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

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: NARRATIVE We propose to develop a novel machine learning platform for automated analysis of hidden heterogeneity and single-cell causal mechanisms from live cell images. This new system will identify molecular mechanisms at single-cell resolution by integrating deep learning with optogenetic treatments. We will apply the developed technology to study the interplay between cell motility and morphodynamics.

PI_NAMEs: LEE, KWONMOO  (contact)

PROJECT_TERMS: Address;automated analysis;cell motility;Cell Physiology;cell type;Cells;Cellular biology;Classification;Communities;Data;Data Analyses;Data Set;deep learning;feature selection;Heterogeneity;Image;insight;Learning;live cell imaging;Machine Learning;machine learning method;Maps;Mechanics;Metabolic;Methods;Microscopy;Modeling;Molecular;Neoplasm Metastasis;novel;optogenetics;Phenotype;Population;preservation;Process;Research;Research Personnel;Resolution;Resources;Series;Shapes;spatiotemporal;System;Technology;Time;tissue regeneration

PROJECT_TITLE: Unraveling heterogeneity of molecular mechanisms in cellular motility and morphodynamics by machine learning


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: CHAPEL HILL

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHARMACOLOGY

ORG_FIPS: US

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: NARRATIVE Progression through the cell cycle is tightly controlled by changes in the abundance of hundreds of cellular proteins. Cells control protein abundance by regulating their degradation, and mis-regulation of this process causes human diseases, including cancer and neurological disorders. This proposal will address the enzymes and substrates involved, and their collective influence on proliferation and the integrity of our genetic material.

PI_NAMEs: EMANUELE, MICHAEL JAMES (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Binding;Biochemical;Biological Assay;Cell Cycle;Cell Cycle Progression;Cell Cycle Proteins;Cell Cycle Regulation;Cells;Chromatin;Cryoelectron Microscopy;Cyclin-Dependent Kinase Inhibitor;Cyclin-Dependent Kinases;Cyclins;Cytoskeleton;Decision Making;Enzyme Kinetics;Enzymes;Eukaryota;Event;Exhibits;G2 Phase;Genetic Materials;Genetic Transcription;genome integrity;Goals;human disease;Kinetics;Maintenance;Malignant Neoplasms;Metabolism;Methods;Molecular;multicatalytic endopeptidase complex;Nervous System Disorder;Pathway interactions;Phase;Phosphotransferases;Play;PLK1 gene;Post-Translational Protein Processing;preference;Process;programs;Proliferating;protein degradation;Protein Dynamics;Proteins;Proteome;Proteomics;proteostasis;Regulation;Regulatory Pathway;Research;response;Role;Signal Transduction;Stress;Structure;System;Time;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Proteostasis signaling in cell cycle control

STUDY_SECTION: MRAC

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: ROCHESTER

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: ROCHESTER INSTITUTE OF TECHNOLOGY

ORG_STATE: NY

PHR: Narrative The overall goal of this research proposal is to understand how cells behave on porous substrates and then engineer ideal membranes to integrate into in vitro tissue barrier and co- culture models. These models will aid in drug candidate screening as well as improve our understanding of how cells communicate under normal and pathological conditions in the body.

PI_NAMEs: GABORSKI, THOMAS R (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: Adopted;Animal Model;Biological;Biological Models;Biomedical Research;biomedical scientist;Biophysics;cell behavior;Cell Communication;Cells;Coculture Techniques;Communication;Complex;Controlled Environment;Development;Disease;disease model;drug candidate;Drug Modelings;drug testing;Engineering;Equilibrium;Goals;improved;In Vitro;induced pluripotent stem cell;Laboratories;Membrane;microphysiology system;Microscopy;migration;Modeling;Molecular;parallelization;Pathologic;Patients;Permeability;Physiological;Porosity;programs;Research;Research Proposals;Resolution;scaffold;screening;Side;Signal Pathway;Substrate Interaction;System;Time;Tissue Microarray;Tissues;Toxicity Tests;Vision

PROJECT_TITLE: Engineering Cell-Substrate Interactions on Porous Membranes to Create Physiologically Relevant Model Systems

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: NEW YORK

ORG_DEPT: CHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY

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

PI_NAMEs: ARORA, PARAMJIT S (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Binding;Biological;Biological Process;Complex;Development;Disease;Double-Stranded RNA;Engineering;Epitopes;Event;Foundations;Gene Expression Regulation;Inosine Diphosphate;Ligands;Mediating;Membrane Proteins;Molecular;molecular size;protein complex;Protein Inhibition;protein protein interaction;Proteins;rational design;receptor;Research;RNA;RNA-Protein Interaction;scaffold;Signal Pathway;Signal Transduction;small molecule;Structure;synthetic protein;Tertiary Protein Structure;Therapeutic;Therapeutic Agents;therapeutic candidate;Therapeutic Intervention;therapeutic target;Work

PROJECT_TITLE: Biomolecular Recognition with Synthetic Protein Mimics

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Compared to the vast number of studies on mRNA expression level regulation, there is a paucity of studies on mRNA splicing. We propose to develop multiple computational and genomics approaches to study the function and mechanism of mRNA splicing. Our work aims to have a broad impact in both basic biology and translational medicine.

PI_NAMEs: LI, YANG  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Biological Assay;Biological Process;Biology;Computing Methodologies;DNA Sequence;Gene Expression Regulation;Genomic approach;Genomics;Goals;Health;Human;Human Biology;human disease;improved;Knowledge;Mediating;Messenger RNA;mRNA Expression;novel;Pharmaceutical Preparations;Regulation;RNA Splicing;small molecule;targeted treatment;therapy design;translational medicine;Work

PROJECT_TITLE: Computational genomics approaches to study mechanisms and function of mRNA splicing

STUDY_SECTION: MRAA

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


ORG_DEPT: BIOCHEMISTRY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: PROJECT NARRATIVE  Regulation of gene expression is a critical aspect of many biological phenomena (e.g. cell growth, development of multicellular organisms, the response to environmental conditions, and evolution), and alteration of normal gene regulation can lead to human disease. This proposal investigates fundamental molecular mechanisms of gene regulation at several levels including the relationships between transcriptional elongation, cleavage/polyadenylation (3' end formation), and mRNA stability. The results will continue to shed new light on fundamental issues in gene regulation and will have a significant impact on our understanding of human biology and disease.

PI_NAMEs: STRUHL, KEVIN  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: 3' Untranslated Regions;Address;Affect;Binding Proteins;Biological Phenomena;cell growth;Cell Nucleus;Cells;Chemicals;Complex;Cytoplasm;Development;Disease;Elements;Eukaryota;Evolution;Experimental Genetics;experimental study;functional genomics;Gene Expression;Gene Expression Regulation;Gene Modified;Generations;Genes;Genomic approach;Human;Human Biology;human disease;improved;Individual;Knowledge;Label;Length;Libraries;Link;Measures;Mediating;Messenger RNA;Metabolic;Methodology;Molecular;Molecular Genetics;mRNA Decay;mRNA Stability;novel;Nucleotides;Organism;Pattern;Physiologic pulse;Poly(A) Tail;Polyadenylation;Prevention;Process;Protein Isoforms;Proteins;Regulation;response;RNA;RNA chemical synthesis;Structure;Transcription Elongation;Transcription Initiation;Transcription Process;transcriptome;Variant;Work;Yeasts

PROJECT_TITLE: Mechanism of yeast gene regulation


NIH_SPENDING_CATS: Natural Products

ORG_CITY: Newark

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: To discover new medicines, new molecules are needed, and the incorporation of saturated carbon atoms and three-dimensional shape correlates with higher probability of those molecule advancing from lead discovery to becoming a drug. The proposed research is relevant to public health, because it will establish efficient new methods to make bonds to saturated carbon atoms from easily available starting materials. The overarching goal is to enable the discovery of new medicines by enabling access to new molecules.

PI_NAMEs: WATSON, MARY P (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Harnessing Alkyl Amines and Alkyl Alcohols in Cross-Coupling Reactions


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

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Extrachromosomal DNAs have emerged as a key contributor to cancer development and progression but have also been identified in healthy cells. This project investigates how extrachromosomal DNAs are produced and facilitate cellular response to environmental stress. This work has the potential to advance understanding of the signaling and regulatory networks that control extrachromosomal DNA production to enable future targeting of extrachromosomal DNA in disease.

PI_NAMEs: BLACK, JOSHUA CRANSTON (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Biogenesis;biological adaptation to stress;Biological Process;Cells;Chromatin;Chromosome 21;comorbidity;Development;Disease;DNA;Down's Syndrome;Drug resistance;Environment;Enzymes;Epigenetic Process;epigenetic regulation;epithelial to mesenchymal transition;Event;extrachromosomal DNA;Future;Generations;Genes;Genetic;Goals;Heterogeneity;Individual;insight;Laboratories;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Metastatic breast cancer;Methods;new therapeutic target;novel;Oncogenes;Pathogenesis;Pathway interactions;permissiveness;Ploidies;prevent;Process;Production;Regulation;Regulatory Pathway;Research Project Grants;response;Role;Signal Pathway;Signal Transduction;Stress;synergism;therapeutic target;Tissues;Trisomy;Work

PROJECT_TITLE: Understanding Epigenetic Regulation of Copy Number Heterogeneity

STUDY_SECTION: MRAF

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: LINCOLN

ORG_NAME: UNIVERSITY OF NEBRASKA LINCOLN

ORG_STATE: NE

PHR: NARRATIVE Enzymes are essential for life but the physical principles dictating their function are still unclear. This proposal will both develop and use new methods in time-resolved X-ray crystallography to observe catalysis by various enzymes in real time, opening a new window into fundamental biochemical processes. What is learned from this project can be used to develop improved treatments targeting enzymes important for health and disease.

PI_NAMEs: WILSON, MARK A. (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Affect;Antibiotics;Biochemical Process;Biochemistry;Catalysis;Charge;Computer Simulation;Crystallography;Cysteine;Development;Disease;enzyme structure;Enzymes;experimental study;Goals;Health;improved;innovation;isocyanide;Learning;Life;Methods;neglect;Nerve Degeneration;new technology;PARK7 gene;Parkinsonian Disorders;Physiological;Quantum Mechanics;Regulation;Resolution;Stress;structural biology;Time;time use;Work;X-Ray Crystallography

PROJECT_TITLE: Time-resolved structural studies of enzyme catalysis and regulation

STUDY_SECTION: MRAE

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: TEMPE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Project Narrative This project is focused on the molecular-genetic mechanisms associated with the evolution of genetic variation, diversification of phenotypes, and the consequences for organismal fitness. The research will: 1) generate a comprehensive understanding of the rates at which cellular errors arise at the DNA, RNA, and protein levels across the Tree of Life and develop theory to explain the patterns; 2) further establish the Daphnia model system to help understand the evolutionary features of genes involved in key functions such as translation, bioenergetics, environmental sensing, and lifespan determination; and 3) develop theory to explain scaling patterns in the emerging field of evolutionary cell biology and the mechanisms by which cells evolve.

