NIH_SPENDING_CATS: Bioengineering;Wound Healing and Care

ORG_CITY: AMES

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: Narrative The goal of the project that this supplement supports is to use engineered extracellular matrix environments leveraging structural and mechanical control over the extracellular matrix to examine the mechanisms by which cells respond to multiple directional migration cues. Cell migration plays an important role in many physiological and pathological processes such as wound healing, development and cancer invasion. Frequently migration is not simply random, but directed towards targets through recognition of aligned extracellular matrix fibers or gradients in stiffness, generating contact guidance and durotaxis, respectively. In many biological contexts these cues are presented simultaneously, forcing cells to integrate this information. For instance, gradients of stiffness and aligned collagen are generated within the wound bed to direct dermal fibroblast migration. Similar fiber structures and gradients stimulate cancer cell migration out of the tumor microenvironment and normal cells including stromal and immune cells towards the tumor microenvironment. While there is a firm understanding of how cells respond to individual directional cues, virtually nothing is known about how cells integrate multiple cues and make migrational decisions based on that integration. Furthermore, there is a hypothesis that contact guidance and durotaxis are overlapping directional cell migration mechanisms, but this has not been rigorously tested. Mechanistic understanding of multi-cue directional migration will require a refined understanding of how the F-actin and microtubule networks operates. Indeed, some evidence suggests that contact guidance and durotaxis may use slightly different F-actin network structures, since contact guidance is thought to be governed by F-actin fiber structures, but durotaxis is not. Engineering approaches will be taken to design in vitro environments that allow for independent tuning of contact guidance and durotaxis in both 2D and 3D environments. Furthermore, the effect of F-actin branching, bundling and contraction in allowing cells to prefer aligned fibers of collagen or gradients of stiffness will be tested. This will uncover shared or competing molecular pathways involved when these two directional migration cues are present in isolation and together. Understanding how cells migrate in response to multiple cues has broad impact on several biomedical fields including tissue engineering and disease therapeutics. Determining how cells respond to multiple cues in vitro will allow us to predict cell responses in wound healing, development, cancer invasion and immune response leading to drug candidates as in cancer or strategies to enhance wound healing and immune response. This goal of this supplement is to purchase a microscope system that will expand our capabilities for live-cell imaging of cell migration and cytoskeletal dynamics. We currently have two older Nikon microscopes that have some limitations. First, the microscope that allows for fluorescence imaging has several issues including a broken filter wheel turret and malfunctioning mirror that automatically flips from Total Internal Reflection Fluorescence (TIRF) mode to epifluorescence mode. This limits the live cell fluorescence imaging we can do. Second, our Photometrics HQ2 CCD that was on that microscope was damaged after a mercury arc lamp bulb rupture. We have since purchased a Photometrics Moment camera, which is a good camera for fixed images, but its sensitivity is much less than the HQ2, diminishing our ability to capture cytoskeletal dynamics in live cells. Third, we do not have ability to access multiple positions during one imaging experiment, because our stage is only a mechanical stage and is not motorized. This tremendously hampers our ability to collect data in a high throughput manner. Finally, while we have successfully used heated stages and closed chambers for imaging live cells, this approach limits the type of media you can use and the length of imaging time. We would like to purchase an environmental control chamber to regulate humidity, temperature and CO2 percentage to allow for control over these very important cell culture conditions and to give us flexibility to image cells over our current window of eight hours. In addition to migration, the multi-positional acquisition and environmental control will allow us to better screen clones of formin and other cytoskeletal CRISPR knock-outs that we are developing. These reasons coupled with the fact that both our microscopes are over twelve years result in relatively high cost for upgrading an old system. Our ability to image cell migration and cytoskeletal dynamics in a high throughput manner and in a more natural environment will support the successful completion of the project.

PI_NAMEs: SCHNEIDER, IAN CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: 3-Dimensional;Biological;Bundling;cancer cell;Carbon Dioxide;Cell Culture Techniques;cell motility;Cells;cellular imaging;Clustered Regularly Interspaced Short Palindromic Repeats;Collagen;Collagen Fiber;cost;Coupled;Cues;Cytoskeleton;Data;Dermal;design;Development;directional cell;Disease;drug candidate;Engineering;Environment;experimental study;Extracellular Matrix;F-Actin;Fiber;Fibroblasts;flexibility;Fluorescence;fluorescence imaging;Goals;Hour;Humidity;Image;Immune;Immune response;In Vitro;Individual;Invaded;Knock-out;Length;live cell imaging;Malignant Neoplasms;Mechanics;Mercury;Microscope;Microtubules;migration;Molecular;Normal Cell;Pathologic Processes;Pathway interactions;Physiological Processes;Play;Positioning Attribute;response;Role;Rupture;Structure;System;Temperature;Testing;Therapeutic;Time;Tissue Engineering;Tissues;tumor microenvironment;virtual;wound bed;wound healing

PROJECT_TITLE: Cell Migration Control through Modulation of Multiple Directional Cues

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: WALTHAM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: BRANDEIS UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative Numerous therapeutic molecules and small-molecule biological probes are synthetic agents, and many of them contain at least one nitrogen atom; therefore, the subject of this application−discovery of novel synthetic methods for efficient synthesis of these nitrogen- containing molecules will advance drug discoveries as well as the basic biomedical and clinical research.

PI_NAMEs: XU, HAO  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Selective Nitrogen Atom Transfer for Applications in Biomedical Sciences

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


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

ORG_CITY: TALLAHASSEE

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative Sexually transmitted infection (STI) rates have been rising at an alarming rate globally for the past decade, indicating that current STI prevention paradigms are not working and that new strategies are urgently needed. Recent open-label studies demonstrated that doxycycline 200mg within 72 hours of STI exposure (doxycycline prophylaxis [doxyPEP]) resulted in 47-66% reduction in STIs among sexual minority men (SMM) and transgender women (TW), which has led to the endorsement of doxyPEP as an option for biomedical STI prevention by public health authorities. The goal of this open-label, randomized trial is to assess efficacy of doxycycline prophylaxis (doxyPEP) to reduce incidence of bacterial sexually transmitted infections (STIs) while also balancing acceptability and resistance to inform public health policy regarding doxyPEP use among people assigned female sex at birth (AFAB).

PI_NAMEs: HIGHTOW-WEIDMAN, LISA B (contact);HOSEK, SYBIL

PROGRAM_OFFICER_NAME: RUSSO, DENISE

PROJECT_TERMS: Address;Adherence;Adolescent;Adolescent and Young Adult;Adolescent Medicine Trials Network;Advocate;aged;assigned female at birth;authority;Chlamydia;chronic pelvic pain;cis-female;cisgender;Clinical;clinical practice;Counseling;Data;Development;Dose;Doxycycline;efficacy evaluation;Enrollment;Exclusion;France;Gender;Goals;Gonorrhea;Guidelines;Hair;Health;Health Policy;HIV/AIDS;Hour;Incidence;Infection;infection rate;Infertility;Intervention;Leadership;Left;Longitudinal Studies;Measures;microbiome;mobile application;Monitor;Morbidity - disease rate;Neisseria gonorrhoeae;open label;Participant;Patient Self-Report;Persons;Plasma;Policies;Population;Prevalence;prevent;Prevention strategy;Prophylactic treatment;Public Health;Randomized;randomized trial;Recommendation;Rectum;Reiter Disease;Resistance;Rest;Risk;Safety;sample collection;Sampling;sex;Sex Behavior;Sexual Health;sexual minority men;Sexually Transmitted Diseases;Specimen;standard of care;Staphylococcus aureus;STI prevention;Surveys;Swab;Syphilis;Testing;Tetracycline Resistance;transgender women;transgender women who have sex with men;United States;Unsafe Sex;Vagina;Visit;Woman;Work

PROJECT_TITLE: Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN)Scientific Leadership Center; DoxyPep: UM2 Admin Suppl


ORG_CITY: UNIVERSITY PARK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Bacterial lipoproteins are structures located on the surface of all bacteria that are critical to bacterial fitness and their potential to cause infections since they are key recognition determinants of the immune system. This project aims to characterize the biosynthetic enzymes that make different lipoprotein structural forms by using ultra high-pressure liquid chromatography (uHPLC) assays.

PI_NAMEs: MEREDITH, TIMOTHY C. (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Active Sites;Acylation;Anabolism;Bacteria;bacterial fitness;Binding;Biochemistry;Biological Assay;Copper;Cysteine;Environment;enzyme mechanism;Enzymes;Firmicutes;Genes;Goals;Growth;High Pressure Liquid Chromatography;Immune system;In Vitro;Infection;insight;Length;Lipoproteins;Medical;Membrane Proteins;Modeling;Modification;N-terminal;oxidation;Physiological;Positioning Attribute;Predisposition;reconstitution;Source;Structure;Surface;System;Testing;ultra high pressure

PROJECT_TITLE: High Pressure Liquid Chromatography (HPLC) System for Analyzing Bacterial Lipoprotein Biosynthesis and Oxidation

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: MANHASSET

ORG_NAME: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: NY

PHR: Project Narrative This is the same as the parent award. The nervous system and immune system communicate with each other to monitor and respond to internal changes and outside threats. Inflammatory mediators present in the periphery must be encoded and signaled up to the brain through sensory neurons, but how this neural representation happens is unknown. Using a novel method to monitor vagal sensory neurons responding to these mediators, we will determine how immune-signals are represented by the peripheral nervous system.

PI_NAMEs: CHANG, ERIC HAU-YUN (contact)

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: Adopted;Afferent Neurons;Biological Response Modifiers;Brain;calcium indicator;Code;Communication;Critical Pathways;cytokine;Detection;Disease;experience;Goals;Homeostasis;Immune;Immune signaling;Immune system;Immunity;In Situ;Infection;Inflammation Mediators;Inflammatory;insight;Mediating;Mediator;Methods;Monitor;Motor;Nervous System;neural;Neuroimmune;Neurons;neuroregulation;Neurosciences;novel;parent project;Peripheral Nervous System;Population;Scientist;Sensory;Signal Transduction;Techniques;tool;Vagus nerve structure;Work

PROJECT_TITLE: Encoding of inflammatory mediators by vagal sensory neurons

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


ORG_CITY: DETROIT

ORG_DEPT: BIOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project narrative – public health relevance  Perturbation of inositol metabolism is associated with pathologies as diverse as psychiatric and neurological illnesses, myopathies, cancer, and diabetes. The proposed studies will lead to the first molecular model of regulation of inositol synthesis in mammalian cells and demonstrate how inositol deprivation affects mitochondrial function and the cellular stress response. The identification of specific pathways that are perturbed as a result of inositol deprivation will provide insights into the tumor-suppressive effects of upregulating inositol synthesis and may suggest candidates for new mood stabilizing inositol-depleting drugs for the treatment of bipolar disorder.

