NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Neurosciences;Sleep Research;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Substance use disorder continues to be a major public health problem with an economic annual cost of over $700 billion in the United States alone and dramatic increases in overdose deaths to heroin, prescription opioids, and cocaine over the last few years. We propose that the development of effective treatments have been slowed, in part, by our lack of mechanistic understanding of circadian rhythms associated with drug craving, seeking, and relapse in substance use disorder. This research will discover how cue-induced cocaine seeking varies across the day and the extent to which this variation is driven by diurnal rhythms in the function of neural substrates (dopamine and acetylcholine systems) that underlie drug seeking, craving, and relapse.

PI_NAMEs: FERRIS, MARK J (contact)

PROJECT_TERMS: Acetylcholine;Animal Model;Animals;Architecture;Association Learning;Behavior;Behavior assessment;behavioral economics;Biological;Brain;brain based;cholinergic;circadian;Circadian Rhythms;Cocaine;cocaine related behaviors;cocaine reward;cocaine seeking;cocaine self-administration;Cocaine use disorder;Consumption;Corpus striatum structure;cost;craving;Cues;Darkness;Data;Dedications;Development;Diurnal Rhythm;Dopamine;Dopamine Receptor;dopamine transporter;drug abuse vulnerability;drug craving;drug of abuse;drug relapse;Economics;effective therapy;Exhibits;extracellular;Fiber;fluorescence imaging;Frequencies;Goals;Heroin;Hour;human model;Incentives;Individual;Interneurons;Learning;Light;Link;Measures;Mediating;mesolimbic system;Modeling;motivated behavior;Motivation;Muscarinic Acetylcholine Receptor;neural;Neurobiology;Neurophysiology - biologic function;Neurotransmitters;Nicotinic Receptors;non-drug;Nucleus Accumbens;optogenetics;Outcome;overdose death;Periodicity;Persons;Pharmaceutical Preparations;Phase;Photometry;Play;prescription opioid;Psychological reinforcement;Public Health;Publishing;Rattus;receptor;receptor function;Relapse;Replacement Therapy;Research;Research Proposals;response;restoration;Rewards;Role;Scanning;shift work;Signal Transduction;Sleep Wake Cycle;Stimulant;Substance Use Disorder;substance use treatment;System;Testing;therapeutic target;Time;United States;Variant;Work;World Health

PROJECT_TITLE: Circadian Rhythms and Cocaine Use Disorder

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: ITHACA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ZOOLOGY

ORG_FIPS: US

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: Microbial and host genetic factors contribute to the progression of intestinal diseases affecting millions in the USA growing body of evidence indicates that gut microbes influence intestinal stem cell activity, and thus play important roles in maintaining healthy gut function. From this proposed study, we will analyze in depth how conserved microbial characteristics (i.e. immunogenicity, virulence) and host pathways determine intestinal stem cell behavior in response to pathogenic versus non-pathogenic gut microbes.

PI_NAMEs: BUCHON, NICOLAS  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Address;Affect;Bacteria;Biological Models;cell behavior;Cell Differentiation process;Cell Lineage;cell type;Cells;Characteristics;Development;Disease;Disease Progression;Drosophila genus;Drosophila melanogaster;Enterocytes;Environment;epidemiology study;Epithelium;Equilibrium;Etiology;Exposure to;Face;Feedback;Food;Future;gastrointestinal epithelium;Gastrointestinal tract structure;gene network;Genes;Genetic;Genetic Models;Goals;gut homeostasis;gut microbes;Health;Homologous Gene;Immune;Immune response;Immune signaling;immunogenicity;immunoregulation;improved;Indigenous;Infection;Inflammatory;Ingestion;insight;Intestinal Diseases;intestinal epithelium;intestinal homeostasis;Intestines;Janus kinase;knock-down;Malignant Neoplasms;Mediating;Microbe;microbial;microbiome;microbiota;model organism;Molecular;Mus;novel therapeutics;Oral;Outcomes Research;pathogen;pathogenic microbe;Pathogenicity;Pathology;Pathway interactions;Pattern;Peptide Initiation Factors;Physiology;Play;Process;progenitor;Proliferating;response;Role;Shapes;Signal Pathway;Signal Transduction;stem cell differentiation;stem cell fate;stem cell proliferation;stem cells;Structure;Testing;tissue regeneration;Tissues;transcriptomics;Transducers;translational study;Virulence;Work;Xenobiotics

PROJECT_TITLE: Gut microbes modulate immune pathways in intestinal stem cells to influence their lineage

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-A(90)]


ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Data Science;Genetics;Human Genome;Infectious Diseases;Microbiome;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: BALTIMORE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Emerging data suggest that a woman’s vaginal microbiome can protect her from acquisition of sexually transmitted infections, pelvic inflammatory disease, and risk of pre-term delivery. This project will reveal how certain bacterial strains and concomitant host immune responses are associated with the recurrence bacterial vaginosis. This proposal will provide career development for the PI in clinical research, biostatistics, and epidemiology, and is relevant to the NIH’s mission to reduce infections and promote women’s health.

PI_NAMEs: HOLM, JOHANNA B. (contact)

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Affect;African Women;Age;aged;American;Anaerobic Bacteria;Antibiotic Therapy;Archives;Atopobium vaginae;Award;Bacteria;Bacterial Vaginosis;Basic Science;Behavioral;Big Data;Bioinformatics;Biological Markers;Biometry;candidate identification;candidate marker;career development;Case/Control Studies;Categories;certificate program;cervicovaginal;Clinical;clinical diagnosis;Clinical Research;clinical translation;Communities;complex data;Data;data integration;data modeling;data reduction;Diagnosis;Ecology;Epidemiologic Methods;Epidemiology;epidemiology study;Ethnic Origin;Evaluation;Funding;Future;Genes;genome sciences;Goals;Grant;Health;HIV;Hygiene;Immune response;Immune Targeting;Immunologic Markers;improved;Infection;Infertility;Inflammatory;insight;Intervention;intraamniotic infection;K-Series Research Career Programs;Lactobacillus;Lavage;Learning;Life Style;Longitudinal Studies;machine learning method;Maryland;medical schools;Mentors;metabolome;metabolomics;metagenome;Metagenomics;Methods;microbial;microbiome;Mission;model development;Modeling;Molecular;Multiomic Data;multiple omics;novel;Outcome;Participant;Pelvic Inflammatory Disease;personalized medicine;Predisposition;Premature Birth;Prognostic Factor;prognostic indicator;programs;Quality of life;Race;Recommendation;Recurrence;Reporting;reproductive;Research;Research Design;Research Personnel;research study;Research Support;Resources;Risk;Sampling;Scientist;screening;Sex Behavior;Sexually Transmitted Diseases;Source;Statistical Models;supervised learning;Symptoms;targeted treatment;therapeutic target;tool;Training;Translating;United States National Institutes of Health;Universities;Vagina;vaginal microbiome;vaginal microbiota;Visit;Woman;Women's Health;women's reproductive health;Work

PROJECT_TITLE: Integrating multi-omics data: Modeling biomarkers and mechanisms to reduce bacterial vaginosis recurrence

STUDY_SECTION: MID

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Tuberculosis;Tuberculosis Vaccine;Vaccine Related

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Adjuvants incorporated into vaccine formulations have a major impact on vaccine efficacy via modulating and prolonging host immune responses; however, our understanding of their underlying mechanism(s) of action in driving specific immune parameters is incomplete. Thus, defining the mechanisms of action of combination adjuvants that generate potent trained immunity and protective Th1/Th17 responses are the overall goals of this proposal. Dissecting the mechanisms of combination adjuvants-mediated immunity as described in this proposal, will have a broad impact on development of vaccines for many infectious diseases, including tuberculosis.

PI_NAMEs: DIVANGAHI, MAZIAR ;KAUSHAL, DEEPAK ;KHADER, SHABAANA A. (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;adaptive immune response;Adjuvant;Agonist;Attenuated Vaccines;Automobile Driving;beta-Glucans;Biological Models;Communicable Diseases;Data;dectin 1;effector T cell;Epigenetic Process;Goals;Health;Helper-Inducer T-Lymphocyte;Hematopoietic stem cells;Human;Immune;Immune response;Immunity;improved;in vitro Model;in vivo;Infection;Innate Immune Response;Licensing;Longevity;Lymphoid;Macaca;Macaca mulatta;Macrophage;Macrophage Activation;Malaria;Maps;Mediating;Memory;metabolic profile;Modeling;monocyte;mouse model;Multipotent Stem Cells;Mus;Mycobacterium bovis;Mycobacterium tuberculosis;Myelogenous;nanoemulsion;Natural Immunity;novel;Outcome;pathogen;Pathway interactions;Pattern recognition receptor;Peripheral Blood Mononuclear Cell;Phenotype;Population;pre-clinical;prevent;progenitor;protective efficacy;Reporter;Resistance;response;T cell differentiation;Testing;TLR7 gene;Training;Translating;Tuberculosis;Tuberculosis Vaccines;Vaccination;vaccine development;vaccine efficacy;vaccine formulation;vaccine-induced immunity;Vaccines

PROJECT_TITLE: Targeting trained immunity and Th1/Th17 axis with combination adjuvants


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: WORCESTER

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project Narrative Cryptococcosis, due to infection by the encapsulated yeasts C. neoformans and C. gattii, is the most common etiological agent of culture-positive meningitis. Nearly 200,000 people, most of whom are HIV-infected, die from this disease annually. The proposed research addresses a global public health need for a cryptococcal vaccine by using carefully designed mouse and human studies to develop a subunit multiantigen vaccine suitable for eventual human testing.

PI_NAMEs: LEVITZ, STUART MICHAEL (contact)

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Address;Adjuvant;Antibodies;Antigens;Area;arm;B-Lymphocytes;capsule;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cessation of life;Clinical Trials;Cryptococcal Meningitis;Cryptococcosis;Cryptococcus;Cryptococcus gattii;Cryptococcus neoformans;Data;Data Protection;design;Development;Disease;Encapsulated;Escherichia coli;Etiology;experimental study;Flow Cytometry;follow-up;Funding;fungus;gain of function;Genetic Variation;global health;Goals;Grant;Helper-Inducer T-Lymphocyte;HIV;HLA Antigens;Host Defense;Human;Immune response;Immune system;immunogenicity;in vivo;Inbred Strains Mice;Infection;insight;Lead;loss of function;Lung;manufacture;Mediating;Memory;Meningitis;Modeling;mouse model;Mus;Patients;Peripheral Blood Mononuclear Cell;Persons;Phase;Population;Population Heterogeneity;Populations at Risk;pre-clinical;preclinical development;protective efficacy;Proteins;Public Health;Recombinants;Research;response;Risk Factors;Role;Sister;Subunit Vaccines;System;T cell response;T-Lymphocyte;Testing;tissue resident memory T cell;Transplant Recipients;Vaccination;Vaccine Antigen;vaccine candidate;vaccine evaluation;vaccine formulation;Vaccines;Virulent;Work;Yeasts

PROJECT_TITLE: A subunit Cryptococcus vaccine

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Accurate and scalable interpretation of genomic variation is a critical component to realize the full potential of high-throughput sequencing in human genetics and genomic medicine. My lab is focused on developing new computational methods to predict functional impact of genomic variation and to integrate multi-modal genomic data sets in genetic analysis by machine learning. These methods will improve the utility of genome sequencing and functional genomics data and enable new discoveries in genetic studies of human diseases and clinical diagnosis.