PI_NAMEs: LYNCH, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Amino Acids;Architecture;asexual;Attention;Automobile Driving;Bioenergetics;Biological Models;Cells;Cellular biology;Collection;Crustacea;Daphnia;design;DNA;Environment;Evolution;fitness;Gene Structure;Genes;Genetic;Genetic Drift;genetic evolution;Genetic Recombination;Genetic Variation;Genome;Genomics;Genotype;Health;Human;insight;Joints;Life;life span;male;Meiotic Recombination;Messenger RNA;Methods;Mitochondria;Modeling;Molecular;Molecular Genetics;Mutation;Natural Selections;Nuclear;Ovum;Pattern;Pest Control;Phenotype;Phylogenetic Analysis;Play;Population;Population Genetics;prevent;Production;protein aggregation;Proteins;Proteomics;Research;Ribosomes;RNA;Role;sex determination;Sexual Reproduction;Structure;Surveys;System;Testing;theories;Toxic effect;trait;Translations;Trees;Variant;Work

PROJECT_TITLE: Causes and Population-genetic Consequences of Molecular Variation


ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: PROJECT NARRATIVE The proteasome is a central effector of protein degradation, and its malfunction has been connected with numerous cancers and other pathologies, such as Alzheimer’s and Parkinson’s syndromes. The proposed research seeks to reveal how cells generate the proteasome—one of the most complex molecular machines—using rigorous quality control during its assembly. This study contributes to public health by paving the way for exploiting the proteasome, a proven therapeutic target, to develop more directed and specific strategies to combat human diseases with protein clearance problems.

PI_NAMEs: PARK, SOYEON  (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Alzheimer's Disease;Binding;Biochemical;Biological;Cell Nucleus;Cell Physiology;Cells;combat;Complex;Cytoplasm;Cytoplasmic Granules;Dedications;Ensure;Enzymes;Goals;Human;human disease;in vivo;Knowledge;Malignant Neoplasms;Mediating;Modeling;Molecular Chaperones;Molecular Machines;Monitor;multicatalytic endopeptidase complex;Nerve Degeneration;Nuclear Localization Signal;Nutritional;Oncoproteins;Parkinson Disease;Pathology;Polyubiquitin;Polyubiquitination;preservation;prevent;Process;protein degradation;Proteins;Proteomics;PSMD10 gene;Public Health;Quality Control;Research;Role;Series;Stress;Syndrome;System;therapeutic target;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Yeast Model System

PROJECT_TITLE: Mechanisms of Chaperone-Mediated Control in the Assembly of the Proteasome


NIH_SPENDING_CATS: Regenerative Medicine;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative: Bone Morphogenetic Protein (BMP) signaling acts in multiple biological contexts to establish the basic body plan, tissues, and organ systems of vertebrates, including humans, whereas aberrant BMP signaling can cause congenital defects, heterotopic ossification, and cancer. Thus, understanding the BMP signaling mechanism and signaling regulation has direct implications in disease, as well as the use of BMP signaling components in orthopedics, endodontics, tissue engineering, and bone repair. Cell polarity is essential to the normal function of all epithelial tissues and organ systems, and loss of cell polarity underlies cancer metastasis, thus understanding mechanisms of cell polarity establishment, as studied here, is of great significance to human health.

PI_NAMEs: MULLINS, MARY C. (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Adult;Alleles;Amyloid;Amyloid Proteins;Balbiani Body;Biological;Body System;bone morphogenetic protein receptor type I;Bone Morphogenetic Proteins;bone repair;Cardiovascular system;Cell Polarity;cell type;Cells;Complex;Congenital Abnormality;Defect;Development;Disease;Dissociation;Dorsal;egg;Embryo;Endodontics;Epithelium;Exhibits;Fiber;Germ Lines;Grant;Hallmark Cell;Health;Heterotopic Ossification;Human;Image;In Vitro;in vivo;Insecta;Kidney Diseases;Malignant Neoplasms;Mammals;Mediating;Medical;Membrane;Mitochondria;morphogens;Natural regeneration;Nature;Neoplasm Metastasis;Neurodegenerative Disorders;Oocytes;Oogenesis;Organ;Orthopedics;Outcome;Pattern;Phase Transition;Phosphotransferases;protein aggregation;Proteins;Proteomics;Pulmonary Hypertension;receptor;Regulation;Ribonucleoproteins;Role;Signal Transduction;Signaling Protein;Specific qualifier value;Structure;Therapeutic;Time;Tissue Engineering;Tissues;trafficking;vertebrate embryos;Vertebrates;Zebrafish

PROJECT_TITLE: Oocyte polarity and BMP-mediated dorsoventral patterning


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biodefense and Related Countermeasures;Brain Disorders;Dementia;Emerging Infectious Diseases;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

ORG_STATE: CA

PHR: Project Narrative The goal of this project is to develop a deeper understanding of the structure and function of proteins that contribute to the Transmissible Spongiform Encephalopathies and Alzheimer’s disease.

PI_NAMEs: MILLHAUSER, GLENN L (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Alzheimer's Disease;Amyloid beta-Protein;Anatomy;Binding;Binding Proteins;Binding Sites;Biochemical;biophysical techniques;Biophysics;Brain;Cell surface;Cells;Central Nervous System;Copper;Creutzfeldt-Jakob Syndrome;cytotoxicity;Dementia;Disease;Endocytosis;Exhibits;Fatal Familial Insomnia;Functional disorder;Glycoproteins;glycosylation;Goals;Grant;Inherited;Ions;Kuru;Label;learning strategy;Maps;Membrane;Membrane Proteins;Metal Ion Binding;Metals;Methods;Mitochondria;Molecular;monomer;Nerve Degeneration;Neurodegenerative Disorders;Neurons;neurotoxicity;Pathway interactions;Peptides;Peripheral;Polysaccharides;Prion Diseases;Process;programs;protein function;protein structure;protein transport;Proteins;PrP;PrPSc Proteins;pyruvate carrier;receptor;Research;Research Project Summaries;Role;Scrapie;Stress;Structure;Surface;Thermodynamics;Tissues;uptake;voltage;Zinc

PROJECT_TITLE: Discovering How Cu(II)/Zn(II) Uptake by the Prion Protein Controls Structure, Function and Neurotoxicity


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

ORG_CITY: BETHLEHEM

ORG_DEPT: BIOLOGY

ORG_NAME: LEHIGH UNIVERSITY

PHR: PROJECT NARRATIVE An all-encompassing goal of our laboratory is to understand the complex network of molecular interactions in various biological systems at the molecular level by developing necessary computational tools. This proposal aims to continue such efforts particularly on CHARMM-GUI for the biomolecular modeling and simulation community, G-LoSA-related tools for structural systems pharmacology, and GlycanStructure.ORG for glycan modeling and simulation and glycan binding site prediction. The proposed project is expected to provide a large and unique scope of research software tools for the biomedical research community to carry out innovative and novel biomolecular modeling and simulation research for the prevention and treatment of human disease.

PI_NAMEs: IM, WONPIL  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: advanced simulation;Binding;Binding Proteins;Binding Sites;Biological;Biological Process;biological systems;Biomedical Research;Catalysis;Cell Physiology;Communities;Complex;computerized tools;cyber infrastructure;Development;Goals;Graph;human disease;innovation;Laboratories;Ligands;macromolecule;Methods;models and simulation;Molecular;novel;Online Systems;Organism;Pharmacology;Polysaccharides;Prevention Research;protein protein interaction;Protein Region;Proteins;Proteomics;rational design;Reaction;Research;simulation;Software Tools;Structure;Surface;System;tool;Work

PROJECT_TITLE: Development of Computational Tools and Their Applications to Various Biological Systems


NIH_SPENDING_CATS: Microbiome

ORG_CITY: ATLANTA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Project Narrative Clinicians and researchers have established clear qualitative correlations between the gastrointestinal (GI) microbiome composition and various aspects of human health. Human microbial ecosystems are tremendously complex and – not surprisingly – are difficult to study at a quantitative level and harder still to manipulate in a prescriptive way. This project will use novel molecular (synthetic) biology tools that will allow us to unravel the detailed interactions and processes that drive the establishment of gut microbiota compositions and their impact on human physiology.

PI_NAMEs: WILSON, COREY J. (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Actinobacteria class;Bacteria;Bacteroidetes;Biology;Cells;Code;Complex;Decision Making;Development;Ecosystem;Evolution;Firmicutes;gain of function;gastrointestinal;gastrointestinal bacteria;Genotype;Goals;gut microbiome;gut microbiota;Health;Horizontal Gene Transfer;Human;Inherited;Investigation;Knowledge;loss of function;Maps;Memory;Microbe;microbial;microbial community;microbiome;microbiome composition;microbiota composition;mimicry;Modality;Molecular;novel;operation;Organoids;Outcome;Phenotype;Physiological;Physiology;Process;Regulation;Research;Research Personnel;Scientist;tool;tool development;Untranslated RNA;Work

PROJECT_TITLE: Domesticating and Mapping Interactions of the Human Gastrointestinal Microbiome


ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: PROJECT NARRATIVE Just as a person’s behavior can be influenced by their surroundings, so too can the functions of individual cells be influenced by the cell’s microenvironment. When cells attach to & ‘sample’ this environment – called the extracellular matrix – they form specialized structures called focal adhesions that not only help the cells attach but also report and control the status of that attachment. This project focuses on a powerful ‘reporting’ or signaling protein, called Protein Kinase A (PKA, for short), that we have recently found is active within focal adhesions, and proposes to investigate what keeps it there, what it’s controlling, and what it’s reporting – all with the hope that by learning more about this particular reporter, we will learn more about how cells are influenced by their surroundings.

PI_NAMEs: HOWE, ALAN K (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: A kinase anchoring protein;Adhesions;Behavior;Binding;Biochemical;Biological;Biophysics;Cell Adhesion;cell motility;Cells;Cellular Structures;Couples;Cyclic AMP-Dependent Protein Kinases;Environment;Event;Extracellular Matrix;Focal Adhesions;Individual;Instruction;Investigation;Learning;Life;Mechanics;mechanotransduction;Mediating;Modification;Molecular;Molecular Conformation;Persons;Phosphorylation;Phosphoserine;Phosphothreonine;Phosphotransferases;Phosphotyrosine;Protein Kinase;Protein Kinase Interaction;Proteins;Regulation;Reporter;Reporting;Sampling;Scaffolding Protein;Signal Transduction;Signaling Protein;Structure;Talin;Tyrosine Phosphorylation

PROJECT_TITLE: Mechanical Regulation of PKA Function in Cell Adhesion and Migration

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


ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY

ORG_STATE: TX

PHR: Project Narrative RNA can fold into three-dimensional structures that are essential for function and thus play critical roles in cellular biology and disease. Despite their profound therapeutic potential, structured RNAs remain underutilized targets for drug development due to difficulties associated with targeting RNA in a structure- specific manner. To overcome this challenge, the proposed research provides an innovative approach for developing structure-specific RNA-binding reagents, the results of which may lead to novel RNA-targeted therapeutics and new research tools to study RNA biology.