PI_NAMEs: GREENBERG, MIRIAM L (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: 3-Methylglutaconic aciduria type 2;Administrative Supplement;Affect;Anabolism;Binding;Biochemical;biological adaptation to stress;Bipolar Disorder;Cell Physiology;Cells;Cellular Metabolic Process;Cellular Stress;Ceramides;Code;deprivation;Diabetes Mellitus;Doctor of Philosophy;drug action;Drug usage;Enzymes;Equipment;Eukaryotic Cell;Exhibits;Gene Expression;Genes;Genetic Transcription;Goals;Grant;Homeostasis;Human;Human Cell Line;Inositol;inositol hexakisphosphate kinase;Inositol Metabolism Pathway;insight;Knock-out;Knowledge;Light;Lipids;Malignant Neoplasms;Mammalian Cell;Mediating;Mental disorders;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;molecular modeling;monolysocardiolipin;Moods;myoinositol;Myopathy;Neurologic;Nuclear;Pathology;Pathway interactions;Pharmaceutical Preparations;Pharmacotherapy;Phosphatidic Acid;Play;Population;Principal Investigator;promoter;Proteins;public health relevance;Regulation;Repression;Research;response;Role;Signal Transduction;Starvation;Stress;Testing;Therapeutic;tumor

PROJECT_TITLE: Regulation of Inositol Biosynthesis and Consequences of Inositol Depletion


NIH_SPENDING_CATS: Complementary and Integrative Health;Digestive Diseases;Liver Disease;Neurosciences;Physical Activity;Physical Rehabilitation;Prevention;Rehabilitation

PHR: Project Narrative  Preoperative exercise therapy (PET) is a highly applicable non-pharmacological-based therapy and has successfully reduced postoperative complications and conferred better recovery from major liver surgery. This Supplement project will utilize the new multi-lane metabolic & telemetric treadmill system tp determine the mechanisms by which PET modulates anti-inflammatory trained immunity in hepatic resident macrophages (Kupffer cells) via activating the cholinergic anti-inflammatory pathway to prevent liver ischemia/reperfusion injury. The finding from this proposal will provide the knowledge foundation for not only optimizing the development of PET against surgery-induced organ injury but also devising exercise- mimicking pharmacological strategies for patients who are exercise intolerant.

PI_NAMEs: HUANG, HAI  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Abdomen;Acetylcholine;Address;Administrative Supplement;alpha-bungarotoxin receptor;Animals;Anti-Inflammatory Agents;Award;Cells;cholinergic;cost;Data;design;Development;Epigenetic Process;Equipment;Excision;Exercise;Exercise Therapy;Foundations;Goals;Hepatic;Immune;Immunity;Inflammation;inflammatory milieu;Inflammatory Response;Injury;innate immune function;instrument;ischemic injury;Knowledge;Kupffer Cells;Liver;liver injury;liver ischemia;liver transplantation;Macrophage;Metabolic;Morbidity - disease rate;mortality;Neurotransmitters;Nicotinic Receptors;Operative Surgical Procedures;organ injury;parent grant;Parents;Pathway interactions;Patients;pharmacologic;Physiologic Monitoring;Postoperative Complications;Postoperative Period;prevent;Process;programs;protective effect;Recovery;Reperfusion Injury;Reperfusion Therapy;Scientific Advances and Accomplishments;surgery outcome;System;Telemetry;Training;treadmill;Vagus nerve structure

PROJECT_TITLE: Preoperative exercise therapy triggers trained immunity in KCs via cholinergic anti-inflammatory pathway


ED_INST_TYPE: SCHOOLS OF MEDICINE

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The requested equipment, a micro/nanoflow high performance liquid chromatograph, is a replacement for a vital component on our analysis platform. The platform enables reading footprints of membrane proteins, which are the communication, transport, and interaction centers for most of the drugs currently in use. The footprints reflect changes in structure and bring insight on how membrane proteins function.

PI_NAMEs: GROSS, MICHAEL L;LI, WEIKAI  (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Cells;Chemicals;Communication;Equipment;Human;insight;Liquid substance;Mass Spectrum Analysis;Membrane Lipids;Membrane Proteins;nano;Performance;Pharmaceutical Preparations;protein function;protein structure;Reading;Structure

PROJECT_TITLE: NEW CHEMICAL PROBES ENABLE MASS SPECTROMETRY-BASED FOOTPRINTING OF HUMAN PROTEIN STRUCTURE IN LIPID MEMBRANES AND CELLS


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

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Narrative The computational methodologies we develop will be applicable to a broad set of metalloenzymes and proteins of biomedical relevance. In particular, we target fundamental mechanistic problems in enzymes that catalyze nucleic acids synthesis/modification and lipid metabolism, since mutations in these enzymes are implicated in numerous human diseases such as cancer, insulin resistance and diabetes. Although our project does not focus on design of drugs, the mechanistic insights into enzyme catalysis and allosteric regulation will broaden strategies that can be used to target various enzymes of biomedical significance.

PI_NAMEs: CUI, QIANG  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Active Sites;Allosteric Regulation;Catalysis;Chemicals;Computer Analysis;computerized tools;Computing Methodologies;Coupled;Coupling;Crystallography;design;Diabetes Mellitus;Directed Molecular Evolution;Distal;Drug Design;enzyme mechanism;Enzymes;Equilibrium;Event;Free Energy;human disease;insight;Insulin Resistance;Ions;Knowledge;lipid metabolism;Machine Learning;Malignant Neoplasms;Membrane;metalloenzyme;Metals;method development;Modernization;Modification;Molecular Conformation;Mutation;mutation screening;Nature;novel;Nucleic Acids;Penetration;Peripheral;Positioning Attribute;Process;Proteins;Reaction;recruit;Regulation;Research;Sampling;Specificity;Speed;Techniques;Time;transcription factor;Water

PROJECT_TITLE: Computational Analysis of Enzyme Catalysis and Regulation


NIH_SPENDING_CATS: Cancer

ORG_CITY: GLASSBORO

ORG_NAME: ROWAN UNIVERSITY

ORG_STATE: NJ

PHR: The discovery of BRAF as a major driver of human cancers led to a substantial clinical success of current BRAF therapies, however, the incomplete understanding of various biological processes that RAF kinases participate has hindered the development of more effective BRAF drugs. We propose to integrate chemical, biochemical, and biophysical tools together with mass spectrometry and cell imaging to address the molecular mechanisms of RAF activation and regulation in normal and disease conditions, specifically cancer. Our findings will provide fundamental insights into how RAF kinases operate at the molecular level and will have an impact on the treatment of BRAF-driven cancers.

PI_NAMEs: WANG, ZHIHONG  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Address;Affinity;Allosteric Regulation;Binding;Binding Sites;Biochemical;biochemical tools;Biological Assay;Biological Process;Biology;biophysical tools;BRAF gene;CDK4 gene;Cells;cellular imaging;chaperone machinery;Chemicals;Client;Clinical;Co-Immunoprecipitations;Complex;Computing Methodologies;Development;dimer;Dimerization;Disease;Dissociation;Drug resistance;Elements;Engineering;Enzymes;Event;Family;Goals;Growth Factor Receptors;Health;Human;In Vitro;inhibitor;insight;interdisciplinary approach;Intervention;Kinetics;Knowledge;Length;live cell imaging;Malignant Neoplasms;MAP Kinase Gene;MAPK Signaling Pathway Pathway;Mass Spectrum Analysis;Measures;Mediating;member;Membrane;Modeling;Molecular;Molecular Conformation;molecular dynamics;multicatalytic endopeptidase complex;mutant;Mutate;Mutation;Mutation Analysis;N-terminal;novel therapeutic intervention;Nucleotides;Oncogenic;Outcome;Output;paralogous gene;Pathologic;Pathway interactions;Peptides;Pharmaceutical Preparations;pharmacologic;phosphoproteomics;Phosphorylation;Phosphotransferases;Photoaffinity Labels;Physiological;Positioning Attribute;preference;Proliferating;protein degradation;Protein Family;Protein Isoforms;Protein Kinase;Protein-Serine-Threonine Kinases;Proteins;Proto-Oncogene Proteins B-raf;prototype;raf Kinases;RAS genes;Ras/Raf;recruit;Regulation;Research;Second Primary Cancers;Serine;Signal Transduction;Sirolimus;Specificity;Structure;success;synergism;System;Tacrolimus Binding Proteins;targeted cancer therapy;Therapeutic;tumor;tumorigenesis;Variant;Work;X-Ray Crystallography

PROJECT_TITLE: Activation and Regulation Mechanisms of the RAF Kinase Family


NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Crohn's Disease;Digestive Diseases;Inflammatory Bowel Disease;Neurosciences;Rheumatoid Arthritis

PHR: Project Narrative Work in principle investigator’s lab launched the field of bioelectronic medicine, a new field that now holds promise as an alternative strategy to develop therapies. The idea is to target molecular mechanisms of inflammation with neuromodulating devices. The studies proposed here will provide significant data that can be used to modulate the neural circuitry to develop therapeutic modalities for the prevention and treatment of inflammatory diseases.

PI_NAMEs: TRACEY, KEVIN J (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Anatomy;Award;Basic Science;bioelectronics;Brain;brain control;clinical investigation;clinical practice;Clinical Trials;Crohn's disease;Data;Devices;Disease;disease model;Electrophysiology (science);Environment;experience;Funding;Imaging technology;Immune system;Immune System Diseases;Immunity;Immunobiology;Immunology;Inflammation;Inflammatory;innovation;Knockout Mice;Lead;Medicine;Methods;Mission;Modality;Molecular;Molecular Target;National Institute of General Medical Sciences;Natural Immunity;Nervous System;neural;neural circuit;Neurobiology;neurophysiology;neuroregulation;neurotransmission;optogenetics;Prevention;programs;Publications;Reflex action;Reporting;Research;Research Personnel;Rheumatoid Arthritis;Series;Therapeutic;therapy development;Transgenic Organisms;Translating;Vagus nerve structure;Work

PROJECT_TITLE: Molecular basis of bioelectronic medicine


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: ProjectNarrative- Parent Award This innovative proposal will address financial wellbeing, an often overlooked but important factor impacting reentry for justice-involved people with mental health challenges, who are disproportionately Black and Latinx. This project will change community level determinants by integrating financial capability supports (one-on-one coaching and access to financial tools and services) into existing services, and training bank and credit union staff to reduce discrimination. It will also support collaborative community efforts working towards upstream policy and legal reforms to reduce the incidence of those financial challenges.

