cancer.

PI_NAMEs: ZHUANG, ZHIHAO  (contact)

PROJECT_TERMS: Biological;Biology;Cell Physiology;Chemicals;Complex;drug development;drug discovery;Endocytosis;enzyme pathway;Goals;Human;human disease;insight;Malignant Neoplasms;Mediating;Modification;multicatalytic endopeptidase complex;Nerve Degeneration;new therapeutic target;novel;Pathway interactions;Polyubiquitin;Post-Translational Protein Processing;protein degradation;Proteins;Reader;receptor;Role;Signal Transduction;Structure;success;System;Therapeutic;Therapeutic Intervention;tool;Ubiquitin;ubiquitin isopeptidase;Ubiquitination;Work

PROJECT_TITLE: Deciphering protein ubiquitination with chemical biology tools


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE A major challenge for quantitative biology and precision medicine is that we lack a clear understanding of the mechanisms that underpin cellular plasticity and heterogeneous cell fate decisions in response to environmental and therapeutic perturbations. Our goal is to fill the gaps in our mechanistic and network-level understanding via hypothesis-driven, systematic genetic and chemical perturbation studies that leverage cutting-edge, high-throughput, multiplexed technologies, and predictive computational modeling. We expect that our studies and the generated results and models will provide opportunities to improve precision medicine via enabling the control of population heterogeneity and guiding cells toward the desired phenotypes.

PI_NAMEs: FALLAHI-SICHANI, MOHAMMAD  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Address;Adopted;Architecture;Biology;Cell Shape;cell type;Cells;cellular imaging;Chemicals;Chromatin;combinatorial;Complex;Computer Models;dimer;Dimerization;epigenome;Exhibits;experimental study;Exposure to;Frequencies;Gene Expression;Generations;Genetic;Genetic Transcription;Goals;Heritability;Heterogeneity;Homo;improved;Individual;Knowledge;Link;Logic;MAP Kinase Gene;Methods;Mitogen-Activated Protein Kinases;Modeling;Nature;novel strategies;Outcome;Pattern;pharmacologic;Phenotype;Population;Population Control;Population Heterogeneity;Post-Translational Protein Processing;precision medicine;Process;programs;Proteins;Recurrence;Research;response;Side;Signal Transduction;System;Technology;Therapeutic;transcription factor;Transcription Factor AP-1;Transcriptional Regulation;Variant;virtual

PROJECT_TITLE: Decoding the logic of cellular signaling through the integration of dynamic, single-cell and multiplexed methods


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Influenza;Pneumonia and Influenza

ORG_CITY: College Station

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

PHR: Project Narrative The proposed research is relevant to public health because the molecular mechanisms by which the influenza A virus evades the host immune system are expected to advance the development of antiviral therapeutics. The mechanisms underlying the strain-specific virulence of influenza A viruses are expected to enhance preparedness for future flu pandemics. Therefore, the proposed research is relevant to the part of NIH’s mission that pertains to developing fundamental knowledge that will advance understanding of human health and disease.

PI_NAMEs: CHO, JAE HYUN  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Advanced Development;Amber;Anti-viral Agents;Anti-viral Response;antiviral drug development;Apoptosis;base;biophysical analysis;Biophysical Process;Cells;Chemicals;Codon Nucleotides;crosslink;Cryoelectron Microscopy;Development;Disease;Evolution;experimental study;Fluorescence Spectroscopy;Future;Genetic Epistasis;Goals;Health;Human;Immune Evasion;Immune response;Immune system;immunoregulation;Influenza A virus;influenza virulence;Innate Immune Response;Interferons;Knowledge;Mission;Molecular;molecular dynamics;Mutate;Mutation;NMR Spectroscopy;Nonstructural Protein;pandemic influenza;pandemic potential;Production;Proteins;Public Health;Readiness;Research;RNA Binding;Role;Science;seasonal influenza;sensor;targeted agent;United States National Institutes of Health;Viral;Viral Genome;Viral Interference;viral RNA;Virulence Factors;virus host interaction;X-Ray Crystallography

PROJECT_TITLE: Mechanistic bases of strain-specific virus-host interactions


NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

ORG_STATE: MI

PHR: PROJECT NARRATIVE DNA methylation is a key epigenetic regulator of genome-templated processes, and dysregulated DNA methylation signaling is a defining molecular feature of human cancer and other diseases. This proposal seeks to understand how DNA methylation is inherited through cell divisions, why DNA methylation patterns change in cancer and aging cells, and how these changes contribute to disease states. As DNA methylation antagonism is a major clinical strategy for epigenetic therapy, these studies also have the potential to identify biomarkers and next-generation therapeutic targets for the management of cancer and other diseases.

PI_NAMEs: ROTHBART, SCOTT  (contact)

PROJECT_TERMS: Affinity;Allosteric Regulation;antagonist;Biochemical;biomarker identification;Cell Aging;Cell division;Cell Physiology;Chromatin;Chromatin Structure;Clinical;combinatorial;Complex;Disease;DNA;DNA Methylation;DNA Modification Methylases;Epigenetic Process;epigenetic regulation;epigenetic therapy;functional outcomes;genetic regulatory protein;Genome;Genomics;Goals;Histones;Human;human disease;Inherited;Malignant Neoplasms;Methods;methylation pattern;Molecular;novel therapeutic intervention;novel therapeutics;Pathologic;Pattern;Post-Translational Protein Processing;Process;Proteins;Proteomics;Reagent;Regulation;Role;Signal Transduction;Substrate Specificity;Technology;therapeutic target;Translating;Ubiquitin;Ubiquitination;Work;Writing

PROJECT_TITLE: Molecular mechanisms of chromatin signaling and epigenetic regulation

STUDY_SECTION: MRAA

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


NIH_SPENDING_CATS: Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE This project investigates the mechanisms by which mitochondrial and peroxisomal dynamics regulate cell fate and identity using induced pluripotent stem cell model systems. Through these efforts, we aim to uncover novel molecular principles by which mitochondrial and peroxisomal remodeling induce signaling and metabolic switches during cell transitions.

PI_NAMEs: GAMA, VIVIAN  (contact)

PROJECT_TERMS: Apoptotic;Area;Automobile Driving;BCL-2 Protein;BCL1 Oncogene;Biological Models;Biology;Cell Differentiation process;Cell Physiology;Cells;Disease;Family;Funding;Homeostasis;induced pluripotent stem cell;Knowledge;Link;Maintenance;MCL1 gene;member;Metabolic;Metabolism;Mitochondria;Modeling;Molecular;Morphology;Mutation;Nature;Neurodevelopmental Disorder;neurogenesis;Neuronal Differentiation;Neuronal Dysfunction;novel;Organelles;peroxisome;pluripotency;Pluripotent Stem Cells;Process;programs;Regulation;Reporting;Role;Signal Induction;Signal Transduction;stem cell biology;stem cell model;stem cells;Work

PROJECT_TITLE: Molecular Principles Governing Mitochondrial and Peroxisomal Remodeling as Drivers of Cell Fate and Identity


NIH_SPENDING_CATS: Natural Products

ORG_CITY: HOUSTON

PHR: Project Narrative/Public Health Relevance The ability to repurpose biological systems for applications in chemical synthesis has broad-ranging impacts on multiple research areas in biomedical science, including medicinal chemistry, drug discovery and green biotechnology development. Enzymatic C–H functionalization, when strategically used, will allow efficient access to new chemical space previously unattainable using contemporary technology, thereby enriching the pool of available small molecules for drug discovery campaigns. By pursuing specific applications on natural product scaffolds with promising bioactivities, our work will provide significant contributions towards the advancement of novel therapeutic candidates and understanding of their modes of action.

PI_NAMEs: RENATA, HANS  (contact)

PROJECT_TERMS: Achievement;Address;Alkaloids;analog;Area;bioactive natural products;biological systems;Biotechnology;chemical synthesis;Chemicals;Complex;Development;drug discovery;Elements;Engineering;Enzymes;Face;Family;Formulation;Funding;Generations;Hydroxylation;innovation;Logic;Macrolides;Methods;Natural Products;Nature;novel;novel therapeutics;Organic Chemistry;oxidation;Pathway interactions;Pharmaceutical Chemistry;programs;public health relevance;Reaction;Research;scaffold;Science;secondary metabolite;small molecule;Structure-Activity Relationship;Technology;therapeutic candidate;tool;Work

PROJECT_TITLE: Applications of Biocatalytic C–H Functionalization in Complex Molecule Synthesis


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: RICHARDSON

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: Public health relevance statement Transmembrane transition metal transporter proteins, and their interacting donor and acceptor metallochaperones, are key cellular hubs that evolved to selectively control metal fluxes across biological membranes, finely regulating metal levels in all prokaryotic and eukaryotic cells. This research program aims at unravelling the fundamental molecular determinants governing metal cargo delivery, selection and vectorial substrate translocation in metal transporter and associated metalloprotein families that feature diverse chemical, mechanistic and energetic requirements, and are central to physiology, disease, and therapy.

