ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

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

ORG_CITY: NASHVILLE

ORG_NAME: MEHARRY MEDICAL COLLEGE

ORG_STATE: TN

PHR: Project Narrative This two-year supplement will expand and enhance the parent NLM R25 award, furthering Fortune Mhlanga's mentoring activities. Specifically, it will establish a mentoring academy to boost the capabilities of NLM R25 faculty mentors, increase student enrollment in the parent award’s R25 program, and enhance the program's mentoring activities. The long-term goal of this administrative supplement is to support and sustain the ongoing and future Principal Investigator's (PI's) efforts in Diversity, Equity, Inclusion, and Accessibility (DEIA).

PI_NAMEs: MHLANGA, FORTUNE  (contact);QIAN, LEI ;UNERTL, KIM M

PROJECT_TERMS: Academy;Administrative Supplement;Administrator;Applied Research;biomedical data science;biomedical informatics;Biomedical Research;career;Collaborations;Complement;Computational Science;Data;Data Science;early-career faculty;Ecosystem;Education Projects;Educational process of instructing;Enrollment;Ensure;equity, diversity, and inclusion;Evaluation;experience;Faculty;faculty mentor;faculty research;Fortune;Fostering;Future;Goals;graduate student;Historically Black Colleges and Universities;improved;Individual;Infrastructure;interest;Knowledge;Leadership;medical schools;member;Mentors;Mentorship;Outcome;parent project;Parents;Participant;Population Heterogeneity;Population Scientist Supplement (R25);Principal Investigator;programs;Publications;Research;Research Project Grants;Schools;Science;Scientist;skills;student participation;Students;summer research;symposium;Talents;Teacher Professional Development;Time;Training;undergraduate student;United States National Institutes of Health;United States National Library of Medicine;Universities;Vocational Guidance;Work

PROJECT_TITLE: The Fisk-Meharry-Vanderbilt Biomedical Informatics Ecosystem to Support Diverse Students in Data Science


ADMINISTERING_IC: HS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: PISCATAWAY

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

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

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Identifying the mechanisms correlated with increased health care use among Black youth in foster care is important for improving health outcomes and reducing the high cost of healthcare. This study utilizes 11 years of linked child welfare and electronic health records data (N~7,500 patients) and incorporates the voices of young people in foster care through the use of a Research Participant Advisory Council to evaluate the salience of multiple social identities on healthcare use variation, coordination of medical care, and health care outcomes. Understanding the mechanisms for racial disparities within the healthcare system for foster youth may increase positive health outcomes, decrease health care costs, and promote equity in health outcomes.

PI_NAMEs: WILLIAMS - BUTLER, ABIGAIL  (contact)

PROGRAM_OFFICER_NAME: COA, KISHA

PROJECT_TITLE: Centering the Needs of Black Children in Foster Care: Healthcare Utilization and Coordinated Medical Homes

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: RESEARCH STRATEGY Background. NIGMS grant R35 GM148220-02 supports research on protein chemistry. This grant is focused on an increasingly important challenge in biomedicine—the traceless delivery of proteins to the cytosol of human cells. This ability provides far-reaching, long-term opportunities for high-impact advances in biomedicine, chemical biology, and allied fields. This supplemental application is for a single piece of equipment that is critical for the completion of the proposed research.  Need for the Requested Equipment. Grant R35 GM148220 proposes the use of diazo compounds to create “protein prodrugs”. In this approach, the esterification of protein carboxylates temporarily “cloaks” the anionic charge in a target protein (Figure 1), enabling membrane transversal. The internalized esters are hydrolyzed by cytosolic esterases, much like small- molecule prodrugs.  This research requires the ability to monitor quantitatively (1) the synthesis of novel diazo Figure 1. Key aspects of the research supported by grant R35 GM148220 and structures of esterified proteins formed from novel cognate α-aryl diazo compounds. Resistance to spontaneous hydrolysis is conferred by either steric interactions or an intramolecular n→π* interaction that elicits the Pauli exclusion principle. Release is achieved by esterase- mediated p-quinone-methide formation. compounds, (2) the rate at which those diazo compounds esterify carboxylic acids, and (3) the kinetic stability of the ensuing esters in both the absence and presence of human esterases. In the first two years of support, we have learned that spontaneous hydrolysis can limit the practical utility of nascent esters. (A typical half-life is a few days.) Accordingly, we are now seeking diazo compounds that generate esters that are stable to spontaneous hydrolysis but removable by cellular esterases. Our strategy is to generate esters that are protected by steric effects or Pauli exclusion (as only one electron pair can occupy an orbital). The esters are designed to be cleaved by p-quinone methide formation. We have conceived of many new α-aryl diazo compounds along these lines (e.g., Figure 1). We now seek to make and test them.  This request arises because there is an urgent, unexpected need for the requested equipment. First, our need for analytical chromatography greatly exceeds that expected upon submission of our grant application in January 2022 because of the need to make and test many new diazo compounds. Second, we have lost our ability to perform any analytical chromatography. Our laboratory had a functioning Agilent 1200 series HPLC instrument for analytical chromatography (Figure 2). This instrument was purchased in 2008 and was a workhorse for 16 years. With this instrument, we characterized hundreds of compounds and performed thousands of assays, leading to dozens of publications. Unfortunately, the instrument is broken and irreparable. We now have a daily need for this instrument that cannot be accommodated elsewhere. For example, the use of instrumentation facilities is slow and inefficient, does not allow for the use of columns appropriate for polar molecules like ours (e.g., C4 and HIC), and is expensive, putting an undue burden on the budget of our NIGMS grant.  Description of the Requested Equipment. We request support for the purchase of an LC/MSD instrument from Agilent Technologies (Lexington, MA). This instrument uses powerful mass-selective detection to enhance analytical precision and is designed for efficiency. Its single quadrupole provides both flexibility and insight. The instrument has these capabilities that are essential for our research: Figure 2. Photograph of the rust-laden, nonfunctional 16-year-old analytical HPLC instrument in our laboratory. · High mass accuracy (±0.005 Da) · Flexibility to detect compounds with ESI, APPI, APCI, and multimode ion sources · Diode array detector with ultrafast scan speeds · Automated multisampler for vials and microplates · Simple, intuitive software that includes the OpenLab chromatography data system (CDS) · Rapid confirmation of interpretations through a library-match search technology This instrument would not only meet the urgent, unexpected need described above but also enhance the overall impact of grant R35 GM148220 by facilitating nearly all of the synthetic and analytical procedures inherent in the proposed research.  Oversight and Training Plan. An engineer from Agilent Technologies would install the equipment, and a representative would provide training, both free of charge. To ensure that the requested instrument is accessible but maintained in like-new condition for the foreseeable future, we have designed a plan for instrument oversight. Specifically, we would house and maintain the instrument in MIT Room 18-344D, which is an equipment room within our laboratory. That location is ideal because of its central location and ready accessibility to personnel.  A postdoctorate in our research group, Dr. Bjarne Silkenath, would facilitate the training of individual users and provide oversight. Dr. Silkenath is a synthetic organic chemist who has much experience in both liquid chromatography and mass spectrometry. He would host training events in which he would present the capabilities of the instrument to potential users. After attending such a session, individual users would contact him to request hands-on training, access to documentation on standard operating procedures, and certification to use the instrument independently. Certified users would be provided with the opportunity to sign up for a particular block of time on a first-come, first-served basis. Lastly, prior to leaving our research group, Dr. Silkenath would be responsible for appointing and training his successor, who would be chosen based on their experience with the instrument and their accountability.  Other Users. The reach of the requested equipment supplement would extend beyond the laboratory of the PI. Specifically, the requested instrument would be shared with other departmental researchers, including Profs. Buchwald (R35 GM122483), Cummins (R01 GM130936), Movassaghi (R01 GM141963), Nolan (R01 GM118695 and R01 GM126376), and Shoulders (R35 GM136354). Notably, we have recently published joint papers with Profs. Buchwald, Cummins, and Movassaghi, and our groups have highly active collaborations.  Cost of the Requested Equipment. We have negotiated a 28% discount on the list price for an LC/MS from Agilent Technologies. The price quote is attached to this application. To supplement this cost, we would provide a computer (~$2000) to operate the equipment, and we would use institutional funds to purchase a yearly service contract for ~$6000 per year (see below).  Maintenance of the Requested Equipment. To ensure that the requested equipment is maintained in like-new condition, institutional funds would support a service contract from Agilent Technologies. The corporate headquarters of Agilent Technologies is in Lexington, MA, which is a 30-minute drive from our laboratory. Our department has many pieces of Agilent equipment and has negotiated a blanket contract to cover the cost of servicing that equipment. We project that the cost of servicing the new equipment would be ~$6,000 per year and would provide us with a yearly planned maintenance visit, technical assistance center service for operational and instrument set-up problems, and remote instrument diagnostics. Finally, we note that funds are not available in the budget of grant R35 GM044783 for the purchase of the requested equipment without the displacement of essential personnel. Summary We thank you for your consideration of this request for an equipment supplement, which is essential for the execution of the research proposed in grant R35 GM044783.

PI_NAMEs: RAINES, RONALD T (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: 16 year old;Accountability;Address;alkalinity;Ally;Antibodies;Applications Grants;Biological Assay;Biology;Budgets;carboxylate;Carboxylic Acids;Cells;cellular targeting;Certification;Charge;Chemicals;chemotherapeutic agent;Chromatography;Collaborations;Computer software;Computers;Contract Services;Contracts;cost;Cytosol;cytotoxicity;design;Detection;detector;Diagnostic;diazo compound;discount;Documentation;Electrons;Endowment;Engineering;Enzymatic Biochemistry;Enzymes;Equipment;Essential worker;esterase;Esterification;Esters;Event;Exclusion;experience;extracellular;flexibility;Funding;Future;genome editing;Goals;Grant;Half-Life;High Pressure Liquid Chromatography;Hormones;Human;Human Resources;Hydrolysis;immunogenicity;Individual;Information Systems;insight;Institution;instrument;instrumentation;Intuition;ion source;Joints;Kinetics;Laboratories;Learning;Libraries;liquid chromatography mass spectrometry;Location;Maintenance;Mediating;Mediation;Medical;Membrane;Methods;Modification;Monitor;National Institute of General Medical Sciences;novel;Organic Chemistry;Paper;Pharmaceutical Preparations;Pharmacopoeias;Physiological;Price;price lists;Procedures;Prodrugs;programs;Protein Chemistry;Proteins;Publications;Publishing;quinone methide;Research;Research Personnel;Research Support;Resistance;Scanning;Series;Services;Shoulder;small molecule;Speed;Structure;success;Technology;Testing;Time;Training;Tumor Suppression;uptake;Vial device;virtual;Visit;Water;Work

PROJECT_TITLE: Protein Chemistry


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Bioengineering;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: BALTIMORE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Cell fate engineering, for example the directed differentiation of pluripotent stem cells or the direct conversion among somatic cell types, holds great promise to improve disease modeling, drug screening, and to lead to regenerative medicine therapies. However, our ability to engineering cell fate with fidelity has been impeded by an incomplete understanding of the biological networks that govern development. In the parent award for this grant, we are addressing this problem through a combination of algorithm development and experimental validation, with an emphasis on cell types related to the synovial joint, as well as their developmental progenitors. The Imaging System that we request in this grant will transform our ability to address the overarching goals of the parent award by enabling us to perform more rigorous, robust, and quantitative imaging of our validation and discovery experiments.