PI_NAMEs: BELLAMY, CHYRELL DENISE;HARPER, ANNIE  (contact)

PROGRAM_OFFICER_NAME: MUJURU, PRISCAH

PROJECT_TERMS: Address;Affect;Attitude;Behavior;Black race;Climate;Communities;community advisory board;Community Health;community reentry;Complex;Criminal Justice;Data Analyses;Data Collection;design;Development;Dimensions;Discrimination;Economics;Ecosystem;Education;Employment;empowerment;Ensure;Environment;Equity;Ethics;Evidence based intervention;Exclusion;experience;Feeling;financial decision making;Financial Hardship;Financial Support;follow-up;Fostering;Glean;Goals;Health;health determinants;Health Disparities Research;Housing;Imprisonment;Incidence;Individual;innovation;insight;interest;Intervention;Interview;Investigation;Justice;Knowledge;Latinx;Legal;lens;Life;Low income;Marketing;Measures;Mental Health;Methodology;Methods;National Institute on Minority Health and Health Disparities;new technology;Occupational;Occupations;Outcome;parent grant;parent project;Parents;Personal Satisfaction;Persons;Play;Policies;Process;professional atmosphere;programs;psychologic;racial health disparity;racial minority population;racism;recidivism;Recording of previous events;Recovery;recruit;Regulation;Research;resilience;Role;Secure;segregation;Self Efficacy;Services;Shapes;Social Network;social stress;Societies;Standardization;Stigmatization;Structure;System;timeline;tool;Training;Vocation;Well in self;Work;Workplace

PROJECT_TITLE: Recovery Finance: Financial health and mental health after incarceration


NIH_SPENDING_CATS: Nutrition

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Cells allocate substantial resources towards monitoring their energy level, and appropriately adjust energy generation rates based on the metabolic demand and nutrients status to maintain homeostasis. This proposal aims to understand how cellular metabolic state regulates mitochondrial function and dynamics, and how it contributes to bioenergetics in the cells. These studies will produce important insights into the biochemical pathways that underlie neuronal functions, cell migration in cancer and wound healing, nervous system development, nutritional and mitochondrial disorders, and obesity.

PI_NAMEs: PEKKURNAZ, GULCIN  (contact)

PROJECT_TERMS: Architecture;Biochemical Pathway;Biochemistry;Bioenergetics;cell motility;Cells;Chemicals;Communication;detection of nutrient;Dimensions;Disease;Energy Supply;Enzymes;Eukaryotic Cell;experimental study;Generations;Goals;Heterogeneity;Homeostasis;Immunity;Impairment;insight;Interdisciplinary Study;Intracellular Space;Intracellular Transport;Kinetics;Malignant Neoplasms;Mammalian Cell;Metabolic;Metabolic Pathway;Metabolism;Mitochondria;Mitochondrial Diseases;Mitochondrial Proteins;Molecular;Monitor;nervous system development;Neurons;Nutrient;Nutrient availability;Nutrition Disorders;Obesity;Organelles;Pathway interactions;Positioning Attribute;Post-Translational Protein Processing;programs;Proteins;Regulation;Research;Resources;Shapes;Signal Pathway;spatiotemporal;Tumor Cell Invasion;wound healing

PROJECT_TITLE: Metabolic Regulation of Mitochondrial Function

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_DEPT: MISCELLANEOUS

PHR: Dynamic rearrangements of the actin cytoskeleton are essential to all eukaryotic cells. Defects in actin regula- tion are associated with various diseases, ranging from immunodeficiency and neurodevelopmental disorders to cancer metastasis and pathogen infection. The proposed research will determine the fundamental mecha- nisms of central actin regulators known as the Wiskott-Aldrich Syndrome Protein (WASP) family proteins, which will lay the foundation for understanding how actin remodeling is dysregulated in diseases and can be treated therapeutically.

PI_NAMEs: CHEN, BAOYU  (contact)

PROJECT_TERMS: Actins;Address;axon guidance;Binding;Binding Sites;Biochemistry;Biology;Cell membrane;cell motility;Collaborations;Complex;Cryoelectron Microscopy;Cytoskeleton;Defect;Development;Disease;DNA Sequence Alteration;Eukaryotic Cell;experimental study;field study;Fluorescence;Fluorescence Microscopy;Foundations;Guanosine Triphosphate Phosphohydrolases;human disease;Human Pathology;Immune;immune activation;Immunologic Deficiency Syndromes;Individual;Infection;interest;Knowledge;Laboratories;Ligands;Link;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Membrane;Membrane Proteins;Monomeric GTP-Binding Proteins;Morphogenesis;Mutation;Names;Neoplasm Metastasis;Neurodevelopmental Disorder;Neurons;novel;Oxidation-Reduction;Parasitic infection;particle;pathogen;Patients;Phosphatidylinositols;Play;polymerization;Polymers;Process;Protein Engineering;Protein Family;Proteins;receptor;Regulation;Research;Role;Series;Signal Transduction;single molecule;Syndrome;Therapeutic;trafficking;vasodilator-stimulated phosphoprotein;Vesicle;WAVE protein;Wiskott-Aldrich syndrome protein;Work

PROJECT_TITLE: Signal Integration from Membranes to the Actin Cytoskeleton


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

PHR: Project Narrative The parent research program seeks to elucidate cell type and tissue specific molecular mechanisms that drive the progression of disease in patients with viral illnesses and to subsequently identify new targets for therapeutic invention. This grant supplement is for the acquisition of the CFX Opus 384 Real-Time PCR System that will enable precise quantitative measurements and ultra-sensitive quantitation of nucleic acid levels to study cellular processes. Accurate measurement of cellular processes, including quantitation of specific levels of cellular RNA and DNA, will provide unbridled insight into biologic function. We assert that our ability to study fundamental biologic processes, to aid in completion of our research objectives, will be greatly enhanced by the routine use of this PCR system to validate results from other scientific approaches that will be employed.

PI_NAMEs: THOMAS, EMMANUEL  (contact)

PROJECT_TERMS: Acute;Biological Markers;Biological Process;Budgets;Cell Differentiation process;Cell Physiology;cell type;Chronic;cost;Disease Progression;DNA;Equipment;Foundations;Funding;graduate student;Grant;Host Defense;Immune response;improved;insight;instrument;invention;Investments;Laboratories;laboratory experiment;large datasets;Measurement;medical schools;Molecular;Multipotent Stem Cells;National Institute of General Medical Sciences;Natural Immunity;new therapeutic target;nucleic acid quantitation;Nucleic Acids;Parents;Patients;programs;Research;Research Personnel;Research Support;RNA;Solid;success;System;Techniques;Time;Tissues;United States National Institutes of Health;Universities;Viral;Virus Diseases;Wages

PROJECT_TITLE: A Multifaceted Approach to Study Tissue and Cell Type Specific Molecular Mechanisms of the Host Response to Acute/Chronic Viral Infection


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: PHILADELPHIA

ORG_NAME: WISTAR INSTITUTE

PHR: Narrative: Most mammalian genes express alternative cleavage and polyadenylation (APA) isoforms with different coding sequences (CDS) and/or 3’ untranslated regions (3’UTRs). Our research goal is to elucidate molecular mechanisms of APA regulation and cellular consequences of APA isoform expression under various physiological and pathological conditions.

PI_NAMEs: TIAN, BIN  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Untranslated Regions;Address;Affect;Autophagocytosis;Cell Differentiation process;Cell Proliferation;cell type;Cells;Cellular Stress;Code;Computational Biology;functional genomics;Gene Expression;Gene Expression Regulation;Genes;Goals;Growth;interdisciplinary approach;Messenger RNA;Metabolic;Metabolism;Molecular;Molecular Biology;Pathologic;Physiological;Polyadenylation;Protein Isoforms;Proteins;Regulation;Research;Role;Secretory Cell;Site;transcription termination

PROJECT_TITLE: Regulation of gene expression by alternative polyadenylation


NIH_SPENDING_CATS: Biotechnology;Regenerative Medicine

PHR: Project Narrative Growth factors are biochemical signals that regulate diverse cellular functions including proliferation, differentia- tion, or metabolic activity. This proposal seeks to develop new reagents and methods to selectively activate or suppress the activity of these signals with spatial and temporal control by tailoring their interactions at the sur- faces of cells. Once established, the tools will enable new biological discoveries and cell-based therapies.

PI_NAMEs: GODULA, KAMIL  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Anabolism;Binding;Biochemical;Biological;Biomedical Research;cancer therapy;Cell Differentiation process;Cell Line;Cell Physiology;Cell Proliferation;Cell surface;Cell Therapy;Cells;Chemicals;Chimera organism;Complex;Elements;Enzymes;Equilibrium;extracellular;Fibroblast Growth Factor;Gene Expression;Genetic Engineering;Growth Factor;Growth Factor Inhibition;Growth Factor Receptors;Harvest;Heparan Sulfate Proteoglycan;Heparitin Sulfate;improved;instrument;Laboratories;Ligands;Lysosomes;Mediating;member;Membrane;Metabolic;Methods;Mutation;Polysaccharides;Proliferating;Property;Protein Family;Reagent;receptor;Recombinants;Regenerative Medicine;response;Signal Pathway;Signal Transduction;Specificity;Structure;Sulfate;Therapeutic;Tissue Engineering;tool

PROJECT_TITLE: Admin Supplement for Instrument for 5 R01GM145913-02


PHR: Project Narrative The focus of this supplement is the purchase of a preparative-scale supercritical fluid chromatography (SFC) instrument. This will greatly enhance the development of Ni-catalyzed synthetic methods, the focus of the parent NIH award, by allowing the isolation of products that are currently inseparable and increasing the number of substrates that can be evaluated. Overall, the project aligns with the NIH's mission to improve human health because it will provide crucial instrumentation to aid in the development of more efficient methods for discovering and synthesizing pharmaceuticals.

PI_NAMEs: HAZARI, NILAY  (contact)

PROJECT_TERMS: Award;Catalysis;catalyst;Chemistry;Chlorides;Collaborations;Complex;Computational Technique;Coupling;design;Development;Esters;experimental study;Generations;Guidelines;Health;Human;improved;In Situ;instrument;instrumentation;Investigation;Kinetics;Libraries;Ligands;Metals;Methods;Mission;Mole the mammal;nano;next generation;Nitrogen;novel;novel strategies;Parents;Pathway interactions;Pharmaceutical Chemistry;Pharmacologic Substance;Process;rational design;Reaction;Reducing Agents;Salts;scale up;Series;Supercritical Fluid Chromatography;System;Transition Elements;United States National Institutes of Health

PROJECT_TITLE: Fundamental Studies of Ni-Catalyzed Organic Reactions


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

ORG_CITY: IRVINE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: The supplement instructions PA-20-272 state: “At minimum, the Research Strategy section should be completed and must include a summary or abstract of the funded parent award or project. Other sections should also be included if they are being changed by the proposed supplement activities.” The original Project Narrative document has not changed as a result of the proposed supplement activities.

PI_NAMEs: ABBOTT, GEOFFREY W (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Achlorhydria;Address;Arrhythmia;Ataxia;Award;base;Biochemical;Biology;Brain;Cell membrane;Complex;Coupled;Data;Diabetes Mellitus;Disease;Electrophysiology (science);Epilepsy;Episodic ataxia;experience;Family;field study;Functional disorder;Funding;Goals;Hypothyroidism;imaging modality;in vivo;in vivo evaluation;Ion Channel;Ions;Knock-out;Knowledge;Link;Molecular;mouse model;National Institute of General Medical Sciences;Neurotransmitters;novel;novel therapeutic intervention;parent project;patch clamp;Physiological;Plant Extracts;plant metabolites;Plants;Potassium;Proteins;Radioligand Assay;Rattus;Research;Rodent;Role;Screening Result;Signal Transduction;small molecule;Sodium;solute;Speed;Structure;sugar;supplemental instruction;Techniques;Therapeutic;Tissues;transcriptomics;Transgenic Organisms;Variant;Vitamins;voltage;Water;Work

PROJECT_TITLE: Ion Channel Transporter Interactions


ADMINISTERING_IC: HL

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

ORG_CITY: GREENSBORO

ORG_NAME: UNIVERSITY OF NORTH CAROLINA GREENSBORO

ORG_STATE: NC

PHR: PROJECT NARRATIVE Black emerging adults (ages 18-28 years) have the highest risks of insufficient sleep and cardiovascular disease, but little is known about how and why these disparities exist. Our project will examine associations between measures of insufficient sleep and race-related stress with measures of arterial stiffness and central hemodynamics (well-known risk factors for cardiovascular disease) in Black emerging adults. By focusing on emerging adulthood – when many individuals establish and solidify lifelong sleep and health behaviors – this project will take an essential first step towards understanding the role of sleep and race-related stress in shaping cardiovascular disease risk in Black adults.