PI_NAMEs: MELONI, GABRIELE  (contact)

PROJECT_TERMS: Address;Affinity;anti-cancer;ATP phosphohydrolase;Bacteria;Bacterial Infections;Biochemical Process;Bioinorganic Chemistry;Biological;Biophysics;Carrier Proteins;Cellular Membrane;chemical property;Chemicals;Chemistry;Cobalt;Copper;Coupled;Detergents;Disease;Disease Progression;Drug resistance;Environment;Enzymes;Eukaryotic Cell;Event;Family;Fluorescence;Health;Homeostasis;Human;innovation;Ions;Iron;Kinetics;Lipid Bilayers;Membrane;metalloenzyme;Metalloproteins;Metals;Molecular;Molecular Chaperones;Molecular Conformation;neglect;neglected tropical diseases;Nickel;Organism;pathogen;Physiology;Platinum;programs;Prokaryotic Cells;Proteins;public health relevance;Pump;Research;Signal Transduction;solute;Specificity;System;Thermodynamics;Time;toxic metal;Trace Elements;Transition Elements;translational applications;translational potential;Transport Process;uptake;Virulence;Virulence Factors;Zinc

PROJECT_TITLE: Principles of selectivity and translocation in transition metal transporters, metallochaperones, and associated metalloproteins


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the study of the structure and binding interactions in biomolecules is central to understanding a large number of processes in living organisms. The approaches proposed are highly relevant to the part of NIH’s mission that relates to developing fundamental knowledge that will help diminish the burdens of human diseases. This research will produce chemical and physical tools to interrogate binding sites, dissociation constants, binding stoichiometry, and the topology of fibrillar nanostructures, particularly amyloids.

PI_NAMEs: MARTI-ARBONA, ANGEL  (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Address;Affinity;alpha synuclein;Amyloid;Amyloid beta-Protein;amyloid structure;Area;Behavior;Binding;Binding Sites;Biological;biophysical techniques;Cells;Chemicals;Collagen;Communication;Complex;Computational Technique;Diffusion;Disease;Dissociation;DNA;Equation;Fibronectins;Fluorescence Anisotropy;Fluorescence Spectroscopy;Goals;human disease;Information Storage;interest;Journals;Knowledge;Length;Light;Messenger RNA;metal complex;Metals;Methods;Mission;molecular site;nano;nanofibrillar;Nanostructures;Nature;Neurons;Organism;Paper;Parkinson Disease;Pathology;Process;programs;Proteins;Public Health;Publishing;Research;Research Personnel;Rhenium;Rice;Roentgen Rays;Role;Ruthenium;Singlet Oxygen;Spectrum Analysis;stoichiometry;Structure;System;Techniques;time use;tool;Toxic effect;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Uncovering New Chemical and Physical Methods to Analyze Biological Fibrillar Nanostructures


NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: ITHACA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative This project involves understanding the basic functioning of genetic elements that play a critical role in making some bacteria pathogenic or difficult or impossible to treat because they allow the development of drug resistance. These elements can be programed as useful CRISPR-Cas tools for gene editing of bacteria individually or in microbiomes with promising modifications for human therapeutic gene editing with the advances in this proposal.

PI_NAMEs: PETERS, JOSEPH E (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Adaptive Immune System;Antibiotic Resistance;Bacteria;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;CRISPR-associated transposons;DNA;DNA Transposons;drug resistance development;Elements;Engineering;Evolution;Family;Future;gene editing technology;Gene Expression Regulation;Genes;genetic element;genetic information;Genome;genome editing;Goals;Guide RNA;Human;Individual;insight;Invaded;Knowledge;microbiome;Mobile Genetic Elements;Modification;Molecular;multi-drug resistant pathogen;Multiple Bacterial Drug Resistance;pathogen;Pathogenesis;pathogenic bacteria;Play;Population;Positioning Attribute;Prokaryotic Cells;Public Health;resistance factors;RNA;Role;side effect;System;Techniques;therapeutic genome editing;tool;Transposase;Virulence Factors;Virus;Work

PROJECT_TITLE: CRISPR-Cas-directed transposition in Tn7-like elements


NIH_SPENDING_CATS: Neurodegenerative;Rare Diseases

ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

PHR: Project Narrative There are a growing number of examples of cells utilizing controlled protein assembly to regulate various cellular processes. However, dysregulation of this functional protein assembly has been linked to various degenerative diseases, including amyotrophic lateral sclerosis and some forms of dementia. Understanding the regulation and dysregulation of these protein assemblies will potentially aid in treatment of these devastating diseases.

PI_NAMEs: ROSS, ERIC D (contact)

PROJECT_TERMS: Amyloid;Amyotrophic Lateral Sclerosis;cell growth regulation;Cell Physiology;Cells;Complex;Degenerative Disorder;Dementia;design;Disease;frontotemporal lobar dementia amyotrophic lateral sclerosis;Genome;Goals;Human;Link;Mediating;Memory;Mutation;novel;Organism;Pathologic;Physical condensation;Physiology;prion-like;Proteins;recruit;Regulation;Role;Specificity;stress granule;Structure;Tertiary Protein Structure;yeast prion

PROJECT_TITLE: Functional and Pathological Assembly of Prion-like Domains


PHR: MIRA Project Narrative This MIRA Renewal will continue efforts in the Lockett Laboratory to develop a modular culture platform for generating readily stackable tissue-like structures. In particular, we will develop technologies to monitor intercellular signaling that alter estrogen signaling in real-time; further develop a method to profile the oxygen-regulated expression of drug-metabolizing enzymes in 3D liver structures; mass spectrometry methods to quantify changes in lipid and metabolite pools in cells under physiologically relevant oxygen tensions.

PI_NAMEs: LOCKETT, MATTHEW RYEN (contact)

PROJECT_TITLE: Paper-based cultures supporting tissue-like structures for biochemical studies of oxygen gradients and screening applications


NIH_SPENDING_CATS: Cancer;Genetics

PHR: PROJECT NARRATIVE The goal of mitotic cell division is for the two resulting daughter cells to contain exactly the same complement of genetic material. Every mitotic cell division must take place with remarkably high fidelity, since errors in mitosis that lead to unequal division of genetic material are intimately linked to human pathologies such as birth defects and cancer. The goals of our research are to understand the molecular mechanisms that ensure error-free mitosis and to determine the causative links between activated cancer signaling pathways and chromosome mis-segregation.

PI_NAMEs: DELUCA, JENNIFER G (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Aneuploidy;Antibodies;aurora B kinase;Biological Assay;cancer cell;cancer initiation;cancer therapy;Cell division;cell transformation;Cells;Centromere;chromosome conformation capture;chromosome missegregation;Chromosome Segregation;Chromosomes;Communication;Complement;Congenital Abnormality;daughter cell;Defect;Ensure;Family;Genetic Materials;Glioblastoma;Goals;Health;Human;Human Pathology;Hyperactivity;In Vitro;Inherited;Kinetochores;Laboratories;Lead;Link;Malignant Neoplasms;MAP Kinase Gene;Methods;Microtubules;Mitosis;Mitotic;Molecular;Pathway interactions;Phosphorylation;Phosphotransferases;Regulation;Research;Role;sensor;Signal Pathway;Signal Transduction;Site;Structure;superresolution imaging;temporal measurement;Therapeutic Intervention;tool;tumor;tumor progression;tumorigenesis

PROJECT_TITLE: Mechanisms of Kinetochore-Microtubule Attachment and Regulation


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE This project will examine the mechanisms that enable beneficial symbionts to colonize and be maintained by a host, such as the ability to eliminate competitors and grow within host niches. The insights into these mechanisms that are gained by this research may promote new strategies for harnessing beneficial symbionts as therapeutics to improve human health.