PI_NAMEs: SHEN, YUFENG  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Amino Acid Sequence;Area;bioinformatics tool;Biological;cell type;Cells;Clinical;clinical diagnosis;clinical practice;Code;Collaborations;Computing Methodologies;Copy Number Polymorphism;Data;deep learning;deep neural network;design;Development;developmental disease;Diagnostic;Disease;disease diagnosis;disease model;Etiology;exome sequencing;Feedback;functional genomics;gene discovery;Genetic;genetic analysis;Genetic Diseases;Genetic Medicine;Genetic Research;Genetic study;genetic testing;genetic variant;Genetic Variation;Genome;genome sequencing;genome-wide;genomic data;Genomic medicine;genomic variation;Genomics;High-Throughput Nucleotide Sequencing;Human;human disease;Human Genetics;improved;Individual;insight;Intuition;Knowledge;Learning;Machine Learning;machine learning model;Malignant Neoplasms;Medical Genetics;Methods;Modeling;Modernization;Molecular;Molecular Profiling;mosaic variant;multimodality;novel;Population;predictive modeling;protein structure;Proteins;Rare Diseases;rare variant;Research;research study;risk variant;Role;tool;Variant;variant of unknown significance

PROJECT_TITLE: Computational methods to interpret genomic variation and integrate functional genomics data in genetic analysis of human diseases

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: Newark

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: Narrative. Cells (including our own) sense and respond to changes in their environment via a variety of cell-surface receptors, which are the target of a majority of pharmaceuticals. Understanding how these receptors function — in the context of their native cellular membranes — is both fundamental and of use for improved pharmaceutical design. The proposed work combines computer simulations and experimental measurements to study how the membrane influences signaling of a broad and important class of cell surface receptors called G-protein coupled receptors.

PI_NAMEs: LYMAN, EDWARD RAY (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: ADORA2A gene;Biological Models;Cell membrane;Cell Surface Receptors;Cells;Cellular Membrane;Charge;Complex;Computer Simulation;design;Environment;Explosion;Family;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Human;improved;Learning;lipidomics;Lipids;Measurement;member;Membrane;Membrane Proteins;Modeling;Molecular Conformation;Pharmacologic Substance;Physiological;receptor;receptor function;Regulation;Reporting;Signal Transduction;simulation;Structure;Surveys;Thermodynamics;Tissues;Work

PROJECT_TITLE: Lipid dependent GPCR signaling: Thermodynamics and mechanisms

STUDY_SECTION: MRAE

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


NIH_SPENDING_CATS: Lung;Pulmonary Fibrosis

ORG_CITY: HERSHEY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: Project Narrative Our research project aims to understand how STIM proteins and Orai proteins in our cells contribute to the development of fibrosis, a common problem in many chronic inflammatory diseases. By studying these proteins, we hope to uncover new insights into the disease mechanisms and develop targeted strategies to combat fibrosis. Ultimately, this research has the potential to improve public health by providing new treatments and interventions for patients suffering from fibrosis and related conditions.

PI_NAMEs: ZHOU, YANDONG  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Address;Animal Model;Biological Models;Borates;Calcium Signaling;cell growth;Cell Line;Cell membrane;Cell model;Cell Physiology;Cells;Chronic Disease;chronic inflammatory disease;combat;Coupling;Development;Disease;Dysplasia;Endoplasmic Reticulum;Fibrosis;Gene Deletion;Generations;Genetic;Genetic Transcription;Goals;Growth;Human;idiopathic pulmonary fibrosis;Imaging technology;immunodeficiency;Immunologics;improved;insight;Intervention;kidney fibrosis;Lead;loss of function;Malignant Neoplasms;Mediating;Mediation;Molecular;Monitor;Morbidity - disease rate;Muscle;Muscle Weakness;Mutation;neural;novel;optogenetics;Pathologic;Pathway interactions;Patients;Peptides;pharmacologic;Process;programs;protein activation;Protein Isoforms;Proteins;Public Health;Research;Research Project Grants;Role;sensor;Signal Pathway;Signal Transduction;Skin;small molecule;STIM1 gene;Structure;Temperature;Tissues;tool

PROJECT_TITLE: The Molecular Basis of the STIM/Orai Signaling Pathway

STUDY_SECTION: MRAC

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NEW HAVEN

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Narrative This project is to develop and evaluate a set of statistically powerful and biologically plausible analytical methods via leveraging the power of multimodal neuroimaging endophenotypes to identify new genetic markers for Alzheimer's disease (AD) risk and progression as well as quantify the pathological mechanism among genetics, brain activities and disease behaviors. Completion of the project will address critical analytical barriers in brain imaging genetics, offer new insights into genetic and neurobiological mechanisms of AD, and subsequently impact neurological and psychiatric research in general and benefit public health outcomes.

PI_NAMEs: ZHAO, YIZE  (contact)

PROGRAM_OFFICER_NAME: BENNANI-BAITI, MICHAEL

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;American;analytical method;Atlases;base;Bayesian Modeling;Behavior;Biological;Biological Markers;biomarker discovery;biomarker identification;Biomedical Research;Brain;brain based;Brain imaging;Clinical;clinical diagnosis;cohort;Complex;computerized tools;Data Analyses;Development;Diagnosis;Disease;disease model;Disease Progression;Disease susceptibility;Dissection;drug development;endophenotype;Etiology;Evaluation;Genetic;genetic analysis;genetic association;Genetic Diseases;Genetic Markers;Genetic study;Genetic Transcription;genetic variant;Genetic Variation;genome wide association study;Goals;Heritability;Image;imaging biomarker;imaging genetics;imaging modality;Individual;innovation;insight;Investigation;Link;Maps;Mediating;Mediation;Methods;Multimodal Imaging;multimodal neuroimaging;multimodality;Nervous System Disorder;neurobiological mechanism;neuroimaging;Neurologic;novel;Outcome;Pathogenesis;Pathologic;Pathway interactions;Persons;Play;pleiotropism;Prevention;Process;Public Health;quantitative imaging;Research;Risk;Role;Signal Transduction;simulation;Statistical Methods;Symptoms;trait;user-friendly

PROJECT_TITLE: Novel integrative imaging genetics analysis for Alzheimer's disease riskand progression

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: DURHAM

ORG_DEPT: CHEMISTRY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Metal–protein interactions are essential for the function of at least one-third to one-half of all proteins in cells. The incorrect binding of a metal to a protein, however, can lead to harmful effects on the cell, including toxicity. The research proposed here is designed to identify the protein targets of metal stress and elucidate molecular mechanisms that lead to toxicity. The outcomes will advance our understanding of how proteins across the proteome respond to exposure to excess levels of biologically relevant Zn and Cu, with important implications for developing pharmacological agents to leverage metal stress against microbial pathogens and cancer.

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

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Address;Affect;anti-cancer;antimicrobial;Binding;Biological;Biological Assay;biophysical properties;Biophysics;cancer cell;Cancer cell line;Candida albicans;Cell Line;Cell Physiology;Cell Separation;Cell Survival;cell type;Cells;Chemicals;cofactor;Collaborations;Copper;Data;design;Development;Environment;Escherichia coli;Escherichia coli Proteins;Event;experience;Exposure to;Foundations;Functional disorder;Global Change;Goals;Growth;Homeostasis;Human;Immune system;In Vitro;Ionophores;Ions;Laboratories;Link;Location;Malignant Neoplasms;Mass Spectrum Analysis;Measurement;Measures;Metabolism;Metal exposure;Metalloproteins;Metals;Methodological Studies;Methods;microbial;Molecular;Monitor;Neurodegenerative Disorders;Nutrient;Nutritional Requirements;Organism;Outcome;Outcome Study;pathogen;pathogenic microbe;Pathway interactions;pharmacologic;Physiologic pulse;Precipitation;Predisposition;prostate cancer cell;protein folding;protein function;protein misfolding;Proteins;Proteolysis;Proteome;Proteomics;Proxy;Publishing;Research;Signal Transduction;Stress;Techniques;Testing;Therapeutic;Time;tool;Toxic effect;Trace Elements;trafficking;Translations;Work

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


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Genetics

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative Microbes employ hundreds of diverse defense systems to provide protection from mobile genetic elements such as viruses, and studying these systems is important for understanding immune system evolution, the implications of phage therapy, and the discovery of new molecular tools such as restriction enzymes and CRISPR-Cas systems. We propose several goals to address critical knowledge gaps in CRISPR-Cas biology and its newfound relationship with cell membrane function. Our goals will help us understand how RNA-targeting containing CRISPR-Cas systems and their membrane-associated proteins function together to enhance viral defense with an eye towards the discovery of new molecular tools.

PI_NAMEs: O'CONNELL, MITCHELL  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Address;Affect;Bacteriophages;Behavior;Biochemical;Biology;biophysical techniques;Cell membrane;Clustered Regularly Interspaced Short Palindromic Repeats;Communication;Coupled;Data;Databases;Enzymes;Evolution;experimental study;Family;fascinate;Genes;Genetic;Genetic Transcription;Goals;Hypothetical Protein;Immune response;Immune system;Knowledge;Ligands;Membrane;Membrane Potentials;Membrane Proteins;Metabolism;Microbe;Mobile Genetic Elements;Molecular;Nucleic Acids;Pore Proteins;protein function;Proteins;Research;restriction enzyme;RNA;Role;Structure;synergism;System;Technology;technology development;tool;transcriptome sequencing;Viral;Virus;Virus Diseases;Work

PROJECT_TITLE: Molecular mechanisms of RNA-targeting CRISPR-Cas systems and their membrane-associated accessory proteins

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Infectious Diseases;Natural Products;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: GAINESVILLE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative. New small molecule probes are critical to illuminating biology in ways that can be harnessed for the treatment of human disease. Our group is developing natural product-inspired chemical biology platforms that integrate chemical synthesis with sophisticated biological investigations to discover new phenomena relevant to priority disease areas (e.g., antibiotic-tolerant biofilm infections, cancer, opioid addiction). During this award, we will (1) expand our tryptoline ring distortion platform to generate new complex and diverse compounds, and perform an array of biological studies to explore their re-engineered activities, and (2) develop robust strategies to expand the spectrum of activity for halogenated phenazine biofilm-eradicating agents to address the underlying cause of chronic and recurring bacterial infections.