PI_NAMEs: MCNEIL, JESSICA NICOLE (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: actigraphy;Adult;Age;arterial stiffness;Arteries;Black race;Blood;Body Weight;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Characteristics;clinically relevant;Contracts;Data Collection;design;diaries;Disparity;Elasticity;emerging adult;emerging adulthood;Energy Metabolism;experience;Feeling;Femur;Floods;follow-up;Goals;Grant;Health behavior;heart function;Heart Rate;hemodynamics;high risk;Hypertension;Individual;Laboratories;Link;Measurement;Measures;Methods;obesity risk;Outcome;parent grant;Parents;Patient Self-Report;peer;Physiologic pulse;Polysomnography;poor sleep;pressure;Protocols documentation;Public Health;Pulse Pressure;Pump;Race;racial discrimination;racial population;Rest;Risk;Role;Shapes;Sleep;sleep behavior;Sleep Deprivation;Sleep Disorders;sleep onset;sleep quality;Slow-Wave Sleep;Stress;System;vigilance

PROJECT_TITLE: Linking insufficient sleep with body weight in Black emerging adults.


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Orphan Drug;Ovarian Cancer;Pancreatic Cancer;Rare Diseases;Women's Health Research

ORG_CITY: CHARLESTON

ORG_DEPT: SURGERY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Narrative Ovarian cancer and pancreatic adenocarcinoma (PDAC) are two of the most lethal cancers and notoriously resistant to standard therapies. We have developed a dual-domain therapeutic, S2/IAPinh, that selectively delivers a drug cargo into cancer cells and induces enhanced tumor cell death. Recent experimental evidence suggests that S2/IAPinh, while far more effective than IAPinh alone, is insufficient to eradicate the tumors as a monotherapy. Here, we will explore a number of new avenues for successful combination cancer therapies.

PI_NAMEs: HAWKINS, WILLIAM G;SPITZER, DIRK M. (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Abraxane;Address;Anticholesteremic Agents;Apoptosis;cancer cell;Cancer Patient;cancer therapy;carcinogenesis;CASP3 gene;Caspase;Cell Death;Cell Line;Cell Survival;Cells;chemical conjugate;Chemicals;chemotherapy;Cholesterol;Clinical;combination cancer therapy;cytotoxic;cytotoxicity;Data;Development;DNA Damage;Dose;drug candidate;Drug Combinations;Drug Delivery Systems;drug development;Drug Efflux;Drug Formulations;Drug Kinetics;Drug resistance;effective therapy;efficacy evaluation;Enhancers;Epithelial ovarian cancer;Evaluation;Excipients;Foundations;Frequencies;gemcitabine;genetic signature;Goals;Gold;Grant;Human;improved;In Vitro;in vivo;Inhibition of Apoptosis;inhibitor;inhibitor therapy;inhibitor-of-apoptosis protein;innovation;Lead;Ligands;Link;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant Neoplasms;Maximum Tolerated Dose;Mediating;Mitochondria;mouse model;neoplastic cell;novel;novel drug combination;novel therapeutics;Ovarian;Paclitaxel;Pancreatic Adenocarcinoma;Pancreatic Ductal Adenocarcinoma;Pathway interactions;Patient-Focused Outcomes;Patients;performance tests;Pharmaceutical Preparations;Pharmacodynamics;Pharmacotherapy;pre-clinical;Pre-Clinical Model;preclinical development;promoter;Regimen;Resistance;resistance mechanism;response;Route;sigma-2 receptor;Signal Transduction;small molecule;Sodium Chloride;Specificity;standard of care;Stress;systemic toxicity;targeted cancer therapy;targeted treatment;Testing;Therapeutic;therapy resistant;TNF gene;Toxic effect;Treatment Protocols;triple-negative invasive breast carcinoma;tumor;tumor eradication;uptake;Variant;Work;x-linked inhibitor of apoptosis protein

PROJECT_TITLE: Preclinical Development of the Novel Inhibitor of Apoptosis Proteins S2/IAPinh for Cancer Therapy

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


NIH_SPENDING_CATS: Genetics

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Contact PD/PI: Freeman, Brian C PROJECT NARRATIVE  Homeostasis relies on precise and dynamic action by nuclear pathways including RNA transcription, DNA repair, and genome organization. While cooperative interactions between proteins and cofactors helps ensure selectivity, the events mediating the rapid action are less well understood. We believe molecular chaperones, especially the Hsp90 system, foster a highly dynamic nuclear environment that is critical for timely and effective DNA-associated pathways. Page 7 Project Narrative

PI_NAMEs: FREEMAN, BRIAN C (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TITLE: Regulation of the Native Protein Landscape in the Nucleus by Molecular Chaperones


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Small RNAs are critical regulators of gene expression and genome organization, pathways that are highly conserved across eukaryotic phylogeny. The goal of this project is to elucidate the fundamental mechanisms of RNA silencing so we can better understand its role in human development and disease. In particular, a critical function of small RNAs is transposon silencing, which, if unregulated represents a major threat to genome integrity and is associated with infertility, birth defects, cancer, and other diseases.

PI_NAMEs: PHILLIPS, CAROLYN MARIE (contact)

PROJECT_TERMS: Affect;Binding Proteins;Caenorhabditis elegans;Cells;Cellular biology;cofactor;Congenital Abnormality;Cytoplasmic Granules;Developmental Biology;Disease;Equipment;Eukaryota;experimental study;Gene Expression;Gene Expression Regulation;Generations;Genes;Genetic;Genetic Transcription;Genome;genome integrity;Germ Cells;Goals;Human;Human Biology;Human Development;human disease;Infertility;Malignant Neoplasms;Messenger RNA;Methylation;Microscopy;Nuclear;Nucleotides;parent project;Pathway interactions;Phase;Phosphorylation;Phylogeny;Physical condensation;Play;Post-Transcriptional Regulation;Post-Translational Protein Processing;Proteins;Regulator Genes;Regulatory Pathway;RNA;RNA Degradation;RNA Interference;Role;Small RNA;Sorting;Specificity;Structure;System;Time;tool;Translational Repression;Work

PROJECT_TITLE: Regulation of gene expression and genome organization by small RNAs


ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: Narrative Equipment supplement – same as the parent grant

PI_NAMEs: CLEMONS, WILLIAM M. (contact);KUROSU, MICHIO

PROJECT_TITLE: Mechanistic details of key integral membrane enzymes for antimicrobial discovery

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


ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE The parent program for this request (R35GM119518) seeks to understand proton-gated coincidence detection by G protein-coupled receptors (GPCRs), the largest and most therapeutically targeted class of human transmembrane receptors. A new program focus is the allosteric modulation of GPCR activity and pH sensitivity by coincident lipids using leading-edge mass spectrometry methodologies and instrumentation. The requested ThermoFisher SPD140P1 speed vacuum concentrator will enable us to extract the intact lipidome without oxidizing or degrading the lipids we seek to quantify.

PI_NAMEs: ISOM, DANIEL  (contact)

PROJECT_TERMS: Acceleration;Acids;Biology;Cell membrane;Cell model;Cell Surface Receptors;Communication;Detection;drug discovery;Endosomes;extracellular;frontier;G-Protein-Coupled Receptors;Human;Immune response;In Vitro;insight;instrument;instrumentation;lipidome;lipidomics;Lipids;mass spectrometer;Mass Spectrum Analysis;Membrane;Membrane Lipids;Methodology;National Institute of General Medical Sciences;parenting intervention;programs;Protons;receptor;receptor function;Regulation;Research;Signal Transduction;Speed;Synapses;therapeutic target;Thick;Tissues;tumor;Vacuum

PROJECT_TITLE: pH regulation of cell surface receptors


NIH_SPENDING_CATS: Bioengineering

PHR: Project Narrative The goal of this project is to develop fundamental understanding of proton-coupled electron transfers and oxygen-atom transfer chemical reactions that are relevant to biology. For many years this work has relied on rapid-scanning diode array spectrophotometers, but our two old instruments of this type have stopped working and are no longer repairable. The requested UV/vis/near-IR spectrophotometer will complement our existing scanning instruments, allowing different and valuable experiments.

PI_NAMEs: MAYER, JAMES M (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Acceleration;Award;biological systems;Biology;chemical transfer reaction;Chemicals;colloidal nanoparticle;Complement;Coupled;Electron Transport;experimental study;Fiber Optics;Funding;Goals;instrument;Laboratories;Molecular;optical spectra;Oxygen;Play;Process;Protons;Research Project Grants;Role;Sampling;Scanning;Services;Spectrophotometry;System;Temperature;Work

PROJECT_TITLE: Coupled Transfers of Electrons and Protons


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative: Phospholipids such as phosphatidylethanolamine are not only fundamental building blocks of cellular and organellar autonomy but additionally have diverse essential biological functions. This proposal focuses on an evolutionarily conserved mitochondrial protein that produces phosphatidylethanolamine, is essential for vertebrate life, and for which there are presently many unresolved questions. As such, results derived from this project will further define the role of mitochondrial phospholipid metabolism in health and disease.

PI_NAMEs: CLAYPOOL, STEVEN MICHAEL (contact)

PROJECT_TITLE: Endoplasmic reticulum-assisted mitochondrial precursor biogenesis and quality control

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

PHR: PROJECT NARRATIVE In this MIRA research program we will investigate how chemical properties of drug compounds affect drug absorption through skin that has been treated with microneedles, and we will study this in the laboratory, in animals, and in patients of different ages. This knowledge will help us identify time and cost-effective methods for developing microneedle products that could be used for a broad range of medical conditions.

PI_NAMEs: BROGDEN, NICOLE K (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: absorption;Affect;Age;age related;Age Years;Animals;Area;Biological;Cavia;Characteristics;Charge;chemical property;clinical application;clinically relevant;cohort;cost effective;Development;Dosage Forms;Dose;Drug Compounding;Drug Delivery Systems;Drug Kinetics;Enrollment;Environment;Formulation;Goals;Health;Human;human subject;hydrophilicity;Hydrophobicity;improved;In Vitro;in vivo;innovation;ionization;Kinetics;Knowledge;Laboratories;Length;Medical;Methods;micropore;Mission;National Institute of General Medical Sciences;Needles;Oral;Pathway interactions;Patients;Permeability;Pharmaceutical Preparations;Pharmacologic Substance;Plasma;programs;Property;Research;Route;Skin;small molecule;Structure;Testing;Time;Transdermal substance administration;translational approach;Work

PROJECT_TITLE: A translational approach to predicting small molecule drug permeation through microneedle-treated skin

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurosciences;Prevention;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: NORTH CHICAGO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI

PHR: Project Narrative Defects in genes involved in replication stress response often lead to neurodevelopmental disorders and predisposition to cancer. The Coats Plus disease, caused by dysfunction of genes involved in combating replication stress, is a rare genetic disease characterized by developmental failure of multiple vital organs including brain, eye and GI tract. The proposed research aims to reveal a new signaling pathway regulating the cellular response to replication stress and is expected to yield new mechanistic insights into how cells protect genome stability during perturbed replication and how genome instability leads to disease development.