PI_NAMEs: MIYASHIRO, TIMOTHY  (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TITLE: Molecular determinants of bacterial interactions and maintenance in the Vibrio fischeri-Euprymna scolopes symbiosis


ED_INST_TYPE: GRADUATE SCHOOLS

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

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: Public Health Relevancy Statement Gene expression is tightly controlled in time and space. RNA binding proteins are essential for post- transcriptional gene expression regulation and are recurrently mutated in diseases. Understanding how the molecular interplay between RNA binding proteins control gene expression dynamics would have a strong impact on biology, disease development and therapeutic applications.

PI_NAMEs: JOVANOVIC, MARKO  (contact)

PROJECT_TERMS: Binding;Biological Process;Biology;Cells;Complex;data integration;data preservation;data quality;Data Set;Development;Disease;embryonic stem cell;experimental study;follow-up;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;insight;Life Cycle Stages;mammalian genome;Maps;Measures;Mediating;Methods;Molecular;molecular dynamics;Mutate;Neurons;novel strategies;Pathologic Processes;Physiological Processes;Post-Transcriptional Regulation;Post-Translational Protein Processing;posttranscriptional;protein function;protein protein interaction;Protein-Protein Interaction Map;Proteins;Public Health;Recurrence;Regulation;Regulator Genes;Resolution;RNA;RNA-Binding Proteins;RNA-Protein Interaction;stem cell differentiation;Synaptic plasticity;Therapeutic;Time;Translations;Work

PROJECT_TITLE: How dynamic molecular interactions of RNA Binding Proteins drive post-transcriptional gene expression changes


ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Narrative The proposed research is relevant to public health because by understanding 4-D developmental pattern formation, it seeks to acquire fundamental knowledge about the mechanisms of embryonic development that are driven by conserved signals and that have the potential to enhance human health by identifying new avenues to prevent or treat patterning- based birth defects. By laying these foundations for new strategies to address skeletal birth defects via increasing our understanding of the fundamental signal-dependent pattern formation processes, the goals of the proposed research are relevant to the mission of NIGMS.

PI_NAMEs: BRADHAM, CYNTHIA A (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: 3-Dimensional;Address;Algorithmic Analysis;Cells;Complex;Computer Models;confocal imaging;Congenital Abnormality;Cues;Data Analyses;Development;Developmental Process;Ectoderm;Embryonic Development;Embryonic Pattern Specification;Foundations;gene regulatory network;Goals;Health;Human;Infant Mortality;innovation;insight;Instruction;Knowledge;Label;Maps;Mediating;Mission;Modeling;Molecular;Morphogenesis;National Institute of General Medical Sciences;network models;novel;novel strategies;Outcome;Pathway Analysis;Pattern;Pattern Formation;prevent;Prevention approach;Process;Production;Public Health;Regulation;Research;response;Role;Sea Urchins;Signal Transduction;single-cell RNA sequencing;skeletal;Skeleton;spatiotemporal;Systems Biology;time use;Tissues;tool

PROJECT_TITLE: Spatiotemporal Regulation of Developmental Pattern Formation


NIH_SPENDING_CATS: Biotechnology

PHR: Narrative How cells divide, grow, and respond to stress differs among tissues and is perturbed in disease, but the molecular mechanisms for these variations remain incompletely understood. This proposal seeks to fill this knowledge gap through investigation of a variant growth program known as the endocycle and by defining new functions of the p53 tumor suppressor. The long- term outcomes will ultimately have a major positive impact on human health by leading to the development of new diagnoses and therapies for developmental malformations and cancer.

PI_NAMEs: CALVI, BRIAN R (contact)

PROJECT_TERMS: Address;Affect;Apoptotic;biological adaptation to stress;Biological Models;cancer therapy;carcinogenesis;Cell Culture Techniques;Cell Cycle;Cell Cycle Regulation;Cell Physiology;cell type;Cells;Clinic;Competence;Development;Developmental Therapeutics Program;Diagnosis;Disease;DNA Damage;Drosophila genus;Drosophila melanogaster;gene repression;genome integrity;Genomic approach;Growth;Health;Human;in vivo;Investigation;Knowledge;malformation;Malignant Neoplasms;Mitosis;Mitotic;Modeling;Molecular;Newly Diagnosed;novel therapeutics;Organism;Outcome;Pathway interactions;Polyploid Cells;Polyploidy;Process;programs;Property;Protein Isoforms;Published Comment;Relapse;Repression;Resistance;response;Signal Pathway;Stress;tissue regeneration;Tissues;TP53 gene;tumorigenesis;Variant

PROJECT_TITLE: Cell cycle and checkpoint variations in development and disease


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Narrative: The overarching goal of this project is to uncover regulatory mechanisms of cell-type-specific alternative splicing. We will develop and integrate single-cell long-read sequencing, multiplexed and conditional CRISPR editing, and RNA-base editing approaches to achieve these goals. This study will generate genetic and transcriptomic tools and resources to investigate cell-type-specific pre-mRNA splicing.

PI_NAMEs: ZHANG, XIAOCHANG  (contact)

PROJECT_TERMS: Alternative Splicing;animal tissue;base editing;Biological;Biological Models;Brain;Cell Line;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;crosslink;Data Set;Deaminase;flexibility;Funding Mechanisms;Genetic;genome editing;Goals;Heterogeneity;Immunoprecipitation;in vivo;mRNA Precursor;Mus;Pattern;Poly(A)+ RNA;protein function;Regulatory Element;Resources;RNA;RNA Splicing;RNA-Binding Proteins;RNA-Protein Interaction;sequencing platform;single-cell RNA sequencing;Technology;Tissues;tool;transcriptomics

PROJECT_TITLE: Mechanisms of Cell-type-specific pre-mRNA Splicing


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

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: NARRATIVE This proposal seeks to develop new computational technologies at the interface of physical models (which generalize broadly but cannot learn from data) and machine learning models (that can learn from data but generally require more data than is available) to accelerate drug discovery when structural biology data is available. A practical outcome will be new methods and software that can be deployed in industry and academic structure enable drug discovery programs that aim to reduce the time, cost, and failure rates of small molecule drug discovery.

PI_NAMEs: CHODERA, JOHN DAMON (contact)

PROJECT_TERMS: Academia;Acceleration;Adoption;Affinity;Amber;Architecture;Bayesian Modeling;Binding;Cell Membrane Permeability;Computer Assisted;Computer software;cost;Cost Analysis;Data;deep learning;drug discovery;Educational process of instructing;Endowment;Engineering;Failure;Free Energy;Generations;Hybrids;improved;Industry;innovation;interest;Ions;Lead;lead optimization;Learning;lipophilicity;machine learning method;machine learning model;Methodology;Methods;Modeling;Molecular Conformation;Outcome;Phase;physical model;physical property;programs;Property;Proteins;protonation;Recording of previous events;Resistance;Sampling;small molecule;Solubility;Statistical Mechanics;structural biology;Structure;tautomer;Technology;Time;tool;Toxic effect;Training;Uncertainty;virtual;Water;Work

PROJECT_TITLE: Teaching free energy calculations to learn


ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Our understanding of health and disease stem from the fundamental details provided by atomic vistas of macromolecules and their higher-order structures. We develop and apply tools in electron microscopy to reveal novel molecular structures of interest to basic, diagnostic or therapeutic science.

PI_NAMEs: RODRIGUEZ, JOSE ALFONSO (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Acute;Amyloid;amyloid structure;Area;Award;Benign;Catalogs;Cellular Structures;Chemicals;Complex;computerized tools;Development;Diagnostic;Disease;Electron Microscopy;Event;experience;Funding;Health;Higher Order Chromatin Structure;Hybrids;improved;In Situ;interest;Life;Machine Learning;macromolecule;Methods;Micro Electron Diffraction;Molecular;Molecular Structure;nanoassembly;novel;Pathogenicity;Pathologic;Phase;Physiological;Physiological Processes;Process;protein complex;Protein Engineering;protein function;protein structure;Proteins;Resolution;Role;Science;single molecule;Speed;stem;structural biology;Structure;Therapeutic;tool;trait;Visualization

PROJECT_TITLE: Micro Electron Diffraction of Toxic and/or Infectious Macromolecular Nanoassemblies


NIH_SPENDING_CATS: Cancer;Genetics;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: NARRATIVE Many tumor types are characterized by altered patterns chemical tags found on the histone proteins that package the human genome, leading to defects in gene regulation and DNA repair. Insights into the molecular mechanism by which cells attach and remove these tags, as well as how the tags regulate gene expression, can be used to devise new treatments. This research is being used to drive efforts to develop drugs to treat cancers that are resistant to current therapies.