PI_NAMEs: SCZEPANSKI, JONATHAN THOMAS (contact)

PROJECT_TERMS: Address;Affinity;aptamer;Aptamer Technology;Base Pairing;Basic Science;Behavior;Binding;Biology;Biomedical Research;Biotechnology;Cell Communication;Cellular biology;Complex;Coupled;Development;Disease;DNA;drug development;drug discovery;Drug Targeting;enantiomer;Environment;Future;Image;improved;In Vitro;inhibitor;innovation;Intervention;Malignant Neoplasms;Mediating;MicroRNAs;new technology;next generation;novel;nuclease;Nucleic Acids;Nucleotides;Oligonucleotides;Oncogenic;Play;programs;Property;Reagent;Research;Resistance;Ribose;RNA;RNA Binding;RNA-targeting therapy;Role;Shapes;small molecule;stereochemistry;Structure;Structure-Activity Relationship;Technology;Therapeutic;three dimensional structure;tool;Vision;Work

PROJECT_TITLE: Mirror Image Aptamers: Next Generation RNA-Binding Reagents for Basic Research and Therapeutic Applications


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Genetics;Human Genome

PHR: PROJECT NARRATIVE Our genomes are packaged inside cells by wrapping around histone proteins to form chromatin. The histone proteins display chemical modifications that regulate genome processes, including gene expression. Our research program aims to understand how histone modifications control gene expression in normal cells and how this system is hijacked in diseases by visualizing the writers, readers, and erasers of histone modifications in action on chromatin.

PI_NAMEs: MCGINTY, ROBERT  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;anaphase-promoting complex;Binding;Biochemistry;Biological Models;Biological Process;Biophysics;Cell Cycle;Cell model;Cells;Cellular biology;Chemicals;Chromatin;chromatin protein;combinatorial;Complex;developmental disease;Disease;disease model;DNA;DNA Repair;drug discovery;Enzymes;Epigenetic Process;Gene Expression;Genome;genome integrity;genomic locus;Genomics;Health;histone modification;Histones;Homeostasis;Human;Knowledge;Lead;Maintenance;Malignant Neoplasms;Modification;Molecular;Molecular Biology;Mutation;Normal Cell;Nuclear;Nucleosomes;Pattern;Physiological;Post-Translational Protein Processing;Process;programs;protein function;Proteins;Proteome;Reader;recruit;Research;Resolution;Signal Transduction;structural biology;Structure;System;Testing;therapeutic development;therapeutic target;ubiquitin ligase;Visualization;Writing

PROJECT_TITLE: Molecular Mechanisms of Chromatin Recognition


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

ORG_CITY: MIAMI

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

ORG_STATE: FL

PHR: PROJECT NARRATIVE  The goal of this project is to develop new, robust, and versatile mass spectrometry- based tools capable of characterizing complex biomolecular systems and provide structural information, not accessible using traditional tools. The new technologies will be applied to model systems associated with several fundamental biological processes, including gene regulation, DNA repair, replication, transcription, translation, and recombination. In particular, the MS-based technologies proposed can study intrinsically disordered and dynamic biomolecular systems and will significantly advance our understanding of the biological machinery associated with disease mechanisms, identification of therapeutic targets and disease prevention.

PI_NAMEs: FERNANDEZ-LIMA, FRANCISCO  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Antibiotics;Area;Biological;biological development;Biological Models;Biological Process;Chromatin;Complex;Coupling;design;Development;Disease;disorder prevention;Dissociation;DNA;DNA biosynthesis;DNA Repair;DNA Topoisomerases;DNA-Protein Interaction;Electrons;Environment;Family;Gases;Gene Expression;Gene Expression Regulation;Genetic Recombination;Genetic Transcription;Goals;High Mobility Group Proteins;Histones;HMGA2 gene;HMGA2 Protein;instrument;intermolecular interaction;ion mobility;Ions;Label;Mass Spectrum Analysis;Methods;Molecular;Molecular Conformation;new technology;Nucleosomes;Phase;Post-Translational Protein Processing;Protein Family;Protein Isoforms;Proteins;Reaction;Research;Resolution;Solvents;Spectrometry;structural biology;Structure;System;Techniques;Technology;therapeutic target;tool;Topoisomerase;Translations;Variant

PROJECT_TITLE: Development of biological structural tools for the study of protein-DNA complexes


NIH_SPENDING_CATS: Aging;Congenital Structural Anomalies;Contraception/Reproduction;Estrogen;Genetics;Infertility;Menopause;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Germ cells are essential for fertility. Our long-term goal is to understand the mechanisms that regulate specification and maintenance of the germline. The immediate goal of our research is to investigate the function and contribution of conserved genes to stem cell specification and sex-specific development of the germline, which has implications for understanding normal reproductive development, Disorders of Sexual Differentiation, and fertility, areas of biomedicine greatly in need of more research.

PI_NAMEs: MARLOW, FLORENCE LOUISE (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Affect;Area;Biomedical Research;Cells;cellular imaging;Development;Dreams;Fertility;gender dysphoria;gene conservation;Genetic;genome-wide;Germ Cells;Germ Lines;Germ-Line Mutation;germline stem cells;Goals;Gonadal Dysgenesis;Gonadal structure;Health;Hormonal;Human;Infertility;Maintenance;Menopause;Molecular;multiple omics;neglect;Perimenopause;Population;Premature Ovarian Failure;preservation;prevent;programs;Puberty;Regulation;reproductive;reproductive development;reproductive success;Reproductive system;Research;Risk;RNA;sex;sex development disorder;Sex Differentiation Disorders;Sexual Development;Somatic Cell;Specific qualifier value;stem cell fate specification;Sterility;tool;Woman

PROJECT_TITLE: RNA regulation in germline development and fertility


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

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Given a person’s genome sequence, it remains challenging to make accurate and unbiased predictions about their risk for most diseases. We are developing computational methods that integrate recent advances in ma- chine learning, the wealth of available genomic data, and evolutionary perspectives to predict how any individ- ual’s unique combination of genetic variants influences the control of genes. These methods will enable identi- fication of new disease mechanisms and more accurate estimation of genetic risk for common diseases.

PI_NAMEs: CAPRA, JOHN ANTHONY (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Address;Africa;Alleles;Area;Basic Science;Biology;Chromosome Mapping;Clinical;Code;Computing Methodologies;Disease;disorder risk;DNA;DNA Sequence;Evolution;flexibility;functional genomics;Funding;Gene Expression;Gene Expression Regulation;Genes;Genetic Risk;genetic variant;Genetic Variation;Genome;genomic data;Grant;Human;human disease;Individual;Machine Learning;machine learning method;Manuscripts;Methods;Mission;Modeling;molecular phenotype;Mutation;Nucleic Acid Regulatory Sequences;Patients;Pattern;Persons;Phenotype;Population;Positioning Attribute;Preventive care;programs;Recording of previous events;Regulatory Element;Risk;Shapes;Source;success;Technology;Testing;trait;Transgenes;trend;Variant;Work

PROJECT_TITLE: The Evolution of Gene Regulation and Human Disease


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: The original Project Narrative document has not changed as a result of the proposed supplement activities.

PI_NAMEs: KAISER, PETER  (contact)

PROJECT_TERMS: Signal Transduction;Ubiquitin

PROJECT_TITLE: Ubiquitin and Metabolite Signaling


NIH_SPENDING_CATS: Genetics

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative New mutations often drive evolution of drug resistance in many bacterial pathogens and cancers or are responsible for host-range expansion in viruses, but our ability to predict such harmful evolution is limited because we do not have a fundamental theory of how new mutations affect important microbial pheno- types and fitness. The central goal of this proposal is to develop such a theory. To do so, my lab will construct mathematical models, measure the effects of mutations on intracellular phenotypes in experi- mentally tractable microbes and empirically observe how microbes evolve and adapt in both laboratory and semi-natural environments.

PI_NAMEs: KRYAZHIMSKIY, SERGEY A. (contact)

PROJECT_TERMS: Affect;Antibiotic Resistance;Architecture;Bacteria;Biochemical;Biochemical Pathway;Complex;Drug resistance;Environment;Escherichia coli;Evolution;fitness;Genetic;Genetic Drift;Genetic Recombination;Genetic Variation;Genotype;Goals;Laboratories;Malignant Neoplasms;marine;mathematical model;mathematical theory;Measures;Microbe;microbial;microbial community;Mutation;Natural Selections;Organism;Outcome;pathogenic bacteria;Pattern;Phenotype;Process;Research;Saccharomyces cerevisiae;Source;Structure;System;Theoretical Studies;theories;Time;tool;transcriptome;Virus;whole genome;Work;Yeasts

PROJECT_TITLE: Empirical and Theoretical Studies of Adaptive Mutations in Microbes and Their Evolutionary Consequences


ORG_CITY: ALBANY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT ALBANY

PHR: Project Narrative The coordinated activity of the large families of Protein Tyrosine Kinases (PTKs) and Protein Tyrosine Phosphatases (PTPs) regulates the function of proteins involved in a plethora of cellular processes, and the disruption of this PTK-PTP balance has been linked to the etiology of several diseases. The oxidation and reduction mechanisms that regulate the catalytic activity of members of the PTP family are far more complex than anticipated, and we now have important insights into new modes of PTP regulation by redox molecules that can potentially be leveraged for novel therapeutic approaches that activate phosphatases in vivo.

PI_NAMEs: BOIVIN, BENOIT  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Biological;Cell Physiology;Cells;Cholesterol;Complex;Coupled;Cysteine;Disease;Enzymes;Equilibrium;Etiology;Family;Goals;Hydrogen Peroxide;in vivo;insight;Knowledge;Link;Mediating;member;Modality;novel;novel therapeutic intervention;Oxidants;oxidation;Oxidation-Reduction;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Pilot Projects;Production;Productivity;programs;Protein Dephosphorylation;Protein Family;protein function;Protein Kinase;Protein Tyrosine Kinase;Protein Tyrosine Phosphatase;Proteins;Publishing;Regulation;Research;Resources;response;Seminal;Signal Transduction;Signaling Protein;small molecule;Therapeutic;translational potential

PROJECT_TITLE: Complexity of Protein Tyrosine Phosphatase Oxidation


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Characterizing the Molecular Basis of Supergene Mimicry in Butterflies Project Narrative Humans have pronounced sexual dimorphism with a number of diseases and traits exhibiting sex-limited polymorphism. My proposal is aimed at characterizing the genetic and developmental basis of sex-limited polymorphism in a mimetic butterfly. This work will greatly expand the known role of the sex determination pathway, and generate general insights into molecular and cellular causes of sexual differentiation, dimorphism, and sex-limited polymorphism.