PI_NAMEs: HUIGENS, ROBERT WILLIAM (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Address;Amines;Anti-Bacterial Agents;antibiotic tolerance;Antibiotics;Area;Award;Bacteria;bacterial community;Bacterial Infections;Biological;Biological Process;Biology;Biomedical Engineering;Cell Survival;Cells;Cessation of life;chemical synthesis;Chemicals;Chronic;Complex;cycloaddition;Development;Disease;Engineering;Expeditions;experimental study;Future;Guidelines;halogenation;Health;Human;human disease;Indole Alkaloids;Infection;insight;Investigation;Malaria;Malignant Neoplasms;Microbial Biofilms;natural product inspired;Natural Products;Opiate Addiction;Parents;pathogen;pathogenic bacteria;persistent bacterial infection;Phenazines;Reaction;Recurrence;scaffold;Series;small molecule;Surface;System;Technology;Transcript;United States

PROJECT_TITLE: Indole Alkaloids and Halogenated Phenazines: Platforms for Discovery

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cardiovascular;Digestive Diseases;Nutrition;Pancreatic Cancer;Rare Diseases;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE The proposed research is focused on studying molecular interactions regulating the calcium- activated chloride channel TMEM16A, which mediates diverse processes in humans ranging from regulating blood flow through the cardiovascular system to the excitability of neurons. The goal of this research is to uncover the mechanisms of how lipids created in the cell and acquired through diet, and physiologic processes regulate channel activity. It is relevant to public health because understanding how these molecular interactions are disrupted in disease will enable better therapeutic design for the wide array of pathologies associated with TMEM16A channels.

PI_NAMEs: CARLSON, ANNE E (contact)

PROJECT_TERMS: African;Arachidonic Acids;Binding;Blood flow;Calcium;Cardiac;Cardiovascular system;Cells;Chloride Channels;Chlorides;craniofacial;design;Development;Diet;Disease;egg;Electrolyte Balance;Embryo;Environment;Event;experimental study;Fertilization;Goals;Human;innovation;Innovative Therapy;Ion Channel;Knockout Mice;Knowledge;Lipids;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Mediating;Membrane;Membrane Lipids;Molecular;Mutation;neuronal excitability;Neurons;Pathology;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phospholipids;Physiological;Physiological Processes;Polyunsaturated Fatty Acids;Process;Public Health;Regulation;Research;Sensory;Signal Transduction;Therapeutic;uterine contractility;Xenopus;Xenopus laevis

PROJECT_TITLE: Physiologic mechanisms of ion channel regulation


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Congenital Structural Anomalies;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will study and engineer new principles of organ development toward building functional human tissue models. Once these new principles are applied, they will spur significant advances in tissue engineering. The proposed research is especially relevant to one of the NIH’s 2021-2025 strategic plan goals, which specifically highlights new cell engineering and bioengineering approaches to building human tissues for disease modeling that will contribute to reducing illness and disability.

PI_NAMEs: HUGHES, ALEX  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Adult;Area;Artificial tissue;Automobile Driving;Behavior;Biological;Biological Models;Biomedical Engineering;burden of illness;Cells;cellular engineering;Congenital Abnormality;Development;disability;Disease;disease model;Drug Targeting;engineered stem cells;Engineering;epithelial stem cell;Epithelium;Funding;Goals;human tissue;Image;in vivo;innovation;intercellular communication;Kidney;Lung;Maintenance;Malignant Neoplasms;Mammary gland;Maps;Mechanics;Medical;Microfluidics;Modeling;Modernization;Morphogenesis;optogenetics;Organ;organ growth;Organogenesis;Organoids;Pathway interactions;Pattern;planar cell polarity;Play;Process;Prostate;Public Health;Regulation;Research;research vision;Science;screening;Shapes;Single-Stranded DNA;stem cell niche;Strategic Planning;Structure;Technology;Tissue Engineering;Tissue Model;tissue support frame;Tissues;United States National Institutes of Health;Work

PROJECT_TITLE: A developmental engineering toolbox for controlled epithelial morphogenesis

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


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_DEPT: GENETICS

PHR: Narrative In animal development the single-celled zygote divides, and its progeny differentiate to produce an incredible diversity of cell types, but we still have much to learn about the molecular changes that occur in cells as they divide and differentiate. This project uses cutting-edge microscopy and genomics tools to study this process in the embryo of the nematode C. elegans, which uses many of the same genes as humans to specify its cell types and allows for rapid experimentation. We will focus on how regulatory genes work in different combinations to allow cells to make different decisions during development, how errors in these decisions are avoided, and how the timing of developmental events is controlled.

PI_NAMEs: MURRAY, JOHN ISAAC (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Animals;Atlases;Caenorhabditis;Caenorhabditis elegans;cell type;Cells;Complex;critical developmental period;Databases;Development;Embryo;embryo cell;Event;gastrulation;Gene Expression;Genes;Genetic Transcription;genome-wide;genomic tools;Human;improved;Learning;Maps;Measures;Methods;Microscopy;Molecular;Nematoda;Organism;Pathway interactions;Pattern;Phenotype;Process;protein expression;Regulation;Regulator Genes;Reporter;Resources;reverse genetics;RNA;single-cell RNA sequencing;Specific qualifier value;System;tool;transcription factor;Whole Organism;Work;zygote

PROJECT_TITLE: Decoding lineage and fate specification in the C. elegans embryo


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Patient Safety

ORG_DEPT: ANESTHESIOLOGY

PHR: Project Narrative General anesthetics are commonly used to induce unconsciousness during surgery, but they have been reported to cause neuronal cell death and cognitive dysfunction. Our research is directed at understanding the underlying mechanisms of these adverse effects at the circuitry, cellular, and molecular levels, with the goal to develop targeted strategies that can help mitigate perioperative neurocognitive disorder.

PI_NAMEs: YANG, GUANG  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Absence of pain sensation;Adverse effects;Amnesia;Anesthesia procedures;Anesthetics;Astrocytes;Attention;Blood - brain barrier anatomy;Brain;brain health;cognitive function;Data;Gene Delivery;General anesthetic drugs;Genetic;Goals;Hippocampus;Hyperactivity;Immobilization;Impaired cognition;in vivo calcium imaging;Knowledge;Laboratories;long term memory;Memory;Memory Loss;Molecular;neonate;neural circuit;Neurocognitive;Neurocognitive Deficit;neurocognitive disorder;Neuroglia;Neuroimmune;neuron loss;Neurons;neurophysiology;novel;older adult;Operative Surgical Procedures;Perioperative;Perioperative Care;post-operative cognitive dysfunction;Prefrontal Cortex;Process;Proteins;receptor;Reporting;Research;response;Role;Sleep;Synapses;synaptogenesis;Testing;Unconscious State;Virus;Vulnerable Populations

PROJECT_TITLE: The roles of anesthetics and neuroimmune interactions in postoperative cognitive dysfunction

STUDY_SECTION: MRAD

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


NIH_SPENDING_CATS: Neurosciences

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Serotonin (5-hydroxytryptamine, 5-HT) mediates human physiology as diverse as cognition, gut motility, and endocrine function, and 5-HT receptors and transporters are thus targeted by both illicit and therapeutic drugs. While structural work has provided limited mechanistic insight into the function of this complex system, the precise signaling mechanisms of serotonin receptors via different transducers are poorly understood and off- target effects of serotonergic drugs at understudied serotonin transporters have not been systemically characterized. Combining cryo-EM, molecular pharmacology, and structure-aided drug discovery, we will thus elucidate fundamental mechanisms of serotonin signaling and transport, and generate novel chemical probes towards exploring the therapeutic potential of distinct signaling pathways and modulation of understudied transporters.

PI_NAMEs: WACKER, DANIEL  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;Affect;Biochemical;Biology;Cardiovascular system;Chemicals;Cognition;Complex;Cryoelectron Microscopy;Development;Drug Binding Site;drug discovery;Drug Interactions;Drug Prescriptions;Endocrine;Family;Goals;GTP-Binding Proteins;Human;In Vitro;in vivo;innovation;insight;Mediating;Medical;medication safety;Molecular;Molecular Conformation;molecular scale;Molecular Target;Moods;Motility;new therapeutic target;novel;Organic Cation Transporter;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological;Physiology;Property;receptor;Receptor Signaling;Reporting;Serotonin;Serotonin Agents;serotonin receptor;Serotonin Receptor 5-HT1A;serotonin transporter;side effect;Signal Pathway;Signal Transduction;Structure;System;Therapeutic;tool;Transducers;vesicular monoamine transporter 2;Work

PROJECT_TITLE: Structural Studies and Drug Discovery Illuminate Serotonin Pharmacology


NIH_SPENDING_CATS: Machine Learning and Artificial Intelligence

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Project Narrative This proposal is focused on the development and application of novel computational methods to map the free energy and fitness landscapes of proteins, with a focus on protein kinases (PKs) which are involved in many cellular signaling pathways. Our goal is to construct an atlas representing key features of the conformational landscapes of PKs using sequence co-variation models and molecular dynamics simulations in an integrated way. This information provides a foundation for understanding the molecular basis for their biological function, how and why mutations cause disease states, and provides insights into the design of therapeutics.

PI_NAMEs: LEVY, RONALD  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Affect;Affinity;anti-cancer therapeutic;Atlases;Base Sequence;Binding;Binding Proteins;Binding Sites;Biological;Biological Process;Chemicals;Communities;Complex;Computing Methodologies;Cryoelectron Microscopy;Cytoplasm;density;design;Development;Disease;fitness;Foundations;Free Energy;G-Protein-Coupled Receptors;Goals;HIV;improved;insight;interfacial;Ligands;Machine Learning;machine learning method;Maps;Membrane Proteins;Methods;Modeling;Molecular;Molecular Conformation;molecular dynamics;molecular recognition;Mutation;novel;Pathway interactions;Peptides;Phosphotransferases;Positioning Attribute;protein complex;Protein Family;Protein Kinase;Proteins;sequence learning;Signal Pathway;Site;small molecule;Solvents;Specificity;Statistical Mechanics;structural biology;Structure;Therapeutic;therapeutic target;Thermodynamics;tool;Water;Work

PROJECT_TITLE: Mapping Fitness & Free Energy Landscapes of Proteins


NIH_SPENDING_CATS: Aging;Genetics;Human Genome

ORG_CITY: KNOXVILLE

ORG_NAME: UNIVERSITY OF TENNESSEE KNOXVILLE

ORG_STATE: TN

PHR: Project Narrative The 3D spatial organization of the human genome inside the nucleus plays a role in gene regulation, DNA replication, and repair, and is often disrupted in disease, but less is known about how this structure interacts with physical disruptions to the cell. This research program will examine how different stressors, such as constricted cell migration, nuclear lamin mutation, and DNA damage affect chromosome structure and gene expression, and how changes in chromosome structure relate to changes in cellular function. Our results will help build a framework in which we can understand, and eventually predict, the impact of certain treatments or conditions on human cells based on their genome structure, opening avenues for future chromosome structure-based disease diagnosis and treatment.