PI_NAMEs: CAHAN, PATRICK  (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Address;algorithm development;Binding Sites;Biological;Calibration;cell type;Cells;Chondrocytes;Chromatin;Computational algorithm;computerized tools;Computing Methodologies;Data;Development;directed differentiation;disease model;Drug Screening;Engineering;experimental study;Genetic Transcription;Goals;Grant;imaging system;improved;Ingestion;meetings;Mesoderm;Orphan;Outcome Assessment;parent project;pluripotent stem cell differentiation;progenitor;quantitative imaging;Recipe;Regenerative Medicine;Signal Pathway;Somatic Cell;Synovial joint;Technology;tool;transcription factor;Validation;Work

PROJECT_TITLE: From intra to intercellular regulatory networks that define cell type identity

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Cancer;Hematology

ORG_CITY: POMONA

ORG_DEPT: BIOLOGY

ORG_NAME: CALIFORNIA STATE POLY U POMONA

ORG_STATE: CA

PHR: Project Narrative Not Applicable. This is an application for Administrative Supplement, per Notice Number: NOT-GM-24-021 [Notice of Special Interest (NOSI): Administrative Supplements for Equipment Purchases for Select NIGMS-Funded Awards]. Per PA-20-272, forms must be completed for the supplemental activities only and must not reflect funding or activities for the previously awarded parent award. There is no change from information submitted and approved for the existing awarded Parent Grant 1R16GM146720-01.

PI_NAMEs: EAR, JASON  (contact)

PROGRAM_OFFICER_NAME: CUPIT, PAULINE

PROJECT_TERMS: Administrative Supplement;Award;equipment acquisition;FLT3 gene;Funding;Gene Fusion;Hematopoietic Neoplasms;interest;Molecular;National Institute of General Medical Sciences;parent grant;parent project;PDGFRB gene

PROJECT_TITLE: Elucidating the molecular mechanism of Daple- FLT3 and Daple-PDGFRB gene fusion in blood cancers


NIH_SPENDING_CATS: Regenerative Medicine;Wound Healing and Care

ORG_CITY: KALAMAZOO

ORG_NAME: WESTERN MICHIGAN UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative The presence of unstable forms of oxygen (reactive oxygen species) are known to have large consequences on wound healing and regenerative outcomes. But it is still not well understood how the same oxygen species regulate these two different processes, even though millions are affected each year by poor wound healing and an inability to restore functional tissue. This project seeks to identify the genes and signaling pathways downstream of reactive oxygen species that control wound healing versus tissue repair, in order to identify new targets for treatment to promote proper healing after injury, surgery, and disease.

PI_NAMEs: BEANE, WENDY SCOTT (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Actins;Affect;care costs;cell injury;Cell Respiration;chronic wound;Cicatrix;Cloning;Data;design;Diabetes Mellitus;Disease;Fibrosis;Fostering;functional restoration;Future;Genes;Goals;Growth;healing;Health;Host Defense;Immune;Immunohistochemistry;Impaired wound healing;In Situ Hybridization;Injury;loss of function;Malnutrition;Mediating;Microsurgery;Natural regeneration;Obesity;Operative Surgical Procedures;Organism;Outcome;Oxygen;Patient-Focused Outcomes;Planarians;Process;Proliferating;Reactive Oxygen Species;recruit;regenerative;repaired;response;restoration;RNA Interference;Role;Signal Pathway;Signal Transduction;Site;Techniques;Testing;tissue repair;Tissues;tobacco abuse;Training;undergraduate student;Work;wound;wound healing;wound response

PROJECT_TITLE: ROS Signaling in Wound Healing vs Tissue Repair


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: MISSOULA

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: The proposed studies will investigate tissue regeneration of functional craniofacial cartilage for transplantation. Neural crest-derived craniofacial cartilage will be created from stem cells in three dimensional cultures with an eye towards regrowth of the cartilaginous structures of the face such as the nose and ears. Our studies also have relevance for understanding craniofacial birth defects and cancers derived from the neural crest.

PI_NAMEs: GRIMES, MARK LINDSAY (contact)

PROGRAM_OFFICER_NAME: VERBRIDGE, SCOTT SPENCER

PROJECT_TERMS: 3-Dimensional;Acceleration;aggrecan;Animal Model;Area;autocrine;Autocrine Communication;base;biofabrication;bioprinting;Birth trauma;BMP5 gene;Cartilage;cartilage cell;cartilage transplantation;cartilaginous;cell injury;Cells;Characteristics;Child;Chondrocytes;Chondrogenesis;Collagen;Collagen Type I;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;crosslink;Data;Derivation procedure;Development;Dimensions;Ear;effective therapy;Elastic Cartilage;Elasticity;embryonic stem cell;experimental study;Extracellular Matrix;Face;Formulation;Functional Regeneration;Gene Expression;Generations;Genomics;Goals;Growth;Growth Factor;Head;Heparin;Histological Techniques;Human;human stem cells;Hyaluronan;Hydrogels;Immunofluorescence Microscopy;Immunosuppressive Agents;in vivo;induced pluripotent stem cell;innovation;Integrins;Knowledge;Laboratories;Laminin;magnetic beads;Malignant Neoplasms;Mass Spectrum Analysis;maxillofacial;Mediating;Mesenchyme;Methacrylates;Methodology;Methods;Morphology;Natural regeneration;Neural Crest;Nose;Organoids;paracrine;Paracrine Communication;Pathway interactions;patient derived induced pluripotent stem cells;Plastic Surgical Procedures;Play;Population;Process;Proliferating;Proteins;Proteomics;receptor;Receptor Signaling;Reconstructive Surgical Procedures;Rehabilitation therapy;repaired;Reproducibility;resilience;response;RNA;Role;scaffold;scale up;self organization;Shapes;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Skin;Sorting;Specific qualifier value;stem cell differentiation;stem cells;Structure;Sulfate;Techniques;Testing;TGFB3 gene;three dimensional cell culture;three dimensional structure;Tissue Engineering;tissue regeneration;Tissue Transplantation;Tissues;transcriptomics;translational applications;translational goal;Transplantation;Trauma;WNT5A gene

PROJECT_TITLE: Craniofacial cartilage differentiation from human neural crest stem cells in 3D cultures

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: CHICAGO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative from the Parent Award Through the application of advanced biophysical methods and computational approaches, we will address a range of exciting yet challenging biological phenomena including voltage-activation of a sensory membrane protein, metabolite transport across a bilayer, membrane protein folding, stress-induced phase separation, and properties of disordered proteins, both soluble and membrane bound. To address these topics in depth, we are expanding the applicability of hydrogen exchange techniques to membrane proteins under an activating voltage, during their folding, and even in vivo to examine their dynamics in cells. Our Upside simulation algorithm is powerful and enhances each of the experimental projects.

PI_NAMEs: SOSNICK, TOBIN R (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Address;Algorithms;Binding;Biological Phenomena;Biological Sciences;biophysical chemistry;biophysical properties;biophysical techniques;Cells;Complex;Computing Methodologies;Disease;experience;experimental study;Hydrogen;improved;in vivo;interest;Knowledge;Learning;Membrane;Membrane Proteins;Methods;Motor;parent project;Pattern;Phase;Physical condensation;Property;protein folding;Proteins;Research;Sensory;simulation;skills;Speed;Stress;System;Techniques;voltage

PROJECT_TITLE: Studies of the function of membrane and soluble proteins and their biophysical properties.


FUNDING_MECHANISM: SBIR-STTR RPGS

ORG_CITY: ATHENS

ORG_NAME: LECTENZ BIO, INC.

ORG_STATE: GA

PHR: PROJECT NARRATIVE Therapeutic glycoproteins (biologics) such as antibodies address critical health care needs, but there are currently no simple methods for analyzing the attached glycans (sugar molecules) during the biologics production. The ability to monitor the glycosylation of biologics during their production would be transformative for biopharmaceutical R&D and would accelerate the creation of new biologics and biosimilars. Our innovative technology enables monitoring of protein glycosylation in near real-time in a robust and convenient manner.

PI_NAMEs: YANG, LORETTA  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Acceleration;Address;Adoption;Affect;analytical method;Antibodies;Basic Science;Biological Products;Biological Response Modifier Therapy;Carbohydrates;Cell Culture Techniques;Chromatography;commercialization;Consumption;cost;Data;design;Equipment;Flow Cytometry;Gases;Glycoproteins;glycosylation;Half-Life;Healthcare;immunogenicity;innovative technologies;Mass Spectrum Analysis;Measurement;Methods;Monitor;novel;novel strategies;Pattern;Performance;pharmacologic;Pharmacologic Substance;Phase;Polysaccharides;Process;Production;Protein Glycosylation;Proteins;Publishing;Reagent;Reporting;research and development;Safety;Sampling;Serum;sugar;Technology;Temperature;Therapeutic;Time;United States Food and Drug Administration;Variant

PROJECT_TITLE: A new approach to monitoring glycosylation during glycoprotein production


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Genetics;Physical Injury - Accidents and Adverse Effects

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Our understanding of tendon cell function is limited by the ability to specifically target subsets of tendon cells during development, homeostasis, and healing. We propose to generate new mouse alleles that would enable an intersectional genetic approach and more specific targeting of tendon cells. Widespread use of these lines would advance our mechanistic understanding of tendon biology and would impact the development of therapies for human tendon injuries.

PI_NAMEs: GALLOWAY, JENNA L (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Ablation;Acceleration;achilles tendon;Affect;Aging;Alleles;Anatomy;Area;Biology;Body Regions;Cell Communication;Cell Lineage;Cell Physiology;cell type;Cells;Cephalic;Cicatrix;Communities;Data;Development;diphtheria toxin fragment A;Dissection;Ensure;Fibrosis;FLP recombinase;Fluorescent in Situ Hybridization;Future;Generations;Genes;Genetic;genetic approach;Genetic Recombination;Goals;healing;Heart;Homeostasis;Human;improved;Individual;injured;Injury;Joints;Keratin;Label;ligament injury;Ligaments;Limb structure;Location;loss of function;mechanical properties;Meniscus structure of joint;Molecular;mouse genetics;Movement;Mus;Musculoskeletal;Neurosciences;novel;Pain;Pathway interactions;Patients;Population;Property;Publishing;Reagent;recombinase;Regional Anatomy;repaired;Research;Research Personnel;Retina;scleraxis;single molecule;single-cell RNA sequencing;Skin;Specificity;Tendon Injuries;Tendon structure;therapy development;Tissues;tool;Trachea;Translating;Validation;Work

PROJECT_TITLE: Generation of intersectional genetic tools for advancing tendon and musculoskeletal research

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Complementary and Integrative Health;Genetics;Hematology;Infectious Diseases;Sepsis

ORG_CITY: Columbus

ORG_DEPT: SURGERY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: No Change from Original Project Narrative Project Narrative Septic survivors exhibit long-term immunologic dysfunction associated with higher rates of disability, depression, subsequent infections, and all-cause mortalities; however, our understanding of the regulation of these responses and their impact on disease is lacking. This proposal will integrate mechanistic in vivo studies with human data and quality of life outcomes measures to provide an in-depth assessment of the systemic epigenetic events that occur during sepsis and how their regulation of the post-septic immunosuppressive response effects the immunologic and functional outcomes of patients. The proposal has the potential to provide fundamental insight into disease regulation and novel therapeutics for the treatment of post-sepsis immunosuppression.

