NIH_SPENDING_CATS: Bioengineering;Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Nanotechnology;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: SEATTLE

ORG_NAME: HDT BIO CORPORATION

PHR: Project narrative The prototypic BG505 SOSIP.664 protein is a potent HIV-1 immunogen currently in two phase I clinical trials. RNA vaccines induce immune pathways distinct from protein-based vaccines, and if successfully developed, our proposed replicating RNA (repRNA) vaccine can complement the clinical vaccine and potentially boost waning immune responses. We will develop a repRNA vaccine expressing BG505 SOSIP.664 and evaluate protective immunity in a non-human primate challenge model.

PI_NAMEs: KHANDHAR, AMIT PRAFUL (contact)

PROGRAM_OFFICER_NAME: PALIN, AMY COLLEEN

PROJECT_TERMS: Achievement;Adjuvant;Affinity;Animals;Antibodies;Antibody Response;Antibody titer measurement;Antigen Presentation;Antigens;B cell differentiation;B-Lymphocytes;Benchmarking;Binding;Biodistribution;Cell Maturation;Child;Clinical;Clinical Trials;Collaborations;comparison control;Complement;Complex;design;Drops;efficacy evaluation;Engineering;Epitopes;Formulation;Future;Goals;Histology;HIV;HIV-1;HIV-1 vaccine;Immune;Immune response;Immunity;Immunization;Immunize;immunoengineering;immunogenicity;Injections;Intramuscular;Lead;Lipids;lymph nodes;Macaca;manufacture;manufacturing capabilities;Measures;Messenger RNA;Modeling;Molecular Conformation;Mucous Membrane;Mus;nanoemulsion;nanoparticle;nanoparticle delivery;neutralizing antibody;nonhuman primate;Normal tissue morphology;novel;Nucleic Acid Vaccines;Oryctolagus cuniculus;Pathway interactions;Phase;Phase I Clinical Trials;preclinical development;protective efficacy;protein expression;Proteins;prototype;Regimen;Reporting;Research Institute;response;RNA;RNA replication;RNA vaccine;Route;SARS-CoV-2 spike protein;screening;Serum;simian human immunodeficiency virus;Site;Squalene;Technology;Testing;timeline;trafficking;Universities;Vaccinated;Vaccination;vaccination strategy;vaccine candidate;vaccine delivery;vaccine development;vaccine formulation;vaccine immunogenicity;Vaccines;Viral;Viral Load result;Virus;Washington;Work

PROJECT_TITLE: Engineering the Immune Response of a Self-replicating and Adjuvanting RNA HIV-1Vaccine


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;HIV/AIDS;Immunization;Immunotherapy;Infectious Diseases;Nanotechnology;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: CAMBRIDGE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_FIPS: US

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: HIV remains a global pandemic with no effective vaccine. Here we propose to combine computational and experimental methods to develop an mRNA nanovaccine which produces broadly neutralizing antibodies to HIV, by engineering antigen composition, mRNA structure, and immunostimulating mRNA nanoformulations for enhanced immunity.

PI_NAMEs: ANDERSON, DANIEL G (contact)

PROGRAM_OFFICER_NAME: MACIEL, MILTON

PROJECT_TERMS: Address;Adjuvant;adoptive B cell transfer;Affinity;Animal Model;Antibodies;Antibody Formation;Antibody titer measurement;Antigen Presentation;Antigen Targeting;Antigen-Presenting Cells;Antigens;B-Lymphocytes;Belief;Biomedical Engineering;Biomimetics;Bolus Infusion;CD8-Positive T-Lymphocytes;CD8B1 gene;cell behavior;Cells;Chemicals;Clinic;clinical development;clinical translation;Clinical Trials;Clonal Expansion;Collaborations;combinatorial;combinatorial chemistry;Complex;Computer Models;cross reactivity;Cytokine Signaling;design;Developing Countries;Development;Dose;efficacy validation;Engineering;env Gene Products;Epitopes;Evaluation;Formulation;Future;Generations;Genetic Transcription;Genetic Variation;Germ Lines;Half-Life;Helper-Inducer T-Lymphocyte;HIV;HIV Antigens;HIV vaccine;HIV-1;HLA-A gene;Human;humanized mouse;Immune;immune activation;Immune response;Immune system;Immunity;Immunization;immunogenicity;Immunoglobulin G;Immunoglobulin M;Immunologic Stimulation;Immunologic Tests;Immunology;improved;in vivo;Individual;Infection;Inflammation;Kinetics;Knock-in Mouse;Laboratories;lipid nanoparticle;Lipids;lymph nodes;Machine Learning;manufacture;Membrane Proteins;Messenger RNA;Methods;Modeling;models and simulation;Modification;molecular dynamics;mouse model;mRNA delivery;Mus;Mutation;nanoformulation;nanoparticle delivery;nanotherapeutic;nanovaccine;neutralizing antibody;next generation;novel;pandemic disease;pathogen;Pathway interactions;Pattern;Process;Production;Property;Protocols documentation;Research Personnel;response;RNA vaccination;RNA vaccine;Scheme;Signal Transduction;Structure;Structure of germinal center of lymph node;System;T cell response;T-Lymphocyte;Tail;targeted delivery;Techniques;Testing;Therapeutic;Time;Toxic effect;Transgenic Mice;Translating;Translations;Vaccination;vaccination protocol;vaccine candidate;vaccine development;vaccine efficacy;vaccine evaluation;Vaccines;Variant;Viral

PROJECT_TITLE: Combinatorial and computational design of bnAb mRNA vaccines for HIV


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Pediatric - AIDS;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse

ORG_CITY: WASHINGTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE Black, Latino/a/e/x, and Multiracial (BLM) sexual and gender minorities who have sex with men (SGMSM) are at disproportionately high risk for HIV infection, yet little research has been powered to examine whether exposure to oppressive socio-structural factors vis-à-vis inequitable risk environments drives BLM SGMSM’s inequitable rates of HIV. In this study, we will establish a large nationwide cohort of BLM SGMSM and follow them longitudinally to examine socio-structural predictors (i.e., state- and local- level laws, policies, and social climate) of HIV seroconversion and access to emerging HIV prevention technologies (e.g., PrEP and ART). We will integrate Intersectionality and the Social Ecological Model to identify modifiable socio-structural targets for future public health policy and community-level intervention, with an emphasis on developing guidelines that can be integrated into the U.S. Ending the HIV Epidemic initiative to promote not only overall reductions in HIV but specifically target drivers of HIV inequities for BLM SGMSM.