PI_NAMEs: MCCORD, RACHEL PATTON (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 3-Dimensional;Affect;aging related disease;Architecture;Behavior;Biological Process;cancer cell;Cardiomyopathies;cell motility;Cell Nucleus;Cell Physiology;Cells;Chromosome abnormality;chromosome conformation capture;Chromosome Structures;Chromosomes;Chronic;Computer Analysis;Computer Models;constriction;Data Analyses;data integration;Diagnostic;Disease;disease diagnosis;DNA biosynthesis;DNA Damage;DNA Repair;Euchromatin;Family;Funding;Future;Gene Expression;Gene Expression Regulation;Genome;Goals;Health;Heterochromatin;Heterogeneity;Hi-C;Human;Human Chromosomes;Human Genome;Image;innovation;Lamin Type A;Lamins;Malignant Neoplasms;Microscopic;migration;Molecular;Molecular Conformation;Mutation;Nuclear Lamin;Patients;Pattern;Phenotype;physical property;physical state;Population;Positioning Attribute;Premature aging syndrome;Progeria;programs;repaired;Research;response;Role;segregation;single cell genomics;Stress;stressor;Structure;System;Techniques;Work

PROJECT_TITLE: Folding, Misfolding, and Unfolding: How human 3D genome structure resists, adapts, or succumbs to physical stresses in health and disease

STUDY_SECTION: MRAA

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


ORG_CITY: ATHENS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative Cancer cells often show evidence of chromosome breakage, changes in DNA methylation and activation of transposable elements. In this proposal we will test the hypothesis that chromosome breakage can lead directly to alterations in DNA methylation and transposon activation.

PI_NAMEs: DAWE, R. KELLY (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Animals;Biological Assay;cancer cell;Centromere;ChIP-seq;Chromosome abnormality;Chromosome Arm;Chromosome Breakage;Chromosomes;Complex;Copy Number Polymorphism;demethylation;Dissociation;DNA;DNA Methylation;DNA Transposable Elements;DNA Transposons;Epigenetic Process;epigenomics;Eukaryota;Event;fungus;Gametogenesis;Generations;Genetic;Genetic Induction;Genome;genome-wide;Genomics;Heterochromatin;insight;Lead;Maize;Malignant Neoplasms;Modeling;Molecular;Mutation;Plants;Reaction;Research;response;Sampling;Shock;System;Testing;Transgenes;transmission process;tumor progression;Work

PROJECT_TITLE: Epigenomic consequences of breakage-fusion-bridge cycling


ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Bioactive immune-modulating nanodrug for sepsis treatment Project Narrative Sepsis, commonly caused by severe trauma and infection, results in dysregulated inflammation leading to tissue damage/organ failure, which unfortunately lacks effective pharmacological interventions in the clinic to improve patient survival. In recent years, my lab has developed a novel unique telodendrimer nanoplatform for both therapeutic delivery and versatile active immune modulation. In the next five years, my research program will focus on the development of the next generation of TD nanodrug for (1) active fine-tuned inflammation control against a broad spectrum of immune stimuli via pleiotropic mechanisms; (2) control of both hyperinflammation and immune suppression in sepsis by blocking cytokine storm and pyroptosis; and (3) delivery of vital antibiotics for simultaneous control of MDR infection and inflammation in sepsis.

PI_NAMEs: LUO, JUNTAO  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Anti-Inflammatory Agents;Antibiotics;Autoimmune Diseases;Cells;Cessation of life;Charge;chronic wound;Clinic;Clinical;Communication;Complex;Critical Illness;cytokine;cytokine release syndrome;design;Development;Disease;Dose;Encapsulated;Endotoxins;Gram-Negative Bacteria;Gram-Positive Bacteria;Hydrophobicity;Immune;Immune response;Immunologic Stimulation;immunomodulatory therapies;immunoregulation;Immunosuppression;improved;Infection;Infection Control;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Bowel Diseases;inhibitor;Injections;innovation;Intervention;Malignant Neoplasms;Molecular;mouse model;multimodality;Multiple Organ Failure;nanocarrier;nanodrug;nanomedicine;nanotechnology platform;nanotherapeutic;Nanotrap;Nature;next generation;novel;Organ failure;pathogen;Pathogenesis;Pathway interactions;Patients;Pattern;Perioperative;Pharmaceutical Preparations;pharmacologic;Plant Resins;prevent;programs;Publications;Reporting;Research;Resolution;Rheumatoid Arthritis;Risk;secondary infection;Sepsis;Series;Signal Transduction;Steroids;Stimulus;Structure;Systemic infection;Therapeutic;therapeutic target;Time;Tissues;TNF gene;Trauma;Traumatic injury


NIH_SPENDING_CATS: Cancer;Genetics

PHR: PROJECT NARRATIVE Selenoprotein K and selenoprotein S are related enzymes that use selenium to mitigate cellular stress. Understanding in detail their functions not only enhances our knowledge of how cells utilize selenium for protection but also uncovers the molecular reasons why the dysfunction of these proteins can lead to illnesses such as cancer, type 2 diabetes, and cardiovascular diseases.

PI_NAMEs: ROZOVSKY, SHARON  (contact)

PROJECT_TERMS: Affect;Binding;Binding Proteins;Biology;Calcium Signaling;Cancer Prognosis;Cardiovascular Diseases;Cell Nucleus;Cell Physiology;Cells;Cellular Stress;Client;Complex;cytokine;Diabetes Mellitus;Disease;Disparate;endoplasmic reticulum stress;Enzymes;experimental study;Family Dasypodidae;Functional disorder;Gene Expression;Genetic Transcription;Genetic Variation;Health;Human;Hydrophobicity;Immune response;in vivo;insight;Knowledge;Leucine Zippers;Location;Malignant Neoplasms;Membrane;Membrane Proteins;migration;Molecular;Non-Insulin-Dependent Diabetes Mellitus;Nuclear;Nucleotides;Oxidation-Reduction;palmitoylation;prevent;Process;protein complex;protein folding;protein transport;Proteins;Quality Control;Research;Resolution;response;Risk;Role;Selenium;selenoprotein;sensor;Signal Pathway;Signal Transduction;Site;Stress;structural biology;Surface;System;Testing;transcription factor;unnatural amino acids;Work

PROJECT_TITLE: Signaling, Sensing, and Enzymatic Roles of Disordered Selenoproteins


NIH_SPENDING_CATS: Biotechnology;Data Science;Genetic Testing;Genetics;Human Genome

ORG_CITY: MILWAUKEE

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE We develop the means to bring powerful computational tools from basic sciences to interpret the effects of genetic changes in a gene named SMARCA4. As genetic data are increasingly available, there is a great need for better tools to interpret their impact and enable more people to benefit from their genomic data. Our study is an innovative approach for its novel combination of computational tools that will provide a more comprehensive and context-aware interpretation than any existing approach, using large amounts of experimental data and showing how to enter the next generation of genomic data interpretation.

PI_NAMEs: ZIMMERMANN, MICHAEL T (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: 3-Dimensional;Affect;Awareness;Base Sequence;Basic Science;Benchmarking;Catalogs;Cells;Chromatin;chromatin remodeling;Clinical;Complex;computerized tools;Data;Data Analyses;Data Science;Development;Diagnosis;Disease;DNA Sequence;Enzymes;Epigenetic Process;Ethnic Origin;Future;gene product;Genes;Genetic;genetic disorder diagnosis;genetic information;Genetic Variation;Genome;genome sciences;genomic data;Genomics;Germ-Line Mutation;Goals;Guidelines;human disease;Human Genetics;improved;Individual;innovation;Knowledge;Malignant Neoplasms;Medical;Methodology;Methods;Mutation;Names;next generation;novel;Organ;Pathogenicity;Patients;Persons;Physiological;Physiology;Population;Procedures;Process;Proteins;Research;SMARCA4 gene;Somatic Mutation;System;Testing;Time;Tissues;tool;Work

PROJECT_TITLE: Advancing Genomic Interpretation for Chromatin Remodeling Enzymes


NIH_SPENDING_CATS: Machine Learning and Artificial Intelligence;Natural Products

PHR: PROJECT NARRATIVE  The proposal will develop analyses, tools, and methods, both computational and experimental, to achieve new, more effective reagents, catalysts, and reactions. New synthetic methods greatly increase access to new materials and pharmaceuticals that benefit society.

PI_NAMEs: KOZLOWSKI, MARISA C (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Area;bioactive natural products;Biomimetics;catalyst;Chemicals;Chemistry;Coupling;design;Development;Goals;graduate student;Hydrogen Bonding;improved;Industrialization;Investigation;large datasets;Libraries;machine learning method;Methods;Modeling;Molecular;natural product inspired;oxidation;Pattern;Pharmaceutical Chemistry;Pharmacologic Substance;Positioning Attribute;Problem Solving;Process;programs;Protocols documentation;Reaction;Reagent;Research;Resistance;Societies;Stream;Structure;tool;Training;wasting

PROJECT_TITLE: Computation and Development of New, Enabling Synthetic Methods


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE Despite the important role they play in shaping the transcriptome and proteome of cells, the mechanisms that dictate the ability of RNA binding proteins (RBPs) to perform different jobs in specialized cell types and respond to environmental stimuli remain unclear. My lab investigates how sensing of microbial components functionalizes RBPs to participate in the macrophage innate immune gene expression program. By illuminating the molecular mechanisms through which RBPs regulate the macrophage transcriptome, this work supports the mission of the NIGMS to understand the fundamental principles of living cells.

PI_NAMEs: PATRICK, KRISTIN LEIGH (contact)

PROJECT_TERMS: Alternative Splicing;Autoimmunity;Cell Nucleus;cell type;Cells;Cellular Stress;Chronic;cohort;Complex;cytokine release syndrome;Data;Disease;exosome;Family;fighting;Funding;Gene Expression;Gene Expression Regulation;Health;Heterogeneous-Nuclear Ribonucleoproteins;hnRNP-F;Human;Immune;Immune response;Immune System Diseases;Infection;Inflammation;Inflammatory;Innate Immune Response;insight;Investigation;Macrophage;Macrophage Activation;microbial;Mission;Molecular;National Institute of General Medical Sciences;novel;Nuclear;Nuclear RNA;Occupations;Organelles;Outcome;pathogen;Pathogen detection;Patients;Pattern;Phosphorylation;Physical condensation;Play;Polyadenylation;Post-Transcriptional Regulation;Post-Translational Protein Processing;programs;Proteome;Regulation;response;Ribonucleoproteins;Risk;RNA;RNA Editing;RNA Splicing;RNA-Binding Proteins;Role;Shapes;Stimulus;Stress;Therapeutic;Transcript;transcriptome;Untranslated RNA;Viral;Work

PROJECT_TITLE: Exploring the role of RNA binding proteins in post-transcriptional regulation of macrophage activation


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative Many human infectious and genetic diseases disrupt G protein pathways, which constitute a conserved eukaryotic signaling mechanism. The proposed research will employ a highly tractable system to provide a comprehensive understanding of the regulation of heterotrimeric G protein biochemistry and signaling by subunit phosphorylation and natural variation in G protein sequence, and will thus identify specific regulatory paradigms that strengthen or impair the G protein cycle, heterotrimer interactions, subcellular localization, and coupling with other proteins. Results obtained will identify new G protein conformations for therapeutics, and will distinguish disruptive and benign natural variants, thereby identifying conditions and opportunities wherein targeted interventions should and can be prioritized to repair dysregulated aspects of G protein signaling while simultaneously avoiding impairment of other G protein functions and phenotypes.