PI_NAMEs: WISLER, JON R (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Animal Model;Area;Clinical;clinical effect;Clinical Investigator Award;Coupled;Couples;Critical Care;Data;Diagnosis;direct application;disability;Disease;DNA Methylation;DNA Modification Methylases;Epigenetic Process;epigenetic regulation;Event;Exhibits;functional decline;functional outcomes;Gene Silencing;human data;immune function;Immune System Diseases;Immunologics;Immunosuppression;improved;in vivo;Infection;innate immune function;insight;Intervention;Investigation;Knowledge;Laboratories;Long-Term Effects;Mediating;Meditation;Mental Depression;Methylation;Molecular;mortality;novel therapeutics;Operative Surgical Procedures;Outcome;Outcome Measure;Patient-Focused Outcomes;Patients;pharmacologic;Phase;Process;Productivity;professor;programs;psychosocial outcome;Quality of life;Recovery;Regulation;Research;Research Personnel;response;restoration;Sepsis;septic;skills;Survivors;survivorship;synergism;therapeutic evaluation;Time;Trauma;Treatment/Psychosocial Effects;United States National Institutes of Health

PROJECT_TITLE: Analyzing the long-term effects of DNA methylation meditated immunosuppression following sepsis


ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Cytoplasmic compartmentalization mechanisms have the potential to influence broad cellular processes and pathways, including how, when, and where mRNAs are translated, silenced, or degraded. The research outlined in this proposal will elucidate the molecular and functional role of a new cytoplasmic niche between membrane- bound organelles and membrane-less RNA-protein organelles. We expect the results from these studies will yield fundamental insights into how cells under duress rapidly switch from bulk mRNA translation to sequestration, as well as, how cells prevent membrane-less organelles from developing into toxic RNA-protein aggregates.

PI_NAMEs: LEE, JASON EDWARD (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: aqueous;Basic Science;Binding;Biochemical;Biophysics;Cell Physiology;Cells;Cytoplasm;Dependence;Disease;Endoplasmic Reticulum;Eukaryotic Cell;Goals;Health;imaging approach;In Vitro;in vivo;insight;Life Cycle Stages;Lipids;live cell imaging;Maintenance;Malignant Neoplasms;Mediating;Membrane;Messenger RNA;Molecular;Morphology;mRNA Translation;Nerve Degeneration;Organelles;Pathway interactions;Physical condensation;Play;prevent;Process;programs;protein aggregation;Proteins;Quality Control;Reaction;recruit;Research;RNA;RNA Processing;RNA Virus Infections;Role;Site;stress granule;Structure;Testing;Translating;translational medicine;vesicle transport;Work

PROJECT_TITLE: Factors and Functions of Contact Sites between Membrane-bound and Membrane-less Organelles


ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: NARRATIVE Cell plasticity, the ability of cells to change their phenotypes without genetic mutations, is crucial for the development and the progress of diseases such as cancer. Post-transcriptional mechanisms are essential for cell plasticity as they offer a route to regulate cell fate, specifically in response to rapid changes in response to environmental cues. This proposal investigates the mechanisms by which translational control and RNA modifications regulate cell plasticity.

PI_NAMEs: KHOSHNEVIS, SOHAIL  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Address;Affect;Area;Binding;Biochemical;Biochemistry;Biological Assay;Black Box;Candida albicans;cell behavior;Cell Fate Control;Cell Physiology;cell type;Cells;Chemicals;Complex;Coupled;Cues;Data;Deposition;Development;Disease;DNA Sequence Alteration;environmental change;Epithelium;Eukaryota;Eukaryotic Initiation Factor-3;Foundations;Future;Gene Expression;Gene Expression Regulation;Genetic;Genetic Transcription;Goals;Homeostasis;Human;Human Cell Line;human disease;Hyphae;Immune response;Impairment;Infection;insight;Knowledge;Laboratories;Malignant Neoplasms;Mediating;Mesenchymal;Messenger RNA;Methylation;model organism;Modification;Molecular Biology;Morphology;mRNA Translation;next generation;next generation sequencing;novel;Organism;oval cell;Pathogenesis;pathogenic fungus;Peptide Initiation Factors;Phenotype;Play;Post-Transcriptional Regulation;posttranscriptional;Process;programs;Protein Biosynthesis;Proteins;Proteomics;Reagent;Research;Research Personnel;response;Ribosomes;RNA;RNA methylation;RNA Splicing;RNA Stability;Role;Route;Saccharomyces cerevisiae;scaffold;stem cells;structural biology;Study models;Tissues;tool;Transcription Process;transcriptome;translation factor;Translation Initiation;Translational Regulation;Translations;Work;yeast genetics;Yeasts

PROJECT_TITLE: Post-transcriptional regulation of cell plasticity

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: HOUGHTON

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MICHIGAN TECHNOLOGICAL UNIVERSITY

PHR: Project Narrative This proposal proposes to purchase and install the up-to-date laser system in the light microscope for discovery of the fundamental mechanism behind cells’ stiffness sensing, especially how this force and mechanosensor, in space and time, elicit different signaling that regulates cell behaviors such as cell survival, proliferation and migration.

PI_NAMEs: HAN, SANGYOON JOSHUA (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Adhesions;Affect;behavior influence;Biological Process;Budgets;cell behavior;Cell Physiology;Cell Survival;Cell-Matrix Junction;Cells;disability;Disease;doctoral student;Equipment;equipment acquisition;Event;Extracellular Matrix;fluorescence imaging;Fluorescence Resonance Energy Transfer;Focal Adhesion Kinase 1;Focal Adhesions;graduate student;grasp;Health;high resolution imaging;Image;imaging capabilities;improved;insight;Knowledge;Lasers;Life;Light Microscope;live cell imaging;mechanical force;Mechanics;mechanotransduction;Methods;migration;Mission;Molecular;Neoplasm Metastasis;novel therapeutic intervention;parent grant;Phototoxicity;Play;Process;Proliferating;Proteins;recruit;Research;response;Role;Sampling;sensor;Series;Signal Transduction;solid state;System;Talin;temporal measurement;Time;Tissues;United States National Institutes of Health;Work

PROJECT_TITLE: Informational flow from mechanosensing to signaling for extracellular matrix stiffness sensing


ADMINISTERING_IC: DC

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: BOYS TOWN

ORG_NAME: FATHER FLANAGAN'S BOYS' HOME

ORG_STATE: NE

PHR: No changes from originally awarded application.  PROJECT NARRATIVE There is a critical need for interdisciplinary research in the area of human communication and its disorders. The Boys Town National Research Hospital postdoctoral training program is designed to provide trainees with the expertise required to develop successful independent research programs through training in a large center comprising a highly collaborative and unique mix of behavioral and clinical translational research programs.

PI_NAMEs: CHATTERJEE, MONITA  (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Communication;Disease;Human;Research

PROJECT_TITLE: RESEARCH IN HUMAN COMMUNICATION AND ITS DISORDERS


ORG_CITY: AUGUSTA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: AUGUSTA UNIVERSITY

PHR: PROJECT NARRATIVE About 40% of prescribed drugs target G protein-coupled receptors (GPCRs), which activate transducer proteins called G proteins and arrestins to produce effects that can be either beneficial or detrimental to human health. It is not known how GPCRs select the correct transducers needed to produce appropriate cellular or therapeutic responses, or how the cellular context affects this molecular mechanism. This project aims to increase understanding of how GPCRs interact with their transducers to produce coordinated cellular signals, and may facilitate the development of drugs with the capacity to fine-tune cell signaling and better treat disease. This supplement request will support acquisition of a BMG Labtech Omega plate reader, which will be essential for studying endogenously-expressed GPCRs and G proteins in their native context in real time. This instrument is the only one available with the capacity to monitor bioluminescence resonance energy transfer (BRET) with high temporal resolution. This supplement request will not change the scope of the project. The requested equipment will replace existing equipment that was used for the project but recently failed.

PI_NAMEs: LAMBERT, NEVIN ALAN (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Affect;Arrestins;Bioluminescence;Cell membrane;Cell model;Coupling;Disease;drug development;Drug Prescriptions;Drug Targeting;Energy Transfer;Equipment;Family;FDA approved;G-Protein-Coupled Receptors;GTP-Binding Proteins;Health;Heterotrimeric GTP-Binding Proteins;Hormones;Human;in vivo;instrument;Ligand Binding;Maps;Modeling;Molecular;Molecular Conformation;Monitor;Neurotransmitters;overexpression;Pharmaceutical Preparations;Pharmacology;Physiological;Physiology;Prevalence;Proteins;Reader;receptor;receptor binding;Receptor Signaling;receptor-mediated signaling;Signal Transduction;Signaling Protein;stoichiometry;temporal measurement;Time;Transducers;Translating;treatment response

PROJECT_TITLE: Conventional and unconventional GPCR-G protein coupling

STUDY_SECTION: MRAB

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


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

ORG_CITY: Princeton

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PRINCETON UNIVERSITY

PHR: Project Narrative Cell division is a key process in biology; it is the process by which cells separate their genetic material (chromosomes) into two identical daughter cells and coordinated by a microtubule-based machinery called the mitotic spindle. Although spindles are essential to the life of a healthy cell, and spindle malfunction can result in cancers and other disease states, we still do not know how microtubules are made at the correct location and time to build the mitotic spindle. Our work seeks to uncover exactly how microtubules make mitotic spindles, which will help explain not only how a cell divides, but can help us understand the origins of diseases that begin in improper cell division and cell regeneration.

PI_NAMEs: PETRY, SABINE  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Binding;Biological Assay;Biology;Cell Cycle Regulation;Cell division;Cell Physiology;cell regeneration;Cells;Cellular biology;Chromosome Segregation;Chromosomes;Complex;Cryoelectron Microscopy;daughter cell;defined contribution;Disease;egg;Generations;Genetic Materials;Importins;insight;Kinetochores;Laboratories;Life;Liquid substance;Location;Malignant Neoplasms;Microtubules;Mitotic spindle;monomer;novel;particle;Pathway interactions;Phase;Physical condensation;Positioning Attribute;Process;protein complex;Proteins;Reaction;Regulation;Role;Scientist;Source;Structure;Time;Tubulin;Visualization;Work;Xenopus

PROJECT_TITLE: Role and Mechanisms of Microtubule Nucleation in Spindle Assembly


NIH_SPENDING_CATS: Biotechnology

PHR: Narrative. The development of enantioselective biocatalysts would significantly facilitate drug development processes. This application proposes the acquisition of an Agilent Ultivo Triple Quadrupole LC/MS System and its application for high-throughput multiplex enantiomeric screening, which will substantially enhance the screening capability for developing enzymes tailored to medicinally relevant enantioselective transformations for drug discovery and synthesis efforts.