PI_NAMEs: WOLBERGER, CYNTHIA  (contact)

PROJECT_TERMS: Acetylation;Biochemistry;Cell Proliferation;Cells;Chemicals;chemotherapy;chromatin modification;Chromosomal Rearrangement;Complex;Cryoelectron Microscopy;Defect;design;Deubiquitinating Enzyme;DNA Packaging;DNA Repair;drug discovery;effective therapy;Event;Foundations;Gene Activation;Gene Expression;Gene Expression Regulation;Genetic Transcription;Goals;Histone H2B;histone modification;Histones;Human;Human Genome;inhibitor;insight;interdisciplinary approach;Malignant Neoplasms;Mediating;Methylation;MLL gene;MLL-rearranged leukemia;Modification;Molecular;molecular drug target;Molecular Machines;Monoubiquitination;Nature;new therapeutic target;Nucleosomes;Pathway interactions;Pattern;Pharmaceutical Preparations;Play;Post-Translational Protein Processing;programs;protein function;Proteins;refractory cancer;Research;Role;SAGA;targeted cancer therapy;Transcription Coactivator;Transcriptional Regulation;tumor;Ubiquitin;ubiquitin isopeptidase;Ubiquitination;X-Ray Crystallography

PROJECT_TITLE: Mechanistic studies of chromatin modification in transcription regulation


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: Project Narrative Riboswitches are ubiquitous mRNA regulatory elements in bacteria that control expression of genes. This research seeks to develop an atomic-level and mechanistic understanding of how riboswitch RNAs regulate gene expression through their ability to directly bind small molecule metabolites and apply our knowledge of riboswitches to develop tools for tagging and tracking single RNA molecules in live mammalian cells. The proposed research will also investigate the role of RNA binding by HMGB transcription factors in the regulation of gene expression.

PI_NAMEs: BATEY, ROBERT T (contact)

PROJECT_TERMS: Address;Affinity;antimicrobial;aptamer;Bacteria;Bacterial Genes;Basic Science;Benchmarking;Binding;Biochemical;Biological Assay;Biological Process;Biophysics;Cells;Chemicals;cis acting element;Communication;Consensus;DNA;Elements;fluorophore;Gene Expression;Gene Expression Regulation;Genes;Goals;HMGB Family Gene;Image;In Vitro;Knowledge;Ligand Binding;Link;Maintenance;Mammalian Cell;Medical;Messenger RNA;Molecular;Mouse Embryonic Stem Cells;neural;novel;pathogen;Performance;pluripotency;programs;promoter;Property;Protein Family;receptor;Regulatory Element;Research;Research Design;RNA;RNA Binding;Role;Site;small molecule;Small RNA;Specificity;Structure;Therapeutic;tool;transcription factor;transcriptome;Virulence;Visualization

PROJECT_TITLE: Riboswitches and their application to RNA visualization and transcription factor interactions with the transcriptome


ORG_CITY: TALLAHASSEE

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Molecular principles of four RNA-mediated machineries including CRISPR-Cas enzymes from bacteria and snoRNPs from yeast will be studied towards construction and testing of innovative anti-cancer therapeutic, genome manipulation and virus detection tools.

PI_NAMEs: LI, HONG  (contact)

PROJECT_TERMS: anti-cancer therapeutic;Bacteria;Biological;Biological Process;Biology;Biophysics;Cell Physiology;chemical reaction;Chemicals;Chemistry;Clustered Regularly Interspaced Short Palindromic Repeats;Cryoelectron Microscopy;Diagnostic;DNA;Engineering;Enzymes;Epigenetic Process;Funding;Gene Expression Regulation;Genome;Goals;Guide RNA;Immunity;innovation;Laboratories;mammalian genome;Mediating;Methods;Methylation;Microbiology;Modification;Molecular;nucleic acid detection;Nucleic Acids;particle;Pathway interactions;Process;Proteins;Research;Ribonucleoproteins;Ribosomal RNA;risk mitigation;RNA;Scientist;Secure;Signal Transduction;single molecule;Small Nucleolar Ribonucleoproteins;structural biology;Testing;Therapeutic;tool;Translations;viral detection;virology;X-Ray Crystallography;yeast genetics;Yeasts

PROJECT_TITLE: Mechanisms and Applications of RNA-mediated Enzymes in Translation and Immunity


NIH_SPENDING_CATS: Biotechnology;Neurosciences

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: SNARE proteins generate force to bring two membranes into close proximity to trigger fusion, while bridge lipid transfer proteins necessitate forces yet to be identified for transporting lipids between two membranes. Our understanding of these proteins is limited by our ability to measure and apply forces at a single-molecule level. By utilizing optical tweezers, fluorescence microscopy, and other complementary approaches, we can gain deeper insight into their functioning mechanisms.

PI_NAMEs: ZHANG, YONGLI  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Biogenesis;Biological Assay;Categories;Cell membrane;Closure by clamp;Complex;Disease;driving force;Environment;Eukaryota;Fluorescence Microscopy;Funding;genetic regulatory protein;Goals;insight;Intervention;laser tweezer;Link;lipid transfer protein;lipid transport;Lipids;Measures;Mediating;Membrane;Membrane Fusion;Membrane Proteins;Molecular;Molecular Chaperones;novel;optic tweezer;Organelles;Pathway interactions;Proteins;reconstitution;Research;sensor;single molecule;Site;SNAP receptor;Structure;Synapses;Synaptic Membranes;Synaptic Vesicles;synaptotagmin I;syntaxin 1;Testing;trafficking;Vesicle

PROJECT_TITLE: Single-molecule studies of SNARE assembly and lipid transfer


ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Proposal Title: Harnessing divergent reactivities of unusual intermediates as platforms to explore high Fsp3 amine chemical space. Project Narrative: Bioactive amine motifs occur in diverse molecules of key importance to human health, but the lack of diversity in current drug libraries has increased interest in high Fsp3 chemical space, defined as the # sp3 C/total # C. This project uses mechanistic insight to tune the reactivities of unusual intermediates (methyleneaziridines, aziridinium ylides, 2-amidoallyl cations) to achieve mild, versatile syntheses of stereochemically rich, densely functionalized N-hetero- and carbocycles, including those in bioactive molecules that bind to specific ribosomal subunits. These modular and unified strategies to build N-heterocycles of varying ring sizes and substitution patterns from a simple pool of precursors is an attractive addition to the synthetic lexicon, given the prevalence of such rings in FDA-approved drugs.

PI_NAMEs: SCHOMAKER, JENNIFER MARIE (contact)

PROJECT_TITLE: Harnessing divergent reactivities of unusual reactive intermediates as platforms to explore high Fsp3 amine chemical space


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


NIH_SPENDING_CATS: Genetics;Human Genome

PHR: Project narrative Each time a cell divides it must produce accurate copies of its chromosomes by replicating the chromosomal DNA. This process is essential and defects in chromosome replication can lead to mutations, chromosomal rearrangements and cancer. This project will generate novel assays and tools for the study of chromosome replication in vitro and elucidate molecular mechanisms that ensure chromosome replication fidelity under normal and replication stress conditions.

PI_NAMEs: REMUS, DIRK  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Binding;Biological;Biological Assay;Biological Process;Cell Cycle Progression;Cell Proliferation;Cells;Chromosomal Rearrangement;chromosome replication;Complex;Defect;Development;Disease;DNA;DNA biosynthesis;DNA replication fork;DNA-Binding Proteins;Ensure;experimental study;G-Quartets;genome integrity;Genome Stability;Genomic Instability;helicase;Human;In Vitro;Individual;Maintenance;Malignant Neoplasms;Molecular;Mutation;non-histone protein;Normal Cell;novel;Outcome;Phosphotransferases;Physically Challenged;Process;Proteins;reconstitution;replication stress;Research;response;restoration;Ribosomal DNA;Saccharomycetales;Site;Source;Structure;System;Time;tool;Work;yeast protein;Yeasts

PROJECT_TITLE: Molecular mechanism of eukaryotic chromosome replication


NIH_SPENDING_CATS: Biotechnology;Immunotherapy

ORG_CITY: CHESTNUT HILL

ORG_NAME: BOSTON COLLEGE

ORG_STATE: MA

PHR: Streamlining PPI Inhibitor Discovery via Chemically Enhanced Phage Display Project Narrative Peptides have recently emerged as a new modality of therapeutics, which can enjoy the combined benefits of small molecule and antibody based drugs. This application seeks to develop new technologies, which will streamline the discovery of peptide therapeutics, particularly against the biological targets previously deemed undruggable by small molecule drugs.