PI_NAMEs: ASSMANN, SARAH M (contact)

PROJECT_TERMS: Amino Acid Sequence;Arabidopsis;Benign;Biochemistry;Cells;Communicable Diseases;Complement;Coupling;Critical Pathways;dimer;Disease;Disease Outcome;Electrophysiology (science);G-Protein-Coupled Receptors;Genetic Diseases;Genetic Epistasis;genetic manipulation;genetic regulatory protein;Genome;Genotype;Goals;GTP-Binding Protein alpha Subunits, Gs;GTP-Binding Proteins;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Health;Heterotrimeric GTP-Binding Proteins;Heterozygote;Human;Image;Impairment;Inbreeding;Individual;Intervention;Laboratories;Ligand Binding;Medical;Membrane;Methods;Missense Mutation;Molecular;Molecular Conformation;molecular phenotype;Mouse-ear Cress;Mutation;Nature;Organism;Pathway interactions;Penetrance;phenome;Phenotype;Phosphorylation;Plant Model;Plants;Protein Biochemistry;Protein Conformation;protein function;Protein Subunits;Proteins;Regulation;repaired;Research;Science;Signal Pathway;Signal Transduction;Signaling Protein;Single Nucleotide Polymorphism;Site;System;Therapeutic;Variant;Whole Organism

PROJECT_TITLE: Phospho- and natural-variant regulation of heterotrimeric G protein signaling


PHR: Project Narrative Enzymes called protein kinases are important regulators of cellular responses to environmental cues, and their deregulation is a hallmark of multiple human diseases. We will study how a group of protein kinases called MAP kinases are themselves regulated, and how they effect changes in cell physiology. This research will help explain both beneficial and undesired effects of drugs targeting MAP kinases and may lead to improved strategies to treat disease.

PI_NAMEs: TURK, BENJAMIN E (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Architecture;Catalytic Domain;Cell Physiology;Complex;Cues;Disease;Docking;Drug Targeting;Enzymes;Eukaryota;extracellular;Feedback;human disease;improved;insight;Knowledge;Life;Mammals;MAPK8 gene;Mediating;MEKs;Methods;Mitogen-Activated Protein Kinases;Monomeric GTP-Binding Proteins;novel;Oncogenic;Output;p38 Mitogen Activated Protein Kinase;Pathway interactions;Phosphoric Monoester Hydrolases;Physiology;Protein Kinase;protein phosphatase 6;Regulation;Research;response;Role;screening;Signal Pathway;Signal Transduction;Specificity;Substrate Specificity;System;Yeasts

PROJECT_TITLE: Decoding mitogen-activated protein kinase signaling networks


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

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Diversity in the biomedical research workforce produces higher quality and more impactful science. Yet, there remains an unmet need to identify evidence-based interventions to improve the diversity of the biomedical research enterprise. The Promoting Diversity, Group Inclusion, and Equity (ProDiGIE) research program will comprehensively and systematically investigate and identify interventions to increase diversity across the physician-scientist career span from trainees to NIH-funded faculty.

PI_NAMEs: BOATRIGHT, DOWIN  (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Academic Medical Centers;Award;Biomedical Research;Black race;career;Clinical Medicine;Clinical Trials;Congresses;Equity;ethnic diversity;Evidence based intervention;Faculty;Fostering;Funding;Grant;improved;innovation;Intervention;Knowledge;Latinx;Medical Education;Physicians;Play;Population;programs;racial diversity;Research;Research Design;Role;Science;Scientist;success;Underrepresented Populations;United States;United States National Institutes of Health

PROJECT_TITLE: Physician-Scientist Research and Medical Education (PRIME) Program


NIH_SPENDING_CATS: Genetics;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Addition of carbohydrates to animal proteins (glycosylation) regulates many aspects of embryonic development and adult physiology, and results in a host of human diseases when impaired. The proposed studies aim to identify target proteins that mediate the effects of glycosylation and deglycosylation in developing animals and might provide a better understanding of the pathophysiology of glycosylation disorders.

PI_NAMEs: JAFAR-NEJAD, HAMED  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Adult;Alagille Syndrome;Animals;Biological;BMP4;Carbohydrates;Cell Culture Techniques;Cell Surface Proteins;cell type;Congenital disorders of glycosylation;Data;Development;Disease;Drosophila genus;Embryonic Development;Endoplasmic Reticulum;Enzymes;Experimental Genetics;fly;Functional disorder;Funding;Gene Mutation;Genes;glucosidase;Glycoproteins;glycosylation;Goals;Human;human disease;Impairment;insight;Intestines;Knowledge;loss of function;Mammals;Mediating;Metabolism;misfolded protein;Modeling;Modification;Molecular;mouse genetics;Muscular Dystrophies;Mutate;Mutation;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of General Medical Sciences;Natural Immunity;Notch Signaling Pathway;novel;novel therapeutic intervention;Organism;Pathogenicity;Pathway interactions;Peptide N-Glycosidase;Phenotype;Physiology;Play;Polysaccharides;Pre-Clinical Model;Process;Protein Glycosylation;Proteins;Publishing;Regulation;Reporting;Research;Research Design;RNA interference screen;Role;Signal Transduction;Structure;sugar;therapeutic target;Variant

PROJECT_TITLE: Roles of Glycosylation and Deglycosylation During Animal Development


ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: All healthy cells depend on a balanced cycle of making and turning over proteins. Our goal is to determine the mechanistic basis of how molecular machines involved in protein synthesis, folding, and unfolding work to perform their protein quality control functions. Our biochemical and structural studies will provide a structural framework that advances understanding of protein quality control machinery in the context of health and disease.

PI_NAMEs: SHEN, PETER  (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Adaptor Signaling Protein;Address;ATP phosphohydrolase;Biochemical;Cell Physiology;Cells;Complex;Cryoelectron Microscopy;Disease;Equilibrium;Functional disorder;Goals;Health;Image;insight;Life;Molecular Chaperones;Molecular Machines;Motion;Multienzyme Complexes;Phenotype;Protein Biosynthesis;protein folding;Proteins;Proteomics;proteostasis;Quality Control;Ribosomes;Stress;trafficking;Translating;Translations;Visualization;Work

PROJECT_TITLE: Visualizing the Mechanisms of Protein Quality Control


NIH_SPENDING_CATS: Pediatric

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narrative: This project addresses the fundamental question of how morphogenesis is controlled precisely during embryonic development. Such precision is required for normal development and function of multicellular tissues. Perturbations of morphogenetic processes can lead to embryonic lethality and diseases, including cancer.

PI_NAMEs: DI TALIA, STEFANO  (contact)

PROJECT_TERMS: Actomyosin;Address;Automobile Driving;Biosensor;Body part;Cell Cycle;Cell Cycle Regulation;Cell Proliferation;Cells;Cytoplasm;Cytoskeleton;Development;Disease;Dorsal;Drosophila genus;Embryo;Embryonic Development;Ensure;experimental study;gastrulation;Generations;Goals;insight;Link;Malignant Neoplasms;Mitosis;Mitotic;Morphogenesis;morphogens;novel;Nuclear;Phosphotransferases;physical property;Positioning Attribute;programs;Regulation;Side;Tissues;Transcriptional Regulation

PROJECT_TITLE: Physical principles of early Drosophila embryogenesis


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Project Narrative  The broad objective of this proposal is to understand the mechanism of homologous recombination and its intersection with DNA replication and chromosome structure. We will reconstitute increasingly more complex reactions that recapitulate the steps of the homologous recombination process, and we will use single- molecule visualization to image key steps and intermediates of these complex biological processes.

PI_NAMEs: KOWALCZYKOWSKI, STEPHEN CHARLES (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Bacteria;Behavior;Biochemical;Biological Process;biophysical techniques;Buffers;chromatin remodeling;Chromosome Structures;Chromosomes;Complex;Detection;DNA;DNA biosynthesis;DNA Repair;DNA Sequence;DNA-Protein Interaction;Enzymes;Escherichia coli Proteins;Filament;Genetic Recombination;helicase;homologous recombination;Image;Individual;Maintenance;Mediator;Nucleoproteins;Process;protein purification;Proteins;Reaction;reconstitution;Regulation;Saccharomyces cerevisiae;Sequence Homology;single molecule;Time;Visualization

PROJECT_TITLE: Single-molecule Visualization and Mechanisms of DNA Recombination and Intersecting DNA Transactions


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Congenital Structural Anomalies;Pediatric;Regenerative Medicine

ORG_CITY: PISCATAWAY

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

ORG_STATE: NJ

PHR: Project Narrative  This proposal investigates mechanisms that control organ growth and shape, focusing on how mechanical forces experienced by cells influence developmental processes. Inappropriate growth during development results in organs that are incorrectly sized or shaped, causing birth defects. Controlling organ growth is also important for understanding how stem cells can be used to repair or replace damaged organs, and the inability to limit growth in mature organisms results in cancer.

PI_NAMEs: IRVINE, KENNETH D (contact)

PROJECT_TERMS: Adherens Junction;alpha catenin;beta Spectrin;Binding;Biochemical;Biomechanics;Blood - brain barrier anatomy;cell behavior;Cell Shape;Cells;Characteristics;Congenital Abnormality;Cytoskeletal Proteins;Cytoskeleton;Defect;Development;Developmental Process;Dorsal;Drosophila genus;experience;F-Actin;Family;Glial Cell Proliferation;Goals;Growth;Homologous Gene;Investigation;Link;Malignant Neoplasms;mechanical force;Mediating;Membrane;Molecular;Morphogenesis;Myosin ATPase;Neuroglia;notch protein;Oncogenic;Organ;organ growth;Organism;Pathologic Processes;Pathway interactions;Phase;Phosphorylation;Phosphotransferases;Physical condensation;Physiological Processes;Physiology;Process;Proteins;recruit;regenerative;Regenerative Medicine;Regulation;repaired;Reproducibility;Research;Shapes;Signal Transduction;Spectrin;stem;stem cells;Stimulus;Symptoms;Syndrome;Testing;transcription factor;tumorigenesis;Wing

PROJECT_TITLE: Regulation of Growth and Morphogenesis


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Neurosciences;Rare Diseases

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative Ion channels pass electrical currents in the form of charged ions and are essential for processes as diverse as the heartbeat, thought, and movement. This project will define new paradigms in ion channel function involving regulation of ion channels by solute transporters (and vice versa) and small molecules and uncover new roles for ion channels in health and disease. These studies will ultimately help produce better therapeutic approaches to treat disorders including epilepsy, pain, inflammation, ataxia, and hypertension.