PI_NAMEs: RENDINA, H. JONATHON  (contact);TAGGART, TAMARA

PROGRAM_OFFICER_NAME: MANDT, REBECCA ELIZABETH KILIAN

PROJECT_TERMS: Address;Adolescent;Adult;Affect;Age;Age Years;aged;AIDS prevention;Behavior;Black race;cisgender;cohort;Color;Communities;community intervention;community partnership;Data;design;digital;digital technology;Disparity population;disparity reduction;Ecological momentary assessment;economic indicator;Enrollment;Ensure;Environment;Epidemic;Epidemiology;Equity;experience;Exposure to;Future;gender diverse;Guidelines;Health Policy;Healthcare;high risk;HIV;HIV disparities;HIV Infections;HIV risk;HIV Seropositivity;Home;Human immunodeficiency virus test;improved;Incidence;Individual;Inequity;Insurance Coverage;intersectionality;Intervention;Latino;Laws;Lesbian Gay Bisexual Transgender Queer;maltreatment;Measures;Medical;medical services inaccessibility;men;Methodology;Methods;Modality;Modeling;multi-racial;next generation;nonbinary;novel;Participant;Persons;Phase;Policies;policy recommendation;Population;pre-exposure prophylaxis;Prevalence;preventive intervention;Public Health;Puerto Rico;Quality of Care;recruit;Research;response;Risk;Risk Behaviors;Risk Factors;Role;Sampling;sex;Sexual and Gender Minorities;sexual minority men;social;Social Environment;social media;social stigma;social structure;socioeconomic disadvantage;socioeconomics;Spanish/English;structural determinants;Structural Models;Structural Racism;Structure;Surveys;System;systematic review;Techniques;Technology;Testing;transfeminine;Translating;transmasculine;transmission process;Unsafe Sex;Update;Viral Load result;Work;working group

PROJECT_TITLE: Multilevel strategies to understand and modify the role of structural and environmental context on HIV inequities for sexual and gender minorities of color


ED_INST_TYPE: GRADUATE SCHOOLS

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;Infectious Diseases;Methamphetamine;Pediatric;Pediatric - AIDS;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Stimulant Use and Misuse;Substance Misuse;Telehealth

ORG_CITY: NEW YORK

ORG_NAME: GRADUATE SCHOOL OF PUBLIC HEALTH AND HEALTH POLICY

ORG_STATE: NY

PHR: NARRATIVE This LITE-2 (RFA-AI-21-018) proposal responds to a resurgent epidemic of methamphetamine (meth) use in sexual minority men (SMM) by: 1) identifying multi-level and bio-behavioral determinants of amplified HIV seroconversion risk in meth-using SMM; and 2) testing the effectiveness of telehealth motivational enhancement interventions for optimizing for optimizing entry or re-entry of SMM who use meth into the PrEP care continuum.

PI_NAMEs: CARRICO, ADAM WAYNE;GROV, CHRISTIAN  (contact)

PROGRAM_OFFICER_NAME: MCKAIG, ROSEMARY G

PROJECT_TERMS: Address;aged;AIDS prevention;Behavior;biobehavior;Biological;Caring;chemokine;Clinical;clinically relevant;cohort;comorbidity;comparative;Complex;contingency management;Continuity of Patient Care;cytokine;density;design;digital;Effectiveness;effectiveness evaluation;effectiveness testing;Enrollment;Epidemic;ethnic minority;evidence base;Funding;Goals;Health;high risk;HIV;HIV Infections;HIV risk;HIV Seropositivity;Human immunodeficiency virus test;Hybrids;Immune;implementation science;Incentives;Incidence;Intervention;Laws;men of color;Methamphetamine;methamphetamine use;methamphetamine user;Methodology;Motivation;motivational enhancement therapy;Participant;Peer Review;people of color;Pharmaceutical Preparations;Policies;pre-exposure prophylaxis;Prevalence;primary outcome;prospective;Protocols documentation;psychologic;psychosocial;public health intervention;racial disparity;racial minority;Randomized, Controlled Trials;Readiness;recruit;Rectum;Reporting;Research;response;Risk;Role;Sampling;Science;sexual minority;sexual minority group;sexual minority men;social;social determinants;Social Network;social stigma;sound;structural determinants;success;syndemic;telehealth;Telephone;Testing;Toxicology;transmission process;Urbanicity;virtual

PROJECT_TITLE: Optimizing HIV prevention for highly vulnerable methamphetamine-using sexual minority men


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

ORG_CITY: Huntington

ORG_DEPT: BIOLOGY

ORG_NAME: MARSHALL UNIVERSITY

ORG_STATE: WV

PHR: RESEARCH STRATEGY FOR THE SUPPLEMENT SCIENTIFIC JUSTIFICATION FOR THE REQUESTED EQUIPMENT  We use Arabidopsis thaliana as model to discover and characterize novel genes and functional natural polymorphisms that control genotype-specific telomere lengths. Aim 1 is focused on characterizing functional natural variation in telomerase function, expression, and enzymatic activity. We also employ innovative and comprehensive genome-wide screens to identify novel trans-regulators of TERT expression and inhibitors and activators of in vivo telomerase activity. In Aim 2, we perform a series of experiments to characterize the role of previously identified candidate genes in telomere biology and length control. We also exploit several cutting-edge genomic approaches to identify additional regulators of telomere length. We have developed an effective research pipeline for candidate gene analysis that led to the identification of several novel genetic factors and pathways and we anticipate making more new discoveries. Our high-throughput assays allow us to screen up to 20 different T-DNA mutants for telomere phenotypes simultaneously. Genetic and transgenic experiments to validate the role of candidate genes in telomere length control include: 1) knock-out analysis of candidate genes for defects in telomere length; 2) transgenic rescue experiments; and 3) quantitative complementation tests. Collectively, these studies will reveal and characterize the complex genetic landscapes that underlie natural variation in telomere length set point.  Both Aims 1 and 2 rely heavily on the measurement of telomere length in hundreds of various transgenic mutants and natural populations of Arabidopsis. This Southern blotting technique requires the use of radioactive P32 oligonucleotide probes to hybridize telomeric DNA in gels and subsequent scanning the signals with a Phosphor Imager. Our lab previously had a Typhoon FLA 7000 machine suitable for these assays, but unfortunately this machine is now not operational. We had a Cytiva technician come to the lab to look at it, and he had indicated that the unit cannot be repaired, as this model is so old that Cytiva is no longer manufacturing parts or providing any service. Thus, currently we do not have a Phosphor Imager, and no other lab at Marshall University has this type of equipment for imaging.  We are currently using X-ray films as an alternative. However, this method has major crucial drawbacks and limitations compared to Phosphor Imaging which substantially slows down work and adds unnecessary costs. Specifically, Phosphor imaging provides a much greater linear dynamic range and higher sensitivity than X-ray film when detecting radiolabels. This allows very precise quantitation of nucleic acids which is incredibly important for our high-throughput project and not really sustainable long-term with X-ray films. With P32 half-life being only 2 weeks, without digital imaging we simply cannot analyze the necessary number of samples with X- rays before the signal disappears, especially when some assays often need to be repeated. Having access to a Phosphor Imaging capability is a major necessity, and it will be routinely used for the duration of the project.  I have received a quote for Azure Sapphire FL Phosphor Imager, which is the next generation of biomolecular imagers with many benefits and extra features over the Typhoon models. It features customizable and user- changeable optical modules, laser based scanning system supporting 375 nm excitation to 900 nm emission, adjustable Z focus, 5-1000 micron resolution. Through the use of laser excitation and photon multiplier tube (PMT) detection, Sapphire FL is able to scan storage phosphor screens with exceptional dynamic range and image quality; these features are integral to the success of our study and provide unparalleled advantages for everyday use in comparison to X-rays. Sapphire FL Phosphor Imager is essential for both aims of our research project and will substantially speed up our progress.  The quote for Sapphire FL Phosphor Imager covers the price of the Imager, Phosphor Standard Optical Module, dedicated Desktop Workstation with External High-Resolution Monitor for Sapphire FL, shipping & handling, device installation and training of the personnel, and AzureSpot Pro software for downstream analysis. Warranty period is for 1 year. The future recurring costs associated with the requested equipment include additional years of service contract, which will be covered through PI’s startup funds.