PI_NAMEs: HUANG, XIONGYI  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: A Chemo-Mimetic Platform to Reprogram Metalloenzymes for Non-Natural Biocatalytic C-H Functionalization Reactions


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: American Indian or Alaska Native;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Primary Health Care;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: PORTLAND

ORG_NAME: MAINEHEALTH

ORG_STATE: ME

PHR: PUBLIC HEALTH NARRATIVE The aging and rural populations of northern New England suffer from numerous chronic health issues, including cancer, obesity, diabetes, cardiovascular disease, and substance abuse. The Northern New England Clinical and Translational Research Network, which includes healthcare, educational and research institutions in Maine, Vermont, and New Hampshire, has helped build a foundation for clinical and translational research in the tri-state region. In this renewal application, our goal is to strengthen our network of clinical and translational research through a learning infrastructure that is supported by the principles of diversity, inclusion, and equity, for the benefit of all residents in our region.

PI_NAMEs: ROSEN, CLIFFORD JAMES (contact);STEIN, GARY S.

PROGRAM_OFFICER_NAME: GARTRELL, KYUNGSOOK

PROJECT_TERMS: Acceleration;Address;Aging;American;Area;Atherosclerosis;Award;Biometry;Cardiovascular Diseases;career;Centers of Research Excellence;Chronic;Clinical Data;clinical investigation;Clinical Investigator;Clinical Research;Clinical Trials;cohort;Collaborations;Communication;Communities;community based research;community engagement;Community Health;community involvement;Community Outreach;Coupled;COVID-19;COVID-19 pandemic;Cultural Diversity;Data;Development;Diabetes Mellitus;Disease;Education;Environment;Epidemiology;Equipment;equity, diversity, and inclusion;Evaluation;Extramural Activities;Faculty;flexibility;food insecurity;Foundations;Funding;Funding Mechanisms;Goals;Governing Board;Grant;Health;health communication;health difference;health disparity;health equity;Healthcare;HPV vaccine hesitancy;Human Resources;Immigrant;improved;Infrastructure;innovation;Institution;Leadership;Learning;learning progression;Link;Maine;Malignant Neoplasms;Mentors;Mentorship;Modeling;Native American population;Native Americans;New England;New Hampshire;novel;novel strategies;Obesity;Opiate Addiction;Opioid;Passamaquoddy;Patient Care;patient oriented;Peer Review;Penobscot;Pilot Projects;Play;Population;Populations at Risk;Post-Acute Sequelae of SARS-CoV-2 Infection;post-COVID-19;practice-based research network;Predisposition;Primary Care;primary care practice;programs;Public Health;Publications;Registries;Research;Research Design;Research Infrastructure;Research Personnel;Research Support;Reservations;Resource Sharing;Resources;Role;Rural;Rural Health;Rural Population;rurality;Services;Site;Substance abuse problem;Substance Use Disorder;suburban communities;technical report;Technology;telehealth;Toxic Environmental Substances;Training;Training Programs;Translational Research;Tribes;underserved community;United States Health Resources and Services Administration;United States National Institutes of Health;Universities;Urban Population;urban underserved;Vermont

PROJECT_TITLE: Northern New England Clinical and Translational Research Network - Equipment


NIH_SPENDING_CATS: Genetics

ORG_CITY: DULUTH

ORG_NAME: UNIVERSITY OF MINNESOTA DULUTH

ORG_STATE: MN

PHR: PROJECT NARRATIVE We are seeking supplemental funding aimed at acquiring a fluorescence microscope to support our current R15 grant. This instrument will facilitate numerous fluorescence imaging assays conducted in our research, focusing on novel epigenetic mechanisms and developmental functions of the Keap1-Nrf2 oxidative and xenobiotic response factors in Drosophila.

PI_NAMEs: DENG, HUAI  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Actins;Architecture;Biological;Biological Assay;Biological Process;Biology;Chromatin;chromatin remodeling;Development;Developmental Gene;Disease;Drosophila genus;Environmental Impact;Epigenetic Process;epigenetic regulation;equipment acquisition;Faculty;fluorescence imaging;fluorescence microscope;Funding;Grant;Health;Image;instrument;Laboratories;Lamins;Malignant Neoplasms;Mediating;member;Microscope;Minnesota;Molecular;novel;NURF;Oxidation-Reduction;Pathway interactions;Physical condensation;Proteins;Research;response;Signal Pathway;Signal Transduction;Stimulus;Testing;Toxic Environmental Substances;undergraduate education;United States National Institutes of Health;Universities;Xenobiotics

PROJECT_TITLE: Epigenetic regulation of chromatin by the Keap1-Nrf2 xenobiotic response signaling in Drosophila


ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE - From Initial Application Every animal that develops from a zygote starts life on a path dictated by maternally provided molecules, and subsequent development involves an interplay of maternal and zygotic genetic effects. To understand how these maternal and offspring genomes jointly shape developmental variation and evolution, this research experimentally dissects the contributions of each genome to phenotypic variation within populations of model organisms that vary in their population genetic characteristics.

PI_NAMEs: ROCKMAN, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Animal Genetics;Animals;Automobile Driving;Biological Models;Biology;Caenorhabditis;Caenorhabditis elegans;Characteristics;Detection;Development;Developmental Gene;developmental genetics;Developmental Process;Dissection;egg;Embryo;Embryonic Development;Evolution;Exhibits;experience;Experimental Models;experimental study;Gene Expression;Generations;Genes;Genetic;genetic analysis;genetic architecture;Genetic Epistasis;genetic pedigree;genetic variant;Genome;Goals;Heritability;Individual;Life;Maintenance;Maps;Measurement;model organism;Molecular;Mothers;Nematoda;offspring;Partner in relationship;Pattern;Phenotype;Play;pleiotropism;Population;Population Genetics;prevent;Property;Quantitative Genetics;Regulation;Research;Resolution;Resources;Role;Self-Fertilizations;Shapes;System;Testing;trait;transmission process;United States National Institutes of Health;Variant;Work;zygote

PROJECT_TITLE: Evolutionary Genetics of Animal Development


ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: RESEARCH STRATEGY: Understanding Double-Stranded RNA Recognition in Human Cells — Instrument Supplement Summary of parent grant R35GM150953 Recognition of double-stranded RNA (dsRNA) structures underlie many important biological processes, such as RNA interference, innate immune sensing of foreign RNAs, and post-transcriptional gene regulation. My lab focuses on two areas of dsRNA recognition: microRNA (miRNA) biogenesis and innate immune sensing. During miRNA biogenesis, Microprocessor, consisting of Drosha and DGCR8, recognizes and cleaves hairpin-like structures from long transcripts called primary miRNAs (pri-miRNAs). My previous work has built a unifying model of human pri-miRNA1 and discovered that some natural, suboptimal miRNA hairpins rely on neighboring optimal miRNA hairpins for efficient Microprocessor cleavage—known as “cluster assistance”2. Nearly 40% of human miRNAs reside in clusters, with many implicated in diseases and influenced by cluster assistance. We propose to dissect this fundamental regulatory mechanism in miRNA biogenesis using biochemical, single-molecule, and structural approaches (Project 1).  Recognition of dsRNA by innate immune sensors such as RIG-I and MDA5 initiates antiviral responses3. Recent studies show that endogenous dsRNAs can also activate these sensors, sometimes resulting in autoinflammatory and autoimmune diseases4. The recognition of self dsRNAs therefore needs to be restricted by proteins that modify, degrade, or shield endogenous dsRNAs. Building on our expertise in dsRNA recognition and processing, we proposed to 1) develop new biochemical methods to identify dsRNA ligands of innate immune sensors (Project 2), and 2) develop new genetic screen methods to identify factors that restrict self dsRNA sensing in innate immunity (Project 3). Together these studies will provide crucial insights into how cellular dsRNAs are sensed and regulated, with therapeutic implications for cancer, autoimmune and infectious diseases. Recent progress and scientific justification For Project 1, we have made important progress dissecting the mechanism of cluster-assisted pri-miRNA procesing. We had envisioned two models of cluster assistance: in a dimerization model, one Microprocessor binds the helper miRNA hairpin and promotes the binding of a second Microprocessor to the recipient hairpin; in a transfer model, Microprocessor binds and cleaves the helper hairpin and is then transferred to the proximal recipient (Figure 1). These processes could be mediated by ERH which I identified biochemically2, and SAFB proteins that the Herzog lab Figure 1. Working models of cluster assistance. identified through a CRISPR screen5.  To test these models biochemically, we utilized an in vitro pri-miRNA cleavage assay, which I previously established using lysates from cells that overexpress Drosha and DGCR8. This in vitro system recapituates cluster assistance, i.e., the defective miR-451 hairpin was cleaved faster in the context of the miR- 144~451 cluster. To test whether cleavage of the miR-144 helper hairpin is required for cluster assistance, we introduced modifications (phosphorothioate linkages flanked by 2′-O methylation) at both cleavage sites of the miR- Figure 2. Blocking miR-144 hairpin cleavage inhibited cluster 144 hairpin, which successfully blocked assistance. The line for each substrate represents the best fit of all of cleavage of the miR-144 hairpin (data not the data to an exponential reaction course, which generated the shown) by Drosha. Importantly, preventing the observed rate constants (k, shown ± 95% confidence intervals). Pri- processing of miR-144 hairpin abolished cluster miR-144*~451 has modifications to block miR-144 hairpin cleavage. assistance (Figure 2). This finding suggests that the dimerization model is unlikely. To strengthen this result, we are testing whether blocking one out of the two Drosha cleavage sites is sufficient to inhibit cluster assistance, and we will also test whether such cleavage-site modifications affect Micrprocessor binding.  1  We have also purified a C terminus-truncated form of SAFB2 and showed that it can enhance the cleavage of miR-451 hairpin in the cluster context in vitro. Therefore, cluster assistance can now be reconstituted using purified Microprocessor, ERH, and SAFB2 (Figure 3). Next, we will map the interaction between SAFB2 and Microprocessor using crosslinking mass spec. We will then introduce mutations that disrupt SAFB2–Microprocessor interactions to identify residues important for cluster assistance. Furthermore, as proposed in the parent award, we will use cryo-EM to provide the structural basis of cluster assistance.  For project 2, we proposed to identify endogenous dsRNAs that activate innate immune Figure 3. Reconstitution of cluster assistance using sensors. We have developed a novel approach using purified Microprocessor. Processing assays of pri-miR-451 mouse oocyte Dicer (mDcrO), which misses the and pri-miR-144~451 using purified Microprocessor, with the helicase domain and cleaves long dsRNAs much presence of SAFB2 and ERH as indicated above. The red star better than full-length mammalian Dicer6,7. We indicates 3′ radiolabel. transiently overexpressed mDcrO in HEK293T cells, performed small RNA-sequencing analyses to identify mDcrO-dependent small RNAs, and then predicted the dsRNAs from which these small RNAs are processed by mDcrO. We used MACS2 peak calling8,9 to identify sRNA clusters. Our initial experiments identified 1297 small RNA clusters derived from intermolecular and intramolecular dsRNAs. The majority (66%) come from intramolecular folding of repetitive elements. We identified 60 stem-loop structures in the 5′ UTR and 41 in the 3′ UTR of mRNA transcripts. We also identified 51 intermolecular dsRNAs formed by overlapping transcripts (27 at the 3′ end, and 24 at the 5′ end). We are currently investigating the editing status of these dsRNAs to understand how editing suppresses innate immune sensing of dsRNAs. Our preliminary data suggest that many of the intermolecular dsRNAs formed by 3′ overlaps do not have extensive editing, and we plan to pull-down these dsRNA pairs and identify potential proteins that prevent them from activating MDA5.  For project 3, we proposed to identify regulators that restrict sensing of endogenous dsRNA in human cells through CRISPR screens. We have made CRISPRi-compatible, GFP knock-in N/TERT-1 cells that reports IFN-β expression. We have verified this cell line in a mock screen (data not shown), and we are currently conducting a genome-wide screen to identify factors whose loss results in increased IFN-β expression. After obtaining the hits, we will verify and focus on RNA-related genes. We will then use biochemical, genetic, and other approaches to understand the mechanism by which these genes suppress endogenous dsRNA sensing. Rationale for the purchase of an ÄKTA pure micro system: Project 1 is a mechanistic project that relies heavily on protein and RNA purification. Although Projects 2 and 3 are discovery-oriented, we expect to move beyond discovery and conduct mechanistic studies using biochemical approaches. Currently we are using an ÄKTA pure 25 M system in the laboratory of my RNA Therapeutics Institute colleague Dr. Li Li. Dr Li’s system meets our current purification needs, but the ÄKTA pure micro system will be much better suited for our proposed cryo-EM studies because of specific requirement of sample concentration and quality. In addition, we routinely use the mammalian expression system (Expi293) for protein purification. The expression system is expensive and does not efficiently produce large quantities of RNA-binding proteins, so our experiments will benefit from the ability to purify minute quantities of proteins and RNA–protein complexes for analyzing protein–protein interactions, oligomerization states, and RNA–protein interactions. The small injection and elution volumes, improved resolution, and sharper peaks offered by the ÄKTA pure micro is ideal in this respect. I have recently hired a postdoc who has extensive experience with cryo-EM analysis of RNA–protein complexes, and who has used the ÄKTA pure micro system before. Therefore, we are prepared to take full advantage of this system. Plans for service contracts The service contract for the requested ÄKTA pure micro system will cost ~$6,600 per year. I will use my startup provided by the RNA Therapeutics Institute (my host department at UMass Chan Medical School) to cover the service contract for the duration of the project. Moreover, our department has dedicated funding and personnel for instrument maintenance, which is available for this proposed equipment.  2 Reference 1 Fang, W. & Bartel, D. P. The Menu of Features that Define Primary MicroRNAs and Enable De Novo  Design of MicroRNA Genes. Mol Cell 60, 131-145, doi:10.1016/j.molcel.2015.08.015 (2015). 2 Fang, W. & Bartel, D. P. MicroRNA Clustering Assists Processing of Suboptimal MicroRNA Hairpins  through the Action of the ERH Protein. Mol Cell 78, 289-302 e286, doi:10.1016/j.molcel.2020.01.026 (2020). 3 Kato, H., Takahasi, K. & Fujita, T. RIG-I-like receptors: cytoplasmic sensors for non-self RNA. Immunol  Rev 243, 91-98, doi:10.1111/j.1600-065X.2011.01052.x (2011). 4 Chen, Y. G. & Hur, S. Cellular origins of dsRNA, their recognition and consequences. Nat Rev Mol Cell  Biol 23, 286-301, doi:10.1038/s41580-021-00430-1 (2022). 5 Hutter, K. et al. SAFB2 Enables the Processing of Suboptimal Stem-Loop Structures in Clustered  Primary miRNA Transcripts. Mol Cell 78, 876-889 e876, doi:10.1016/j.molcel.2020.05.011 (2020). 6 Flemr, M. et al. A retrotransposon-driven dicer isoform directs endogenous small interfering RNA  production in mouse oocytes. Cell 155, 807-816, doi:10.1016/j.cell.2013.10.001 (2013). 7 Ma, E., MacRae, I. J., Kirsch, J. F. & Doudna, J. A. Autoinhibition of human dicer by its internal helicase  domain. J Mol Biol 380, 237-243, doi:10.1016/j.jmb.2008.05.005 (2008). 8 Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol 9, R137, doi:10.1186/gb-  2008-9-9-r137 (2008). 9 Feng, J., Liu, T., Qin, B., Zhang, Y. & Liu, X. S. Identifying ChIP-seq enrichment using MACS. Nat  Protoc 7, 1728-1740, doi:10.1038/nprot.2012.101 (2012). 3