PI_NAMEs: KRONFORST, MARCUS  (contact)

PROJECT_TERMS: Animals;Architecture;Behavior;Behavioral;Biodiversity;Biological;Biological Assay;Butterflies;CRISPR/Cas technology;Development;Developmental Biology;dimorphism;Disease;Evolution;Exhibits;experimental study;functional genomics;gene regulatory network;Genes;Genetic;Genetic Polymorphism;Genetic Processes;genome editing;Genomics;Goals;Human;insight;Investigation;lens;Life;mimetics;mimicry;Molecular;Molecular Biology;Molecular Genetics;Mutation;Natural Selections;Nature;Neurobiology;novel;Organism;Pathway interactions;Pattern;Phylogeny;Planet Earth;Population Genetics;Process;Recording of previous events;Research;Role;sex;sex determination;Sex Differentiation;sexual dimorphism;sexual role;success;System;Techniques;Time;tool;trait;Wing;Work


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: NEW YORK

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative Typical human cells contain 46 chromosomes, but most cancer cells have abnormal numbers of chromosomes, often accompanied with aberrant structural changes. The most fundamental structural component of chromosomes is the nucleosome. We develop innovative methods to understand how the nucleosome structure and function are regulated to sense and prevent these chromosome alterations.

PI_NAMEs: FUNABIKI, HIRONORI  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: 3-Dimensional;Binding;cancer cell;Cell Cycle Stage;Cell Extracts;Cell Proliferation;Cell-Free System;Cells;Centromere;Chromosome abnormality;chromosome number abnormality;Chromosome Structures;Chromosomes;Complex;Cryoelectron Microscopy;Cyclic GMP;Development;Disease;DNA;DNA Methylation;DNMT3B gene;egg;Event;Failure;HELLS gene;Human;Immunodeficiency and Cancer;immunodeficiency-centromeric instability-facial anomalies syndrome;Induction of Apoptosis;Inflammation;innovation;Link;Malignant Neoplasms;Methods;Mitotic;Mitotic Chromosome;Molecular;Mutation;Natural Immunity;Nonhomologous DNA End Joining;Nucleoproteins;Nucleosomes;Organism;paralogous gene;Pathogenicity;Pattern;prevent;Process;programs;receptor;Regulation;Reporting;Research;Resolution;Role;Signal Transduction Pathway;Structure;Xenopus

PROJECT_TITLE: Regulation of chromosome inheritance and integrity


NIH_SPENDING_CATS: Genetics;Infectious Diseases;Microbiome

ORG_CITY: STANFORD

ORG_DEPT: GENETICS

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Evolution underlies the emergence of drug resistance in infectious diseases, as well as the progression of cancer. This research will characterize and contrast evolutionary outcomes and their trade-offs from both abiotic and biotic selection pressures. A detailed understanding of such evolutionary outcomes opens the possibility of predicting evolutionary trajectories and improving the design of multi-drug therapy for better patient outcomes.

PI_NAMEs: SHERLOCK, GAVIN J (contact)

PROJECT_TITLE: Fitness Effects of Beneficial Mutations


ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Project Narrative Metabolomics will play a key role in identifying metabolites that are mechanistically important and biologically active. We will continue to build upon our metabolomics platform and previously developed key technologies within the context of biomedical applications to identify biomarkers, characterize pathway and systems biology perturbations, and facilitate the identification of active metabolites. Our platform will provide insight into disease mechanisms, facilitate existing drug therapies, and identify novel endogenous metabolite therapeutics.

PI_NAMEs: SIUZDAK, GARY E (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;Area;bioinformatics tool;Biological;biological systems;Biology;biomarker discovery;biomarker identification;Biomedical Research;Cell Maturation;cloud based;cognitive computing;Communities;Data;Data Analyses;data integration;Data Sources;Databases;Development;Diabetes Mellitus;Disease;Environmental Exposure;exhaustion;Faculty;Funding;Goals;Immune response;Immunotherapy;improved;insight;ion mobility;Malignant Neoplasms;Mass Spectrum Analysis;Measurement;Measures;Metabolic;Metabolism;metabolomics;Modeling;Molecular;multiple sclerosis treatment;Natural regeneration;Nervous System Disorder;novel;oligodendrocyte progenitor;organ repair;Participant;Pathway Analysis;Pathway interactions;Pharmacotherapy;Phenotype;Play;precision medicine;Process;Research;Research Personnel;Spectrometry;Systems Biology;T-Lymphocyte;Technology;Therapeutic;Time;user-friendly;virology;Work

PROJECT_TITLE: Metabolomics Technologies to Advance Biomedical Research


ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE Organisms acquire genetic information that could help or hurt the species. This project will study how organisms identify genes and decide whether to turn them on or off at each generation. This work will reveal conserved pathways that control inherited gene regulation.

PI_NAMEs: MELLO, CRAIG C (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Animals;Caenorhabditis elegans;Cell Nucleus;Cells;Chloroplasts;Chromatin;Communication;Complex;Dangerousness;Disease;DNA;Double-Stranded RNA;Ensure;Equilibrium;Gene Expression;Gene Expression Regulation;Generations;Genes;genetic information;Genome;Germ Lines;Guide RNA;Heterochromatin;Human;Inherited;innovation;insight;Investigation;Licensing;Life Cycle Stages;Mathematics;Messenger RNA;Nuclear;offspring;Organism;Pathway interactions;piRNA;Process;RNA;RNA Binding;RNA Interference;RNA-Binding Proteins;Signal Transduction;Small RNA;Source;Specificity;System;Time;transcriptome;Work

PROJECT_TITLE: Investigation of RNA interference and related gene regulatory mechanisms


PHR: PROJECT NARRATIVE  The folding of a genome into specific 3D structures is essential for organizing functional interactions between gene promoters and distant enhancers, but the elements and features that regulate these interactions are poorly characterized. We will develop a series of complementary approaches to functionally identify the genetic determinants of this largely uncharted level of regulation of gene expression, determine how genetic variants within these elements may affect their activity, and ultimately design new ways to manipulate enhancer-promoter interactions. By better understanding the nature and the determinants of the activity of these elements, we will be able to assess the impact of genomic alterations better and predict the physiological consequences of structural variants found in patients.

PI_NAMEs: SPITZ, FRANCOIS  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: 3-Dimensional;Address;Affect;Architecture;Cell model;cell type;Complex;Data;design;Development;Distant;DNA Sequence Alteration;Elements;Embryonic Development;Enhancers;Epigenetic Process;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic;Genetic Determinism;Genetic Transcription;genetic variant;Genome;Genome engineering;genome-wide;genomic locus;Genomics;Human;Human Genome;Human Pathology;innovation;insight;Instruction;Light;Link;Malignant Neoplasms;Measures;Modeling;mouse model;Nature;Patients;Pattern;Phenotype;Physiological;Play;Process;Program Development;promoter;Quantitative Genetics;Regulation;Regulatory Element;Research;Role;Series;Specificity;System;three dimensional structure;tool;trait;transcriptomics;Untranslated RNA;Variant;vertebrate genome;Vertebrates

PROJECT_TITLE: Genetic and Epigenetic Controls of Enhancer-Promoter Interactions


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Infectious Diseases;Wound Healing and Care

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: Project Narrative The goal of this application is to develop broadly enabling synthetic biology tools and strategies for engineering yeast biosensors, yeast therapeutics, and yeast sense-respond communities. To meet this goal, we plan to develop yeast that can sense different bacterial infections in wounds, secrete different antibiotics in wounds, and finally can secrete specific antibiotics in response to the bacteria present in the wound.

PI_NAMEs: CORNISH, VIRGINIA W (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Antibiotics;arm;Bacteria;Bacterial Infections;Biosensor;Cells;cellular engineering;Communities;Disease;Engineering;Genetic;Goals;human disease;In Situ;Mammalian Cell;Methods;Pharmaceutical Preparations;Positioning Attribute;protein purification;Research;response;Saccharomyces cerevisiae;Site;small molecule;synthetic biology;Technology;Therapeutic;Therapeutic community technique;tool;wound;wound healing;Yeasts

PROJECT_TITLE: Living Yeast Sense-Respond Therapeutic Communities Engineered with Synthetic Biology


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Using active electronic health records (EHR), the parent grant will develop a Passive Digital Marker for the Prediction of Childhood Asthma Treatment Response to reduce errors in identifying at-risk children and can enable clinicians to scale up treatment decisions that are cost-effective, feasible, and timely. The proposed project will focus on one aspect of the parent project, i.e., adding hematologic markers, an important component of child nutrition and asthma care that may modify treatment response. The proposed project will use existing EHR data on hematologic tests and ML decision-rules- based algorithm from the parent study to assess the role of iron status on asthma treatment response.

PI_NAMEs: OWORA, ARTHUR HAMIE (contact)

PROGRAM_OFFICER_NAME: MILLS, JUSTIN

PROJECT_TITLE: Effect of iron status trajectories on lung function and asthma risk

STUDY_SECTION: HITR

STUDY_SECTION_NAME: Healthcare Information Technology Research[HITR]


ORG_CITY: HOUSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE The bacterial type IV secretion systems are widely used by many medically important pathogens for transfer of mobile genetic elements that harbor genes for antibiotic resistance and for formation of antibiotic-resistant biofilms. These systems also are deployed by many pathogens to deliver virulence factors into the human host to aid in infection processes. The type IV secretion systems are relevant for public health as they represent novel targets for therapeutics directed to blocking antibiotic resistance spread, production of robust biofilms, and disease progression.

PI_NAMEs: CHRISTIE, PETER J. (contact)

PROJECT_TERMS: Antibiotic Resistance;Architecture;Back;Bacteria;Bacterial Adhesins;Bacterial Genome;Biochemical;Biogenesis;Biological;cell envelope;Cell surface;Cells;Chromosomes;Collaborations;Cryo-electron tomography;Cryoelectron Microscopy;Derivation procedure;Disease Progression;DNA;Emerging Technologies;Escherichia coli;F Factor;Fimbriae Proteins;fitness;Fluorescence Microscopy;Genes;Genetic Recombination;Genetic study;Human;In Situ;in vivo;Infection;Investigation;Knowledge;Label;macromolecule;Maleimides;Mediating;Medical;Membrane;Microbial Biofilms;Mobile Genetic Elements;Modeling;multidisciplinary;nanomachine;new therapeutic target;particle;Partner in relationship;pathogen;Pilum;polymicrobial biofilm;Population;Process;Production;Proteins;Public Health;recruit;Research Support;Resolution;Route;Science;Sex Pili;Shapes;Site;Structure;Structure-Activity Relationship;Surface;System;Therapeutic Intervention;therapy design;trait;transmission process;Type IV Secretion System Pathway;ultra high resolution;vector;Virulence Factors

PROJECT_TITLE: Biological and structural diversity of bacterial type IV secretion systems


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

ORG_CITY: SAINT LOUIS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The past decade has witnessed significant interest in the isolation of “naïve” human pluripotent stem cells that more closely resemble pluripotent cells found in the human blastocyst in vivo. However, naïve human pluripotent stem cells generated with currently available methods display irreversible erasure of parent- specific imprinting, retain an epigenetic memory of the inactive X chromosome in female cells, and are not directly responsive to embryonic lineage cues. This proposal will design rational strategies to resolve this epigenetic instability and establish a robust in vitro platform to model early human development and X- linked disorders.