PI_NAMEs: SHAKIROV, EUGENE V (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Administrative Supplement;Arabidopsis;Architecture;Biological Assay;Biology;Candidate Disease Gene;candidate identification;Complex;Computer software;Contract Services;cost;Dedications;Defect;Detection;Devices;digital imaging;DNA;Doctor of Philosophy;Epigenetic Process;Equipment;experimental study;Funding;Future;Gel;Genes;Genetic;Genetic Complementation Test;Genetic Polymorphism;genome wide screen;Genomic approach;Genotype;Grant;Half-Life;high throughput screening;Human Resources;Image;imager;imaging capabilities;in vivo;inhibitor;innovation;Knock-out;Lasers;Length;manufacture;Measurement;Methods;Modeling;Monitor;Mouse-ear Cress;mutant;National Institute of General Medical Sciences;next generation;novel;nucleic acid quantitation;Oligonucleotide Probes;Optics;Pathway interactions;Phenotype;Phosphorus 32;Photons;Population;Price;Principal Investigator;Radioactive;radiotracer;Recurrence;repaired;Research;Research Project Grants;Resolution;Roentgen Rays;Role;Sampling;Sapphire;Scanning;Series;Services;Shipping;Signal Transduction;Southern Blotting;Speed;success;Support System;T-DNA;Techniques;Telomerase;telomere;Training;Transgenic Organisms;Tube;Universities;Variant;Work;X-Ray Film

PROJECT_TITLE: Genetic and epigenetic architecture of natural telomere length variation

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative This information has not changed from the Parent Award While successful genome inheritance requires that each gamete – sperm or egg – receives one copy of each chromosome, an estimated 35% of human zygotes contain an incomplete chromosome set, resulting in miscarriages and birth defects. The research proposed here addresses the mechanisms that regulate interaction and information exchange between the parental chromosomes during sexual reproduction, which is essential for correct chromosome segregation into gametes. A better understanding of the structure and dynamics of chromosomes during sexual reproduction will elucidate the mechanistic principles that control chromosomes across biological processes, ranging from gene expression to cell division, and will ultimately shed light on the chromosomal dysfunctions that lead to cancer.

PI_NAMEs: ROG, OFER  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Administrative Supplement;Appearance;Applied Genetics;Biological Process;Cell division;Chromatin;Chromatin Loop;chromosome missegregation;Chromosome Segregation;Chromosome Structures;Chromosomes;Coiled-Coil Domain;Congenital Abnormality;Cytology;DNA;egg;Electron Microscopy;Emerging Technologies;Equipment;Functional disorder;Funding;Gene Expression;Generations;genetic approach;genetic information;Genome;Germ Cells;Human;Infertility;instrument;Karyotype;Label;Liquid substance;Malignant Neoplasms;Meiosis;Microscopy;Molecular;Molecular Conformation;Nematoda;novel strategies;parent project;Parents;Process;Property;protein complex;protein protein interaction;Research;Resolution;Role;Saccharomycetales;Sexual Reproduction;single molecule;Sister;Sister Chromatid;sperm cell;Spontaneous abortion;Structure;Synaptonemal Complex;three dimensional structure;Visualization;Work;zygote

PROJECT_TITLE: Administrative Supplement for the purchase of a SEC-MALS instruments

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


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: PITTSBURGH

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: The proposed project seeks to explore the development of synthetic molecules that mimic complex protein structures and functions. The public health relevance of the work stems from the potential applications of these molecules as bioactive agents as well as their utility in shedding light on fundamental issues related to natural protein behavior.

PI_NAMEs: HORNE, WILLIAM SETH (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Address;analog;Area;Award;Behavior;Biological;biomacromolecule;Biomedical Research;Biomimetics;Characteristics;Chemicals;Complex;design;Development;Disease;Engineering;functional group;Goals;Laboratories;Life;Light;mimetics;mimicry;Mutagenesis;National Institute of General Medical Sciences;Nature;Pattern;Peptides;Production;programs;Property;protein complex;protein folding;protein function;protein structure;Proteins;prototype;public health relevance;Research;scaffold;stem;Structure;Tertiary Protein Structure;Vertebral column;Work

PROJECT_TITLE: Exploring the Impact of Altered Backbone Composition on Protein Folding and Function

STUDY_SECTION: MRAB

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


ADMINISTERING_IC: FD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: Columbus

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Veterinary diagnostic laboratories (VDLs) play a pivotal role in maintaining animal health, aiding veterinarians, animal owners, researchers, and those involved in the veterinary sector. These laboratories are also integral to the public health sector's efforts in monitoring and preventing zoonotic diseases. There is a crucial need to build and maintain the capability of VDLs. Collaborative efforts among VDLs should also be coordinated to maximize the use of resources. This project seeks funding to enhance and sustain the Clinical Diagnostic Laboratory (CDL) at The Ohio State University's Veterinary Medical Center. The CDL will actively engage in the CVM FDA Vet-LIRN program, focusing on three key areas: 1) contributing bacterial samples for the Vet-LIRN Whole Genome Sequencing Project, 2) upgrading laboratory equipment, and 3) facilitating staff development through training and participation in proficiency tests.

PI_NAMEs: DIAZ-CAMPOS, DUBRASKA V (contact)

PROGRAM_OFFICER_NAME: CERIC, OLGICA

PROJECT_TITLE: Laboratory capacity FDA CVM Vet-LIRN veterinary diagnostic laboratory program

STUDY_SECTION_NAME: Special Emphasis Panel[ZFD1 CVM-K (01)]


ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative Emergence of antibiotic resistance continues to be a threat to both human and animal health around the world, and this burden can be reduced with the prudent use of antibiotics through culture and susceptibility testing. The AHDC Bacteriology laboratory is engaged to continue its cooperative agreement with the FDA Vet-LIRN to promote the areas of food and feed surveillance, antibiotic susceptibility testing, quality management, animal health, food safety, and food security. As a continued participant in the Vet-LIRN network of veterinary diagnostic laboratories, the AHDC Bacteriology laboratory can provide surge capacity for large-scale testing in the event of an emergency.