PI_NAMEs: ABBOTT, GEOFFREY W (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Achlorhydria;Address;Arrhythmia;Ataxia;Award;base;Biochemical;Biology;Brain;Cell membrane;Charge;Complex;Coupled;Data;Diabetes Mellitus;Disease;Electrophysiology (science);Epilepsy;Episodic ataxia;experience;Family;field study;Functional disorder;Goals;Health;Hypertension;Hypothyroidism;imaging modality;in vivo;in vivo evaluation;Inflammation;Ion Channel;Ions;Knock-out;Knowledge;Link;Molecular;mouse model;Movement;Neurotransmitters;novel;novel therapeutic intervention;Pain;Plant Extracts;plant metabolites;Plants;Potassium;Process;Proteins;Radioligand Assay;Rattus;Regulation;Research;Rodent;Role;Screening Result;Signal Transduction;small molecule;Sodium;solute;Structure;sugar;Techniques;Therapeutic;Tissues;transcriptomics;Transgenic Organisms;Variant;Vitamins;voltage;Water;Work

PROJECT_TITLE: Ion Channel Transporter Interactions


ORG_CITY: BALTIMORE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Genome maintenance is essential for accurate cell and tissue function. The proposed research seeks to understand how dynamic changes in two fundamental regulators of mammalian DNA transactions, chromatin and nuclear RNAs, control DNA repair outcome to ensure genome integrity across distinct physiological contexts. This work will have implications for diseases driven by impaired genome maintenance, from degenerative disorders to cancer.

PI_NAMEs: OBERDOERFFER, PHILIPP  (contact)

PROJECT_TERMS: Affect;Alternative Splicing;Cell Differentiation process;cell type;Cells;Chromatin;Coupled;Defect;Degenerative Disorder;Disease;DNA;DNA Damage;DNA lesion;DNA Repair;DNA Repair Pathway;Ensure;Environment;Genome;genome integrity;Genomic approach;Goals;Histone H2A;Impairment;innovation;interest;Knockout Mice;Link;Maintenance;Malignant Neoplasms;Modification;Molecular;mouse genetics;mouse model;Nuclear;Nuclear RNA;Outcome;Pathway interactions;Physiological;Protein Isoforms;Public Health;recruit;repair function;repaired;Research;response;RNA;RNA Splicing;screening;Single-Stranded DNA;Tissues;tool;Validation;Variant;Work

PROJECT_TITLE: Probing the mechanisms that control DNA repair pathway choice.

STUDY_SECTION: MRAF

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


PHR: Project Narrative Genetic variation influences genome function and organismal phenotypes, while providing the fundamental substrate for natural selection. Understanding the mechanisms that link these layers of variation and drive phenotypic evolution within natural populations is a major goal at the intersection of evolutionary biology and quantitative genetics. Using humans as a model, we propose to develop and apply computational and statistical methods for analyzing large-scale DNA sequence and functional genomic data, toward a more complete understanding of genetic diversity and evolution shaping genome function, reproduction, and development.

PI_NAMEs: MCCOY, RAJIV CHAMPION (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Aneuploidy;Biology;blastocyst;Blood Cells;Cells;Chromosome Segregation;Computing Methodologies;Data;Data Set;Development;diverse data;DNA;DNA Sequence;DNA sequencing;egg;European ancestry;Event;Evolution;fitness;functional genomics;Gene Expression;Genetic Crossing Over;genetic evolution;Genetic Models;Genetic Recombination;Genetic Variation;Genome;genomic data;Genomics;Germ Cells;Germ Lines;Goals;Haploidy;Haplotypes;Hematopoiesis;Hematopoietic stem cells;Home;Human;Human Genetics;Individual;Link;Location;Meiotic Recombination;Methods;Modeling;Natural Selections;novel;Pattern;Phenotype;phenotypic data;Phylogenetic Analysis;Point Mutation;Population;Population Genetics;Population Heterogeneity;protein function;Protein Isoforms;Publishing;Quantitative Genetics;Reproduction;Resolution;RNA;RNA Splicing;Sampling;Shapes;simulation;single molecule;sperm cell;Spliced Genes;Statistical Methods;Structure;System;Testing;tool;transcriptome sequencing;Variant;Work

PROJECT_TITLE: Function and fitness consequences of human genetic variation


ORG_CITY: TROY

ORG_NAME: RENSSELAER POLYTECHNIC INSTITUTE

PHR: PROJECT NARRATIVE  Normal cellular function requires that proteins responsible for sending and receiving signals be transported from the place in the cell where they are produced to the places in the cell where they are needed. It is known that a group of specialized proteins called kinesins is responsible for transporting proteins to the correct location, but the current understanding of how the right kinesin is paired with a particular protein and how they are directed to the right location is largely unknown. This project is designed to answer these questions, with the long-term goal of informing additional research on the roles of these proteins in preserving human health or contributing to disease.

PI_NAMEs: BENTLEY, MARVIN  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TITLE: Mechanisms of vesicle trafficking and kinesin regulation


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Large toxic particles that accumulate in the cytoplasm of mammalian cells such as viruses or protein aggregates drive disease ranging from infection to neurodegeneration to cancer. To respond to these insults, cells begin producing tens to hundreds of new organelles called autophagosomes, that encapsulate each cytoplasmic challenge and deliver them to lysosomes for destruction. How the cell martials the millions of lipids needed to grow these organelles is poorly described, but recent work from our lab has described the components of a novel lipid-scrambling and lipid-transporting complex potentially sufficient to drive this essential disease response pathway.

PI_NAMEs: MELIA, THOMAS JAMES (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TITLE: Mechanisms of autophagosome biogenesis


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

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Narrative We are developing computer-based methods for designing new protein structures and complexes. Proteins are the most versatile molecules in nature and improved methods for controlling their activity will enable the creation of therapeutics and critical reagents for understanding biological processes.

PI_NAMEs: KUHLMAN, BRIAN A (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Affinity;Amino Acid Sequence;Area;Benchmarking;Binding Proteins;Biological Process;Biology;Biosensor;Computing Methodologies;deep learning;deep learning model;design;Development;Disease;Goals;graph neural network;improved;Medicine;Methods;model design;Modeling;Molecular Conformation;molecular mechanics;Nature;neural network;novel;Population;Process;protein B;protein complex;Protein Engineering;protein function;protein protein interaction;protein structure;Proteins;Reagent;Research;Set protein;Side;Specific qualifier value;Specificity;Structure;Surface;Testing;Therapeutic;Training

PROJECT_TITLE: Computational Design of Protein Structures and Complexes


ORG_CITY: ITHACA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative Cell migration is critical for many physiological processes, such as wound healing and immune cell response, and also plays an important role in cancer metastasis, i.e. the spreading of tumor cells to distant sites in the body. As cells migrate through the body, they must frequently pass through tight spaces within tissues, placing substantial physical stress on the nucleus, which can result in DNA damage and changes in chromatin organization. The studies proposed in this application will (1) determine how cells move their large and relatively rigid nucleus through tight spaces, (2) elucidate the molecular mechanisms responsible for the changes in chromatin organization, and (3) identify the consequences of such confined migration on cellular fate and function, with the goal to obtain a better understanding of how migration through confined environments can modulate the function of normal cells but may also promote cancer progression and resistance to therapies.

PI_NAMEs: LAMMERDING, JAN  (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Area;Biological Assay;cell motility;Cell Nucleus;Cell Physiology;cell type;Cells;Chromatin;chromatin modification;Clinical;Collection;Confined Spaces;Cytoskeleton;Development;Distant;DNA Damage;Environment;Eukaryotic Cell;Gene Expression;Genetic Transcription;genome integrity;genome-wide analysis;Goals;Immune;Immune response;improved;in vivo;Inflammation;insight;interstitial;Laboratories;live cell imaging;mechanical force;migration;Molecular;Molecular Biology;Neoplasm Metastasis;neoplastic cell;Normal Cell;novel;Nuclear;Nuclear Envelope;Nuclear Structure;Organelles;Pathologic;physical property;Physiological;Physiological Processes;Play;programs;Research;response;Role;Rupture;Site;Stress;targeted treatment;Therapeutic;therapy resistant;Tissues;treatment response;tumor progression;Visualization;wound healing

PROJECT_TITLE: Nuclear mechanobiology in confined migration


ADMINISTERING_IC: EB

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Biomedical Imaging

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Narrative Diagnostic imaging with Magnetic Resonance Imaging (MRI) is an emerging field with ever expanding capabilities and roles in both basic medical research and clinical applications. This proposal is a request for funding of an institutional combined predoctoral Training Program for MRI in Radiology and Biomedical Engineering at Northwestern. Our goal is to train the next generation of scientists for a medical imaging career in academia, hospital, or industry.

PI_NAMEs: MARKL, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Magnetic Resonance Imaging;Training Programs

PROJECT_TITLE: Graduate Training Program for Magnetic Resonance Imaging

STUDY_SECTION_NAME: Special Emphasis Panel[ZEB1 OSR-D (J1)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

PHR: Project Narrative This MIRA project will help predict RNA folding in vivo and provide insight into the dynamics of RNA folding under in vivo-like conditions and in the cell. It will also help discover and elucidate novel functions for RNA enzymes and RNA motifs with rare charged and tautomeric bases. This work helps understand RNA gene regulation and identifies RNA targets for therapeutic tools.

PI_NAMEs: BEVILACQUA, PHILIP C (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: base;Binding;Biochemical;Bioinformatics;Biological;Biology;Biophysics;Catalysis;Catalytic RNA;Cells;Charge;cheminformatics;Development;Enzyme Precursors;Enzymes;Equilibrium;Exons;Fluorescence;Gene Expression Regulation;Genes;Genomics;Goals;Health;Human;in vivo;insight;Kinetics;loss of function;Methods;Molecular;Mutation;new technology;next generation sequencing;novel;nucleobase;Oligonucleotides;Pathway interactions;RNA;RNA Folding;RNA Probes;RNA-targeting therapy;Structure;tautomer;Temperature;Therapeutic;time use;tool;Vision;Work

PROJECT_TITLE: RNA folding and catalysis at the interface of biophysics and genomics


ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative In this MIRA application, the Sun group will advance top-down proteomics using capillary electrophoresis-mass spectrometry (CE-MS) to achieve a draft of the proteoform atlas of human cells, which will be an extremely valuable resource for fundamental and translational research. The Sun group will apply the novel CE-MS techniques to developmental biology to discover crucial proteoforms that modulate early cellular differentiation and zygotic genome activation during early vertebrate embryogenesis using zebrafish as the model organism.