PI_NAMEs: THEUNISSEN, THOROLD  (contact)

PROJECT_TERMS: Biomedical Research;blastocyst;Cell Line;Cells;Chemicals;Competence;Cues;Data;Development;Disease;DNA Methylation;Ectoderm;Embryo;Endoderm;Epiblast;epigenetic memory;Epigenetic Process;epigenome editing;Female;genetic approach;Genetic Induction;Genetic Transcription;Germ Layers;Goals;Human;Human Development;human disease;human model;human pluripotent stem cell;human stem cells;Impairment;implantation;imprint;In Vitro;in vivo;interest;Link;Maintenance;Mesoderm;Methods;Modeling;natural Blastocyst Implantation;Parents;phosphoproteomics;pluripotency;preimplantation;preservation;Property;Publishing;rational design;Regulatory Element;Reporter;Research;Signal Transduction;Stem Cell Research;Work;X Chromosome

PROJECT_TITLE: Resolving epigenetic instability during pluripotent state transitions: a roadmap for exploiting the biomedical potential of dynamic human stem cell states


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative: Our research will generate fundamental knowledge on how cells divide, how microtubules are organized and protected from chemical damage, and how neurons maintain viability over decades. This knowledge will help spur new treatments for cancer, inflammatory disease and motor neuron disease (ALS).

PI_NAMEs: MITCHISON, TIMOTHY J (contact)

PROJECT_TERMS: amyotrophic lateral sclerosis therapy;Biochemistry;Biological Models;Biology;Biopsy;cancer therapy;Cell Communication;Cell division;Cells;Cellular Structures;Chemicals;Congenital Abnormality;Cultured Cells;Cytoprotection;Disease;egg;Filament;Genetic;Glioblastoma;Health protection;Human;human disease;Image;Individual;Inflammation;Inflammatory;interest;Knowledge;Lipids;Malignant Neoplasms;Measures;Mechanics;Microscopy;Microtubules;Mitosis;Motor Neuron Disease;Motor Neurons;Movement;Nerve Degeneration;Neurons;Normal Cell;Pharmaceutical Preparations;Phosphotransferases;Proteins;Rana;Research;Role;stathmin;Testing;Tubulin;Work;Xenopus

PROJECT_TITLE: Cell and Chemical Biology of Microtubules

STUDY_SECTION: MRAD

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


ORG_CITY: BOZEMAN

ORG_NAME: MONTANA STATE UNIVERSITY - BOZEMAN

ORG_STATE: MT

PHR: Project Narrative The goal of this project is to develop fundamental chemical insight into the mechanisms of radical initiation and control in radical SAM enzyme reactions. Radical SAM enzymes are remarkable biological catalysts that carry out difficult and unusual chemical reactions; their presence in humans as well as in both beneficial and pathogenic microbes lends high significance to understanding their fundamental properties and mechanisms. With better understanding of radical SAM reactions and mechanisms, these enzymes could serve as pharmaceutical targets to treat infections and/or disease, and as tools to synthesize new bio-derived therapeutic agents.

PI_NAMEs: BRODERICK, JOAN B (contact)

PROJECT_TERMS: Alzheimer's Disease;Antibiotics;beneficial microorganism;Biochemical;Biological;Biology;catalyst;chemical property;chemical reaction;Chemicals;cofactor;Complex;Disease;DNA Repair;Electron Nuclear Double Resonance;Electron Spin Resonance Spectroscopy;Enzymes;formate acetyltransferase activating enzyme;Freezing;Goals;Human;Individual;Infection;insight;Life;member;Metals;Modification;pathogenic microbe;Peptides;Pharmacologic Substance;Process;Property;Proteins;Reaction;Research;Ribosomes;System;Therapeutic Agents;time use;tool;X-Ray Crystallography

PROJECT_TITLE: Radical SAM Enzymes: Radical Mechanisms Central to Biology


ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE The slow pace of drug discovery is often defined by a limited pool of chemical compounds used to detect drug candidates, and inefficient try-and error approaches to designing and optimizing new ligands. Computational technologies being developed by our group, including V-SYNTHES Giga- and Terra-scale screening and structure based design of ligands with new functional properties, will enable rapid discovery of chemical probes and streamline early drug discovery efforts for challenging targets in key human conditions like pain, drug abuse, Alheimer, and cancer.

PI_NAMEs: KATRITCH, VSEVOLOD  (contact)

PROJECT_TERMS: Alzheimer's Disease;Biochemical;Biological Assay;Chemicals;Clinical;clinically relevant;computational platform;Data;design;DNA;Drug abuse;drug candidate;drug discovery;drug testing;experience;Human;Hybrids;improved;in vivo;Libraries;Ligands;Machine Learning;Malignant Neoplasms;Methods;novel;Pain;Performance;pharmacologic;Process;Property;rational design;Research;screening;Structure;Substance abuse problem;Technology;therapeutic target;tool;Validation;virtual screening

PROJECT_TITLE: Computational approaches to discover ligands with new chemotypes and functional properties


ORG_CITY: RIVERSIDE

ORG_DEPT: ZOOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: PROJECT NARRATIVE  Signaling lipids, such as steroids, terpenoids, and eicosanoids, are critical regulators of animal physiology. However, in contrast to proteinaceous signaling molecules such as peptide hormones and cytokines, modern molecular genetic tools have not been fully utilized for studying signaling lipids. This project aims to fill existing knowledge gaps regarding modes of action of signaling lipids, particularly concerning their transmembrane transport mechanisms, using fruit fly genetics.

PI_NAMEs: YAMANAKA, NAOKI  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Animals;Cell membrane;Cells;cytokine;Development;Diffuse;Drosophila genus;Ecdysone;Eicosanoids;Endocrinology;Ensure;Genes;Genetic;Hormones;Human;Immune response;in vivo;Insecta;Juvenile Hormones;Knowledge;Lipids;lipophilicity;Mediating;Membrane Transport Proteins;Modeling;Modernization;Molecular Genetics;novel;peptide hormone;Personal Satisfaction;Physiological Processes;Physiology;Reproduction;Research;Research Personnel;Signal Pathway;Signal Transduction;Signaling Molecule;steroid hormone;Steroids;Terpenes;tool;Transmembrane Transport

PROJECT_TITLE: Molecular genetics of signaling lipids


ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative Gene regulation is essential for proper cell function. We use the worm Caenorhabditis elegans as a model organism to elucidate the basic molecular mechanisms that regulate gene expression. Our research has the potential to provide insights into human health, because many of the proteins we study is conserved across worm to humans, and their homologs have been found to be disrupted in diseases such as cancers.

PI_NAMEs: ERCAN, SEVINC  (contact)

PROJECT_TERMS: Address;Area;Binding;Binding Proteins;Caenorhabditis elegans;Cell Cycle;Cell division;Cell Nucleus;Cell Physiology;cell type;Cells;Chromatin;Chromatin Remodeling Factor;Chromatin Structure;Chromosomes;cohesin;Complex;condensin;Development;Disease;Distant;DNA;DNA Polymerase III;Dosage Compensation (Genetics);Eukaryota;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genome;Health;Hermaphroditism;histone modification;Homologous Gene;Human;in vivo;Individual;insight;Interphase;Life;Maintenance;Malignant Neoplasms;Mediating;Mitosis;Mitotic;model organism;Molecular;Nematoda;Organism;programs;Proteins;Regulation;Regulatory Element;Repression;Research;RNA;RNA Polymerase III;Site;System;Transcriptional Regulation;Transfer RNA;Translations;Untranslated RNA;Work;X Chromosome

PROJECT_TITLE: Mechanisms of condensin-mediated gene regulation in C. elegans


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

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS ENGINEERING EXPERIMENT STATION

PHR: Project Narrative Mechanisms by which gene variations, especially protein mutations, cause diseases or confer drug- resistance are critical to diagnostics and treatments but are unfortunately often unknown. This project will develop a systematic and rigorous computational framework that will interface with experimental data both ways to discover and validate mechanisms behind variants. It will also facilitate infrastructures for trans- disciplinary collaborations among computational, experimental, and clinical researchers.

PI_NAMEs: SHEN, YANG  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: biobank;Biological;Clinical;clinically significant;Code;Collaborations;Communities;computer framework;Computing Methodologies;Data;data integration;data platform;design;Diagnostic;Disease;disease phenotype;Disease Resistance;Drug resistance;Experimental Designs;experimental study;Feedback;Friends;generative models;Genes;genetic variant;genomic data;Goals;graph learning;Healthcare;human disease;Infrastructure;interdisciplinary collaboration;Knowledge;Learning;Ligands;Machine Learning;Molecular;molecular modeling;multimodal learning;Mutagenesis;Mutation;Pathway Analysis;Phenotype;phenotypic data;Physics;Predisposition;prognostic;Protein Engineering;Proteins;Research;Research Personnel;Resources;response;System;Testing;Therapeutic;therapeutically effective;Translating;Variant

PROJECT_TITLE: Unraveling molecular and system-level mechanisms of human disease-associated protein mutations


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

ORG_CITY: MIAMI

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

PHR: Project Narrative The proposed research is relevant to public health because understanding Mass Spectrometry (MS) based omics can allow systematic analysis of thousands of proteins with the promise of discovering new proteins, and biomarkers for various disease conditions and better understanding of human systems biology. Artificial intelligence and machine- learning tools are needed to explain the high-dimensional MS data and such accurate tools will be instrumental in elucidating the microbiome and cell function which affects virtually all aspects of human health. Therefore, this MIRA proposal is relevant to NIH’s broader mission which support fundamental and innovative research strategies which can become the basis of protecting and improving human health.

PI_NAMEs: SAEED, FAHAD  (contact)

PROJECT_TERMS: Affect;algorithmic methodologies;Algorithms;Artificial Intelligence;Big Data;Biological Markers;Cell Physiology;Communities;Complex;complex data;Computational Technique;Computing Methodologies;Data;Data Analyses;data quality;Data Set;design;Development;Disease;Exhibits;expectation;experimental study;Foundations;Funding;generative models;Goals;Grant;Health;high dimensionality;Human;improved;innovation;Investigation;Knowledge;Label;Learning;Libraries;Machine Learning;machine learning model;Mass Spectrum Analysis;metaproteomics;Methods;microbiome;Mission;Modeling;novel;Outcome;Peptides;Predisposition;Proteins;proteogenomics;Proteomics;Public Health;Reproducibility;Research;Scientist;software infrastructure;Systems Biology;tool;Traction;Training;Uncertainty;United States National Institutes of Health;virtual;wasting;Work

PROJECT_TITLE: Machine-Learning Models for big data omics


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative The cell membrane is the only organelle shared by all varieties of life. Unequal distribution of ions across selectively permeable lipid bilayers results in the generation of an electrical potential, or voltage. Our research program seeks to develop and apply methods to optically measure bioelectrical signals between and within cells outside of the brain.