PI_NAMEs: GUARINO, CASSANDRA  (contact)

PROJECT_TITLE: Antimicrobial Resistance Monitoring in Bacteria of Veterinary Significance


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Narrative Scientific data, such as the trajectories of biomolecular simulations, is being produced at prodigious rates, making analysis increasingly difficult using traditional methods. Here, we propose to build a cloud-based module that will train scientists in using machine-learning approaches for analysis of molecular dynamics simulation trajectories in order to extract novel insights from otherwise large and noisy datasets.

PI_NAMEs: GUMBART, JAMES C.;QIU, PENG  (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Methods;protein protein interaction

PROJECT_TITLE: Identifying critical protein-protein interactions with ML methods

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - B[TWD-B]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences;Sleep Research

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY

ORG_STATE: TX

PHR: Project Narrative Rhythmic behaviors and physiological processes are temporally organized by the central circadian pacemaker to occur at the optimal time of day. Disruption of this precise organization due to disease or lifestyle (shift work, artificial light at night) is associated with negative health outcomes including metabolic, cardiovascular, and mood disorders. Our research program aims to determine the interaction between the genes, neurons, and circuits that time rhythmic behaviors, which will provide a foundation for the investigation of the mechanisms of circadian dysfunction that both lead to, and are a symptom of, disease.

PI_NAMEs: JONES, JEFFREY R (contact)

PROGRAM_OFFICER_NAME: SESMA, MICHAEL A

PROJECT_TERMS: Address;African;Animals;Behavior;Behavioral;Biological;Brain;Cardiovascular Diseases;Chronobiology;circadian;circadian biology;Circadian Dysregulation;circadian pacemaker;Circadian Rhythm Sleep Disorders;Communication;Curiosities;Disease;Etiology;ex vivo imaging;Exhibits;Food;Foundations;Gene Expression;Genes;genome editing;Goals;Health;Human;in vivo;Investigation;Laboratory mice;Life Style;Light;Link;Machine Learning;Metabolic Diseases;Molecular;molecular clock;Mood Disorders;multilevel analysis;Mus;Neurons;Neurophysiology - biologic function;novel;Outcome;Output;parent project;Partner in relationship;Periodicity;Physiological Processes;Predatory Behavior;preference;programs;Research;Rest;shift work;Signal Transduction;suprachiasmatic nucleus;Symptoms;Time

PROJECT_TITLE: Circadian output mechanisms in nocturnal and diurnal animals

STUDY_SECTION: MRAD

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


ORG_CITY: Auburn

ORG_NAME: AUBURN UNIVERSITY AT AUBURN

ORG_STATE: AL

PHR: Project Narrative This FDA Vet-LRN Cooperative Agreement Program will strengthen the overall food safety system by developing increased capacity and capabilities to detect pathogens which could affect animals and spread antimicrobial resistance to human beings.

PI_NAMEs: WANG, CHENGMING  (contact)

PROJECT_TITLE: FDA Vet-LIRN Veterinary Diagnostic Laboratory infrastructure funding program to strengthen sample analysis capacity and capabilities related to animal food-borne diseases


ADMINISTERING_IC: NS

ED_INST_TYPE: OVERALL MEDICAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurosciences

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Astrocytes are highly elaborate cells that are key regulators of brain development, function, and maintenance, and astrocyte dysfunction results in devastating neurological conditions. We propose to dissect a novel, evolutionarily conserved pathway that is required for normal astrocyte growth and brain function. Our work will define fundamental cellular mechanisms that control astrocyte development, their contributions to brain health and function, and should provide critical insights into our understanding of astrocyte dysfunction in human disease.

PI_NAMEs: FREEMAN, MARC R;MONK, KELLY R (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Alexander Disease;Animal Behavior;Astrocytes;autism spectrum disorder;Axon;Biological Assay;Blood Vessels;Brain;brain cell;brain health;cell growth;cell motility;Cell Physiology;cell type;Cells;Cellular biology;Central Nervous System;comparison control;Data;Defect;Development;Drosophila genus;Endoderm;Environment;Enzymes;Epilepsy;Exhibits;extracellular;fly;Foundations;Functional disorder;G-Protein-Coupled Receptors;gene conservation;Genes;Genetic;genetic approach;Genetic Models;Genetic Screening;Germ Cells;Goals;Growth;Homeostasis;Homologous Gene;Human;human disease;Image;in vivo;in vivo imaging;Individual;Infiltration;insight;ionic balance;knock-down;Light;lipid phosphate phosphatase;Lipids;live cell imaging;Maintenance;Membrane;Molecular;Molecular Genetics;Morphogenesis;Morphology;Mus;mutant;Mutation;nervous system development;Nervous System Disorder;neural circuit;Neuroglia;Neurologic;neuronal cell body;Neurons;Neuropil;Neurotransmitters;novel;Nutrient;Organism;Orthologous Gene;Pathway interactions;Phenocopy;Physiology;Process;Protein phosphatase;Regulation;RNA Interference;RNA interference screen;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Specific qualifier value;Synapses;synaptogenesis;timeline;tool;Vertebrates;Visualization;wasting;Work;Zebrafish

PROJECT_TITLE: Timeline and molecular pathways regulating astrocyte endfoot morphogenesis

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR-M]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

PHR: Project Narrative The goal of this VA CDA-2 proposal is to develop the candidate into a successful VA research scientist and determine how immunotherapy can be used in combination with standard chemotherapy (FOLFOX) in colon and rectal cancer. Colon and rectal cancer affects a large number of veterans. Despite excellent screening programs, a sizable number of these patients present with advanced disease. While treatment for patients has improved, there is still significant need for progress. An ideal area to target is combination immunotherapy with FOLFOX. Cytotoxic T cells are associated with improved survival and treatment response in colorectal cancer and are the primary mediator of anti-tumor immunity. In this proposal, we will test how FOLFOX chemotherapy alters cytotoxic T cells in the tumor and the abiliy to combine these therapies. The data garnered in this study will serve to establish the PI's research program and develop future clinical trials.

PI_NAMEs: MITCHEM, JONATHAN B. (contact)

PROJECT_TERMS: advanced disease;Affect;antigen-specific T cells;Antigens;Antitumor Response;Area;arm;cancer diagnosis;career;Cell Count;Cell Death;cell injury;Cell Physiology;cell type;chemotherapy;Chemotherapy-Oncologic Procedure;Clinical Trials;Clinical Trials Design;colon cancer patients;Colon Carcinoma;Colorectal Cancer;Combination Drug Therapy;Combination immunotherapy;Combined Modality Therapy;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;design;Development;early phase trial;Education;Ensure;exhaustion;Funding;Future;Generations;Goals;Human;Immune;immune checkpoint blockade;Immune response;Immune signaling;Immune system;Immune Targeting;immunogenicity;Immunologic Adjuvants;Immunotherapy;improved;Individual;Inflammatory;innate immune sensing;Interferon Type I;Interleukin-12;male;Malignant Neoplasms;Mediator;Memory;Mentorship;Methods;Microsatellite Instability;Modeling;mouse model;multidisciplinary;Mutation;novel therapeutics;Pathway interactions;Patients;pre-clinical;programs;Publishing;Radiation therapy;recruit;Rectal Cancer;Regimen;Research;Resistance;response;Scientist;screening program;Signal Transduction;skill acquisition;Stimulator of Interferon Genes;success;System;T cell infiltration;T-Lymphocyte;Testing;The Cancer Genome Atlas;Therapeutic;TLR3 gene;TNF gene;Treatment Efficacy;treatment response;tumor;tumor growth;Tumor Immunity;tumor microenvironment;United States National Institutes of Health;Veterans;Work