PI_NAMEs: CHAI, WEIHANG  (contact)

PROJECT_TERMS: Bilateral;Binding;Binding Proteins;Biochemical;biological adaptation to stress;Biological Assay;Blood Vessels;bone;Brain;calcification;Calcium;Cells;Coats plus syndrome;Coats' disease;Complex;Cytoprotection;Defect;design;Development;developmental disease;Disease;DNA;Ensure;Eye;Failure;Functional disorder;gastrointestinal;Gastrointestinal tract structure;Genes;Genetic Diseases;genome integrity;Genome Stability;Genomic Instability;Goals;Growth;Human;insight;Life;loss of function mutation;Malignant Neoplasms;Molecular;Neurodevelopmental Disorder;novel;Organ;pathological aging;Pathological Dilatation;Pathway interactions;Phosphorylation;Predisposition;preservation;prevent;Proteins;rare genetic disorder;recruit;replication stress;Research;response;Retina;Signal Pathway;Signal Transduction;single molecule;Single-Stranded DNA;Site;SS DNA BP;System;Telangiectasis;therapeutically effective

PROJECT_TITLE: Molecular Basis of Coats Plus Disease


NIH_SPENDING_CATS: Arctic;Climate-Related Exposures and Conditions;Natural Products

PHR: NARRATIVE As part of the parent RO1 Grant propose to establish a Collaborative Program involving the basic research and development of the discorhabdin class of marine iminoquinone alkaloids as highly potent and selective controls for a diversity of diseases. Due to the lack of availability of the natural products through isolation from the Arctic sponges, studies have been designed to develop innovative natural product synthesis methodologies to facilitate their assessment in biological models and develop these highly unique alkaloid natural products as potential therapeutics. Aleutianamine possesses ideal features for the development of innovative synthesis methodologies and because the molecule is small, strained and may effectively penetrate unique tissue types and serve broadly as a model for effective disease management for a variety of diseases for which viable treatment options do not currently exist thus as part of this supplement we are proposing to acquire equipment to establish a state-of-the-art metabolomics and small molecules facilities.

PI_NAMEs: HAMANN, MARK T (contact);TIUS, MARCUS ANTONIUS;VALERIOTE, FREDERICK AUGUSTUS

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Alaska;Aleutian Islands;Alkaloids;Anabolism;Applied Research;Arctic Regions;Basic Science;bioactive natural products;Biological Models;Chemicals;Chemistry;cold temperature;Construction Materials;Data;deep ocean;design;Development;Disease;Disease Management;Environment;equipment acquisition;Generations;Grant;iminoquinone;in vivo;Inflammation;innovation;Investigation;Malaria;marine;marine organism;member;metabolomics;Methodology;Modeling;National Oceanic and Atmospheric Administration;Natural Products;ocean ecosystems;parent grant;Parents;Penetration;Pharmaceutical Preparations;Pharmacology;Play;Porifera;pressure;programs;research and development;Route;small molecule;Therapeutic;Tissues;ultraviolet irradiation;Viral Cancer;Virus Diseases

PROJECT_TITLE: Synthesis and Optimization of the Aleutianamine Class of Alkaloids

STUDY_SECTION: SBCB

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


ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Project Narrative This proposal investigates how mRNAs with early stop codons are repressed. The proposal focuses on the biochemistry and requirements for effectors of the mRNA cleavage step, and the role that ribosomes and the protein UPF1 have in mRNA targeting. Results from this work will illuminate mechanisms of translation and mRNA degradation for a class of genetic mutations (early stop codons) present in a substantial fraction (~11%) of disease-causing alleles.

PI_NAMEs: ARRIBERE, JOSHUA  (contact)

PROJECT_TERMS: Affect;Alleles;Animals;ATP phosphohydrolase;Binding;Biochemical;Biochemical Reaction;Biochemistry;Caenorhabditis elegans;Cells;Complex;Confusion;CRISPR/Cas technology;Cryoelectron Microscopy;Dependence;design;Detection;Dimerization;Disease;disease-causing mutation;Dissociation;DNA Sequence Alteration;Equipment;Event;experimental study;Funding;Genetic;Genetic Diseases;Genetic Variation;Goals;Heart;Hereditary Disease;Human;human disease;In Vitro;in vivo;Licensing;Maps;Mediating;Messenger RNA;Modeling;Molecular;mRNA Decay;mRNA Transcript Degradation;mutant;Mutation;nanopore;Nature;Nonsense Codon;nuclease;Nucleic Acids;Pathway interactions;Phenotype;Phosphorylation;Point Mutation;premature;Process;Production;Protein Biosynthesis;protein degradation;Protein Truncation;Proteins;Reaction;recruit;Reporting;Repression;Ribosomes;RNA;RNA Binding;RNA Biochemistry;RNA Decay;RNA Helicase;Role;Signal Transduction;Site;structural biology;Structure;System;targeted treatment;Techniques;Terminator Codon;Testing;Therapeutic;transcriptome sequencing;Translations;Work

PROJECT_TITLE: Equipment for the sensitive and quantitative detection of proteins and nucleic acids


ADMINISTERING_IC: OD

FUNDING_MECHANISM: OTHERS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Data Science;Genetics;Health Services;Human Genome;Precision Medicine

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PI_NAMEs: GABRIEL, STACEY  (contact);LENNON, NIALL JOHN;REHM, HEIDI L;TOPPER, SCOTT

PROGRAM_OFFICER_NAME: DUTKA, TARA

PROJECT_TERMS: Acceleration;Adoption;Agreement;All of Us Research Program;assay development;Automobile Driving;Award;biobank;Biological;Biological Assay;Biomedical Research;Clinical;cohort;Collaborations;Collection;Color;Communities;Complex;cost;Cost Control;Cost Sharing;Counseling;Data;Data Security;Data Set;design;Diagnosis;Disease;Disease Management;DNA;Ecosystem;empowerment;Environment;Epigenetic Process;Equity;Funding;Future;gene environment interaction;Generations;Genetic;Genetic Services;Genome;genome resource;genome sequencing;genome wide association study;Genomics;Genotype;Goals;Hand;Head;Health;Human;human disease;Human Genome Project;improved;Individual;innovation;insight;Institution;invention;Investments;Knowledge;Laboratories;Leadership;Longitudinal Studies;method development;Mission;multimodal data;Multiomic Data;multiple omics;new technology;novel;novel marker;Ownership;Participant;Persons;Phase;Phenotype;Play;Population;Population Heterogeneity;programs;Proteomics;Regulation;Research;Resources;Risk Assessment;Role;Sampling;Science;Secure;Source;Specimen;Speed;success;Technology;Time;trait;United States National Institutes of Health;Validation;Variant;Vision;whole genome

PROJECT_TITLE: Broad-Color: The Genome Center for the Future of All of Us


ORG_CITY: SAINT LOUIS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: WASHINGTON UNIVERSITY

PHR: The inductive and morphogenetic processes that establish the vertebrate body plan during gastrulation must be coordinated in space and time to ensure normal development. We are investigating the molecular mechanisms through which the key regulators of gastrulation, including Gpr125 adhesion G Protein- Coupled Receptor, Wnt/Planar Cell Polarity and Dachsous, interact to coordinate gastrulation movements with embryo patterning. We will also take an unbiased genetic approach to identify new essential regulators of gastrulation. As mutations in the components of these pathways cause miscarriages, birth defects and diseases, our studies can advance their understanding, diagnosis and facilitate development of therapies.

PI_NAMEs: SOLNICAKREZEL, LILIANNA  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Adhesions;Award;Behavior;Cadherins;Cell Shape;Cells;Complex;Congenital Abnormality;Development;Diagnosis;Disease;Embryo;embryo tissue;embryonic cleavage;Embryonic Development;Ensure;Experimental Genetics;Funding;Future;G-Protein-Coupled Receptors;Gastrula;gastrulation;gene product;Genetic;genetic approach;Genetic Screening;genome editing;Germ Layers;Goals;Impairment;insight;Investments;Membrane;Mesenchymal;Microtubules;Mission;Molecular;Morphogenesis;Morphology;Movement;Mutation;Pathway interactions;Pattern;planar cell polarity;polarized cell;Process;Proteomics;receptor;Research;Research Personnel;Shapes;Signal Pathway;Signal Transduction;Specific qualifier value;Spontaneous abortion;Testing;therapy development;Time;tool;Work;Zebrafish

PROJECT_TITLE: Inductive and morphogenetic processes shaping the zebrafish embryonic axes


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

ORG_CITY: STANFORD

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Nearly 40% of descendants from East Asia possess a genetic variant severely limiting their ability to metabolize reactive aldehydes. In addition, several other genetic differences in the lipid peroxidation pathway also occur in Asians which may impact organ injury, particularly during surgery. This project will develop tools in the basic science laboratory to better understand how genetic differences in the lipid peroxidation pathway may impact organ damage and translate these strategies to monitor and reduce organ damage in humans undergoing surgery.

PI_NAMEs: GROSS, ERIC RICHARD (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Aldehydes;Analgesics;Anesthesia procedures;Anesthetics;Asian Americans;Asian population;Basic Science;Biological;Biological Assay;Caring;Cause of Death;cell injury;Ethnic Origin;Far East;Functional disorder;Genetic;Genetic study;genetic variant;Health Care Costs;Human;Human Genetics;improved;insight;Knock-in Mouse;Laboratories;Lipid Peroxidation;Medical;Metabolism;Methods;Monitor;mortality;mouse model;novel;novel strategies;Operative Surgical Procedures;Organ;organ injury;Other Genetics;Pathway interactions;Persons;Phenotype;Population;precision medicine;programs;Quality of Care;Rodent;Time;tool;Translating;treatment strategy;TRP channel;United States

PROJECT_TITLE: Precision medicine for Asian Americans requiring anesthesia


NIH_SPENDING_CATS: Genetics;Human Genome

PHR: Project Narrative Cells maintain sophisticated mechanisms that ensure replicated chromosomes are accurately transmitted to daughter cells during division. When these mechanisms fail, cancer and other diseases are the result. The studies described in this grant examine an unsuspected and unexplored set of mechanisms that operate during the final stages of cell division (anaphase/telophase) to ensure accurate chromosome transmission.