PI_NAMEs: FANG, WENWEN  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Untranslated Regions;5' Untranslated Regions;Affect;Anti-viral Response;Area;Autoimmune Diseases;autoinflammatory diseases;Binding;Biochemical;biochemical model;Biogenesis;Biological Assay;Biological Process;Cell Line;Cells;ChIP-seq;Communicable Diseases;Complex;Confidence Intervals;Contract Services;cost;CRISPR interference;CRISPR screen;crosslink;Cryoelectron Microscopy;Cytoplasm;Data;Dedications;design;Development;Dimerization;Disease;Double-Stranded RNA;ds RNA-Binding Proteins;Equipment;experience;experimental study;Funding;Genes;Genetic;Genetic screening method;Genome;genome wide screen;Goals;helicase;Human;human model;Human Resources;Immune;Immune response;improved;In Vitro;Injections;innate immune sensing;insight;instrument;Interferon-beta;Knock-in;Laboratories;Length;Ligands;Maintenance;Malignant Neoplasms;Maps;Mediating;medical schools;Messenger RNA;Methods;Methylation;Microprocessor;MicroRNAs;microsystems;Modeling;Modification;Mus;Mutation;Natural Immunity;novel strategies;Oocytes;overexpression;parent grant;parent project;phosphorothioate;Post-Transcriptional Regulation;Postdoctoral Fellow;prevent;Process;Production;protein complex;Protein Isoforms;protein protein interaction;protein purification;Proteins;radiotracer;Reaction;receptor;reconstitution;Regulation;Repetitive Sequence;Reporting;Research;Resolution;Retrotransposon;RNA;RNA analysis;RNA Interference;RNA purification;RNA-Binding Proteins;RNA-Protein Interaction;SAFB gene;Sampling;sensor;single molecule;Site;Small Interfering RNA;Small RNA;stem;Structure;System;Testing;Therapeutic;therapeutic RNA;Transcript;transcriptome sequencing;Viral;Work

PROJECT_TITLE: Understanding double-stranded RNA recognition in human cells


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Clinical Research;Clinical Trials and Supportive Activities;Depression;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Human Genome;Major Depressive Disorder;Mental Health;Mental Illness;Serious Mental Illness;Social Determinants of Health;Substance Misuse

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: People living with HIV (PLWH) show heightened distress and increased inflammatory burden, leading to greater complex morbidity including high prevalence of cannabis use disorder and major depressive disorders. However, the mechanisms governing stress-immune interactions in PLWH, and their associated distress and drug use are not well understood. Applying a powerful and novel cross-diagnostic human experimental paradigm with multiple complementary approaches, in this application, we will investigate the epigenetic mechanisms regulating “stress- genome” at cell type resolution among PLWH with complex comorbidities of cannabis use disorder and major depressive disorder.

PI_NAMEs: SINHA, RAJITA ;XU, KE  (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Acute;acute stress;Address;Adrenal Glands;Affect;Anxiety;ATAC-seq;Behavioral;Biological Assay;Biological Markers;Biology;biomarker identification;biomarker validation;Blood Cells;Blood Pressure;Cannabis;cannabis craving;cell type;Cells;Chromatin;Chronic stress;cohort;Cohort Studies;comorbidity;Complex;Corticotropin;craving;cytokine;Data;Development;Diagnostic;diagnostic strategy;differential expression;Distress;distress tolerance;DNA;Drug usage;Ecological momentary assessment;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;Ethnic Origin;Exhibits;experimental study;feature selection;Future;Gender;Gene Expression;Genes;Genetic Fingerprintings;Genetic Transcription;Genome;Heart Rate;High Prevalence;HIV;HIV-1;Homeostasis;Hormones;Human;Hydrocortisone;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Immune;immune activation;immune function;Immune response;Immunocompromised Host;Impairment;Individual;Individual Differences;Inflammatory;Interleukin-1;Interleukin-10;Interleukin-6;Link;machine learning method;Major Depressive Disorder;marijuana use;marijuana use disorder;Measures;medication compliance;Mental Depression;Methylation;methylome;mood symptom;Moods;Morbidity - disease rate;multiple omics;Neurosecretory Systems;novel;Pain;Participant;pathogen;Pathology;Peripheral;Peripheral Blood Mononuclear Cell;Persons;Physiological;Pituitary Gland;Plasma;Play;population based;Positioning Attribute;potential biomarker;Predisposition;preventive intervention;prospective;psychobiologic;Psychosocial Stress;Race;Recording of previous events;Research;resilience;Resolution;Risk;Role;Sampling;sex;single nucleus RNA-sequencing;social health determinants;Stress;stress reactivity;substance use;Symptoms;Testing;transcriptome;Trauma

PROJECT_TITLE: Stress-immune mechanisms for people living with HIV, CUD and Depression

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 MXS-N (A1)]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Aging;Assistive Technology;Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Neurosciences;Rehabilitation;Stroke

ORG_CITY: CHARLESTON

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE One of the aims of the COBRE in Stroke Recovery at the Medical University of South Carolina (MUSC) is to strengthen innovative scientific cores that support/advance stroke recovery research. This equipment supplement will allow MUSC to purchase the NeuroFUS PRO Neuronavigated tFUS System that will not only provide cutting edge access to technology not typically available to stroke recovery researchers, but also will create novel, personalized tFUS interventions that have promise to treat a wide variety of post-stroke deficits by visualizing and administering precision noninvasive deep brain stimulation. This system is a first-in-class, state- of-the-art platform.

PI_NAMEs: KAUTZ, STEVEN A. (contact)

PROGRAM_OFFICER_NAME: BASKIR, RUBIN SAM

PROJECT_TERMS: Administrative Supplement;Anatomy;Area;Behavioral;Brain;Centers of Research Excellence;Cephalic;cranium;Deep Brain Stimulation;Dose;Electric Stimulation;Equipment;Equipment Design;experience;experimental study;Focused Ultrasound;functional improvement;Funding Opportunities;Impaired cognition;Individual;innovation;Intervention;Interventional Ultrasonography;Magnetic Resonance Imaging;Medical;Mental Depression;Methods;motor recovery;Nature;neural;Neurologic Effect;Neuronal Plasticity;Neuronavigation;new technology;noninvasive brain stimulation;novel;Pain;Parents;Penetration;Phase;Population;post intervention;post stroke;Process;programs;Quality of life;Recovery;Research;Research Personnel;Resolution;Sonication;South Carolina;Stroke;stroke recovery;stroke rehabilitation;stroke therapy;System;Technology;Tissues;Transcranial magnetic stimulation;Translating;Ultrasonics;ultrasound;United States National Institutes of Health;Universities;Visualization

PROJECT_TITLE: COBRE in Stroke Recovery Administrative Supplement:  Equipment


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Prevention;Rural Health;Social Determinants of Health;Substance Misuse

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Kentucky (KY) is a high priority Ending the HIV Epidemic (EHE) jurisdiction due to heavy rural HIV burden and exceptionally high rates of new HIV diagnoses driven by injection drug use. A central pillar of EHE is the prevention of new HIV infections through scale up of Pre-Exposure Prophylaxis (PrEP) in people who inject drugs (PWID). The proposed study will deploy a novel, stepped-care intervention within rurally-located syringe service programs (SSPs) and conduct a robust test of efficacy on PrEP initiation and persistence among rural PWID, which is critical for achieving progress toward EHE goals.