PROJECT_TITLE: Optimizing anti-tumor immunity for maximal therapeutic efficacy in Colorectal Cancer


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: IOWA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative (3 sentences) This doctoral readiness program, Iowa Diversifying Research Experiences And Mentorship (iDREAM), capitalizes on an outstanding T32 supported (JSPTPN) Neuroscience Graduate program with a highly successful track record of training neuroscientists from diverse backgrounds, particularly those from backgrounds underrepresented in STEM. It integrates an outstanding interdisciplinary neuroscience research environment with evidence-based practices designed to cultivate self-efficacy and a strong sense of belonging within the local and global neuroscience research communities. In doing so, iDREAM is designed to provide high quality research experiences and didactics to post-baccalaureate students from institutions that do not offer undergraduates substantial research opportunities, ultimately empowering trainees to be competitive for and successful in rigorous, top-tier neuroscience graduate programs and beyond.

PI_NAMEs: HULTMAN, RAINBO  (contact);TRANEL, DANIEL T.;VOSS, MICHELLE WEBB

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Admission activity;Applications Grants;Area;Awareness;career;career development;Climate;Communication;Communities;Critical Thinking;Data;design;Development;diversity and inclusion;Doctor of Philosophy;education research;Educational workshop;Elevator;empowerment;Ensure;Environment;equity, diversity, and inclusion;essays;evidence base;Evidence based practice;expectation;experience;Faculty;faculty research;Funding;Future;Gender;Goals;graduate school;hands on research;Healthcare;innovation;Institution;interest;Interview;Iowa;Laboratories;Laboratory Research;Lead;Leadership;matriculation;meetings;member;Mentors;Mentorship;Methodology;Mission;Neurosciences;Neurosciences Research;Paper;Parents;Participant;peer;Persons;Positioning Attribute;Postbaccalaureate;Process;programs;Qualifying;Readiness;recruit;Reporting;Research;Research Project Grants;response;responsible research conduct;Running;Schools;Self Efficacy;skills;Structure;Students;success;Talents;Teacher Professional Development;tenure track;Training;Training Programs;undergraduate student;underrepresented minority student;Underrepresented Students;Universities;university student;verbal;Vision;Writing

PROJECT_TITLE: Iowa-Diversifying Research And Mentorship (iDREAM)


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_CITY: AUSTIN

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative Both cognitive aging and epigenetic change appear to be highly influenced by life experiences, and this project will examine how these are linked. The project has two main objectives: (1) to examine how DNA methylation and RNA transcriptomes are tied to several measures of cognitive status and change, and (2) to examine how life experiences are biologically embedded via epigenetic mechanisms to impact cognitive aging. Findings from this study will add significantly to research on the life course origins of dementia and cognitive aging by taking into account how lifetime social and environmental exposures and their timing impact cognition in older life via DNA methylation and gene expression, and it may point to potential areas of intervention to improve the cognitive health of the population.

PI_NAMEs: FARINA, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: HOOKER, EMILY DIANE

PROJECT_TERMS: Acceleration;Address;Adult;Age;Aging;Alzheimer's Disease Pathway;Alzheimer's disease related dementia;Amyloid;Area;Award;Biological;Biological Markers;Biological Process;Biometry;Biosocial;Black Populations;Brain;brain health;Brain Pathology;California;cardiovascular risk factor;Childhood;Cognition;Cognitive;Cognitive aging;cognitive change;cognitive function;Collection;Data;Dementia;dementia risk;Demography;Deterioration;Development;Disease;DNA Methylation;Doctor of Philosophy;Down-Regulation;Economic Conditions;Environment;Environmental Exposure;Epidemiology;epigenetic clock;epigenetic marker;Epigenetic Process;Etiology;experience;Exposure to;falls;Flow Cytometry;Gender;Gene Expression;Genes;Genome;Gerontology;Health;Health and Retirement Study;Hippocampus;human old age (65+);immune function;Impaired cognition;improved;Inflammation;insight;Intervention;late life;Life;Life Cycle Stages;Life Experience;Link;Measures;Methodology;Methods;Modification;multidisciplinary;National Institute on Aging;Nature;older adult;Outcome;Pathway interactions;Physiological;Policies;Population;population health;Population Study;Postdoctoral Fellow;professor;Public Health;Race;Research;Research Personnel;Research Project Grants;Risk;RNA;Sampling;Schools;sex;Shapes;Site;skills;social;Social Conditions;social genomics;Sociology;Structure;Synapses;Techniques;tenure track;Testing;Texas;Training;transcriptome;transcriptome sequencing;United States;Universities;Up-Regulation;Venous blood sampling;Work

PROJECT_TITLE: Epigenetic Mechanisms Linking Lifetime Social and Environmental Exposures to Cognitive Aging

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Genetics

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Narrative (Relevance to public health) The proposed research will contribute to elucidating the mechanisms of gene regulation involving nucleosomes and chromatin modifications. Results from this project will help develop diagnoses and treatments of the diseases and disorders associated with erroneous gene regulation such as various types of cancer and neurodegenerative diseases.

PI_NAMEs: LEE, TAE-HEE  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;Affect;Area;Biochemical;cancer type;centromere protein A;chromatin modification;Complex;Core Protein;Development;Diagnosis;Disease;DNA;DNA Methylation;ds-DNA;Enzyme Interaction;Enzymes;Eukaryota;Failure;Fluorescence;Fluorescence Resonance Energy Transfer;Gene Expression Regulation;Genes;Genetic;Goals;Histone Acetylation;Histones;improved;Investigation;leukemia;Methods;Methylation;Molecular;Molecular Conformation;Molecular Machines;Motion;Multienzyme Complexes;Neurodegenerative Disorders;Nucleosomes;Optics;Pathogenesis;Play;Process;programs;Public Health;Reporting;Research;RNA Polymerase II;Role;single molecule;structural biology;Structure;Sumoylation Pathway;System;tool;ultra high resolution;Variant

PROJECT_TITLE: Dynamics of DNA-histone interactions


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Latinx individuals are 1.5 times more likely to develop Alzheimer's disease and related dementias (ADRD) than non-Latinx whites, and have higher rates of under-diagnosis. As the proportion of US Latinx older adults is expected to increase five-fold over the next 30 years, it has become obvious that they experience unique barriers to access ADRD care services. This proposal seeks to perform a comprehensive assessment of the barriers experienced by Latinx individuals, and co-design with stakeholders a human-centered intervention that can increase access to ADRD services in low resource settings.