PI_NAMEs: MILLER, EVAN WALKER (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Address;bioelectricity;Brain;Budgets;Cancerous;Cell Cycle Progression;Cell membrane;Cell Physiology;cell type;Cell Volumes;Cells;Cellular biology;Chemicals;Chemistry;Circadian Rhythms;Development;Dyes;Ecosystem;electric field;electrical potential;Electrodes;Energy Metabolism;fluorophore;Generations;Heart;Intracellular Membranes;Ion Channel;Ions;Life;Link;Lipid Bilayers;live cell imaging;Measures;Membrane Potentials;Methodology;Methods;Morphologic artifacts;Muscle;Optical Methods;Optics;Organ;Organelles;Permeability;Pharmaceutical Preparations;Physiology;programs;Proliferating;Regulation;Research;Shapes;Signal Transduction;Synthesis Chemistry;translational approach;tumor;Visualization;voltage

PROJECT_TITLE: Chemical Approaches to Visualize and Quantify Cellular Physiology


NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence

ORG_CITY: NORFOLK

ORG_NAME: OLD DOMINION UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative This project will help biological electron microscopists bridge a broad range of resolution levels, from the atomic to the living organism. The results of our research in electron microscopy and tomography will be new computer codes for modeling the structures of macromolecular assemblies. As the basic functional units of biological cells, macromolecular assemblies furnish targets for drug design because deficiencies in the assembly architecture are frequently linked to health problems.

PI_NAMEs: WRIGGERS, WILLY R (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TITLE: Multi-Resolution Docking Methods for Electron Microscopy


ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Narrative The transfer of protein coding information from our genome to the protein synthesis machinery occurs through a messenger RNA (mRNA) intermediate. Defective mRNA processing contributes to many human diseases including cancer, spinal muscular atrophy, cystic fibrosis and diabetes in complex ways that are poorly understood. This project will improve human health through the identification of regulatory sequences and mechanisms controlling two of the most important aspects of RNA processing, alternative pre-mRNA splicing and mRNA translation.

PI_NAMEs: SANFORD, JEREMY ROBERT (contact)

PROJECT_TERMS: Affinity Chromatography;Alleles;Alternative Splicing;Biochemical;Biochemistry;Biological Assay;Cell Line;Cells;Chromosomes;Code;Complement;Complex;Cystic Fibrosis;Diabetes Mellitus;Elements;Environment;Exhibits;Funding;Gene Expression;Genes;Genome;Genomics;Goals;Health;Hereditary Disease;Human;human disease;improved;insight;Malignant Neoplasms;Messenger RNA;Modeling;Molecular;Molecular Biology;novel;novel strategies;Nucleotides;Pan Genus;Pattern;Polyribosomes;Post-Transcriptional Regulation;Process;Protein Biosynthesis;protein function;Protein Isoforms;Proteins;Regulation;Regulatory Element;Reporter;RNA;RNA Processing;RNA Stability;RNA, Messenger, Splicing;RNA-Binding Proteins;Role;Spinal Muscular Atrophy;Translations;Untranslated RNA

PROJECT_TITLE: Regulation of mRNA Fate


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: American Indian or Alaska Native;Arctic;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Suicide;Suicide Prevention

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative Our proposal addresses American Indian/Alaska Native (AIAN) youth suicide, an urgent health inequity that is difficult to address in underserved rural and remote AIAN communities. We test a promising translational intervention that leverages strong social networks in rural AN communities to increase uptake of evidence-based and culturally responsive suicide prevention strategies, with a goal of reducing the risk of suicide and promoting safety and mental health of young people in AIAN communities. This kind of evidence-informed, community-led intervention has potential to scale to other AIAN and underserved communities to address the growing crisis of youth suicide.

PI_NAMEs: WEXLER, LISA M. (contact)

PROGRAM_OFFICER_NAME: ROONEY, MARY

PROJECT_TERMS: Address;Adult;affection;Age;Air;Alaska Native;American Indians;Anxiety;Behavior;behavior change;behavioral health;Buffers;care seeking;Caring;Collaborations;Communities;Community Health Aides;community led intervention;Community of Practice;Community Practice;Community Workers;comparison group;contagion;design;Diffusion;Distress;dosage;education pathway;Educational Materials;effectiveness testing;efficacy/implementation trial;Elderly;evidence base;experience;Family;Feeling suicidal;firearm access;Friends;Future;Goals;Growth;Harm Reduction;Health;health inequalities;help-seeking behavior;Home;Hour;Human Resources;implementation barriers;implementation framework;implementation study;improved;Intervention;Intervention Studies;Knowledge;Learning;Measures;member;Mental Depression;Mental Health;Mental health promotion;Mental Health Services;Mentors;Methodology;Methods;Modeling;Native Americans;native youth;non-Native;Occupations;Outcome;Output;Parents;Participant;Patient Self-Report;Personal Satisfaction;Persons;prevent;Prevention;Prevention Research;Prevention strategy;preventive intervention;Process;protective factors;Psyche structure;Random Allocation;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Readiness;recruit;reducing suicide;Reporting;Research;Risk;Risk Reduction;Role;Rural;rural Alaska;rural Americans;rural underserved;Safety;Schools;Self Efficacy;Series;social;Social Network;social stigma;Social support;Structure;Students;suicidal risk;Suicide;Suicide prevention;suicide rate;teacher;Testing;therapy resistant;Time;Training;Translating;Tribes;Trust;underserved community;uptake;virtual;Well in self;Work;young adult;Youth

PROJECT_TITLE: Intervention Research to Improve Native American Health

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


PHR: Project Narrative The maintenance of telomeres by telomerase is necessary to support continued cell growth. Telomere and telomerase dysfunction arise in the large majority of human cancers and certain rare genetic syndromes. This work will signiﬁcantly advance our understanding of the molecular mechanisms governing telomere length control and pave the way for the development of novel therapeutic interventions for human disease.

PI_NAMEs: STONE, MICHAEL D (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Apoptosis;Biochemical;Biology;biophysical techniques;Cell Aging;Cell division;cell growth;chromatin remodeling;chromosome fusion;Chromosomes;Compensation;Complex;Development;Disease;DNA;DNA Damage;Enzymes;flexibility;Functional disorder;Funding;Genetic;genome integrity;Homeostasis;Human;human disease;insight;Laboratories;Length;Malignant Neoplasms;Methodology;Modeling;Molecular;Molecular Conformation;National Institute of General Medical Sciences;novel;novel therapeutic intervention;Pathology;Pathway interactions;Positioning Attribute;prevent;Preventive measure;Protein Subunits;Proteins;recruit;Regulation;Research;Resources;response;RNA-Directed DNA Polymerase;single molecule;spatiotemporal;Structure;Syndrome;Telomerase;Telomerase RNA Component;telomere;Telomere Maintenance;Vertebrates;Work;Yeasts

PROJECT_TITLE: Structure and Dynamics of Telomeres and Telomerase


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Cells assemble functionally diverse actin cytoskeleton networks to facilitate a wide range of fundamental processes such as cytokinesis, motility, and polarization. We are investigating how cells simultaneously self-organize multiple actin filament networks at the correct time and place from a common pool of actin monomers and actin regulatory proteins. Understanding the underlying molecular mechanisms that govern actin cytoskeleton self-organization will help elucidate the general rules by which cells assemble and maintain large, macromolecular structures and organelles.

PI_NAMEs: KOVAR, DAVID R (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actin-Binding Protein;Actins;Address;Architecture;Binding;Biochemical;Biological Models;Caenorhabditis elegans;cell assembly;Cells;Characteristics;Cytokinesis;Cytoplasm;Cytoskeleton;density;Embryo;F-Actin;Fission Yeast;G Actin;genetic regulatory protein;Goals;Microfilaments;Molecular;Molecular Structure;monomer;Motility;Organelles;Peptide Initiation Factors;Play;Process;profilin;Property;Proteins;recruit;Role;self organization;Sorting;System;Time

PROJECT_TITLE: Actin Cytoskeleton Network Self-Organization


NIH_SPENDING_CATS: Regenerative Medicine

ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative The ability of thousands of cells to coordinate their behaviors is a critical part of healing and regeneration, organ assembly, and even invasive disease. This MIRA takes a ‘rules and tools’ approach to such collective cell behaviors, working to improve both our understanding of these phenomena as well as our ability to control how large groups of cells behave. This work is firmly motivated by biomedical needs, and progress here may help to accelerate injury healing, delay invasive disease progression, and better grow organs for regenerative medicine.

PI_NAMEs: COHEN, DANIEL  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acceleration;Area;Behavior;bioelectricity;cell behavior;Cell division;cell motility;Cells;Collection;Complex;Cues;Disease;Disease Progression;Gene Activation;Gene Expression Profile;Goals;healing;improved;Injury;Motion;Natural regeneration;Normal tissue morphology;Organ;Process;programs;Regenerative Medicine;regenerative tissue;Research;response;Shapes;Sheep;stem cell differentiation;Tissue Engineering;Tissues;tool;Work

PROJECT_TITLE: Understanding and controlling collective cell behaviors


ORG_CITY: CHESTNUT HILL

ORG_NAME: BOSTON COLLEGE

ORG_STATE: MA

PHR: Project Narrative Nature has essentially bypassed the element boron in the evolution of life. We are developing synthetic technologies to include the element boron in organic small molecules and biologically relevant macromolecules and thereby expand the chemical and functional space beyond what Nature can achieve. New boron-specific tools for synthetic and biomedical research will be developed as part of this work.

PI_NAMEs: LIU, SHIH-YUAN  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Expanding the Chemical and Functional Space with Boron-Nitrogen Heterocycles


ORG_CITY: STANFORD

ORG_DEPT: BIOPHYSICS

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Mitochondrial membrane transport proteins are vital for cellular energetics and signaling. Our goal is to elucidate the molecular workings of three key mitochondrial transport systems, addressing critical knowledge gaps in the field. The insights gained from these studies will reveal new facets of normal physiology and pathophysiology, facilitating the development of targeted, mechanism-driven therapeutic drug candidates.