PI_NAMEs: SURRATT, HILARY L (contact)

PROGRAM_OFFICER_NAME: JENKINS, RICHARD A

PROJECT_TERMS: access restrictions;adaptive intervention;Address;Adoption;age effect;Appalachian Region;Biological Markers;care delivery;care outcomes;Caring;Case Management;Categories;Clinical;Communities;community advisory board;Consensus;Consultations;County;Data;Disparity;Drug user;Education;Effectiveness;efficacy testing;Eligibility Determination;Epidemic;evidence base;experience;Female;Foundations;Frequencies;Goals;HIV;HIV diagnosis;HIV Infections;HIV risk;Home;housing instability;Injecting drug user;injection drug use;Injections;interest;Intervention;Interview;Kentucky;Knowledge;male;Measures;medical specialties;Needle-Exchange Programs;Newly Diagnosed;novel;Oral;outreach;Participant;Pathway interactions;Patients;Pattern;peer;pilot trial;point of care testing;Population;Poverty;pre-exposure prophylaxis;Prevention;primary care setting;Recommendation;relative effectiveness;Reporting;response;risk perception;Rural;Rural Appalachia;rural area;Rural Population;rural underserved;scale up;Sequential Multiple Assignment Randomized Trial;Services;social stigma;Subgroup;Test Result;Testing;Text Messaging;therapy design;transmission process;trial design;uptake;Visit

PROJECT_TITLE: Optimizing PrEP Care Delivery through Adaptive Intervention Strategies for Underserved Rural People who Inject Drugs

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 TXT-E (A1)]


ORG_CITY: STILLWATER

ORG_DEPT: PHYSICS

ORG_NAME: OKLAHOMA STATE UNIVERSITY STILLWATER

ORG_STATE: OK

PHR: Project Narrative Many serious human diseases are caused by malfunctioning of proteins, including cancers. Understanding the structure-function relations of proteins is expected to guide and accelerate drug discovery process. The objectives of this proposal are to develop new experimental tools based on advanced Fourier transform infrared technologies to enhance such research.

PI_NAMEs: XIE, AIHUA  (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: Acceleration;Amino Acids;Bioenergetics;Biological Models;Biology;Chemicals;Data Analyses;detector;Devices;drug discovery;Equipment;experience;experimental study;Fourier Transform;Funding;Goals;Histidine;human disease;Hydrogen Bonding;Isotopes;Light;Magnetic Resonance Imaging;Malignant Neoplasms;Medical;Microfluidics;Microscope;millisecond;Minority Participation;minority student;Molecular Biology;Mutation;nanosecond;Native Americans;Oklahoma;parent project;Photoreceptors;Positioning Attribute;Process;programs;Protein Dynamics;protein function;protein structure;Proteins;protonation;Protons;Regulation;Research;Resolution;Sampling;Scanning;Scholars Program;Side;Signal Transduction;Site;Solvents;Spectroscopy, Fourier Transform Infrared;Spectrum Analysis;structural biology;Structure;Students;symposium;System;Techniques;Technology;Time;tool;Translating;undergraduate student;Universities;Woman

PROJECT_TITLE: Advanced Infrared Biology of Protein Structure & Dynamics


NIH_SPENDING_CATS: Biotechnology;Precision Medicine

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: PUBLIC HEALTH RELEVANCE The proposed research will be focused on technology development for ultra-high sensitivity deep proteomic analysis of limited biological and clinical samples. Comprehensive proteome characterization of such samples at the level of digests, intact proteoforms, native non-covalent protein complexes, and protein interactions is presently an insurmountable challenge in bioanalytical research. The proposed technology offers an unprecedented opportunity for expanding our knowledge of molecular mechanisms of disease processes and identifying new paths toward the discovery of diagnostic and prognostic biomarkers using minuscule sample amounts. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

PI_NAMEs: IVANOV, ALEXANDER R. (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Biological;Biological Models;Biological Process;Biomedical Research;Biopsy;Cancer cell line;Cell Differentiation process;Cells;Characteristics;Clinical;clinically relevant;Complex;data acquisition;Data Analyses;Development;Diagnostic;diagnostic biomarker;Diagnostics Research;Disease;Hematopoietic stem cells;Immune;Individual;innovation;insight;Knowledge;Ligands;liquid biopsy;Liquid substance;Malignant neoplasm of ovary;Malignant Neoplasms;Mass Spectrum Analysis;Methods;Microscopic;Molecular;Neoplasm Circulating Cells;new therapeutic target;novel;novel strategies;Peptides;personalized medicine;Pharmaceutical Preparations;Phase;Play;Population;Post-Translational Protein Processing;Preparation;Process;prognostic;Prognostic Marker;protein complex;Proteins;Proteome;Proteomics;public health relevance;Research;research and development;response biomarker;Role;Sampling;screening;Specimen;STAT3 gene;Techniques;Technology;technology development;therapeutic biomarker;Therapeutic Studies;therapeutic target;transcription factor;X-Ray Crystallography;yeast two hybrid system;Yeasts

PROJECT_TITLE: Robust ultra-high sensitivity proteomic technologies for limited samples


ED_INST_TYPE: UNIVERSITY-WIDE

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

ORG_CITY: NORMAN

ORG_NAME: UNIVERSITY OF OKLAHOMA

PHR: Skin color is genetically derived traits that is highly variable between human subpopulations and is determined by the quantity, type and distribution of melanin pigment. Variable melanin production by skin pigment cells not only drives skin color variation but also contributes to differential disease susceptibility among humans. This proposal seeks to understand the epigenetic and transcriptional mechanisms that govern variable melanin production resulting in human pigmentation diversity and has implications for human evolution, health and disease.

PI_NAMEs: BAJPAI, VIVEK KUMAR (contact)

PROGRAM_OFFICER_NAME: KRASNEWICH, DONNA M

PROJECT_TERMS: Affect;Anatomy;Automobile Driving;Biological Assay;Candidate Disease Gene;Cells;Chromosome Mapping;Code;Color;Control Locus;CRISPR screen;Darkness;differential expression;Disease;Disease susceptibility;DNA;Enhancers;Epigenetic Process;epigenomic profiling;Evolution;experimental study;Gene Dosage;Gene Expression;Genes;Genetic;Genetic Screening;Genetic study;Genetic Transcription;Genome;Genome engineering;genome wide association study;genome-wide;Genotype;Goals;Hair Color;Health;Human;Human Development;human population study;In Vitro;insight;Instruction;Knowledge;Light;Location;Maps;Measurement;Melanins;melanocyte;Melanogenesis;Methods;Modeling;Molecular;mouse model;Mus;Natural Selections;Normal Range;novel;Phenotype;Pigmentation physiologic function;Pigments;Play;pluripotent stem cell differentiation;Postdoctoral Fellow;Production;programs;Reporter;Role;skin color;skin disorder;Skin Pigmentation;trait;transcription factor;Transgenic Mice;Validation;Variant;Work

PROJECT_TITLE: Epigenetic and transcriptional mechanisms driving melanogenesis in health and disease


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: SALT LAKE CITY

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Cortico-striatal networks are affected in many neurological and psychiatric disorders. This project will investigate the development of human cortico-striatal connectivity under normal and pathological conditions using stem cell-derived cortico-striatal organoids. The ability to create disease-related cortico-striatal organoids will provide a new approach to enable the development of new diagnostics and treatments.

PI_NAMEs: SHCHEGLOVITOV, OLEKSANDR  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: 3-Dimensional;Action Potentials;Address;Affect;Anatomy;Animal Model;Astrocytes;autism spectrum disorder;Brain;Brain Diseases;Brain region;brain tissue;Cells;Chronic;Coculture Techniques;Communication;Complex;Corpus striatum structure;Development;Disease;disease model;drug discovery;Electrodes;Electrophysiology (science);excitatory neuron;Exhibits;Functional impairment;Genetic Materials;Human;human model;human stem cell-derived;human stem cells;Immunohistochemistry;Implant;inhibitory neuron;innovation;insight;Mental disorders;Methods;Modeling;Molecular;Molecular Abnormality;Morphology;multi-electrode arrays;nerve stem cell;Nervous System;Nervous System Disorder;neural;neural network;Neurodevelopmental Disorder;Neurologic;Neurons;novel;novel diagnostics;novel strategies;novel therapeutics;Oligodendroglia;optogenetics;Organoids;patch clamp;Pathologic;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Phelan-McDermid syndrome;Phenotype;Physiological;Physiology;Population;precision drugs;Property;Protocols documentation;Quantitative Reverse Transcriptase PCR;rabies viral tracing;Reproducibility;Science;self organization;single cell mRNA sequencing;single-cell RNA sequencing;Slice;stem cells;Synapses;system architecture;Techniques;Testing;With laterality;Work

PROJECT_TITLE: Assembly and characterization of human cortico-striatal neural networks


NIH_SPENDING_CATS: Aging;Arthritis;Chronic Pain;Clinical Research;Neurosciences;Osteoarthritis;Pain Research

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE In this proposed career development supplement to the RE-JOIN consortium, we will collect paired clinical pain data that occurs with both activity and rest in knee osteoarthritis with tissue level data. To better understand mechanisms of pain – a goal that compliments that of the consortium - we will collect patient-reported pain mapping, quantitative sensory testing, and magnetic resonance imaging and link it with histopathological data from the medial and lateral knee joints of discarded tissue from knee replacement surgeries in osteoarthritis patients. Through the acquisition, analysis, and dissemination of this knowledge, we hope to make major strides in our long-term goal to improve patient outcomes for those suffering from osteoarthritis.

PI_NAMEs: LOTZ, MARTIN K;MALFAIT, ANNE-MARIE  (contact);MILLER, RICHARD J

PROGRAM_OFFICER_NAME: MANCINI, MARIE

PROJECT_TERMS: Anatomy;bone;career development;Cartilage;Chronic disability;chronic pain;clinical pain;Data;Degenerative polyarthritis;Development;Discipline;Elderly;experience;Goals;Growth;Health;Helping to End Addiction Long-term;Heterogeneity;Histologic;Histology;Histopathology;Human;improved;Institution;Joints;K-Series Research Career Programs;Knee joint;Knee Osteoarthritis;knee pain;knee replacement arthroplasty;Knowledge;Lateral;Link;Location;Magnetic Resonance Imaging;Maps;Medial;meetings;Mentorship;Methods;Modeling;Molecular;multidisciplinary;Musculoskeletal Diseases;Nerve;Operative Surgical Procedures;Oranges;osteoarthritis pain;Outcome Measure;Pain;Pain Map;Pain Measurement;pain reduction;Pain Research;Pathologic;Patient Outcomes Assessments;Patient-Focused Outcomes;Patients;Pattern;Phenotype;phenotypic data;Physicians;Population;Quantitative Evaluations;recruit;Reporting;Research;Research Personnel;Rest;Rheumatology;Sensory;Severities;Site;Special Hospitals;Synovial Membrane;Testing;Tissues;Training;United States National Institutes of Health;working group

PROJECT_TITLE: Precision Mapping of Knee Pain in Osteoarthritis: Understanding differences between pain with activity and rest


ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Narrative This is an application for an administrative supplement for NIGMS R35GM127098 MIRA grant, with a goal to add a confocal scanner and multi-array detector (NSPARC) to the existing Nikon TEi2-E microscope, currently equipped for TIRF imaging. This would allow for low-light 3D detection of ultra-fine structural information beyond the resolution limit and significantly push forward every research direction in the Kaverina laboratory.