PI_NAMEs: MORA PINZON, MARIA CAROLINA (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Acceleration;acceptability and feasibility;Acculturation;Address;Adult;Affect;Alzheimer's disease diagnosis;Alzheimer's disease patient;Alzheimer's disease related dementia;Area;Award;Behavior;behavior change;Behavioral Model;Belief;care seeking;care systems;career;Caregivers;Characteristics;Chicago;Cities;Clinic;Clinical;Clinical Research;Communities;Community Health;Consolidated Framework for Implementation Research;contextual factors;Data;dementia care;design;Diagnosis;Disease;Effectiveness of Interventions;effectiveness testing;experience;Factor Analysis;Focus Groups;Funding;Future;Goals;Health;health care availability;Health Care Seeking Behavior;health care service;health care service utilization;health disparity;Health Personnel;health service use;Health Services Accessibility;Healthcare;Human;Improve Access;improved;Individual;informant;innovation;instrument;Intervention;Interview;Knowledge;Language;Latinx;Latinx population;Lead;Linguistics;Link;Location;Los Angeles;Malignant Neoplasms;Maps;Measures;meetings;Methods;Mexican Americans;Modeling;National Institute on Aging;Neurobehavioral Manifestations;New York;nonalzheimer dementia;normal aging;older adult;Outcome;Patient-Focused Outcomes;Patients;Phase;Planning Theory;poor health outcome;pragmatic trial;Process;programs;prototype;recruit;Research;Research Methodology;Research Personnel;Resource-limited setting;Resources;response;Sampling;Series;Services;sociocultural determinant;socioeconomics;Spanish/English;Subgroup;Surveys;Symptoms;System;Testing;theories;Theory of Change;therapy development;Thinking;tool;Training;underserved area;Use Effectiveness;Validation

PROJECT_TITLE: Improving Access to Alzheimer's disease and Related Dementias care services for Latinx individuals at Community Health Clinics. A multiphase mixed methods study.


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: OMAHA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CREIGHTON UNIVERSITY

ORG_STATE: NE

PHR: PROJECT NARRATIVE This project is an equipment supplement request to Center of Biomedical Research Excellence (COBRE) application 5P20GM139762 establishing the Translational Hearing Center (THC) at Creighton University. Funds requested will be evenly matched by the institution to purchase a state-of-the-art Bigfoot five-laser 53 parameter cell sorter from Life Technologies Corporation to replace and upgrade an obsolete FACSAria II cell sorter. The Bigfoot will be applied to ongoing hearing-related research by THC investigators, and will offer new high-dimensional analysis capability, gentle and fast sorting, and improved biosafety that, taken together, will greatly improve research opportunities to THC investigators and the larger Creighton research community.

PI_NAMEs: STEYGER, PETER STEPHEN (contact)

PROGRAM_OFFICER_NAME: KOVBASNJUK, OLGA NIKOLAEVNA

PROJECT_TERMS: Antibodies;Award;boys;Cells;Centers of Research Excellence;Color;Communities;Core Facility;design;dimensional analysis;Disease;Drug Delivery Systems;drug discovery;Ensure;Equipment;Etiology;Flow Cytometry;Funding;Goals;Hearing;hearing impairment;hearing preservation;hearing restoration;high dimensionality;high throughput screening;Hospitals;Human Resources;improved;Infrastructure;innovation;Institution;instrument;Lasers;Learning;Life;Medical center;Nebraska;repaired;Research;Research Infrastructure;Research Personnel;Safety;Sampling;Sorting;Students;Technology;Therapeutic Intervention;Training;Translational Research;translational scientist;Universities;Vestibular dysfunction;Vestibular function

PROJECT_TITLE: Bigfoot Cell Sorter


ORG_CITY: MANHATTAN

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: KANSAS STATE UNIVERSITY

ORG_STATE: KS

PHR: Project Narrative Innate immune responses of insect vectors of human diseases are likely to affect the their ability to transmit pathogens to hosts. The long term goals of this research is to gain understanding of proteins in insect hemolymph that mediate innate immune responses, using a model system, Manduca sexta, well suited for biochemical studies. The knowledge gained from this project will enhance understanding of the evolution of innate immune mechanisms and can be applied to future investigations of arthropod disease vectors.

PI_NAMEs: KANOST, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Affect;Arthropods;Biochemical;Biological Models;Complex;disease transmission;Disease Vectors;Environment;Evolution;Future;Goals;Gram-Positive Bacteria;Hemolymph;human disease;Immune;Immune response;Immunity;Immunologic Tests;Infection;innate immune mechanisms;Innate Immune Response;Innate Immune System;Insect Vectors;Insecta;Invaded;Investigation;Iron;Knowledge;Laboratories;Mammals;Manduca sexta;Mediating;microorganism;Modeling;Modification;Monophenol Monooxygenase;Oxidation-Reduction;Parasites;pathogen;Pathway interactions;Peptide Hydrolases;Peptidoglycan;Plasma;Plasma Proteins;Proteins;Regulation;Research;Serine Protease;Sulfhydryl Compounds;transmission process;Work

PROJECT_TITLE: Function of hemolymph plasma proteins in insect immune responses

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


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative The objective of this project is to develop a sophisticated new set of light activated chemical reactions that selectively form covalent bonds with specific types of biological structure. These new reactions will facilitate advances in biomedical sciences by enabling the design of new therapeutics and new approaches for the study the molecular nature of disease states; ultimately leading to opportunities for developing more effective treatments. In this project, we extensively employ LC-MS for biological mass spectrometry and proteomicsbased analytical workflows, and this supplement will support the acquisition of a new UHPLC system that will enhance our LC-MS capabilities and, in turn, our ability to perform these essential analytical workflows.

PI_NAMEs: TAYLOR, MICHAEL T (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Biological;Biology;biomaterial compatibility;chemical reaction;Chemicals;Chemistry;comparative;covalent bond;design;Disease;effective therapy;Electron Transport;experimental study;Genetic;Kinetics;Label;Light;Mass Spectrum Analysis;Methods;Mitochondria;Molecular;Nature;novel strategies;novel therapeutics;Optics;Outcome;Oxidation-Reduction;Post-Translational Protein Processing;Process;Property;Reaction;Reagent;Salts;Science;Sodium Chloride;spatiotemporal;Structure;System;tool;Tryptophan

PROJECT_TITLE: New Chemical Tools for Optically Controlled Protein Modification


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Precision Medicine;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Understanding how ethnic and racial factors modify Alzheimer’s disease risk can yield new insights into race- dependent biological mechanisms which in turn can inform future diagnostic and therapeutic interventions. An unbiased proteomic approach will be employed to examine the diagnostic and prognostic ability of plasma exosomes as biomarkers for AD. Successful completion of this study will significantly advance the field of exosome biology in neurodegeneration and may lead to the identification of novel biological targets for therapeutic development of Alzheimer’s disease.