PI_NAMEs: GAO, JIANMIN  (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Amines;Anti-Bacterial Agents;anti-PD-1/PD-L1;anti-PD-L1 antibodies;Antibiotic Resistance;Antibodies;Bacteriophages;Binding;Biological;Chemicals;Chemistry;Complex;Elements;forging;Immune Evasion;inhibitor;interest;Libraries;Lysine;Malignant Neoplasms;Modality;Modeling;Modification;Molecular;new technology;novel;Oral;pathogen;Penetration;peptide drug;Peptide Library;peptide natural products;peptide structure;Peptides;Persons;Phage Display;Pharmaceutical Preparations;pharmacologic;protein protein interaction;Proteins;Rapid screening;Research;Rewards;screening;Series;Side;small molecule;Structure;success;Therapeutic;Time;Tissues;Vertebral column;Work


ORG_STATE: CA

PHR: Defective RNA processing is frequently associated with genetic diseases as evidenced by mutations in RNA exosome subunits resulting in Pontocerebellar Hypoplasia. Several of the proteins studied in this proposal such as Rexo4 or Bromodomain proteins are also associated with cancer. Our studies of the control of gene expression by the RNA exosome and Rexo4, and of the regulation of the expression of bromodomain factors will shed light on the molecular mechanisms involved in diseases affecting RNA metabolism.

PI_NAMEs: CHANFREAU, GUILLAUME F (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Affect;Area;Biogenesis;Bromodomain;Chromatin Remodeling Factor;Cytoplasm;Degradation Pathway;Disease;Exonuclease;exosome;Gene Expression;Genetic Diseases;Genetic Transcription;global transcript level;Hybrids;in vivo;Laboratories;Link;Malignant Neoplasms;Messenger RNA;Molecular;Mutation;Nuclear;Nuclear RNA;Play;Pontocerebellar hypoplasia;posttranscriptional;Process;Proteins;Proteome;Quality Control;Regulation;Research;response;Ribonuclease III;Ribonucleases;Ribosomal RNA;Ribosomes;RNA;RNA Degradation;RNA metabolism;RNA Processing;RNA Splicing;Role;Small Nucleolar RNA;Stress;Transcript;Transcription Process;transcriptome;transcriptome sequencing;Translations;Work

PROJECT_TITLE: The control of gene expression by eukaryotic ribonucleases


ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

PHR: Project Narrative DNA replication and gene expression are fundamental processes to the propagation of all cellular life on the planet. The machineries that effect these processes have to navigate DNA substrates that have undergone multiple levels of packaging to ensure the DNA molecules can be accommodated within cells. Using a simple model system, we will investigate the functional interplay between machineries that effect packaging and those responsible for genome duplication and expression.

PI_NAMEs: BELL, STEPHEN DAVID (contact)

PROJECT_TERMS: Archaea;Architecture;Biological Models;Cells;Chromosomes;DNA;DNA biosynthesis;Ensure;Epigenetic Process;Eukaryota;Evolution;Gene Expression;Genetic Transcription;Genome;In Vitro;in vivo;insight;Life;Mediating;microorganism;Molecular;Molecular Biology;Molecular Conformation;novel;Planets;Process;Proteins;Role;single molecule;Sulfolobales;Sulfolobus;System;Work

PROJECT_TITLE: Archaeal Chromosome Dynamics


NIH_SPENDING_CATS: Aging;Bioengineering;Cancer;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: ATLANTA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Project Narrative This proposal seeks to build and apply new predictive medicine technology that enables multifactorial, multi- scalar data integration to identify disease causes, develop cures, and optimize patient care for all of general medicine.

PI_NAMEs: MITCHELL, CASSIE S (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Active Learning;Address;Adult;Algorithms;Alzheimer's Disease;Amyotrophic Lateral Sclerosis;artificial intelligence algorithm;Artificial Intelligence enhanced;Beds;Cardiovascular Diseases;Chronic Leukemia;Clinical Trials;cohort;Collaborations;Communicable Diseases;Complex;Computer software;data integration;deep learning;Development;Disease;disease model;drug repurposing;Equity;Event;health outcome disparity;high school;human-in-the-loop;innovation;journal article;Knowledge;knowledge graph;Laboratories;Literature;machine learning algorithm;Malignant Neoplasms;Medicine;Meta-Analysis;Methods;multimodal learning;Natural Language Processing;Nervous System Disorder;novel;Parkinson Disease;Pathology;Patient Care;patient stratification;pediatric acute leukemia;Solid Neoplasm;Supervision;Technology;Testing;undergraduate student

PROJECT_TITLE: Integrative predictive medicine to identify disease causes, develop cures, and optimize patient care


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Wound Healing and Care

ORG_CITY: Nashville

ORG_DEPT: PHARMACOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

PHR: Project narrative-relevance statement Lipids are a source of important signaling molecules that regulate health and disease in the body. Our research is focused on how lipid oxidizing enzymes called lipoxygenases produce novel lipid signals and how these act in the body. An understanding of the role of these lipid metabolizing enzymes and of the lipid oxidation products will ultimately lead to more rational treatments of a spectrum of conditions including inflammation and skin diseases.

PI_NAMEs: BRASH, ALAN R. (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;adduct;Anabolism;Animals;arm;Artificial skin;Binding;Biochemical;Biological Assay;Burn injury;Ceramides;Collection;Congenital ichthyosis;Cyclization;cyclopentenone;diabetic ulcer;Disease;Enzymes;Epidermis;Epoxy Compounds;Esterification;Esters;Evolution;Fatty Acids;Fish Oils;Freedom;Funding;Genetic;Health;Hemeproteins;high standard;Human;Inflammation;Knockout Mice;Lead;Leadership;linoleates;Linoleic Acids;lipid mediator;Lipids;Lipoxygenase;LOX gene;member;Metabolic Pathway;Mus;Nature;Neonatal;novel;oxidation;Oxides;oxidized lipid;Oxidoreductase;Oxygenases;Pathway interactions;Permeability;Production;programs;propadiene;Protein Chemistry;Proteins;Proteomics;Recombinants;Research;Resolution;Resources;Role;seal;Secure;Series;Signal Transduction;Signaling Molecule;Skin;skin barrier;skin disorder;social;Source;Sum;Synthesis Chemistry;Vision;Water

PROJECT_TITLE: Analytical approaches to fatty acid oxygenases and their lipid mediator products


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Vector-Borne Diseases

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative. Rapid evolutionary processes such as CRISPR gene drives promise novel strategies for the control of vector-borne diseases by enabling the dissemination of transgenes that suppress vector populations or reduce pathogen transmission. However, important questions still loom large about the practicality of these approaches in real-world applications. The goal of the proposed research is to develop simulation approaches and population genetic models that can better incorporate rapid evolutionary processes, to help us gain a better understanding of their expected outcomes.

PI_NAMEs: MESSER, PHILIPP W (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Affect;Alleles;Antibiotic Resistance;Biological;computerized tools;CRISPR gene drive;Culicidae;Dengue;Development;Disease;Drug resistance;Engineering;Evaluation;Evolution;Face;fascinate;gene drive system;Genes;Genetic;Genetic Models;genomic data;Goals;Humanities;improved;Individual;insight;Malaria;Methods;Modeling;new technology;novel strategies;Outcome;outcome prediction;Partner in relationship;pathogen;Population;Population Dynamics;Population Genetics;Process;real world application;Research;Research Personnel;Risk;SARS-CoV-2 variant;simulation;Structure;supervised learning;Target Populations;Transgenes;transmission process;vector;vector control;vector mosquito;Vector-transmitted infectious disease;Work

PROJECT_TITLE: Population genetics of rapid evolutionary processes


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Neurosciences

ORG_CITY: EUGENE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: NARRATIVE A person's health and welfare depend on making decisions that are in his or her best interest, but the neuronal mechanisms of decision making are poorly understood. The proposed research delineates the neural circuit for human-like decision making in a model organism whose genes can be manipulated directly, quickly, and inex- pensively. Successful completion of the proposed research will establish a new model system in which to as- sess the function of networks of human genes associated with complex behavioral traits.