PI_NAMEs: FENG, LIANG  (contact)

PROJECT_TERMS: Address;Calcium;Calcium Signaling;calcium uniporter;Cardiovascular Diseases;Carrier Proteins;conformational conversion;Cytosol;Defect;Development;Disease;drug candidate;Drug Targeting;Functional disorder;glucose transport;Goals;inhibitor;insight;interdisciplinary approach;Ions;Knowledge;Mediating;Membrane;Membrane Proteins;Membrane Transport Proteins;Metabolic;Metabolic Diseases;Mitochondria;Mitochondrial Matrix;mitochondrial membrane;Molecular;Movement;Neurodegenerative Disorders;novel;novel therapeutics;Pathology;Pathway interactions;Patients;Physiology;Play;Process;Production;Pyruvate;pyruvate carrier;rational design;Regulation;Role;Signal Transduction;small molecule;System;Therapeutic;Transmembrane Transport;Transport Process;uptake;Veins;Work

PROJECT_TITLE: Molecular mechanisms of mitochondrial membrane transport systems in cellular energetics


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative The research proposed here uses Drosophila as a model system to investigate the consequences of variation in genome structure by employing state-of-the-art genomics techniques to discover genetic variation previously overlooked by older techniques. Such mutations are often in repetitive regions of the genome and, in humans, are often associated with traits important for human health and well-being, including disease causing mutations (like those often found in cancer or genetic diseases like Huntington's disease) as well as mutations common in disease vectors (like those that confer insecticide resistance in mosquitoes). This research will lead to a greater understanding of how genome structural changes impact evolution and the development tools to enhance discovery of such mutations.

PI_NAMEs: EMERSON, JAMES JORDAN (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Biological Models;Catalogs;Chromosomes;cost effectiveness;Culicidae;Disease Vectors;disease-causing mutation;DNA Sequence Alteration;Drosophila genus;Drosophila melanogaster;Equipment and supply inventories;Evolution;Exhibits;functional genomics;Gene Duplication;Genetic;Genetic Diseases;Genetic Variation;Genome;genome sequencing;Genomics;Genotype;Goals;Health;Human;human disease;Huntington Disease;Individual;Insecticide Resistance;Maintenance;Malignant Neoplasms;Measurement;Methods;Mutation;Personal Satisfaction;pesticide resistance;Phenotype;Play;Repetitive Sequence;Research;Retinal blind spot;reverse genetics;Role;Sampling;scaffold;Structure;Surveys;Techniques;Technology;telomere;Time;tool;tool development;trait;Uncertainty;Variant;whole genome

PROJECT_TITLE: The origin, maintenance, and adaptive consequences of variation in genome structure


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

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: Project Narrative: This proposal is expected to develop a collection of chemical biology tools to interrogate biological functions of protein methylation events with disease relevance. The revealed mechanisms can elicit disease-associated biology and lead to novel therapeutic strategies.

PI_NAMEs: LUO, MINKUI  (contact)

PROJECT_TITLE: Interrogating Complex Methylome Network with Integrated Chemical Biology Tools


NIH_SPENDING_CATS: Genetics;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: NARRATIVE Although females have two X chromosomes, each cell keeps only one X active, while the other is inactivated, but some genes are expressed from both X chromosomes in females. Some of these genes are also present on the Y in XY males, who therefore also express two copies, and this group of genes is thought to be lacking in dosage when one of the sex chromosomes is missing (karyotype 45,X), typically resulting in miscarriage. This research program aims to understand why development requires two copies of these genes, and elucidate the mechanisms that enable these genes to remain active on an otherwise inactive X, which is also relevant to other X-linked diseases.

PI_NAMEs: PINTER, STEFAN F. (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;Alleles;biological sex;Blood Vessels;Cardiac;Cell Line;Cells;Development;Disease;dosage;Epigenetic Process;Event;Female;Gene Expression;Generations;Genes;genetic approach;Germ Lines;Health;Heterozygote;Human;human induced pluripotent stem cells;Impairment;in vitro Model;insight;Karyotype;Link;Maintenance;male;malformation;Metabolism;Modeling;Molecular Genetics;mosaic;mouse model;novel;parity;Pathway interactions;Phenotype;Placenta;placental mammal;Process;programs;Repression;Research;Resources;Sampling;sex;Sex Chromosomes;Sex Differences;Shapes;Spontaneous abortion;tool;trophoblast;Turner's Syndrome;X Chromosome;X Inactivation;Y Chromosome

PROJECT_TITLE: Developmental constraints shaping human sex chromosomes and escape from X inactivation


ORG_DEPT: PHYSIOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The atomic-level details of lipid/enzyme interactions and the determinants of their specificity remain poorly understood, despite their importance in biosynthesis and modification of cellular membranes, and in the assembly and use of lipid conjugates for essential cellular functions such as glycosylation. By applying a structural biology-based integrated approach to enzymes that are involved in assembly of the peptidoglycan layer and modification of the lipopolysaccharide component of the outer membrane of Gram-negative bacteria, biosynthesis of the mycobacterial cell well and processes of protein glycosylation, we will gain testable hypotheses on the basic principles of substrate recognition, and on how membrane, membrane enzymes, and lipidic substrates interact to facilitate these reactions. These data should also provide pathways toward new classes of therapeutics targeting lipid/enzyme active sites.

PI_NAMEs: MANCIA, FILIPPO  (contact)

PROJECT_TERMS: Active Sites;Anabolism;Antibiotics;aqueous;Attention;Biochemical;Biochemical Reaction;Biochemistry;Biological Process;Catalysis;Cell Physiology;Cells;Cellular Membrane;Charge;chemical property;chemical reaction;chemical synthesis;Computational Biology;crosslink;Cryoelectron Microscopy;Data;Diphosphates;Environment;Enzyme Interaction;Enzymes;experimental study;Generations;Genetic;glycosylation;glycosyltransferase;Gram-Negative Bacteria;hydrophilicity;Hydrophobicity;Individual;interest;Knowledge;Ligands;Lipids;lipophilicity;Lipopolysaccharides;macromolecular assembly;Mass Spectrum Analysis;Mediating;Membrane;Membrane Proteins;Modification;Molecular;mycobacterial;particle;Pathway interactions;Peptidoglycan;Physiological;Play;Process;Production;protein function;Protein Glycosylation;Proteins;Proteomics;Reaction;reconstitution;response;Role;Signal Transduction;Specificity;structural biology;Structure;Substrate Interaction;Substrate Specificity;sugar;System;therapeutic target;Time;tool;Work

PROJECT_TITLE: Structural basis of integral membrane enzyme function


NIH_SPENDING_CATS: Aging;Genetics

ORG_CITY: PHILADELPHIA

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: PROJECT NARRATIVE The accumulation of somatic mutations in mitochondrial DNA has been associated with many degenerative diseases and is known to promote aging, however, the biochemical mechanisms underlying the formation of mutations are not well defined. This research will provide insight into the molecular mechanisms underlying faithful mitochondrial DNA replication and repair by determining the structure and function of the human mitochondrial replication and transcription machinery during different stages of replication.

PI_NAMEs: TEMIAKOV, DMITRY  (contact)

PROJECT_TERMS: Aging;Binding;Biochemical;Biological Assay;Blindness;Cell Survival;Cells;Complex;crosslink;Cryoelectron Microscopy;Defect;Degenerative Disorder;Disease;DNA;DNA biosynthesis;DNA polymerase gamma;DNA Repair;DNA Repair Gene;DNA-Directed RNA Polymerase;driving force;Enzymes;Family;Genetic Transcription;hearing impairment;helicase;Human;insight;Knowledge;Maintenance;Mammals;Mass Spectrum Analysis;melting;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial DNA mutation;mitochondrial genome;Molecular;Molecular Structure;Mutation;Myopathy;particle;Point Mutation;Polymerase;pro-aging;Process;promoter;reconstitution;recruit;Regulation;Repair Complex;Replication Initiation;Replication Origin;Research;RNA chemical synthesis;scaffold;Somatic Mutation;Structure;Superhelical DNA;Topoisomerase;Transcription Elongation;transcription factor;Transcription-Coupled Repair;ultraviolet damage;Work

PROJECT_TITLE: Molecular Mechanisms of Mitochondrial Transcription and Replication


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project Narrative In the past, humans interbred with archaic humans like Neanderthals and Denisovans, and these events introduced new genetic variation into modern human populations that survives in present-day human populations. The genetic variation that exists in present-day genomes can be studied to characterize whether admixing with archaic humans or with other populations helped humans adapt to different environments. The goal of these research projects is to develop new methods and empirical analysis to boost our ability to address how admixture events in the past have helped humans survive throughout their history.

PI_NAMEs: HUERTA-SANCHEZ, EMILIA  (contact)

PROJECT_TERMS: Address;Admixture;Affect;Complex;Environment;Event;Evolution;Frequencies;Genetic;Genetic study;Genetic Variation;Genome;Goals;Historical Demography;Human;Human Genome;insight;Internet;Methods;Modernization;mosaic;Mutation;Natural Selections;Pattern;Population;Recording of previous events;Research Project Grants;Sampling;Shapes;Statistical Methods;Structure;Time

PROJECT_TITLE: Characterizing modes of natural selection via diverse ancient and modern samples


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative Our research aims to investigate the role of transmembrane receptors, which play crucial roles in essential processes like heart and muscle function, kidney function, and blood pressure regulation. By studying these receptors, we aim to improve our understanding of their function and regulation, focusing on understanding how small molecules, lipids, and protein regulators interact with these proteins and alter their function. This knowledge not only enhances our understanding of cell signaling but also has broader implications for developing drugs to treat various diseases associated with dysfunction in transmembrane receptors.

PI_NAMEs: DES GEORGES, AMEDEE  (contact)

PROJECT_TERMS: Address;beta-adrenergic receptor;Biological Models;biophysical techniques;blood pressure regulation;Calcium Signaling;Classification;Cryoelectron Microscopy;design;Deuterium Exchange Measurement;Disease;drug development;Family;Functional disorder;G-Protein-Coupled Receptors;Goals;Heart Diseases;heart function;Image;improved;innovation;insight;interest;Ion Channel Gating;Ions;Knowledge;Laboratories;Ligand Binding;Ligands;Lipids;Mass Spectrum Analysis;Membrane;Membrane Proteins;Methodology;Modeling;Molecular;Molecular Conformation;molecular dynamics;Muscle function;Mutagenesis;Myocardium;Myopathy;Output;Pathway Analysis;Pathway interactions;Pharmaceutical Preparations;Play;Process;Proteins;receptor;Receptor Activation;receptor function;Regulation;Renal function;Research;Role;Ryanodine Receptor Calcium Release Channel;Shapes;side effect;Signal Transduction;Skeletal Muscle;small molecule;System;Techniques;Therapeutic

PROJECT_TITLE: Understanding membrane proteins’ allosteric modulation with cryo-EM


NIH_SPENDING_CATS: Bioengineering;Nutrition

ORG_CITY: BOSTON

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: NARRATIVE This project will result in mechanistic understanding and predictive models of the impact of lipids in drug delivery systems and food on absorption of orally ingested compounds (e.g., drugs, nutrients, toxins). Ingested lipids and food can result in almost ten-fold positive or negative changes in compound absorption, but these effects are currently poorly understood and not possible to predict. The experimental framework and predictive model developed in this project will be useful in streamlining the drug development process, enabling efficient design of oral delivery systems to mitigate a potentially dangerous “food effect” on absorption, or, alternatively, exploitation of the “food effect” to enable oral delivery of compounds that may otherwise require injection, and ultimately replacement of some clinical food effect studies.