PI_NAMEs: WINSTON, CHARISSE N (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Address;advanced dementia;African American;African American population;Algorithms;Alzheimer disease detection;Alzheimer's Disease;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;Antibodies;Astrocytes;Attenuated;Autopsy;Award;Behavioral;Binding;biobank;Biological;Biological Markers;Biology;biomarker discovery;biomarker identification;biomarker validation;blood-based biomarker;Cell Separation;cell type;Clinical;cohort;Complement;cost effective;cytokine;cytotoxicity;Data;Dementia;Diagnosis;Diagnostic;diagnostic biomarker;diagnostic value;Disease;Disparity;Enzyme-Linked Immunosorbent Assay;ethnic difference;ethnic disparity;Ethnic Origin;ethnoracial;exosome;Funding;Future;Home;Human;Immunoassay;In Vitro;in vivo;Individual;Inflammatory;Infrastructure;insight;Institution;interdisciplinary approach;Interleukin-10;Laboratories;Learning;Macrophage;magnetic beads;Mass Spectrum Analysis;member;Membrane;Membrane Proteins;Mentors;Mentorship;Methods;Minority Groups;nanoparticle;Nerve Degeneration;neural;Neuroglia;Neurons;Not Hispanic or Latino;novel;novel marker;Oligodendroglia;Pathologic;Pathology;Patients;Phase;Physiological;Plasma;Preventive measure;primary care patient;primary care setting;Productivity;prognostic;Prognostic Marker;prognostic value;Proteins;Proteomics;Publishing;Race;racial difference;racial disparity;Reagent;Reporting;Research;Risk;ROC Curve;Sampling;Scientist;Screening procedure;Shapes;Surface;Symptoms;targeted treatment;tau Proteins;tau-1;Testing;therapeutic development;Therapeutic Intervention;Time;tool;Training;Transmission Electron Microscopy;treatment strategy;United States National Institutes of Health;validation studies;Vesicle;Work

PROJECT_TITLE: Ethnoracial Impact on Blood-Based Biomarker Detection of Alzheimer's in Primary Care Patients


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: NEW YORK

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative We propose to characterize the transcription cycle structurally and functionally in the actinobacteria phylum, focusing on the pathogen Mycobacterium tuberculosis. RNA polymerase, the central enzyme of transcription, is a proven target for antimicrobials, and regulators of the transcription cycle are often clade-specific but essential for viability and virulence. Understanding how these factors regulate Mycobacterium tuberculosis RNA polymerase informs us on unified and clade-specific mechanisms, providing a more comprehensive understanding of the transcription cycle that can lead to new therapeutics against specific bacterial pathogens.

PI_NAMEs: CAMPBELL, ELIZABETH A (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Actinobacteria class;Antibiotic Resistance;Antibiotics;antimicrobial;Bacteria;Biochemical;Biological;Biophysics;Cell Physiology;Cells;Cessation of life;Complex;Coupling;Cryo-electron tomography;Cryoelectron Microscopy;DNA Sequence;DNA-Directed RNA Polymerase;Enzymes;Escherichia coli;experimental study;Funding;Genetic;Genetic Transcription;genome-wide;Genomic DNA;Genomics;Genus Mycobacterium;global health;In Situ;interdisciplinary approach;Methods;Molecular;mycobacterial;Mycobacterium tuberculosis;novel therapeutics;particle;pathogen;pathogenic bacteria;pleiotropism;Regulation;Regulator Genes;Regulon;Reporting;Resolution;response;Ribosomes;Rifampin;RNA Polymerase Inhibitor;RNA purification;Role;Signal Transduction;Stress;Structure;Transcript;transcription factor;Transcription Initiation;transcriptome sequencing;Tuberculosis;tuberculosis treatment;Virulence;Vision

PROJECT_TITLE: Structural and functional studies of the mycobacterial transcription cycle


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Infectious Diseases;Prevention;Rare Diseases;Stomach Cancer

ORG_CITY: TUSKEGEE INSTITUTE

ORG_NAME: TUSKEGEE UNIVERSITY

PHR: Narrative Communication between cells of gastric epithelial glands and surrounding stromal cells is indispensable for normal stomach function and misregulation of the signaling networks executing this communication can cause inflammation and precancerous lesions that can become cancerous. Helicobacter. pylori infection, the highest risk factor for gastric cancer, disrupts signals originating from stromal cells that maintain normal growth and function of epithelial glands and prevent inflammation. The current proposal will define how misregulation of protein kinase A (PKA) signaling causes inflammation and precancerous lesions via disrupting stromal-epithelial communication.

PI_NAMEs: PURI, PAWAN  (contact)

PROGRAM_OFFICER_NAME: RICHARDS, CRYSTAL LYNETTE

PROJECT_TERMS: Alleles;American Society of Clinical Oncology;Antibiotic Therapy;Atrophic;Atrophic Gastritis;Automobile Driving;Cancer Etiology;Cancerous;Cause of Death;Cells;Cessation of life;Chronic;Communication;conditional mutant;constitutive expression;Cyclic AMP-Dependent Protein Kinases;Down-Regulation;effective therapy;Epithelial-Stromal Communication;Epithelium;Equipment;gastric carcinogenesis;gastric intestinal metaplasia;gastric pre-neoplasia;Gastritis;Genetic;Gland;Growth;Helicobacter;Helicobacter felis;Helicobacter Infections;Helicobacter pylori;high risk;Homeostasis;Incidence;Infection;Inflammation;Inflammatory;inhibitor;Intestinal Intraepithelial Neoplasia;Lesion;malignant stomach neoplasm;Mediating;Mesenchymal;Mesenchyme;Metaplasia;Modeling;Molecular;Mucous Membrane;Mus;Mutant Strains Mice;Neoplasms;neoplastic;novel;Outcome;Pathologic;Pathology;Pathway interactions;Patients;premalignant;Preneoplastic Conditions;prevent;Prevention strategy;Research;Risk;Risk Factors;Role;Series;Severities;Signal Transduction;spasmolytic polypeptide;Stomach;Stromal Cells;Testing;Transgenic Mice;treatment strategy

PROJECT_TITLE: Adminstrative equipment supplement for 5R16GM149389-02:Role of Protein Kinase A (PKA)-mediated mesenchymal-epithelial crosstalk in gastric preneoplasia


ORG_CITY: PITTSBURGH

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: The Administrative supplement is requested to enable capabilities for high-speed three-dimensional imaging of living cells by the Lattice LightSheet system to study the endocytosis of epidermal growth factor receptor (EGFR) and the role of endocytosis in EGFR signaling. EGFR plays important roles in mammalian development, wound healing, tissue regeneration and tissue homeostasis in adults. EGFR is also involved in various cell abnormalities, most notably, tumorigenesis and metastatic processes. The mechanisms regulating EGFR endocytosis and its role in signaling are incompletely understood. The proposed research will address the fundamental question of how multiple intertwining signaling pathways activated by EGFR are regulated by the subcellular localization dynamics of the constituents of those pathways.