PI_NAMEs: KAVERINA, IRINA  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: 3-Dimensional;Administrative Supplement;Architecture;Cells;data quality;Detection;detector;Equipment;fluorescence imaging;Fluorescence Microscopy;Funding;Goals;Grant;insight;Laboratories;Light;live cell imaging;Microscope;microscopic imaging;Microtubules;National Institute of General Medical Sciences;parent grant;Research;Resolution;Sampling;superresolution imaging;System;Thick;Tissue Sample;Ultrafine

PROJECT_TITLE: Dynamic architecture and function of microtubule networks


NIH_SPENDING_CATS: Aging;Genetics

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative Telomeres are closely involved in stem cell differentiation and cancer cell proliferation. The results of this study will lead to new mechanistic principles of telomere length homeostasis and chromosome stability in cells. Therefore, valuable targets for mechanism-driven design of anti-premature aging and cancer therapeutics may be identified through this research.

PI_NAMEs: QIAO, FENG  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Address;aging related disease;Biochemical;Biogenesis;cancer cell;Cell Proliferation;Cells;Chromosomal Stability;Chromosomes;Complex;Degenerative Disorder;design;Development;Disease;DNA;Ensure;Fission Yeast;Foundations;Functional disorder;genome integrity;Homeostasis;Individual;insight;Investigation;Length;Link;Maintenance;Malignant Neoplasms;Molecular;Mutation;National Institute of General Medical Sciences;novel therapeutic intervention;Play;Positioning Attribute;Premature aging syndrome;Process;programs;Proliferating;Quality Control;Research;Resolution;RNA Folding;Role;stem cell differentiation;Structure;success;Telomerase;Telomerase RNA Component;telomere;Therapeutic;X-Ray Crystallography

PROJECT_TITLE: Molecular Mechanisms of Telemere Length Homeostasis

STUDY_SECTION: MRAA

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


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Genetics;Neurodegenerative;Neurosciences;Sleep Research

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE Relevance to public health: Circadian clocks are biological timers that govern physiology and behavior; however, the underlying regulatory mechanisms are not fully understood. Utilizing an integrative approach, the proposed research will reveal novel genetic regulators of circadian rhythms and decipher molecular and physiological mechanisms governing tissue physiology. The fundamental insights will advance our understanding of biological timing and may ultimately lead to novel chronotherapies against clock-related diseases.

PI_NAMEs: YOO, SEUNG-HEE  (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: age related neurodegeneration;Behavior;Biochemical;Biological;Biological Clocks;Breeding;Cell Physiology;Cells;Chronotherapy;circadian;circadian pacemaker;Circadian Rhythms;Disease;Dissection;exome sequencing;Foundations;Generations;Genes;Genetic;Genetic Screening;Genetic Transcription;glycogen synthase kinase 3 beta;Goals;Health;Hypothalamic structure;Image;insight;interest;Knowledge;Mammals;Methodology;MicroRNAs;Molecular;mouse genetics;Mus;Muscle function;mutant;Myocardium;novel;Periodicity;Phenotype;Physiological;Physiological Processes;Physiology;Play;Proteins;proteostasis;Public Health;Reagent;Regulation;Reporter;Reporting;Research;Role;Running;Sarcomeres;Scheme;screening;Skeletal Muscle;Striated Muscles;suprachiasmatic nucleus;System;Tissues;ubiquitin-protein ligase;Variant

PROJECT_TITLE: Mammalian circadian rhythms: from genes to mechanisms


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: QUEENS

ORG_NAME: ST. JOHN'S UNIVERSITY

PHR: Project Narrative A diverse array of chemicals and drugs including certain chemical warfare agents (sulfur mustard, lewisite), intravenous chemotherapy drugs (mechlorethamine-MEC, paclitaxel, liposomal doxorubicin), and environmental toxins (snake venom metalloproteinases and blister beetle cantharidin) can disrupt the dermal-epidermal junction (DEJ) and cause blistering, thereby placing a patient at risk for infection, loss of fluid and electrolyte homeostasis, and scarring; moreover, an effective antidote to blistering is still lacking and current medical treatments for blistering are limited to supportive therapy. The overall goal of the studies proposed here is to investigate the influence of rationally selected mast cell-derived mediators (histamine and tryptase), neutrophil-derived mediators (myeloperoxidase, MPO and matrix metalloproteinase 9, MMP-9) and keratinocyte-specific collagens (collagen IV, COL4 and collagen XVII, COL17) in the cutaneous response to DEJ disruption over time. The achievement of proposal objectives will more fully describe the complex response of skin to DEJ disruption and provide novel targets for the discovery of drugs capable of reducing blistering and restoring the DEJ.

PI_NAMEs: BILLACK, BLASE CHRISTOPHER (contact)

PROJECT_TERMS: 3-Dimensional;Achievement;Adverse effects;Affect;analog;animal care;Animals;Antidotes;Antihistamines;Antineoplastic Agents;Apoptosis;Appearance;Biological Assay;Biopsy;Bulla;CASP3 gene;CASP9 gene;Cell Culture Techniques;Cells;chemical reduction;Chemical Warfare Agents;Chemicals;chemotherapy;Chemotherapy-Oncologic Procedure;Cicatrix;Collagen;Collagen Type IV;Collagen Type XVII;Complement 3d;Complex;Computer software;Cream;Cutaneous;Data;Dermal;Dermis;Dimethyl Sulfoxide;DNA;Dose;Doxepin;Ear;ebselen;Edema;Electrolytes;Enzyme-Linked Immunosorbent Assay;Epidermis;Experimental Designs;experimental study;Exposure to;Extravasation;falls;Formalin;Foundations;Future;Gases;Gelatinase B;Goals;Harvest;Histamine;Histology;Homeostasis;Human;human tissue;Immunohistochemistry;In Vitro;in vivo;Incidence;infection risk;Infiltration;Inflammation;inhibitor;insight;Intravenous;keratinocyte;Kinetics;Knockout Mice;Learning;Leupeptins;lewisite;light microscopy;Lipid Peroxidation;Liposomal Doxorubicin;Liquid substance;Literature;mast cell;Mechlorethamine;Mediator;Medical;Metalloproteases;Modeling;Mus;Mustard Gas;neutrophil;Neutrophil Infiltration;novel;Nuclear;Order Coleoptera;Organoselenium Compounds;Paclitaxel;Pain;Paraffin Embedding;Patients;Peroxidases;Pharmaceutical Preparations;Poison;Predisposition;protein expression;Proteins;prototype;Reaction;Reporting;Research Proposals;response;response to injury;Role;Saline;Sampling;Serine Protease;skills;Skin;Skin Tissue;Snake Venoms;Students;Supportive care;Swelling;Techniques;Testing;Time;Tissue Embedding;Tissues;Topical application;Toxic effect;Toxic Environmental Substances;Tryptase;Western Blotting;Wild Type Mouse;Work;World War I

PROJECT_TITLE: Dermal-Epidermal Junction Disruptors: Toxicodynamic Mechanisms


NIH_SPENDING_CATS: Microbiome;Nutrition

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: The gut microbiota has a profound effect on human health and physiology, providing benefits to the host such as modulation of immune development, inhibition of pathogen colonization, digestion of dietary fibers and absorption of nutrients, while abnormalities in microbiota composition, or dysbiosis, have been implicated in numerous and diverse disease states. Microorganisms possess varied and efficient strategies for competing for nutrients in the human gut, on which they depend as a critical energy source, the molecular mechanisms of which remain poorly understood and are the focus of the studies proposed here. Our research will allow us to build an intellectual framework for the design of methods and molecules with which to remodel the composition of the gut microbiota in order to improve human health.

PI_NAMEs: SUNDBERG, ERIC JOHN (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Address;Asparagine;Bacteria;Bacterial Antibiotic Resistance;bacterial metabolism;Bacteroidetes;Binding Proteins;Biochemical;biophysical techniques;Carbohydrates;Cell surface;Collaborations;Colon Carcinoma;Complex;Consensus;design;Development;Diet;Dietary Fiber;Digestion;Disease;Disparate;dysbiosis;Employment;Endoglycosidases;Energy-Generating Resources;Environment;Enzymes;Event;Exhibits;Exoglycosidases;Gatekeeping;Genes;Genetic;Genetic Techniques;Glycobiology;Glycoproteins;Goals;Growth;gut bacteria;gut microbes;gut microbiome;gut microbiota;Health;Human;human disease;Hydrolysis;immunoregulation;improved;Individual;Inflammatory;Inflammatory Bowel Diseases;innovation;Intestines;Kinetics;Link;link protein;Mannose;Mass Spectrum Analysis;Measures;member;Membrane;Metabolism;Methods;Microbe;microbial community;microbiota;microbiota composition;microorganism;Molecular;Mucins;Mucous Membrane;novel;novel therapeutics;Nutrient;nutrient absorption;Obesity;pathogen;pathogenic bacteria;Pathway interactions;Physiology;Play;Polysaccharides;Process;Proteins;Research;Role;sensor;Specificity;Structure;Substrate Specificity;superresolution microscopy;Work

PROJECT_TITLE: Gatekeeping glycan metabolism in the human gut microbiome

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Narrative Cytokine signaling is essential to immune function and is an area with great clinical therapeutic potential. Dozens of cytokine families have different roles in the immune system which all signal through their specific combinations Janus kinases (Jaks) and STAT proteins. We propose using biochemistry, biophysics, and protein engineering to understand how the different cytokine receptor families interact with the Jaks and STATs which will identify new targets for tuning cytokine signaling.

PI_NAMEs: MENDOZA, JUAN LUIS (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: adaptive immune response;Adaptive Immune System;Apoptosis;Area;Binding;Biochemistry;Biophysics;Cell Nucleus;Clinical;cytokine;Cytokine Receptors;Cytokine Signaling;Defense Mechanisms;Dimerization;Disease;Engineering;Equipment;Family;Genes;Health;Hematopoiesis;Human;immune function;Immune response;Immune system;Infection;Inflammation;Innate Immune System;Interferon Type II;Interferons;Interleukin-2;Janus kinase;Knowledge;Malignant Neoplasms;microbial;Molecular;novel therapeutic intervention;Phosphorylation;Play;Protein Engineering;protein protein interaction;Proteins;receptor;response;Role;Shapes;Signal Transduction;STAT protein;System;T cell response;Technology;Therapeutic;Therapeutic Intervention;Time;tool development

PROJECT_TITLE: Shedding new light on cytokine signaling through molecular engineering - equipment supplement


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);Neurosciences;Pediatric;Social Determinants of Health;Substance Misuse

ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: PROJECT NARRATIVE This Diversity Supplement to the large national longitudinal pediatric study – HBCD, will provide invaluable insight into the barriers and facilitators of recruitment and retention of pregnant people, with particular focus on those using substances during pregnancy, in the context of a standardized intensive longitudinal protocol. These data can then be used both within HBCD and for other studies to optimize recruitment and retention, supporting more generalizable, translatable, and ultimately more inclusive and equitable science for all people.