PI_NAMEs: SULLIVAN, WILLIAM T. (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Anaphase;Behavior;Cell Cycle;Cell division;Cell Nucleus;Cells;Chromatin;chromosome replication;Chromosomes;Congresses;Cytokinesis;Daughter;daughter cell;Disease;DNA;DNA Damage;DNA Repair;Drosophila genus;Electron Microscope;Ensure;Eukaryotic Cell;Excision;fluorescence microscope;Genetic;Genome;genome integrity;Genomics;Goals;Grant;Induction of Apoptosis;Interphase;Kinetochores;Malignant Neoplasms;Metaphase;Microtubules;Mitotic;Molecular;novel;Nuclear Envelope;response;Secure;segregation;Sister;telophase;Time;transmission process

PROJECT_TITLE: Mitotic transmission of acentric chromosome fragments


NIH_SPENDING_CATS: Cystic Fibrosis;Dental, Oral, and Craniofacial Disease;Lung;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Chronic rhinosinusitis is burden disease regulators enable  a disease of the sinonasa l airways that causes significant morbidity and economic but for which the etiology is unknown. In this proposal, we seek to define causative mechanisms for this through defining alterations in the structure and function of the nasal submucosal glands, as well as key of glandular development and remodeling in both mice and humans. Outcomes from this study will the design of therapeutics for the treatment and cure of this chronic and debilitating disorder.

PI_NAMEs: MAY, ALISON  (contact)

PROGRAM_OFFICER_NAME: LIU, QIAN

PROJECT_TERMS: Adult;Affect;Airway Disease;Breathing;burden of illness;Cells;Chronic;chronic rhinosinusitis;curative treatments;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;design;Development;Disease;Duct (organ) structure;Economic Burden;Economics;Embryo;Epithelium;Etiology;Facial Pain;Functional disorder;Gland;gland development;Human;insight;intercellular communication;Measures;Mediating;Molecular;Morbidity - disease rate;Morphogenesis;Morphology;mouse model;mucus hypersecretion;Mus;Mutation;Nasal Polyps;Nose;Outcome;Outcome Study;parent grant;Pathology;Patients;Pattern;Penetrance;Phenotype;Polyps;Population;Preventive treatment;Process;Quality of life;Regulator Genes;Resolution;respiratory;rhinosinusitis;Role;Signal Transduction;socioeconomics;Specific qualifier value;Structure;Submucosa;Symptoms;Techniques;Testing;Therapeutic;Tissues;transcriptomics

PROJECT_TITLE: Defining the role of respiratory gland patterning in rhinosinusitis

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Behavioral and Social Science;Mental Health;Women's Health Research

ORG_CITY: ATLANTA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative  (Not Required)

PI_NAMEs: MEHTA, PUJA KIRAN (contact)

PROJECT_TERMS: Coronary;Microvascular Dysfunction;Psyche structure;stress reactivity;Woman

PROJECT_TITLE: Mental Stress Reactivity in Women with Coronary Microvascular Dysfunction


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Heart Disease;Human Genome;Pediatric;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Narrative Defects in embryonic patterning result in a variety of common birth defects (heart, orofacial, limb, etc) affecting nearly 3% of children born in the US. The genetic causes of these defects have been difficult to determine and a growing body of research points to defective gene regulation during embryonic development. This proposal seeks to understand how common and rare variation in regulatory sequences contribute to congenital heart defects and identify genes that they control during human heart organogenesis.

PI_NAMEs: COTNEY, JUSTIN LEE (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;Architecture;Brain;cardiogenesis;Child;Code;Congenital Abnormality;Congenital Heart Defects;craniofacial development;Defect;Development;Diabetes Mellitus;Disease;disorder risk;Embryo;Embryonic Development;Evolution;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic;Genetic Code;Genome;genome annotation;Health;Heart;Human;Human body;Individual;Life;Limb structure;Link;Malignant Neoplasms;Modeling;Molecular;Natural Selections;Neurologic Dysfunctions;Organogenesis;Organoids;orofacial;orofacial cleft;Pattern;Phenotype;postnatal development;prevent;Process;Proteins;Regulation;Regulatory Element;Research;Rest;Tissues;Variant;Work

PROJECT_TITLE: Unraveling mechanisms of genome regulation to understand and improvehuman health

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


ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Some genetic diseases result not because cells make a defective protein component, but rather because they don’t make enough of the component. We have identified a widely applicable, targeted approach to induce cells to increase the protein output from a single ‘good’ copy of a gene. We aim to define all such clinically relevant targets, and to apply our existing knowledge to a mouse model of specific, incurable, fatal disease called pulmonary arterial hypertension.

PI_NAMEs: BARASH, YOSEPH  (contact);HAND, NICHOLAS JOSEPH

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: 5' Untranslated Regions;Affect;BMPR2 gene;Cells;clinically relevant;Code;Data;Disease;disease phenotype;Evolution;Exhibits;Gene Proteins;Genes;Genetic Databases;Genetic Diseases;Goals;Hereditary Disease;Heritability;Human;Initiator Codon;Intervention;Knowledge;Messenger RNA;mouse model;novel;Open Reading Frames;Output;parent grant;Peptides;preservation;protein expression;Proteins;Publishing;pulmonary arterial hypertension;Regulatory Element;targeted treatment;Terminator Codon;Therapeutic Intervention;translational approach;Translations;Variant;Work

PROJECT_TITLE: Identifying regulatory uORFs as a targetable axis for hereditary disease

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Endocrine Disruptors;Neurosciences;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative This Diversity Supplement aims to characterize the developmental neurotoxicity (DNT) of lower-chlorinated polychlorinated biphenyls (LC-PCBs) and to assess how the route of exposure (dietary vs. inhalation) influences neurotoxic outcomes in weanling pups of rat dams exposed to PCB 28 during gestation and lactation. These studies are relevant to public health because they will provide data critically needed to assess the risk these emerging environmental contaminants pose to the developing brain and they will provide insights regarding strategies for mitigating this risk in vulnerable human populations. Moreover, this supplement will enhance the diversity of the scientific community that have the training needed to conduct rigorous scientific research focused on understanding how environmental stressors impact living systems in order to develop strategies for enhancing health and reducing the burden of human disease.

PI_NAMEs: LEHMLER, HANS-JOACHIM ;LEIN, PAMELA J (contact)

PROGRAM_OFFICER_NAME: LAWLER, CINDY P

PROJECT_TERMS: Address;Adolescent;Air;Axon;Brain;career;career networking;Child;Coculture Techniques;Communities;CREB1 gene;CYP2B6 gene;Data;developmental neurotoxicity;Diet;dietary;Dose;Ensure;Environmental Pollutants;environmental stressor;exposure route;Exposure to;Generations;Goals;Growth;Health;Human;human disease;In Vitro;in vivo;Ingestion;Inhalation;insight;Knockout Mice;Knowledge;Lactation;Maternal Exposure;Mediating;Metabolism;Molecular;mouse model;neurobehavioral;neurodevelopment;Neurodevelopmental Deficit;Neurodevelopmental Disorder;Neuroglia;Neurons;neurotoxic;novel;Organism;Outcome;Outcomes Research;parent grant;Polychlorinated Biphenyls;Population;Pregnancy;Pregnant Women;Preparation;Process;Proteins;Public Health;pup;Rattus;Research;Research Activity;research study;Risk;Risk Assessment;risk mitigation;Schools;Serum;skills;Sprague-Dawley Rats;success;teacher;Technical Expertise;Testing;Training

PROJECT_TITLE: Diversity Supplement to Molecular and Cellular Basis of PCB Developmental Neurotoxicity (Mendieta)


NIH_SPENDING_CATS: Neurosciences;Women's Health Research

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: PROJECT NARRATIVE The Notch signaling pathway has been implicated in a wide range of biological and pathological processes. Using the Drosophila ovarian model, the proposed studies will lead to improved understanding of the diverse effects and regulatory mechanisms of Notch signaling during development and tissue homeostasis. The findings from the proposed studies will help designing new therapeutic strategies for diseases related to aberrant Notch signaling.

PI_NAMEs: DENG, WU-MIN  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Address;Back;Biological;Biological Models;Biological Process;Cell Communication;Cell Cycle;Cell Death;Cell Differentiation Induction;cell growth;Cell Physiology;Cell Polarity;Cell Proliferation;Cell Survival;Cells;Cessation of life;design;Development;Disease;Drosophila genus;egg;Ensure;Environmental Risk Factor;environmental stressor;Epithelial Cells;Event;Feedback;Feeds;Genes;Genetic;Germ Cells;Germ Lines;Growth;Homeostasis;Homologous Gene;human disease;improved;MAPK8 gene;Mitotic;Mitotic Cell Cycle;Modeling;Molecular;neuronal cell body;notch protein;Notch Signaling Pathway;novel;novel therapeutic intervention;Nuclear;Oocytes;Oogenesis;Output;Ovarian;Pathogenesis;Pathologic;Pathologic Processes;Pathway interactions;Phagocytes;Phagocytosis;Physiological;Play;programs;Regimen;Regulation;Role;Series;Signal Induction;Signal Transduction;Somatic Cell;System;Temperature;Testing;Tissues;Tumor Suppressor Proteins;Up-Regulation

PROJECT_TITLE: Notch signaling and germline-soma interactions in the Drosophila ovarian model


PHR: NARRATIVE The overlying goal of the research program is to understand how timing of cell activities - patterning, signaling, and movement - is regulated in the Drosophila early embryo as development proceeds. In particular, the proposed experiments will investigate how initiation of zygotic gene expression is controlled; and how this results in the activation of cell signaling, including through FGFs, which is instrumental for the support of cell movements at gastrulation to transform the blastoderm embryo into multiple layers with distinct tissue types. This work has the potential to provide insight into how diverse cellular functions are coordinated to support normal embryonic development in higher animals, as the regulatory mechanisms are likely conserved.

PI_NAMEs: STATHOPOULOS, ANGELIKE  (contact)

PROJECT_TERMS: Actins;Adherens Junction;Affect;Animals;Blastoderm;cell motility;Cell Physiology;Cells;Cellular Morphology;Chromatin;Code;combinatorial;Comparative Study;CRISPR/Cas technology;Cytoskeleton;Data;Development;Dominant-Negative Mutation;Dorsal;Drosophila genus;Embryo;Embryonic Development;Enhancers;epithelial to mesenchymal transition;experimental study;Fibroblast Growth Factor;Fibroblast Growth Factor Receptors;Funding;gastrulation;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Homologous Gene;Hour;Image;in vivo evaluation;in vivo imaging;insight;Ligands;morphogens;Movement;Output;Pattern;preimplantation;Process;Production;programs;Proteins;Regulatory Element;Research;Running;Sequence Deletion;Series;sex;Signal Pathway;Signal Transduction;Signaling Molecule;Supporting Cell;System;Testing;Time;Time Factors;Tissues;Transcript;transcription factor;Variant;Work

PROJECT_TITLE: Temporal control of cell patterning, signaling, and movement in early embryos


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: TNF (tumor necrosis factor) is a critical innate immune response gene that has a profound impact on a number of autoimmune and infectious diseases outcomes. We have discovered long-range regulatory elements, which control expression of TNF in a cell-type specific manner. Understanding how these elements control TNF gene expression will provide fundamental knowledge about the regulation of TNF and potentially other genes and we expect will lead to novel and specific therapeutic strategies for autoimmune and infectious disease where TNF causes immune pathology.