PI_NAMEs: SUN, LIANGLIANG  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: analytical tool;Atlases;Biological;Biological Markers;biological systems;Cancer Biology;Cancer cell line;Capillary Electrophoresis;Cell Differentiation process;Cells;Code;colon cancer cell line;colorectal cancer metastasis;Complex;Development;Developmental Biology;Embryo;embryo stage 2;Embryonic Development;Event;Focus Groups;fundamental research;Generations;Genes;Genome;Hela Cells;Heterogeneity;Human;insight;Mass Spectrum Analysis;Measurement;model organism;Neurosciences;novel;Peptides;Play;protein complex;Proteins;Proteome;Proteomics;Research Project Summaries;Resolution;Resources;Role;Sampling;Techniques;Translational Research;tumor;Zebrafish

PROJECT_TITLE: Advancing top-down proteomics with capillary electrophoresis-mass spectrometry


NIH_SPENDING_CATS: Genetics

PHR: PROJECT NARRATIVE Human introns contain a significant number of pseudo splice sites that can result in cryptic splicing, leading to the incorrect insertion of intronic elements into mRNA. We propose to investigate the molecular mechanisms underlying the repression of cryptic splicing and its downstream consequences on cellular function. As cryptic splicing is associated with neuronal degeneration and cancer, knowledge gained from this research could help identify novel therapeutic interventions.

PI_NAMEs: CHENG, CHONGHUI  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Affect;Binding;Bioinformatics;cell behavior;Cell Physiology;Cells;Code;Disease;Double-Stranded RNA;Elements;Eukaryota;Event;Exons;Failure;fitness;Gene Expression Regulation;Genes;Human;insight;Interferons;Introns;Knowledge;Learning;Malignant Neoplasms;Mammals;Mediating;Messenger RNA;Molecular;mRNA Precursor;Nature;Nerve Degeneration;Nonsense-Mediated Decay;novel therapeutic intervention;Nuclear;Pathology;Pathway interactions;Phenotype;Process;Protein Truncation;Proteins;Regulation;Repetitive Sequence;Repression;Research;response;Ribonucleoproteins;RNA Splicing;RNA-Binding Proteins;Role;Site;small hairpin RNA;Spliceosomes;Surveys;Transcript;transcriptome;Up-Regulation;whole genome;Work

PROJECT_TITLE: Regulation and consequences of cryptic splicing


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Bioengineering;Climate-Related Exposures and Conditions;Clinical Research;Complementary and Integrative Health;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Lung;Social Determinants of Health

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative Decades of research in epidemiology, mathematical modeling, and public health have generated critical tools for epidemic monitoring and management, and these tools played a vital role during the COVID-19 pandemic to augment situational awareness and inform public health decisions. Now is the time we must enhance this toolkit with new data collection and modeling methods to enable improved management of COVID-19 and enhance preparedness for future emerging pathogens. The work will leverage mathematical modeling and large datasets to address key public health challenges: producing timely and accurate estimates of infection incidence and severity, quantifying the effectiveness of behavioral interventions, predicting seasonality, and addressing public health inequities.

PI_NAMEs: BANSAL, SHWETA  (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: 2019-nCoV;Address;Alternative Therapies;Awareness;Behavior;Behavior Therapy;Behavioral;burden of illness;Case Study;climate change;Clinical;Communicable Diseases;Communities;COVID-19;COVID-19 pandemic;Data;Data Collection;data modeling;Data Set;data streams;design;Dimensions;Disease;disease heterogeneity;disease model;Disease Outbreaks;Disease Outcome;Disease Surveillance;Economics;Effectiveness;Elements;emerging pathogen;Environment;Epidemic;Epidemiology;Feedback;Future;Geography;Health;health care availability;health inequalities;Health Policy;Health system;Heterogeneity;Immunize;Improve Access;improved;Incidence;Income;Individual;Inequality;Infection;infectious disease model;Influenza;innovation;Institutional Racism;Intervention;large datasets;mathematical model;Methods;model development;Modeling;Monitor;neglect;pandemic disease;pathogen;Play;Policy Maker;Politics;Population;Process;programs;Public Health;Readiness;Research;Resource Allocation;respiratory;Respiratory Disease;respiratory virus;Role;Seasons;Severities;social;Social Behavior;social factors;spatial epidemiology;spatiotemporal;System;theories;Time;tool;transmission process;United States;Variant;Virus;Work

PROJECT_TITLE: Integrating opportunistic data into respiratory disease models to enhance surveillance, explain seasonality, and reveal spatial transmission landscapes


ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: Project Narrative Chemical genetics is powerfully enabling for biological discovery and therapeutics development. We propose to leverage breakthroughs in precision genome-editing technologies and multi-omics to transform chemical genetic approaches, allowing us to illuminate small molecule mechanism and endogenous protein structure-function at scale and in high resolution. By applying these innovative approaches to critical and diverse protein targets, we expect to advance our fundamental understanding of drug mechanism of action and protein complex structure and function.

PI_NAMEs: LIAU, BRIAN  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Address;Alleles;Allosteric Regulation;Androgen Receptor;Binding;Biological;Biology;Cells;Cellular biology;chemical genetics;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;Computational Biology;Development;Disease;drug mechanism;Drug Targeting;Environment;Future;genetic approach;Genetic Screening;genome editing;genomic platform;Genomics;In Situ;innovation;Malignant Neoplasms;Molecular Biology;Molecular Mechanisms of Action;multicatalytic endopeptidase complex;multiple omics;mutant;Mutation;mutation screening;new technology;Oncogenes;Pathway interactions;Phenotype;protein complex;Protein Complex Subunit;protein degradation;protein structure function;Proteins;Research;Resolution;Signal Transduction;small molecule;structural biology;Structure;System;Technology;Testing;therapeutic development;tool;transcription factor;Ubiquitin;Work

PROJECT_TITLE: Integrating Chemical Genetic Approaches with Precision Genome Editing


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

ORG_CITY: ROCHESTER

ORG_NAME: ROCHESTER INSTITUTE OF TECHNOLOGY

ORG_STATE: NY

PHR: Narrative: This research will contribute to the development and validation of robust computational tools for biomedical research, along with their implementation using a more affordable, accessible manner, in support of computer- integrated diagnostic and therapeutic data science. These tools will operate on standard-of-care multi-modality and multi-dimensional data to answer fundamental questions underlying health and disease. The subsequent utilization of these tools has the potential to change the traditional disease diagnosis and treatment paradigms, by assisting clinicians with the early and accurate diagnosis, the identification of the most appropriate course of treatment, and the monitoring and delivery of less invasive and more effective therapies. 1

PI_NAMEs: LINTE, CRISTIAN A (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: accurate diagnosis;Adoption;Algorithms;Artificial Intelligence;Biological;Biomedical Computing;biomedical imaging;biomedical informatics;Biomedical Research;Body System;Brain;Cardiac;clinical translation;Collaborations;Communities;Computer Models;Computer-Assisted Diagnosis;computerized tools;Computers;Data;Data Science;Detection;Development;Diagnosis;Diagnostic;Dimensions;Disease;disease diagnosis;Disease Progression;Early Diagnosis;Education;effective therapy;Fostering;Goals;Health;Human body;Hybrids;Image;image visualization;imaging biomarker;imaging informatics;improved;industry partner;informatics tool;innovation;Interdisciplinary Study;Intervention;Label;large scale data;Lung;Medical Education;Medical Imaging;Mentors;minimally invasive;Modeling;Monitor;multidimensional data;multimodality;Noise;novel;Orthopedics;patient population;Performance;Physics;programs;Research;Route;Scientist;Signal Transduction;simulation;skills;standard of care;Stream;Techniques;Therapeutic;Time;tool;Training;training data;Uncertainty;Validation;Vertebral column;Vision;Visualization;Visualization software;Work

PROJECT_TITLE: Biomedical Computing and Visualization Tools for Computer-integrated Diagnostic and Therapeutic Data Science


NIH_SPENDING_CATS: Genetics;Human Genome

PHR: Narrative Chromatin, the DNA and its associated proteins, underlies the genetic blueprint of the cell, but can also serve in a non-genetic capacity as a material that impinges on the mechanical properties of the nucleus in which it is housed. This proposal seeks to define the mechanisms by which modulation of chromatin state influences nuclear mechanics, establish the extent to which forces exerted on chromatin are propagated along the chromatin polymer, and identify biologically-relevant, force-modulated genes for mechanistic study.

PI_NAMEs: KING, MEGAN C (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Area;Biology;biophysical properties;Black Box;Cell Line;Cell Nucleus;Cells;Chromatin;Chromosomes;Complex;Cytoskeleton;Data;Disease;DNA;Epigenetic Process;epigenome;experimental study;Fission Yeast;Gene Expression;Gene Expression Regulation;Genes;Genetic;genome integrity;Genomics;Goals;histone modification;In Vitro;in vivo;insight;Length;Literature;mechanical properties;Mechanics;mechanotransduction;mouse model;non-genetic;Nuclear;Nuclear Envelope;Play;Polymers;Positioning Attribute;Process;programs;Property;Proteins;Research;response;Role;simulation;tool;transcriptome;Translating;Translations;transmission process

PROJECT_TITLE: The genetic and non-genetic responses of chromatin to force


NIH_SPENDING_CATS: Bioengineering;Genetics;Nanotechnology

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: NARRATIVE The proposed research will use DNA nanotechnology to develop a new generation of molecular tension probes and nanodevices to be used in mechanobiology and structural biology. If successful, the project will provide answers to many important questions related to T cell signaling and activation, and impact the development of new immunotherapeutic methods. It will also open up a new paradigm for understanding mechano-biological processes involving other protein mechanosensors.

PI_NAMEs: KE, YONGGANG  (contact)

PROJECT_TERMS: Adaptive Immune System;Address;Autoimmunity;B-Lymphocytes;Binding;bioimaging;Biological Process;biological research;biological systems;Biomedical Research;Biosensing Techniques;cancer therapy;Cell surface;Cells;Cellular biology;Collaborations;Complex;Cryoelectron Microscopy;Detection;Development;Devices;Disease;DNA;DNA Structure;Generations;Immune system;Immunotherapeutic agent;improved;in vivo;Lymphocyte;Malignant Neoplasms;mechanical signal;Mechanoreceptors;Messenger RNA;Methods;Molecular;Molecular Conformation;Molecular Probes;multidisciplinary;Nanoarray Analytical Device;nanodevice;Nanostructures;Nanotechnology;next generation;novel;Positioning Attribute;Process;Proteins;Publishing;Reaction;receptor;Regulation;Research;Research Activity;self assembly;sensor;Signal Transduction;single molecule;small molecule therapeutics;Small RNA;structural biology;synergism;System;T-Lymphocyte;targeted treatment;tool;ultra high resolution;Virus Diseases;Visualization;Work

PROJECT_TITLE: DNA nanodevices for molecular interrogation and regulation of lymphocytes in adaptive immune system


NIH_SPENDING_CATS: Natural Products

PHR: This research program will rationally expand the chemical space of terpenes and terpenoids using mechanistic insights obtained from computaional chemistry experiments, thereby providing new input for the testing and development of terpene-like compounds with potential biological activities relevant to human health. Known members of the terpene/terpenoid class of natural products have anti-cancer, anti-inflammatory, analgesic, anti-convulsive, anti-depressant, neuroprotective, anti-allergic, antibiotic, and other activities, and we endeavor to provide compounds with improved and/or altogether new activities that result from their new, previously inaccessible, structures.