PI_NAMEs: CARRIER, REBECCA L (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TITLE: Impact of lipids and food on oral compound absorption: mechanistic studies and modeling


NIH_SPENDING_CATS: Aging

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE Mitochondria are home to a wide array of metabolic process and their dysfunction is implicated in many rare and common human disease. However, the nature and cause of mitochondrial dysfunction is often unclear in large part due to the fact that hundreds of mitochondrial proteins have unclear functions. The long-term goal of this proposal is to achieve a more comprehensive understanding of mitochondrial biology and pathophysiology by systematically defining the functions of orphan mitochondrial proteins and their roles within disease-related processes.

PI_NAMEs: PAGLIARINI, DAVID J (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Address;Alzheimer's Disease;Anabolism;Antioxidants;Automobile Driving;Biochemical;Biochemical Process;Biochemistry;Biology;cell type;Cells;Chemicals;cofactor;design;Diagnosis;dimensional analysis;Disease;empowerment;Eukaryotic Cell;Functional disorder;Genetic Screening;Goals;Home;Human;human disease;Hydrophobicity;In Vitro;in vivo;Inborn Errors of Metabolism;Investigation;knockout gene;Malignant Neoplasms;Mass Spectrum Analysis;Metabolism;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;Mitochondrial Proteins;multiple omics;mutation screening;Nature;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Organelles;Orphan;Oxidation-Reduction;Parkinson Disease;Pathway interactions;Process;programs;protein function;Proteins;Research;Role;Signal Transduction;small molecule;Structure;System;systematic biology;Therapeutic;Ubiquinone;Yeasts

PROJECT_TITLE: Systems-to-structure approaches for defining mitochondrial protein function


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CHAMPAIGN

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PROJECT NARRATIVE Approximately 10% of the 16 million patients >60 years of age undergoing surgery in the United States annually suffer from postoperative neurocognitive disorder (poNCD), which is associated with increased morbidity and mortality. We propose to study molecular and cellular mechanisms and the involvement of specific neuronal and non-neuronal cell types underlying the development of poNCD in aged individuals, and its reversal by increasing the availability of 5-containing GABAA receptors on cell surface membranes and by positive allosteric modulation of 5-containing GABAA receptors using a multidisciplinary approach involving genetically modified animals, viral transduction approaches, molecular biological, biochemical, transcriptomic and behavioral techniques, as well as calcium imaging of defined neuronal populations in behaving animals. The proposed research is expected to provide fundamental knowledge with translational impact, as when allosteric modulators of 5-containng GABAA receptors, which are currently being developed by others for mild cognitive impairment in Alzheimer’s disease with support of the NIH, become available, clinical trials in humans can be envisioned.

PI_NAMEs: RUDOLPH, UWE  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Age Months;age related;Age Years;Age-associated memory impairment;Aging;aging population;aging related;Alzheimer's Disease;Anesthesia procedures;Animals;Astrocytes;Attenuated;attenuation;Behavioral;Biochemical;Biological;Calcium;Cell surface;cell type;Cells;Cellular Membrane;cellular targeting;Chronic;Clinical Research;Clinical Trials;Cognitive;Cognitive deficits;cognitive function;Development;Gene Expression;General anesthetic drugs;Genetically Modified Animals;glial activation;Hippocampus;Human;Image;Impaired cognition;improved;in vivo calcium imaging;Inflammation;interdisciplinary approach;Interneurons;Knowledge;Lead;Membrane;Memory;Memory impairment;Microglia;mild cognitive impairment;Mitochondria;Molecular;Monitor;Morbidity - disease rate;mortality;Mus;neurocognitive disorder;Neuroglia;Neurons;old mice;older patient;Operative Surgical Procedures;Pathway interactions;Patients;Population;positive allosteric modulator;Postoperative Period;Prevention;Prevention strategy;Process;Propofol;receptor;Research;Risk Factors;Role;Science;System;Techniques;Testing;transcriptomics;translational impact;United States;United States National Institutes of Health;Viral;Work;young adult

PROJECT_TITLE: Postoperative Neurocognitive Disorder - Strategies for Prevention or Reversal Based on Molecular ad Cellular Mechanisms


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

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Transcriptional condensates are dynamical assemblies that form via phase separation of disordered proteins and RNAs. However, much is still unknown about their formation, interactions, and effects on chromatin organization and transcriptional regulation. The proposed studies aim to apply computer simulations to systematically characterize biomolecular condensates, evaluate hypotheses on their roles in transcription, and suggest new therapeutic strategies for their modulation.

PI_NAMEs: ZHANG, BIN  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Acceleration;Address;Biochemical Reaction;Cell Physiology;Cells;Chemicals;Chromatin;Chromatin Loop;Chromatin Structure;Computer Simulation;deep learning;design;Disease;DNA;Equilibrium;Evaluation;Genetic Transcription;Goals;Grain;graph neural network;Heterogeneity;in silico;in vivo;Modeling;Molecular;multi-scale modeling;next generation;novel;novel therapeutic intervention;Phase;Physical condensation;Play;protein protein interaction;Proteins;Research;Resolution;RNA;Role;Scheme;self assembly;Sequence Analysis;simulation;small molecule;spatiotemporal;Techniques;transcription factor;Transcriptional Regulation

PROJECT_TITLE: Probing and Perturbing Transcriptional Condensates with Multiscale Modeling and Deep Learning


NIH_SPENDING_CATS: Genetics;Infectious Diseases

PHR: NARRATIVE My lab has pioneered work defining the regulation of cell quiescence and elucidating the role of copy number variation in adaptive evolutions. We aim to extend these advances by studying i) remodeling of gene expression and cell biology in quiescent cells and ii) the dynamics and functional effects of copy number variation. These studies build on our prior work and will contribute to our understanding of cell quiescence and copy number variation in the context of human health and disease.

PI_NAMEs: GRESHAM, DAVID  (contact)

PROJECT_TERMS: anti-fungal agents;Area;Biogenesis;Candida albicans;Candida glabrata;Cells;Cellular biology;Copy Number Polymorphism;Costs and Benefits;Crowding;Cyclic AMP-Dependent Protein Kinases;Defect;Disease;Drug Tolerance;Effectiveness;Environment;Evolution;fitness;fitness test;Gene Expression;Genetic;Genetic Variation;Health;Heritability;Heterogeneity;Human;Label;live cell imaging;Mass Spectrum Analysis;Mediating;Messenger RNA;Metabolic;Methods;microbial;Modeling;mutant;nanoparticle;nutrient deprivation;Nutritional;Organelles;Organism;pathogenic fungus;pathogenic microbe;Pathogenicity;Phenotype;Population;programs;protein expression;Regulation;Reporter;Research;Resistance;response;Ribosomes;Role;Signal Pathway;single-cell RNA sequencing;Source;Stress;System;Testing;Therapeutic;Vacuole;Variant;Work

PROJECT_TITLE: Regulated and evolutionary responses to nutritional stress


NIH_SPENDING_CATS: Complementary and Integrative Health;Natural Products

PHR: PROJECT NARRATIVE  The proposed research is relevant to public health because the development of new chemical methods will provide new ways to synthesize biomedically important chemicals, including drugs and biochemical tools, and because bioactive natural products can provide starting points for the development of new chemotherapies. This proposal aims to tackle challenges associated with the synthesis of several natural products with anticancer activity and develop new, selective reactions of alkenes, which are abundant starting materials for the synthesis of valuable compounds, including drugs. The project is relevant to the part of the NIH’s mission that pertains to the development of fundamental knowledge that lays the foundation for advances in disease treatment.

PI_NAMEs: PRONIN, SERGEY  (contact)

PROJECT_TITLE: Development of new methods and strategies for the synthesis of complex molecules


ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Project Narrative This proposal highlights our planned approaches to investigate how dying cells in animal bodies are clearer efficiently through phagocytosis and degradation, using the nematode C. elegans as our model organism. The clearance of dying cells protects humans from the harmful inflammatory and auto-immune responses induced by the contents of the dying cells. Understanding the mechanisms controlling this process will have important therapeutic implications, in fighting chronic inflammatory and autoimmune diseases, and in developing new strategies to target cancer cells for engulfment and digestion.

PI_NAMEs: ZHOU, ZHENG  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Adult;Animals;anti-cancer research;Apoptosis;Apoptotic;Area;Autoimmune Diseases;Autoimmune Responses;Autophagocytosis;Autophagosome;axon injury;Biogenesis;Caenorhabditis elegans;cancer cell;cancer therapy;Cell Communication;Cell Physiology;cell suicide;Cells;chronic inflammatory disease;Coin;Cytoprotection;Defect;Development;Digestion;Eating;Event;fighting;Health;Human;human disease;Inflammatory Response;Invaded;Learning;Lysosomes;Mammals;Membrane;model organism;Molecular;Necrosis Induction;Nematoda;novel;Organelles;Outcome;pathogen;Pathologic;Pathway interactions;Phagocytes;Phagocytosis;Phagosomes;Process;protein aggregation;Proteins;receptor;Regulation;Research;senescent cell;Signal Pathway;Stress;Surface;Synapses;Therapeutic;Tissues;Translating;wound healing

PROJECT_TITLE: Molecular mechanisms that regulate the degradation of dying cells


ORG_CITY: AUSTIN

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative The transition-metal-catalyzed alkene difunctionalization reactions for the formation of two C–functional group bonds (C, N, O, S, P, Br, Cl, F, or B) in a single transformation is developed. The work focuses on expanding the diversity of the reactions, with a focus on regio-, chemo-, and stereoselective functionalization.

PI_NAMEs: HULL, KAMI LEE (contact)

PROJECT_TERMS: Alkenes;Carbon;catalyst;Copper;Development;drug candidate;drug discovery;Elements;Fluorine;functional group;Hydrogen;Lead;Libraries;Marketing;Methodology;Nitrogen;novel strategies;Organic Synthesis;Oxygen;Palladium;Pharmaceutical Preparations;Pharmacologic Substance;pi bond;Process;Reaction;Reagent;Research;Structure-Activity Relationship;Testing;Transition Elements;Work

PROJECT_TITLE: Transition Metal-Catalyzed Alkene Functionalization


ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: Project Narrative - Catalytic nitrogen fixation and C–N bond constructions mediated by iron and copper as models of biocatalysis and tools for organic synthesis Nitrogen fixation is essential to life and carbon–nitrogen bonds are key components of essentially all bioactive molecules, including medicinal drugs. We pursue highly efficient functional models of biocatalytic nitrogen fixation and new methods for catalytic C–N bond constructions, with associated mechanistic studies.

PI_NAMEs: PETERS, JONAS C (contact)

PROJECT_TITLE: Catalytic Nitrogen Fixation and C-N Bond Constructions Mediated by Iron and Copper as Models of Biocatalysis and Tools for Organic Synthesis