PI_NAMEs: GOLDFELD, ANNE  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: 2019-nCoV;Acute;Architecture;Area;Arthritis;Autoimmune Diseases;CCCTC-binding factor;Cell Line;cell type;Cells;ChIP-seq;Chromatin;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;Communicable Diseases;Data;Data Set;Disease;disease model;Disease Outcome;Distal;Elements;Enhancers;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;genomic locus;Genomic Segment;Genomics;Goals;Hi-C;Human;IL6 gene;Immune;Immune Response Genes;Inbred BALB C Mice;Infection;Innate Immune Response;insight;Interferon Type II;Knowledge;Ligands;LTA gene;LTB gene;Macrophage;Mediating;Molecular Conformation;monocyte;Mouse Strains;Mus;Mycobacterium tuberculosis;next generation sequencing;nonhuman primate;novel;Pathology;Phylogenetic Analysis;programs;recruit;Regulation;Regulator Genes;Regulatory Element;RNA;RNA Viruses;Role;Sepsis;Site;Stimulus;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Three-dimensional analysis;TNF gene;Untranslated RNA;XCL1 gene

PROJECT_TITLE: Discovery of novel regulatory territories in the TNF/LT locus


ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: PARENT PROJECT NARRATIVE Nearly all cellular processes are influenced by small RNAs and their dysregulation has been implicated in fertility defects and disease. This study uses genetics and genomics to advance our understanding of how small RNAs control gene expression in the germline. The results will uncover new roles for small RNAs and mechanisms underlying small RNA function that preserve fertility and health from one generation to the next.

PI_NAMEs: MONTGOMERY, TAIOWA AKONI (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Address;Affect;Animals;Area;Biological Assay;Caenorhabditis elegans;Cell Physiology;Deposition;Development;Disease;DNA;Elements;Embryo;Ensure;Essential Genes;Fertility;Fertility Disorders;fertility preservation;fly;Functional disorder;Gene Expression;Gene Silencing;Generations;Genes;Genetic;genome editing;Genomics;Germ Lines;Health;Heritability;Human;Knowledge;Length;Malignant Neoplasms;Messenger RNA;MicroRNAs;Molecular;Nematoda;Nucleotides;parent project;Pathway interactions;piRNA;Process;Proteins;Reporting;Research;RNA;RNA Interference;Role;sensor;Small Interfering RNA;Small RNA;Sterility;Structure;System;Transcript;Translational Repression;transmission process

PROJECT_TITLE: Mechanism and function of small RNAs in development and gene silencing in the germline


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Project Narrative Metabolism is the process by which food is converted into energy and the molecular building blocks necessary for life. It is highly dynamic and changes rapidly with different conditions, for example after a large meal or vigorous exercise. We can measure a great number of metabolites in chemical extracts or biofluids, but there are few methods to measure metabolites in living systems. This project is to develop a better method to measure metabolism in a living microorganism in different conditions.

PI_NAMEs: EDISON, ARTHUR S (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TITLE: Platform for in vivo Metabolism - Equipment Supplement


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Our research focuses on molecular interactions, and we develop methods for protein-protein docking and the characterization of ligand binding properties of proteins. Predictive tools for these applications will be substantially improved by integrating classical biophysical approaches with recently developed machine learning tools. However, adding the later methods requires major increase in available computational resources, primarily GPUs.

PI_NAMEs: VAJDA, SANDOR  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Antibodies;Antigen-Antibody Complex;Area;Binding;Binding Proteins;Binding Sites;biophysical techniques;Cells;Computer software;Computers;computing resources;design;Development;Docking;Epitopes;Free Energy;functional group;Goals;Hot Spot;improved;interest;Libraries;Ligand Binding;Ligands;Machine Learning;Maps;Methods;Modeling;Molecular Probes;molecular recognition;molecular size;Multiprotein Complexes;neural network;neural network algorithm;novel;pharmacophore;Positioning Attribute;predictive tools;preference;process improvement;programs;Property;Protac;Protein Analysis;protein degradation;protein protein interaction;Protein Region;Proteins;Research;Resources;Running;Sampling;Site;small molecule;Structure;Surface;tool;Weight

PROJECT_TITLE: Analysis and Prediction of Molecular Interactions


ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: This project is to investigate the molecular processes that control the association of protein tyrosine kinases with other cellular proteins. Dysregulation of these associations can lead to aberrant function in immunological response, cell proliferation or cell survival, and lead to disease including autoimmune disorders and cancer. The value of the research is to provide knowledge that can be used to either fuel future efforts to understand disease through biosensors or develop effective drugs against autoimmune disease or metastatic cancer.

PI_NAMEs: POST, CAROL B. (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Affinity;Amino Acid Sequence;Animal Model;Antineoplastic Agents;Autoimmune Diseases;Binding;biophysical analysis;Biophysics;Biosensor;C-terminal;Catalytic Domain;Cell Physiology;Cell Proliferation;Cell Survival;Cells;Chemicals;Clinical;Complex;Computer Simulation;Computing Methodologies;Cytoplasm;Databases;Disease;Disseminated Malignant Neoplasm;DNA;Docking;drug development;Drug usage;Electrostatics;enthalpy;Entropy;Enzymes;Event;Exhibits;experimental study;Future;G-Protein-Coupled Receptors;Genes;Health;Human;Immune response;Immunologic Receptors;improved;In Vitro;inhibitor;ITAM;Knowledge;Libraries;Ligands;Malignant Neoplasms;Mediating;Membrane;Methods;Microscopic;Molecular;molecular dynamics;Motion;Outcome;Pattern;peptide structure;Peptides;Pharmaceutical Preparations;Phosphorylation;Phosphotransferases;Play;polypeptide;Post-Translational Protein Processing;Process;protein complex;Protein Conformation;Protein Kinase;protein protein interaction;Protein Region;Protein Tyrosine Kinase;Protein-Serine-Threonine Kinases;Proteins;receptor;recruit;Research;Role;Scientific Advances and Accomplishments;screening;Serine;Side;Signal Pathway;Signal Transduction;Signaling Protein;Site;small molecule;src Homology Region 2 Domain;src-Family Kinases;Structure;Substrate Interaction;SYK gene;Thermodynamics;three dimensional structure;Tyrosine Kinase Inhibitor;Tyrosine Phosphorylation

PROJECT_TITLE: NMR Structure of Peptide and Protein Complexes Supplement

STUDY_SECTION: MSFB

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


NIH_SPENDING_CATS: Genetics;Patient Safety

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Significance to Public Health Organic anion transporting polypeptides OATP1B1 and OATP1B3 mediate the uptake of many drugs and endogenous compounds from blood into the liver. The proposed research will elucidate novel regulatory mechanisms that modulate the function of these important liver-specific transport proteins. Such information is essential to predict clinically relevant drug-drug and drug-disease interactions.

PI_NAMEs: YUE, WEI  (contact)

PROJECT_TERMS: Abbreviations;Acetylation;Adherence;Adverse drug event;Aging;Anti-diabetic Drugs;Antibiotics;Antibodies;Antineoplastic Agents;Award;Blood;Blood capillaries;Cardiac Glycosides;Carrier Proteins;Cell Line;Cells;Clinical;clinical predictors;clinically relevant;Data;Data Analyses;data sharing;Deacetylase;Deacetylation;Detection;Disease;drug disposition;Drug Interactions;Drug Transport;Embryo;Enzymes;Epigenetic Process;epigenetic regulation;experimental study;FDA approved;Functional disorder;Funding;Gel;Genetic;Goals;Hepatocyte;Histone Acetylation;Histone Deacetylation;Histones;Human;Immunosuppressive Agents;improved;inhibitor;Kidney;Knock-out;Knowledge;Lipids;Liver;Lysine;Mediating;Molecular;Muscle;Mutagenesis;new chemical entity;novel;novel therapeutics;OATP Transporters;Outcome;Pharmaceutical Preparations;Pharmacotherapy;Phosphorylation;Policies;Post-Translational Protein Processing;programs;Protein Acetylation;Protein Analysis;Proteins;Public Health;rational design;Regulation;Reproducibility;Research;Rhabdomyolysis;side effect;Site;System;Toxic effect;Toxic Environmental Substances;Toxin;Transfection;treatment effect;tubacin;United States National Institutes of Health;uptake;Variant;Vorinostat

PROJECT_TITLE: Regulation of OATP1B1 and OATP1B3 by lysine acetylation and lysine deacetylase inhibitors

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


NIH_SPENDING_CATS: Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_DEPT: CHEMISTRY

PHR: Ubiquitination regulates virtually every cellular process in eukaryotes. Results from our study will reveal information on molecular basis of virulence of bacterial pathogens and on the mechanism of signaling in hosts, which will provide novel strategies for prevention and treatment of infectious diseases.

PI_NAMEs: DAS, CHITTARANJAN  (contact);LUO, ZHAO-QING

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Actins;ADP ribosylation;appendage;Arginine;Autophagocytosis;Binding;Binding Sites;Biochemical;Cell Physiology;Cryoelectron Microscopy;Databases;Deubiquitination;Enzymes;Eukaryota;Family;Hand;Hydrolase;infectious disease treatment;insight;Legionella;Legionella pneumophila;Legionnaires' Disease;Life Cycle Stages;Molecular;Natural regeneration;novel;novel strategies;Nutrient;Orthologous Gene;paralogous gene;particle;pathogen;pathogenic bacteria;Pathway interactions;phosphoric diester hydrolase;Poisoning;Prevention strategy;Process;Proteins;Reaction;Resistance;Serine;Side;Signal Transduction;Sorting;trafficking;Ubiquitin;ubiquitin isopeptidase;Ubiquitination;virtual;Virulence;Work;X-Ray Crystallography

PROJECT_TITLE: Mechanism of atypical ubiquitination and deubiquitination by bacterial effectors

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


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

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: PROJECT NARRATIVE Deciphering the complex coordination of transcription factor binding to cis-regulatory elements along DNA is fundamental to understand transcriptional regulation. Deep learning has demonstrated great promise at modeling functional genomics data, but it remains difficult to understand how they come to their decisions. This project will develop new model interpretability methods to decipher the motifs and their syntax learned by genomic DNNs, providing a suite of timely computational tools for the biomedical community that will have direct applications to fundamental problems in basic biological science as well as to the understanding and treatment of human diseases.

PI_NAMEs: KOO, PETER K (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;base;Binding;Biological;Biological Assay;Biological Sciences;biological systems;Biology;Black Box;cell type;Communities;Complex;Computer software;computerized tools;Computing Methodologies;Data;deep learning;deep neural network;Development;direct application;DNA;Ensure;functional genomics;Future;genomic data;Genomics;human disease;improved;insight;Learning;Maps;Methods;Modeling;Nucleotides;open source;Performance;Positioning Attribute;Regulatory Element;Resolution;Single Nucleotide Polymorphism;syntax;TensorFlow;Training;transcription factor;Transcriptional Regulation;Untranslated RNA;user-friendly

PROJECT_TITLE: Reliable post hoc interpretations of deep learning in genomics


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE Despite effective antiretroviral therapy, HIV-1-infected cells persist and proliferate. Using cutting-edge single-cell multi-omic profiling, we will examine mechanisms of HIV-1 persistence and decipher T cell clonal expansion dynamics. Understanding the cellular environment of HIV-1-infected cells will guide the design of therapeutic strategies for HIV-1 eradication.