PI_NAMEs: LOCKERY, SHAWN R (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: addiction;Address;Behavior;Behavioral;Biological Models;biological systems;Brain;Brain Injuries;Caenorhabditis elegans;Cognitive deficits;Complex;Computer Models;cost;Decision Making;Development;Disease;drug of abuse;Economics;food quality;Foundations;gene function;gene interaction;Genes;Genetic;genetic analysis;Health;Human;Image;Individual;interest;Invertebrates;Investigation;Laboratories;Learning;Link;Mathematics;Mental disorders;Microfluidic Microchips;model organism;Nematoda;neural circuit;Neurodegenerative Disorders;Neurons;novel;Organism;Orthologous Gene;Pathway interactions;Personality;Persons;Procedures;Research;Resolution;response;Societies;Testing;Time;trait;Transgenic Organisms;Translating;welfare;Work

PROJECT_TITLE: Neuronal and theoretical analysis of subjective value representations


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

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Program Director/Principal Investigator (Liang, Jie): Project Narrative We will develop computational models and tools to construct probability landscapes of networks of stochastically interacting proteins, DNA/RNAs, and other molecules, and to quantify the flow maps of fluxes and the exact topology of these landscapes, so their behavior and roles in influencing cellular phenotypes can be better understood. In addition, we will study the biophysics of 3D genome folding, and will develop computational tools based on polymer modeling to identify the minimal sets of genomic driver interactomes that dictate the 3D conformations of chromatin loci and identify those that persists across tissues and those that are formed adaptively in different cell types. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

PI_NAMEs: LIANG, JIE  (contact)

PROJECT_TERMS: 3-Dimensional;Algorithms;Behavior;Biological;biophysical analysis;Biophysics;Biopolymers;Cell Physiology;cell type;Cells;Chemicals;Chromatin;Chromatin Structure;Chromosomes;Complex;Computer Models;computerized tools;Data;Development;DNA;Elements;Embryonic Development;Enzymes;Epigenetic Process;Equation;Event;frontier;Genetic Transcription;Genome;genome-wide;genomic locus;Genomics;Grain;Heterogeneity;Hi-C;high dimensionality;improved;insight;Investigation;Kinetics;Maintenance;Maps;Messenger RNA;Methods;Modeling;Molecular;Molecular Conformation;network architecture;non-genetic;Nuclear;Nuclear Envelope;Phenotype;Polymers;Potassium Channel;preservation;Principal Investigator;Probability;Process;programs;Proteins;Reaction;RNA;RNA Splicing;Role;Sampling;scaffold;Signaling Molecule;stem cell differentiation;Structural Genes;Structure;three-dimensional modeling;Tissues;tool;transcription factor;Work

PROJECT_TITLE: Models and Algorithms for Biological Networks and Polymers: Stochastic Probability Landscape and Chromatin Ensembles


NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The present proposal uses advanced spectroscopic and computational methods to uncover the coupling between structural dynamics and function of proteins and nucleic acids. The underlying premise is that such coupling plays a fundamental role in biological processes, including folding, recognition, allostery, regulation, and catalysis. Thus, elaboration of the roles of conformational dynamics in actuating and regulating these processes is essential for understanding human health and disease.

PI_NAMEs: PALMER, ARTHUR G (contact)

PROJECT_TERMS: Active Sites;Affinity;Binding;Biological;Biological Process;biological systems;Biophysics;Breathing;bZIP Protein;Cadherins;Catalysis;Cell Adhesion Molecules;Computing Methodologies;conformational conversion;Core Protein;Coupled;Coupling;design;Development;Dimerization;Disease;DNA;DNA Repair Gene;Drug resistance;enzyme activity;Enzymes;Equilibrium;Event;experimental study;Feedback;Goals;Health;Homologous Gene;HOX protein;Human;improved;insight;Investigation;Kinetics;Laboratories;Ligand Binding;Ligands;loss of function mutation;Measurement;member;Modification;Molecular Conformation;molecular dynamics;molecular recognition;Motion;non-Native;novel;Nucleic Acids;nucleotidyltransferase;pathogen;Pathology;Pharmacologic Substance;Play;Process;protein activation;protein function;protein protein interaction;Proteins;Psychological Techniques;Reaction;Regulation;Relaxation;Research;resistance mutation;Resolution;ribonuclease H1;Role;Scientist;Site;Structure;System;Techniques;transcription factor

PROJECT_TITLE: Macromolecular dynamics and conformational changes in biological function


PHR: Project Narrative Our research program over the next five years will employ powerful advances in molecular genetics, light microscopy and atomic force microscopy to investigate mechanisms that regulate the cytoskeleton during cell division in the model organism Caenorhabditis elegans. Our major goals are to (i) advance our understanding of cytoskeletal regulation in general, as lessons gained from C. elegans oocytes and early embryos are likely to prove relevant in a wide variety of animal cell contexts; (ii) more specifically to advance our understanding of acentrosomal spindle assembly, which is important for both meiosis and mitosis; (iii) explore the C. elegans oocyte cortex as a model for investigating the role of microtubules in an animal cell cortex; and (iv) collaboratively apply Atomic Force Microscopy to isolated C. elegans blastomeres and oocytes to investigate the biophysical properties of animal cell cortices.

PI_NAMEs: BOWERMAN, BRUCE A (contact)

PROJECT_TERMS: Animals;Atomic Force Microscopy;Auxins;Biological Models;biophysical properties;Bypass;Caenorhabditis elegans;cell cortex;Cell division;Cells;Chimeric Proteins;CRISPR/Cas technology;Cytoskeleton;Embryo;embryo stage 2;Essential Genes;Fertility;gene function;gene replacement;Genes;Genetic;genetic approach;Goals;Human;in vivo;Investigation;Laboratories;light microscopy;live cell imaging;Malignant Neoplasms;Meiosis;Microtubules;Mitosis;model organism;Modeling;Molecular Genetics;Mutation;Nematoda;novel;Oocytes;Process;programs;Proteins;Regulation;Research;Resolution;Role;Temperature;Tissue Engineering

PROJECT_TITLE: Cytoskeletal Function in C. elegans Embryos


ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Otopetrin (OTOP) channels conducts protons across cell membranes and are found throughout the body, including in the digestive tract where their expression has been correlated with disease progression. This funding will support a multidisciplinary approach using powerful biophysical and genetic and imaging methods to characterize the subcellular distribution, gating and permeation properties of OTOP2 and OTOP3 channels with the goal of shedding light on their physiological functions in health and disease.

PI_NAMEs: LIMAN, EMILY R. (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Acids;biomineralization;Biophysics;Cell membrane;Cell Physiology;Chemosensitization;Chimera organism;Development;Disease;disease prognosis;Disease Progression;Elements;Family;Funding;Gastrointestinal tract structure;Genetic;Goals;Grant;Health;imaging modality;interdisciplinary approach;Invertebrates;Ion Channel;Light;Mouse Strains;National Institute of General Medical Sciences;novel;otoconia;Physiological;Physiological Processes;Property;Protein Family;Protons;Research;Role;Site-Directed Mutagenesis;Skeleton;Structure;System;taste system;Testing;Vertebrates;vestibular system;Visualization

PROJECT_TITLE: Cellular physiology of Otopetrin Proton Channels


ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: PROJECT NARRATIVE The regulation of transcription in humans has a significant impact on many aspects of health and disease, but the effects on phenotypes are not fully understood, especially in the context of new genes and their functional innovation. We propose to use fruit flies as a model to investigate the extent of gene expression variation and the role of transcription factors in the evolution of new genes and new expression. The findings of this research will be valuable in our understanding of transcription-associated disorders such as Li-Fraumeni syndrome and verbal dyspraxia, as well as the regulatory mechanisms underlying sperm fertility.