PI_NAMEs: BELL, MARTHA ANN ;HOSIG, KATHRYN W;HOWELL, BRITTANY ROLLINS (contact)

PROGRAM_OFFICER_NAME: PRABHAKAR, JANANI

PROJECT_TERMS: adverse outcome;Alcohols;Anxiety;Behavior;Behavioral;Biological;Biomedical Research;Birth;Brain;Cannabis;Caring;Characteristics;Child;Child Development;Childhood;Clinical;Cognition;Cognitive;Communities;Congenital Abnormality;contextual factors;Data;Development;Disease;disparity gap;Eligibility Determination;emotion regulation;Enrollment;Ensure;Environmental Exposure;Environmental Impact;Epigenetic Process;Equity;ethnic minority;Evaluation;fetal;Fetal Growth;Fetal Reduction;fetal substance exposure;Foundations;Future;Genetic;Geography;Goals;Health;Healthcare;Helping to End Addiction Long-term;Human Resources;improved;inattention;Individual;Infant;insight;Intervention;Interview;Knowledge;Language Delays;Language Development;Link;Literature;Longitudinal cohort study;longitudinal, prospective study;Low Birth Weight Infant;Maps;Memory impairment;Metabolic;Mothers;neonatal health;neuroimaging;opioid use;Outcome;Participant;participant retention;Pathway Analysis;Patient Recruitments;Persons;Play;Policies;Population;Pregnancy;pregnant;Pregnant Women;Premature Birth;prenatal exposure;Procedures;Process;programs;prospective;Protocols documentation;Psychopathology;racial minority;racism;Recommendation;recruit;Research;Research Personnel;response;retention rate;Risk;Sampling;Science;Site;social;social health determinants;Standardization;Structure;substance use;task analysis;Tobacco;tool;Translations;Trauma;Underrepresented Populations;United States;United States National Institutes of Health;Vulnerable Populations

PROJECT_TITLE: An examination of recruitment and retention for clinical infant neuroimaging studies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(51)-R]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer

PHR: Public Health Relevance The Center proposal aims to develop and disseminate new technologies to measure the mechanical forces in living cells. If successful, these new technologies will reveal the forces that guide cellular processes such as normal and abnormal cell growth, immune responses, and clotting. As such, center technologies will improve our ability to diagnose and treat diseases ranging from cancer metastasis to stroke.

PI_NAMEs: SALAITA, KHALID S. (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Abnormal Cell;Acceleration;Address;adhesion receptor;Adoption;Automobile Driving;Binding;Blood Platelets;cancer cell;cell growth;Cell Physiology;Cell Separation;Cell Surface Receptors;Cells;Cellular biology;Coagulation Process;commercialization;Communities;community engagement;Custom;Data Analyses;design;Diagnosis;Disease;Dissociation;DNA;DNA Probes;DNA Structure;Educational workshop;Enzyme-Linked Immunosorbent Assay;Equipment;Event;Flow Cytometry;Fluorescence Polarization;Focal Adhesions;force sensor;Frequencies;Geography;Heterogeneity;high throughput analysis;Image;Immune response;improved;Industry;Internet;Mainstreaming;Maps;Measures;mechanical force;Mechanics;mechanotransduction;Mediating;Methods;Microscope;Molecular;Molecular Probes;Neoplasm Metastasis;new technology;Normal Cell;Pathway interactions;Preparation;Proteins;Proteomics;Protocols documentation;prototype;public health relevance;Publications;Publishing;Reagent;receptor;Resolution;response;Role;Series;Stroke;Surface;symposium;T-Cell Receptor;T-Lymphocyte;Techniques;Technology;technology development;Testing;Time;tool;Training;virtual;Work

PROJECT_TITLE: Equipment Supplement: Cell sorting flow cytometry to support the BTDD


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

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE (Parent Grant) This project is devoted to the development of a novel integrative, structure-based, artificial intelligence driven methodology for rapid chemical probe discovery against any target protein. The candidate molecules will be experimentally validated for three selected targets, transcription factor brachyury, hydrolase NUDT5, and bromodomain BAZ2B, and then optimized, using computational algorithms, into lead molecules to seed chemical probe development. We expect that our AI-based computational approach to convert crystallographically- determined chemical fragments into lead compounds coupled with the experimental validation of computational algorithms will accelerate the discovery of new chemical probes, expand the coverage of druggable proteome, and support future drug discovery studies.

PI_NAMEs: TROPSHA, ALEXANDER  (contact);WILLSON, TIMOTHY M

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Acceleration;Administrative Supplement;Affinity;Antibodies;Artificial Intelligence;Binding;Brachyury protein;Bromodomain;Chemicals;Computational algorithm;computational chemistry;Consensus;convolutional neural network;Coupled;Crystallography;Databases;design;Development;drug discovery;Future;Goals;Graph;Human;Hybrids;Hydrolase;innovation;interest;iterative design;Lead;Libraries;Ligand Binding;Ligands;macromolecule;Methodology;Methods;Nature;novel;novel strategies;parent grant;Proteins;Proteome;screening;small molecule;small molecule libraries;Specificity;Structure;Synthesis Chemistry;Testing;transcription factor;Validation

PROJECT_TITLE: Administrative Supplement to: Enabling the Accelerated Discovery of Novel Chemical Probes by Integration of Crystallographic, Computational, and Synthetic Chemistry Approaches

STUDY_SECTION: MSFD

STUDY_SECTION_NAME: Macromolecular Structure and Function D Study Section[MSFD]


ORG_CITY: Newark

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: PROJECT NARRATIVE The Delaware Center for Musculoskeletal Research (DCMR) was funded by a NIH COBRE (P20 GM139760, 2/1/2021-1/31/2026). In this equipment supplement, we would like to request funds ($250,000) to purchase a Bruker Dimension Icon Atomic Force Microscopy (AFM) system. The addition of this key equipment will fill a critical need in the Research Core, and align with the overall goal of the DCMR COBRE in promoting transformative preclinical and translational musculoskeletal research at University of Delaware.

PI_NAMEs: ELLIOTT, DAWN M (contact)

PROGRAM_OFFICER_NAME: PEI, WUHONG

PROJECT_TERMS: Administrative Supplement;Atomic Force Microscopy;Biopsy;Cartilage;Cells;Centers of Research Excellence;Delaware;Dimensions;Equipment;Extracellular Matrix;Funding;Goals;Ligaments;Measurement;Mechanics;Meniscus structure of joint;Multiscale Mechanics;Muscle;Musculoskeletal;pre-clinical;Research;Research Personnel;Rodent;Scientist;System;Tendon structure;Testing;Tissues;Training;United States National Institutes of Health;Universities

PROJECT_TITLE: Delaware Center for Musculoskeletal Research, Administrative Supplement for Equipment


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD)

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

PHR: Narrative Biomedical research produces vast quantities of raw data that require analysis with suitable tools and interpretation to draw meaningful conclusions. The self-learning training module we propose aims to facilitate the analysis of extensive genomic datasets in a cloud environment, utilizing standardized tools without the necessity of local server downloads. This approach obviates the need for establishing a local IT infrastructure to handle large-scale data analysis, thereby democratizing access to data and resources across all institutions.

PI_NAMEs: SORGEN, PAUL L (contact)

PROGRAM_OFFICER_NAME: MATUKUMALLI, LAKSHMI KUMAR

PROJECT_TERMS: Address;ATAC-seq;Binding Sites;Bioinformatics;bioinformatics infrastructure;Biological;Biomedical Research;brahma;Cells;ChIP-seq;Chromatin;chromatin modification;Cleavage Under Targets and Release Using Nuclease;cloud based;Cloud Computing;Collaborations;Collection;Complex;Computer Analysis;computer infrastructure;computing resources;Data;Data Analyses;Data Set;data tools;Dedications;Democracy;Development;differential expression;Discipline;DNA-Protein Interaction;Educational process of instructing;Effectiveness;Ensure;Environment;experience;Explosion;Funding;Gene Expression;Gene Expression Regulation;genome annotation;genome-wide;genome-wide analysis;genomic data;Genomics;Human Resources;Individual;Infrastructure;innovation;insight;Institution;instructor;large scale data;Learning;Learning Module;Libraries;Location;Maintenance;Maps;Measurement;Measures;Mediating;member;Methodology;Methods;National Institute of General Medical Sciences;Nebraska;next generation sequencing;Output;Parents;Postdoctoral Fellow;Preparation;Prevalence;Process;programs;Proteins;public database;Qualifying;Research;Research Personnel;Resources;response;Running;Sampling;Sequence Read Archive;Services;single cell ATAC-seq;skills training;software development;Software Tools;Standardization;Students;success;Techniques;Technology;Testing;Time;Tissue-Specific Gene Expression;tool;Training;Training Activity;Training and Infrastructure;transcription factor;transcriptome sequencing;United States National Institutes of Health;user-friendly

PROJECT_TITLE: A cloud-based learning module to analyze ATAC-seq and single cell ATAC-seq data


ADMINISTERING_IC: EB

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research

ORG_CITY: FAYETTEVILLE

ORG_NAME: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE

ORG_STATE: AR

PHR: PROJECT NARRATIVE  We are transforming our biomedical engineering education by introducing series of courses as part of an educational toolkit for bioengineering design, entrepreneurship, and service learning into our curriculum. In an inclusive learning environment, students will engage with our local healthcare community to identify healthcare gaps and disparities and inspire the next generation of engineers by mentoring high school pre-engineering students. Our aim is to graduate biomedical engineers who are outstanding stewards of their education, serving their communities, and translating healthcare innovations for a broader impact.

PI_NAMEs: RAO, RAJ RAGHAVENDRA (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Address;Award;Bachelor's Degree;Biomedical Engineering;Clinical;commercialization;Communities;community engagement;design;Development;Disparity;Disparity population;Education;education research;educational atmosphere;Educational Curriculum;Engineering;Entrepreneurship;equity, diversity, and inclusion;Ethics;Evaluation;experience;Funding;Generations;global health;Goals;Graduate Degree;graduate student;health disparity;Healthcare;healthcare community;high school;innovation;Instruction;Leadership;Learning;marginalized population;Mentors;Mentorship;Mind;Modernization;next generation;novel;parent project;programs;project-based learning;Publications;Research;Role;Science;Series;service learning;simulation;skills;social;student mentoring;student participation;Students;symposium;Translating;undergraduate student;virtual reality environment;Work

PROJECT_TITLE: Educational Toolkit for Bioengineering Design, Entrepreneurship and Service Learning