PI_NAMEs: HO, YA-CHI  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Accounting;Acute;Anatomy;Antigen Presentation;Antigens;antimicrobial;antiretroviral therapy;ATAC-seq;Blood;CD4 Positive T Lymphocytes;cell killing;cell motility;Cell Proliferation;Cell Separation;Cell Survival;cell type;Cells;Clonal Expansion;Clone Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Cues;cytokine;cytotoxic;cytotoxic CD8 T cells;design;Dimensions;DNA;Environment;Enzymes;exhaustion;FDA approved;Flow Cytometry;Funding;Genetic Transcription;genome-wide;Goals;Heterogeneity;high dimensionality;HIV-1;Immune;immune clearance;Immune Evasion;Immune response;Immunity;Individual;Infection;inhibitor;integration site;Knock-out;lenalidomide;Length;Location;Mediating;Membrane Proteins;Memory;memory CD4 T lymphocyte;mesenteric lymph node;Methods;migration;Mothers;multiple omics;overexpression;peripheral blood;Persons;Pharmaceutical Preparations;Phylogenetic Analysis;polarized cell;programs;Proliferating;protein biomarkers;protein profiling;restoration;RNA;Role;Sampling;Site;Specificity;T cell clonality;T cell receptor repertoire sequencing;T-Cell Depletion;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;therapeutic target;Time;Tissues;trafficking;transcription factor;transcriptome;transcriptome sequencing;Viral;Viral Cytopathogenic Effect

PROJECT_TITLE: Role of clonal expansion in HIV-1 persistence

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: Project Narrative  Metalloredox reactions lie at the heart of many key biological processes, from the one electron Fe2+/Fe3+ redox cycle in ferroptosis-associated neurodegenerative diseases and bacterial infection to the multi-electron enzymatic transformations that power biological respiration and the global nitrogen and sulfur cycles, but the structure-function relationships underpinning these phenomena are key gaps in our knowledge that hamper our ability to address significant health challenges. To fill these gaps, we propose to engineer i) novel metal ion sensors for the spatiotemporal imaging of metal ion redox states in biological systems, ii) protein-based structural and functional mimics of complex metalloenzymes responsible for multi-electron reactions, and iii) DNA-cleaving DNAzymes for smaller and more robust alternatives to restriction enzymes and CRISPR/Cas. Achieving these goals will not only advance our knowledge of redox processes in metalloproteins and biological systems, but also expand the toolbox for designing metalloenzymes, real-time diagnostic imaging of mobile metal ions, and customizable recombinant DNA cloning and high-fidelity genome editing.

PI_NAMEs: LU, YI  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Address;Affinity;Bacterial Infections;Binding;Biochemical;bioimaging;Biological;Biological Process;biological systems;Catalytic DNA;Cells;Cloning;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;Complex;copper oxidase;design;Diagnostic Imaging;DNA;ds-DNA;Electrons;Engineering;Enzymes;Exhibits;functional mimics;gene editing technology;Generations;Genetic Engineering;genome editing;Goals;Health;Heart;Heme;heme a;high risk;Image;imaging agent;In Vitro;Individual;insight;Ions;Knowledge;metalloenzyme;Metalloproteins;Metals;Methods;Modeling;Neurodegenerative Disorders;nitric oxide reductase;Nitrogen;novel;Organism;oxidation;Oxidation-Reduction;Peptide Nucleic Acids;Process;Proteins;Reaction;Recombinant DNA;Respiration;restriction enzyme;Role;scaffold;Scaffolding Protein;sensor;spatiotemporal;Specificity;Structure;Structure-Activity Relationship;Sulfite reductase;Sulfur;Time;tool;Tyrosine

PROJECT_TITLE: Design and Selection of Novel Metalloenzymes for Biocatalysis, Bioimaging, and Genetic Engineering


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Breast Cancer;Cancer;Nanotechnology;Neurosciences;Women's Health Research

ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative Accurate diagnosis and assessment of brain metastases in patients with systemic cancers has important implications for patient prognosis and treatment strategy. The proposed two-way magnetic resonance tuning nanoprobes and complementary subtraction imaging technology with ultra-high tumor-to-normal tissue ratios will provide neuroradiology practice with a highly capable, accurate and consistent approach for detecting and evaluating early brain metastases. This new imaging technology has great potential to be translated in clinic to improve survival and reduce the mortality rate in patients with brain metastases in the near future.

PI_NAMEs: LI, YUANPEI  (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: 4T1;accurate diagnosis;angiogenesis;Biological;Biological Markers;Blood - brain barrier anatomy;Brain;brain magnetic resonance imaging;Brain Neoplasms;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;Breast Carcinoma;Cancer Detection;Cancer Etiology;Cancerous;Cell division;Cells;Central Nervous System;Central Nervous System Neoplasms;chelation;chemical synthesis;Clinic;cohort;contrast enhanced;Contrast Media;Coupled;crosslink;Crosslinker;Death Rate;design;Detection;Diagnosis;Diagnostic Procedure;Diffusion;Disease;Dose;Drug Controls;Drug Delivery Systems;Drug Kinetics;Drug Monitoring;effective intervention;Encapsulated;Endothelial Cells;Engineering;Experimental Designs;Future;Genetic Transcription;Goals;Grant;Health;Human;Image;image-guided drug delivery;imaging approach;imaging platform;Imaging technology;Immunotherapy;improved;In Vitro;in vivo;in vivo monitoring;inhibitor;Injections;insight;iron oxide nanoparticle;Magnetic Resonance;Magnetic Resonance Imaging;Maintenance;Malignant Breast Neoplasm;Malignant Epithelial Cell;Malignant Neoplasms;Measures;member;Metastatic breast cancer;Metastatic malignant neoplasm to brain;Methods;Modeling;Molecular;Monitor;mortality;mouse model;Mus;nano;Nanodelivery;nanoparticle;nanoprobe;nanotechnology platform;Neoplasm Metastasis;neoplastic cell;non-invasive imaging;Normal Cell;Normal tissue morphology;novel;Operative Surgical Procedures;optical imaging;Organoids;Parents;Pathologic;patient derived xenograft model;patient prognosis;Patients;Penetration;Pharmaceutical Preparations;Pharmacotherapy;pheophorbide a;Phosphorylation;Population;pre-clinical research;Proliferating;Publishing;Radiation;Resolution;response;Sialic Acids;Signal Transduction;Site;SLC2A1 gene;Specificity;STAT3 gene;stem cells;Structure;superparamagnetism;Surface;synergism;System;targeted treatment;Techniques;Technology;Testing;Therapeutic;Tight Junctions;Time;Tissues;tool;Toxic effect;Training;transcytosis;Translating;treatment planning;treatment response;treatment strategy;tumor;tumor microenvironment;Tumor Tissue;Visualization;Western Blotting

PROJECT_TITLE: Two-way Magnetic Resonance Tuning Nanoprobe Enhanced Subtraction Imaging for Precision Diagnosis of Brain Metastasis


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: CORVALLIS

ORG_NAME: OREGON STATE UNIVERSITY

ORG_STATE: OR

PHR: Public Health Relevance We hope to be able to solve atomic structures of any biologically related materials including proteins. The information will be instrumental for understanding mechanisms of diseases and for designing efficient therapeutic drugs.

PI_NAMEs: KONG, WEI  (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Address;Biological;Cations;Cells;Charge;Collection;Computer software;computerized data processing;cryogenics;cryostat;Data;Data Analyses;density;design;detector;digital;dimer;dipole moment;Disease;drug discovery;Drug Screening;electric field;Electron Beam;electron diffraction;Electrons;Electrospray Ionization;Electrostatics;Elements;Explosion;Foundations;Freezing;Generations;Goals;Guns;Helium;Heterogeneity;high risk;Individual;innovation;instrument;ion source;Ions;Label;Lasers;Ligands;macromolecule;mass spectrometer;Mass Spectrum Analysis;member;Membrane Proteins;Methods;Microfluidics;Molecular;Molecular Conformation;Mutation;nanocrystal;nanoelectrospray;nanoionics;nanomaterials;Noise;particle;Pattern;Pharmaceutical Preparations;Phase;Physiologic pulse;Process;Property;protein complex;protein protein interaction;Proteins;public health relevance;Pyrenes;recruit;Resolution;Retrieval;risk mitigation;Sampling;Shapes;Signal Transduction;small molecule;Source;Specialist;structural biology;Structure;Technology;Temperature;Therapeutic;Time

PROJECT_TITLE: Cryostat for generation of superfluid helium droplets

STUDY_SECTION: EBIT

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: NARRATIVE Many characters of interest in biomedicine evolved long ago and are fixed in a particular species, distinguishing it from unaffected relatives; finding the genes underlying any such ancient trait has been a central challenge in the field. We have developed a method, RH-seq, for genetic dissection of interspecies trait variation, and applied it in invertebrate models. We now propose to study how species-defining alleles confer their effects, alone and together, in a yeast model system, and we propose to port our approaches for interspecies genetics to mouse cells, with a focus on cellular senescence.

PI_NAMEs: BREM, RACHEL BETH (contact)

PROJECT_TERMS: Acceleration;Aging;Alleles;biological adaptation to stress;Biological Models;Cell Aging;Cell model;Cells;Chromosome Mapping;Complex;Dissection;Evolution;Funding;Genes;Genetic;Goals;Individual;Inflammatory;interest;Invertebrates;Literature;Maps;method development;Methods;Modeling;Molecular;Mus;Nature;Phenotype;Polygenic Traits;programs;reproductive;senescence;Sister;System;Testing;Time;tool;trait;Variant;Work;Yeast Model System;Yeasts

PROJECT_TITLE: Mapping deep evolutionary divergences in cellular models of stress response


ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE: Ribonucleases are enzymes that act on RNAs to process them to their mature, functional form, or to degrade them when they are no longer needed by the cell. A newly discovered ribonuclease in the model microorganism, Bacillus subtilis, is the prototype for a large family of similar proteins that are found in many bacterial organisms. Elucidating the structure and function of this ribonuclease could lead to the design of antibiotics that inhibit this enzyme and thereby reduce bacterial virulence. Project Narrative has not changed since original application.

PI_NAMEs: BECHHOFER, DAVID H (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 5'-exoribonuclease;Affinity;anti-microbial drug;antibiotic design;Bacillus subtilis;Binding Proteins;cell growth;Cells;Characteristics;design;Endoribonucleases;Enzyme Inhibition;Enzymes;Escherichia coli;experimental study;Family;genomic RNA;Gram-Positive Bacteria;Homologous Gene;in vitro activity;in vivo;Laboratories;Ligands;member;Messenger RNA;microorganism;Modeling;mRNA Decay;Mutagens;Names;novel;Oligonucleotides;Organism;Play;Polyribonucleotide Nucleotidyltransferase;Procedures;Process;Property;Protein Biochemistry;Protein Family;Proteins;prototype;Publishing;Regulation;Ribonucleases;RNA;RNA Binding;RNA Sequences;Role;SARS coronavirus;Small RNA;Structure;Tertiary Protein Structure;thermophilic organism;three dimensional structure;Virulence;Work

PROJECT_TITLE: YloC, a new ribonuclease of Bacillus subtilis