PI_NAMEs: ZHAO, LI  (contact)

PROJECT_TERMS: Biological;cell type;Chromatin;Complex;deep learning;Development;Disease;Distant;Dosage Compensation (Genetics);Drosophila genus;Elements;Enhancers;Epigenetic Process;Evolution;Fertility;Gene Expression;gene expression variation;Genes;Genetic;Genetic Transcription;Goals;Health;Human;innovation;insight;Laboratories;Li-Fraumeni Syndrome;Life;Meiosis;Modeling;Morphology;novel;Organ;Pattern;Phenotype;Process;promoter;Regulation;Research;Research Project Summaries;Research Proposals;Role;Sex Bias;single cell ATAC-seq;single-cell RNA sequencing;sperm cell;Structure;Techniques;Tissues;trait;transcription factor;transcription regulatory network;Transcriptional Regulation;Verbal Dyspraxia

PROJECT_TITLE: The Genetic and Epigenetic Mechanisms of Phenotypic Innovation


NIH_SPENDING_CATS: Microbiome

ORG_CITY: MAYWOOD

ORG_NAME: LOYOLA UNIVERSITY CHICAGO

PHR: Project Narrative Pathogenic and symbiotic bacteria interact with animal hosts and protect themselves from their environment and antimicrobials such as antibiotics when they grow in biofilms, communities of microorganisms that are attached to each other and/or to a surface using self-secreted molecules such as polysaccharides, and they can leave these protective reservoirs to seed infections elsewhere. We seek to understand the signals and underlying mechanisms that trigger bacteria to form and leave from biofilms using a simple animal model system comprised of the bacterium Vibrio fischeri and its animal host whose natural association depends on these processes. Building on past work, we are poised here to understand how the environmental signals—both inside and out of the animal—trigger production and secretion of specific molecules including the polysaccharides that promote attachment, where and when those molecules are produced, and how bacteria extract themselves to migrate elsewhere, a set of studies that we anticipate will help inform on strategies to treat problematic biofilms that occur in the context of human infection.

PI_NAMEs: VISICK, KAREN L (contact)

PROJECT_TERMS: Address;Adherence;Adhesives;Animal Model;Animals;Antibiotics;antimicrobial;Area;Bacteria;Biological Models;cell community;Cell surface;Cells;Cleaved cell;Communities;Environment;Euprymna scolopes;Event;Extracellular Matrix;Gene Expression;Genes;Genetic Transcription;genomic locus;host colonization;Host Defense;host-associated biofilms;Human;In Situ;Infection;insight;Investigation;Light;macromolecule;medical implant;Microbe;Microbial Biofilms;microorganism;migration;Modeling;Organ;Outcome;Pathogenicity;Physiological;Play;Polysaccharides;posttranscriptional;prevent;Process;Production;Proteins;Research;Role;Signal Transduction;Site;Squid;Surface;Symbiosis;Therapeutic;Tissues;Vibrio fischeri;Visualization;Work

PROJECT_TITLE: Host-associated biofilm formation and dispersal mechanisms


NIH_SPENDING_CATS: Genetics

ORG_CITY: PISCATAWAY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: PROJECT NARRATIVE The goal of this project is to understand how selfish genetic elements known as transposons are able to escape or evade silencing by specialized host pathways that target TE activity. This research is relevant to human health because almost half of the human genome is composed of transposons and transposons are major contributors to genetic variation among individuals. Understanding the biological functions of transposon- derived DNA is important for interpreting the human genome and inferring traits and disease risk from patient genotypes, thereby supporting the NIH’s mission to enhance health and reduce illness.

PI_NAMEs: ELLISON, CHRISTOPHER EUGENE (contact)

PROJECT_TERMS: Affect;arms race;Atrophic;Biological Process;Cell Physiology;cell type;Cells;Chromosomal Rearrangement;Chromosomes;Conflict (Psychology);derepression;Disease;disorder risk;DNA;DNA Damage;DNA Insertion Elements;DNA Transposable Elements;Drosophila genus;Elements;Embryo;Eukaryota;Extinction;Family;Fertility;Gene Silencing;Genes;Genetic;Genetic Transcription;Genetic Variation;Genome;genotyped patients;Goals;Gypsies;Health;Host Defense;Human;Human Genome;Hybrids;Immune Evasion;Immune response;Individual;Mission;Mothers;Mutation;novel;Parasites;Pathway interactions;permissiveness;Phenotype;Post-Transcriptional Regulation;programs;Research;Retrotransposon;Selfish Genes;Small RNA;Sterility;telomere;Time;trait;United States National Institutes of Health;Virus

PROJECT_TITLE: Transposon strategies to escape host silencing


PHR: Project narrative The mTOR signaling pathway is a conserved regulator of cell growth that is linked to common human diseases, including cancer, diabetes, and neurologic disorders. A central mTOR function is to control the translation of mRNAs. This proposal seeks to discover how these mechanisms target specific classes of mRNAs and understand their function in vivo.

PI_NAMEs: THOREEN, CARSON CORNELL (contact)

PROJECT_TERMS: Anabolism;Bioinformatics;Biological Assay;cell growth;Cell Physiology;Cells;Complex;Dependence;detection of nutrient;Diabetes Mellitus;Eukaryota;FRAP1 gene;Gene Expression;Gene Expression Regulation;Goals;Growth;human disease;in vivo;insight;Laboratories;Link;Malignant Neoplasms;Messenger RNA;Molecular;mRNA Stability;mRNA Translation;mTOR Signaling Pathway;Nervous System Disorder;Nutrient availability;Organism;Pathway interactions;Physiology;Post-Transcriptional Regulation;Process;programs;promoter;Proteins;Regulation;Reporter;Research;Ribosomal Proteins;Signal Pathway;Signal Transduction;Structure;System;Tissues;transcriptome;transcriptomics;translation factor;Translations;Variant

PROJECT_TITLE: Post-transcriptional control of gene expression by the mTORC1 signaling pathway


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: ITHACA

ORG_DEPT: OTHER BASIC SCIENCES

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

PI_NAMEs: SEVIER, CAROLYN S (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

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

PROJECT_TITLE: Molecular mechanisms of cellular redox signaling


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: CHAMPAIGN

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: Molecular motors are proteins that use ATP to carry a wide variety of cellular cargoes throughout cells. As in a city where trucks move cargoes, molecular motors are essential, and diseases result when they are misregulated. Understanding molecular motors’ detailed conformations is essential for understanding how they move. To learn more about molecular motors, novel techniques are required, and several new ones are being developed.

PI_NAMEs: SELVIN, PAUL R (contact)

PROJECT_TERMS: Amaze;Blinking;Cell membrane;Cell Membrane Permeability;Cell Nucleus;Cells;Cities;Clinical;Cytoplasm;Dihydrofolate Reductase;Disease;Dynein ATPase;Epidermal Growth Factor Receptor;Escherichia coli;Farm;Fluorescence;fluorescence imaging;Fluorescence Microscopy;Fluorescent Probes;fluorophore;Goals;Illinois;In Vitro;in vivo;invention;Kinesin;Label;Laboratories;Learning;Measurement;Measures;Membrane Proteins;Microscope;millisecond;Molecular Conformation;Molecular Motors;Monitor;Motor;Myosin ATPase;nanodiamond;nanometer;nanoscale;novel;optic trap;optical traps;Oxygen;Penetration;peroxisome;Pharmaceutical Preparations;Photobleaching;photonics;Proteins;Publishing;Quantum Dots;Radial;Resolution;response;single molecule;Site;Speed;statistics;Streptolysins;Techniques;Time;Transfection;ultra high resolution;Work

PROJECT_TITLE: New Super-Accurate and Super-Resolved Fluorescence Microscopy Techniques and Probes for Studying Single Molecular Motors


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Germ cell differentiates into an oocyte that helps launch the next generation by supplying a maternal contribution of RNAs, proteins, complexes, and organelles that is critical to establish a totipotent zygote. Nevertheless, the mechanisms that establish this maternal contribution during oogenesis are incompletely understood. Using Drosophila as a model system, my lab has discovered a germ cell-to-maternal transition, wherein RNAs that promote germ cell-specific programs, such as those that promote germ cell differentiation, and entry into meiosis are excluded from maternal contribution to promote fertility.

PI_NAMEs: RANGAN, PRASHANTH  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Address;Biological Models;Cell Cycle;Cell Differentiation process;Cell Nucleus;Complex;Cytoplasm;Degradation Pathway;Development;Developmental Biology;Drosophila genus;Embryo;Etiology;Excision;Exclusion;Fertility;Gene Expression;Gene Targeting;Genes;Genome;Germ Cells;germline stem cells;Haploidy;Heterochromatin;Human;Infertility;Mediating;Meiosis;Molecular;next generation;novel;Oocytes;Oogenesis;Organelles;programs;Proteins;Regulation;RNA;RNA Degradation;Somatic Cell;Specific qualifier value;stem cell self renewal;Totipotency;Totipotent;Transcript;Work;zygote

PROJECT_TITLE: Regulation of Germ cell to maternal transition


ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: NARRATIVE Anion channels, transporters, and scramblases of the TMEM16 and CLC families play key roles in physiology, controlling processes such as muscle excitability and repair, salt reabsorption, homeostasis of intracellular compartments and blood coagulation. While it is known that missense mutations that impair activity of members of both families cause a multitude of inheritable disorders, the lack of atomic level understanding of how disease- causing mutations impair the function of these proteins significantly hinders the development of tools specific pharmacological aiming to ameliorate these conditions. The goal of our project is to overcome these limitations by elucidating at atomic detail how TMEM16 and CLC proteins operate, and how disease mutation impair their activation.