PI_NAMEs: TANTILLO, DEAN  (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Active Sites;Analgesics;Anti-Allergic Agents;anti-cancer;anti-depressive agents;Anti-Inflammatory Agents;Antibiotics;Biological;Biological Testing;carbon skeleton;Catalysis;Chemicals;Chemistry;computational chemistry;computer studies;Cyclization;design;Development;Docking;enzyme substrate;Enzymes;Experimental Designs;experimental study;Health;Human;improved;insight;Isoprene;member;Methods;methylation pattern;Modeling;Modernization;multi-scale modeling;Natural Products;Nature;neuroprotection;programs;quantum chemistry;Reaction;Research;Series;Shapes;simulation;Structure;Substrate Interaction;System;Techniques;terpene synthase;Terpenes;Testing;Vision

PROJECT_TITLE: Understanding and manipulating biosynthetic mechanisms for formation of terpenes relevant to human health


NIH_SPENDING_CATS: Biotechnology;Regenerative Medicine

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The conversion of skin cells into therapeutically useful cell types promises new treatments for many diseases. However, most lineage reprogramming protocols are inefficient, and the cells produced often do not fully recapitulate the properties of the target cell type. Here, we propose to investigate mechanisms of cell fate reprogramming using novel experimental and computational genomic technologies. Our work aims to reveal fundamental mechanisms governing cell identity regulation and reprogramming that will be translatable to any cell or tissue type and thus broadly applicable to stem cell biology and regenerative medicine.

PI_NAMEs: MORRIS, SAMANTHA ANNETTE (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Address;Biological;Biological Models;cell fate specification;Cell fusion;Cell Reprogramming;cell type;Cells;Cellular biology;cellular engineering;Development;Disease;disease model;Engineering;Event;Gene Expression Regulation;gene regulatory network;Genes;Genomics;improved;innovation;insight;Knowledge;Maintenance;Mediating;Methods;Modeling;Molecular;multiple omics;National Institute of General Medical Sciences;novel;nuclear transfer;Outcomes Research;permissiveness;Population;programs;Property;Protocols documentation;Regenerative Medicine;Regulation;Research;Research Support;Skin;stem cell biology;Technology;Therapeutic;Tissues;transcription factor;Transfer Factor;Work

PROJECT_TITLE: Decoding the Molecular Mechanisms Governing Regulation and Reprogramming of Cellular Identity


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Microbes are a constant presence in our environment and impact humanity in diverse ways, yet we incompletely understand the many ways that our immune system has evolved to defends against pathogens, and the ways that pathogens evolve to avoid or defeat our defenses. This project takes an evolution-guided approach to discover new critical mechanisms that underlie host susceptibility to viral infection by identifying and characterizing human genes that have repeatedly evolved to contend with pathogen infections in the past. Such an unbiased approach will allow us to discover new players in the ongoing conflict between hosts and viruses, and leverage the diversity that is already found in nature to develop ways to diagnose, prevent and treat infectious diseases.

PI_NAMEs: DAUGHERTY, MATTHEW  (contact)

PROJECT_TERMS: Address;Affect;Animals;Back;Binding;Biochemistry;Cell Physiology;Cessation of life;Communicable Diseases;comparative genomics;Conflict (Psychology);cross-species transmission;Defense Mechanisms;Diagnosis;Environment;Evolution;fitness;Genes;Genetic;Genetic Variation;Horizontal Gene Transfer;Host Defense Mechanism;host-microbe interactions;Human;Humanities;Immune;Immune Evasion;Immune system;Infection;innovation;insight;interdisciplinary approach;interest;Microbe;microbial;microbial genome;Mission;Natural Immunity;Nature;novel;pathogen;Pathway interactions;posttranscriptional;Predisposition;pressure;prevent;Proteins;Research;Side;Time;Viral;virology;Virus;Virus Diseases;Work;Zoonoses

PROJECT_TITLE: Evolution of innate antiviral defense mechanisms and other microbe-driven genetic innovations


ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: PROJECT NARRATIVE The brain is a highly-guarded organ with physiological barriers, in particular, the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier, limiting access of most drugs. Interestingly, a bug – Cryptococcus neoformans (CN) has adapted special mechanisms to bypass the BBB. Herein, we seek to understand the underlying mechanisms of innate immune cell vomocytosis of CN through combinatorial engineering and biological tools. Therefore, the proposed program is highly relevant to the mission of the National Institute of General Medical Sciences (NIGMS), which pertains to supporting research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention.

PI_NAMEs: LEWIS, JAMAL S (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;Behavior;Biochemistry;Biocompatible Materials;Biological;Biological Process;Blood - brain barrier anatomy;blood cerebrospinal fluid barrier;Brain;Bypass;Cell Physiology;Cells;combinatorial;Comprehension;Cryptococcus;Cryptococcus neoformans;Cytoplasm;Dendritic Cells;design;Development;Disease;disease diagnosis;Drug Delivery Systems;Engineering;Enzymes;Exocytosis;Florida;Foundations;Goals;Hybrids;Immune;Immune system;Immunology;immunoregulation;Immunotherapeutic agent;in vivo;innate immune mechanisms;Knowledge;Laboratories;lymph nodes;lymphoid organ;Macrophage;Mediating;Mission;Motivation;multidisciplinary;National Institute of General Medical Sciences;Neurologic;next generation;Nonlytic;novel;Organ;particle;Particulate;Particulate Matter;pathogen;Peripheral;Phagocytes;Phagocytosis;Phagosomes;Pharmaceutical Preparations;Physiological;Prevention;Process;programs;Reactive Oxygen Species;Research;Research Support;Role;Site;System;therapeutically effective;Tissues;tool;Universities;Vaccines;Vacuole;Work

PROJECT_TITLE: Leveraging Engineering Approaches to understand Cryptococcal Vomocytosis from Immune Cells


ORG_CITY: MANHATTAN

ORG_NAME: KANSAS STATE UNIVERSITY

ORG_STATE: KS

PHR: Project Narrative Loss of gene expression control is a fundamental component of many diseases. My lab uses the model organism Caenorhabditis elegans to study how microRNA-mediated gene repression is regulated in the complex context of a developing organism. The proposed research will advance our fundamental understanding of gene regulation in development and will help address how it goes awry in disease.

PI_NAMEs: ZINOVYEVA, ANNA  (contact)

PROJECT_TERMS: Address;Biogenesis;Caenorhabditis elegans;cofactor;Complex;Defect;Development;Disease;Foundations;Gene Expression;Gene Expression Regulation;gene repression;Gene Silencing;Genes;Genetic;Goals;Health;Homeostasis;human disease;in vivo;Lead;Malignant Neoplasms;Mediating;Methodology;MicroRNAs;model organism;Molecular;Neurodegenerative Disorders;Organism;overexpression;Play;Post-Transcriptional Regulation;programs;Regulation;Repression;Research;Role;Specificity;Untranslated RNA

PROJECT_TITLE: Molecular control of microRNA gene-regulatory activity.


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative  In our cells, our DNA genetic information is packaged with histone proteins into chromatin. Recent studies have shown that histone proteins can be decorated by histone modification enzymes with small molecules or proteins, and these decorations can be recognized by reader proteins to regulate gene expression in normal and diseased cells. Our studies will visualize how different histone modification enzymes and reader proteins associated with stem cells and cancer perform their functions.

PI_NAMEs: TAN, SONG  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Basic Science;Binding;Biochemical;Biological Assay;Cells;Chromatin;Complex;Cryoelectron Microscopy;Data;Development;Disease;DNA;Enzymes;Epigenetic Process;Eukaryotic Cell;Gene Expression;Gene Expression Regulation;Genetic;genetic information;Genomics;histone modification;Histones;human disease;Malignant Neoplasms;Modeling;Modification;new therapeutic target;Nucleosomes;Physiological;Post-Translational Protein Processing;Proteins;Reader;Regulation;Signal Transduction;small molecule;stem cells;Structural Models;therapeutic gene;Visualization

PROJECT_TITLE: Structural studies of chromatin complexes


ORG_CITY: College Station

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

PHR: PROJECTIVE NARRATIVE Asymmetric cell division (ACD) generates diverse cell types and is universally required for development and morphogenesis in multicellular organisms. One fundamental mechanism that controls ACD is cell polarization, which involves the asymmetric distribution of molecules, structures, and functions within a cell. This project aims to establish the molecular and cellular paradigms governing cell polarization, cell division, and cell-fate differentiation during stomatal ACD in Arabidopsis, a system highly amenable to genetic analysis and cell biological examination.

PI_NAMEs: DONG, JUAN  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Arabidopsis;Area;Biochemistry;Biological;Cell Cycle Regulation;Cell Differentiation process;Cell division;Cell membrane;Cell Polarity;cell type;Cells;Cellular biology;design;Development;Dissociation;Endosomes;Genetic;genetic analysis;Glycogen Synthase Kinases;Guanosine Triphosphate Phosphohydrolases;insight;Label;Membrane;Membrane Proteins;Microscopic;Mitogen-Activated Protein Kinases;Mitosis;Molecular;Morphogenesis;Organism;paralogous gene;Pattern;Peripheral;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphotransferases;Plant Epidermis;Plant Model;Plants;Play;polarized cell;Process;Protein Dynamics;Proteins;Proteomics;Recycling;Research;Role;Scaffolding Protein;Signal Transduction;stem cells;Stomas;Structure;System;trafficking;United States National Institutes of Health;Variant;Vesicle

PROJECT_TITLE: Cell polarity, asymmetric cell division and differentiation in plants.


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

ORG_STATE: MA

PHR: PROJECT NARRATIVE This project is relevant to public health because it will identify molecular and cellular mechanisms for how pluripotent stem cells can be established in embryos, retained into adulthood, and then regulated for the formation of differentiated cell types in the context of a whole animal. An understanding of these mechanisms is essential for progress in human regenerative medicine and therefore relates to the NIH’s mission to acquire fundamental knowledge about living systems that can be applied to human biology to reduce disability.

PI_NAMEs: SRIVASTAVA, MANSI  (contact)

PROJECT_TERMS: Adult;Animals;Biological Models;Biology;Cell Adhesion;Cell Differentiation process;Cell Lineage;cell regeneration;cell type;Cells;Chromatin;CRISPR/Cas technology;Development;disability;Embryo;Embryonic Development;Evolution;experimental study;flexibility;functional genomics;gene function;Gene Transfer Techniques;Genes;Genetic Transcription;genome-wide;Genomic approach;Goals;Hand;Human;Human Biology;Image;in vivo;innovation;Invertebrates;Knowledge;Label;mature animal;Methods;Mission;Molecular;Natural regeneration;novel;novel strategies;Organism;Planarians;pluripotency;Pluripotent Stem Cells;programs;Public Health;Regenerative Medicine;Regenerative research;Regulation;Research;RNA Interference;stem cell biology;stem cells;System;Techniques;tissue regeneration;Tissues;transcriptome;United States National Institutes of Health;Vertebrates

PROJECT_TITLE: Stem cell regulation during development and whole-body regeneration