PI_NAMEs: ACCARDI, ALESSIO  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: absorption;Anions;Blood coagulation;Bone Diseases;Brain;Chloride Channels;CLC Gene;CLC-1 channel;Coupled;Data;Development;Disease;disease-causing mutation;Dysplasia;Epithelium;Family;Functional disorder;Goals;Hereditary Disease;Homeostasis;Human;Impairment;insight;Integral Membrane Protein;Ion Channel;Kidney;Limb-Girdle Muscular Dystrophies;Lipids;loss of function mutation;member;Membrane Fusion;Membrane Transport Proteins;Missense Mutation;Molecular;Molecular Conformation;molecular recognition;Muscle;Mutate;Mutation;Myopathy;Myotonia Congenita;neuromuscular;pharmacologic;phospholipid scramblase;Physiological;Physiology;Play;Process;Property;protein function;Proteins;rational design;Regulation;repaired;Research;Sodium Chloride;Stimulus;Structure;Structure-Activity Relationship;targeted treatment;tool;tool development;voltage;Work

PROJECT_TITLE: Structure and function of chloride channels, transporters and scramblases


ORG_CITY: STANFORD

ORG_DEPT: PATHOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Understanding how information is maintained and transferred in biology will illuminate the fundamental mechanisms that our cells use (i) to properly control the activity of each of their genes and (ii) to protect themselves from unwanted genetic activity in the form of viruses and other genomic parasites. This research program applies a variety of information-based and experimental approaches directed toward that understanding.

PI_NAMEs: FIRE, ANDREW Z. (contact)

PROJECT_TERMS: Anatomy;Biological Models;biological systems;Biology;Caenorhabditis elegans;Cells;detection platform;Development;Epigenetic Process;Fire - disasters;Gene Expression;Genes;Genetic;Genome;genome annotation;Genomics;Germ Lines;Invaded;Modeling;Mutation;National Institute of General Medical Sciences;Nucleic Acids;Organism;Parasites;Pathogenicity;Pattern;Physiology;Process;programs;Protocols documentation;Research;response;RNA;System;Techniques;Therapeutic;tool;Virus

PROJECT_TITLE: Cellular Response to Genetic Change


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

PHR: Project Narrative Relevance of this research to public health: Ionotropic Glutamate Receptors (iGluRs) are major mediators of excitatory synaptic transmission, essential for neurotransmission and proven factors for neurodegenerative and cognitive conditions. Plant ionotropic Glutamate Receptors (GLRs) are useful and tractable models to understand structure function relationships of iGluRs and are structurally akin to the human orphan Glu∂ iGluR family, the least studied and understood in human physiology. Dysfunction of human Glu∂ receptors is associated with cognitive deficits, cerebellar long term depression (LTD), cerebellar ataxia and atrophy, retinal dystrophy and schizophrenia, and some of these dysfunctional aspects have been mechanistically linked to mutations which are physiological for GLRs, turning the study of their functions in plants particularly relevant.

PI_NAMEs: FEIJO, JOSE A (contact)

PROJECT_TERMS: Address;Affect;Amino Acids;Animals;Arabidopsis;Atrophic;Calcium Signaling;Cell Communication;Cells;Cerebellar Ataxia;Cognitive;Cognitive deficits;Collection;Communication;Complement;Computer Simulation;Cryoelectron Microscopy;desensitization;Disease;Dominant-Negative Mutation;Evolution;extreme temperature;Family;Functional disorder;Gene Dosage;Genetic;genetic regulatory protein;Genetic Transcription;Glutamate Receptor;Glutamates;Grant;Homeostasis;Homologous Gene;Human;Image;Ion Channel;Ions;Ligands;Link;Long-Term Depression;Mediator;Medical;Methodology;Modeling;Modification;molecular dynamics;mutant;Mutate;Mutation;Natural Immunity;Nerve Degeneration;Nervous System;neurotransmission;novel;Organ;organ regeneration;Orphan;pathogen;Pathology;Pathway interactions;Phenotype;Physiological;Physiology;Plants;predictive modeling;Property;Proteins;Protocols documentation;Public Health;receptor;receptor function;Research;Retinal Dystrophy;Role;Schizophrenia;Sexual Reproduction;Signal Transduction;Specificity;Speed;Stress;Structure;Structure-Activity Relationship;Synaptic Transmission;System;transcriptomics;Validation

PROJECT_TITLE: Merging Signaling with Structure: Functions and Mechanisms of Plant Glutamate Receptor Ion Channels, and their implications for the evolution of aminoacid based ion-signaling systems


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

ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

PHR: NARRATIVE Bacterial natural products are small organic molecules that are synthesized and released into the environment where they carry out a number of functions, including chemical warfare against competing organisms or communication with host cells. Recently, we have learned that only a small fraction of these natural products can be accessed by conventional methods and that the human microbiome is an especially intriguing source of small molecules that could have important impacts on health and disease. In this research proposal, we tackle both unresolved issues by applying new methods for the discovery and characterization of these hard-to-find or `cryptic' natural products, especially those in the human microbiome, and by expanding the chemical space and functional scope of microbial natural products.

PI_NAMEs: SEYEDSAYAMDOST, MOHAMMAD R (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Address;Anabolism;Antibiotics;Back;Bacteria;Bacterial Genome;Bacterial natural products;Biogenesis;Bioinformatics;Biology;Cells;Chemical Warfare;Chemicals;Chemistry;Collection;Communication;Complex;Dedications;Disease;Dose;Environment;Enzymatic Biochemistry;Enzymes;Genes;Genome;Genomics;Health;holistic approach;Human Microbiome;human microbiota;insight;Learning;Light;Maps;Metabolism;metalloenzyme;Methods;microbial;Microbial natural product;Microbial Physiology;microbiome;Natural Products;Natural Source;novel;Organism;Pathway interactions;peptide natural products;Play;Production;Protocols documentation;Reaction;Research;Research Proposals;Ribosomes;Role;secondary metabolite;Selenium;small molecule;Source;Structure;Therapeutic Uses;Virulence Factors;Vision;Work

PROJECT_TITLE: From Genes to Molecules and Back: Expanding the Chemical Space of Microbial and Microbiome Natural Products


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: College Station

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

PHR: Determining the mechanisms of extracellular vesicle release, function, and clearance Project Narrative Cells release and take up extracellular vesicles during normal development as well as disease, but the in vivo functions of extracellular vesicles are still unclear. This work aims to define how extracellular vesicle budding is regulated, identify how they are processed after uptake, and determine their signaling and functional roles. Our findings will provide fundamental knowledge to design approaches to induce biomarker production, develop efficient drug delivery methods, and influence diseases from inflammation to cancer metastasis to viral spread.

PI_NAMEs: WEHMAN, ANN M (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Autophagocytosis;Behavior;Binding;Biogenesis;Biological;Biological Assay;Biological Markers;Biological Models;Biology;Caenorhabditis elegans;Cell division;Cell fusion;Cell membrane;Cell Physiology;Cells;design;Development;diagnostic biomarker;Disease;Disease Progression;Drug Delivery Systems;Drug Targeting;extracellular vesicles;gene discovery;Genetic;Genetic Screening;Goals;Homeostasis;Human;Image;Immune response;immunoregulation;in vivo;Individual;Inflammation;insight;interest;Knowledge;Label;Lipids;Malignant Neoplasms;Membrane;Metabolism;Methods;Microscopy;Molecular;Neoplasm Metastasis;novel;Optics;Pathway interactions;Phagocytes;Phagocytosis;Phagosomes;Phosphatidylethanolamine;Process;Production;Proteins;Regulation;Role;Signal Transduction;Techniques;tool;uptake;Vesicle;vesicular release;Viral;Virus;Vision;Work