PI_NAMEs: SORKIN, ALEXANDER D (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Abnormal Cell;Actins;Address;Administrative Supplement;Adult;Biological Assay;Cells;Cellular Assay;Chimeric Proteins;Clathrin;Complex;Development;Endocytosis;Endosomes;Enzymes;Epidermal Growth Factor Receptor;Eukaryota;experimental study;Family;Fluorescence;Funding;Gene Fusion;Generations;Genes;Homeostasis;Human Pathology;in vivo;Label;Ligands;Light;Mass Spectrum Analysis;Measures;Mediating;metastatic process;Methods;Modeling;Molecular;Monitor;National Institute of General Medical Sciences;novel;novel strategies;p38 Mitogen Activated Protein Kinase;Pathway interactions;phosphoproteomics;Play;Positioning Attribute;Process;Proteins;Proteome;ratiometric;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Regulation;Research;Role;screening;Signal Pathway;Signal Transduction;Sorting;spatiotemporal;Speed;Stress;System;temporal measurement;Three-Dimensional Imaging;tissue regeneration;Tissues;trafficking;tumorigenesis;VAV2 gene;Vesicle;wound healing

PROJECT_TITLE: R35 - ADMIN SUPPLEMENT - EGF Receptor Endocytosis: Mechanisms and Role in Signaling

STUDY_SECTION: MRAC

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


ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Narrative Just like the skeleton in our body, cells have a cytoskeleton, which provides a framework for their shape and thus their function. The key cytoskeletal element, microtubules, are generated at precise locations and times in order to build cellular structures. In this proposal, I will determine how MT nucleation is used to drive the formation of two microtubule-based structures, the mitotic spindle and neuronal dendrites, which will provide the underlying principles of microtubule self-organizing and how it gives rise to specialized cell architecture and function.

PI_NAMEs: KRAUS, JODI  (contact)

PROJECT_TERMS: Affect;Architecture;Automobile Driving;Binding;Biochemical;Biochemical Pathway;Biological Models;Cell Physiology;Cell Shape;Cells;Cellular Structures;Centrosome;Chromosomes;Complex;confocal imaging;Coupled;Cytoskeleton;Dendrites;Development;Diameter;Drosophila genus;Drosophila inturned protein;Elements;Embryonic Development;Endosomes;Exhibits;Gamma-Tubulin Ring;Genetic Screening;Goals;Golgi Apparatus;Image;Imaging Techniques;In Vitro;insight;Invaded;Investigation;knock-down;Label;Length;Location;Mass Spectrum Analysis;Microscopy;Microtubule-Associated Proteins;Microtubule-Organizing Center;Microtubules;Minus End of the Microtubule;Mitosis;Mitotic spindle;Molecular;Molecular Motors;Morphogenesis;Morphology;Motor;nanoscale;Neurons;Pathway interactions;Pattern;Phase;Play;Process;programs;Property;protein purification;Proteins;reconstitution;recruit;Research;Resolution;RNA Interference;RNA interference screen;Role;Running;self organization;Shapes;Side;Site;Skeleton;skills;spatiotemporal;Structure;superresolution imaging;Techniques;Testing;Time;Tubulin;ultra high resolution;Visualization;Work

PROJECT_TITLE: Building Dendrite Architecture via Microtubule Nucleation

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 TWD-A (MK)]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision

ORG_CITY: AKRON

ORG_NAME: UNIVERSITY OF AKRON

PHR: Project Narrative Fluorescent molecular imaging reagents for blood vessel detection have important applications for medical diagnosis. For example, fluorescein is widely used in ophthalmology to check any blood vessel abnormalities during eye exams. The proposed project acquires a modern fluorescence spectrometer, which will be used to aid the development of new imaging reagents for selective detection of blood vessels. Success in the study could lead to novel imaging reagents, which will enable simplified applications and facilitate a wide range of developmental studies by using zebrafish model organism.

PI_NAMEs: PANG, YI  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: biomedical imaging;Blood Vessels;Cellular Structures;Detection;Development;Diagnosis;flavonoid probes;Fluorescein;Fluorescence;Goals;Image;instrument;Medical;model organism;Modernization;molecular imaging;Molecular Probes;novel;ophthalmic examination;Ophthalmology;Play;Process;Property;Reagent;Research Project Grants;Role;Speed;success;United States National Institutes of Health;Zebrafish

PROJECT_TITLE: Developing Activatable Fluorescent Flavonoids for Vascular Imaging


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease

ORG_CITY: GAINESVILLE

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Although the blue-light hazards in dentistry are well known to date, there are no alternatives to this problem because of the lack of photoinitiators that absorb longer wavelengths and few studies evaluating the safety of longer wavelengths in the oral cavity. We aim to fill this gap by investigating a novel red-light activated photoinitiator and the human pulp and gingival tissues responses to red light following its application to restorative dental treatments compared to blue light. The results of this work will lay the groundwork to achieve our long-term goal of using red light as a safer and more effective treatment strategy to improve oral health.

PI_NAMEs: OLIVEIRA, DAYANE  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: absorption;Alkaline Phosphatase;Amalgam;anthropogenesis;Anti-Inflammatory Agents;Area;Award;Biocompatible Materials;Biological;career development;Cell Death;Cell Physiology;Cell Proliferation;Cells;Cellular Stress;chemokine;Classification;Clinical;clinical application;clinical care;clinical practice;Collagen;Collagen Type I;Composite Resins;Custom;cytokine;Data;Dental;Dental Care;Dental caries;Dental Materials;Dental Pulp;Dentistry;design;Devices;Double-Blind Method;effective therapy;Ensure;Environment;experience;Exposure to;Extracellular Matrix;Fibroblasts;Fingerprint;Future;Generations;Gingiva;Goals;Growth;hazard;Health;Human;Immune;Immunologics;improved;In Vitro;in vivo;Inflammation;Inflammatory Response;Laboratory Finding;Legal patent;Light;light effects;Maintenance;Measures;Medical Device;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Mercury Compounds;mercury release;Mitochondrial DNA;Modeling;multidisciplinary;Necrosis;Nitric Oxide Synthase;novel;Odontoblasts;Oral cavity;Oral health;Outcome;patient oriented;Patients;Persons;Phase;phase 2 study;Procedures;Process;programs;Publishing;Randomized;Reactive Oxygen Species;Research;research and development;Research Support;Research Training;response;restorative dentistry;restorative material;restorative treatment;Risk;Safety;Scientist;Side;Signal Transduction;soft tissue;Temperature;Tissues;Training;Translating;Translational Research;treatment comparison;treatment strategy;United States Food and Drug Administration;Work;wound healing

PROJECT_TITLE: Temperature changes and inflammatory response in pulpal and gingival tissues surrounding dental restorative treatments performed using blue and red wavelengths: an in vivo and ex vivo study

STUDY_SECTION: DSR

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


ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE This project develops new methods for DEER spectroscopy. DEER is a technique that measures the internal motions of proteins, which are crucial for many molecular-level processes in the human body. The resulting data are essential for understanding the molecular basis of life and disease and for providing the knowledge base necessary to develop new drugs

PI_NAMEs: STOLL, STEFAN  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Address;Amino Acids;Bayesian Analysis;Biomedical Research;Computing Methodologies;Cryoelectron Microscopy;Data;Data Analyses;deep learning;Disease;drug development;Electrons;Environment;Equipment;experimental analysis;Fluorescence Resonance Energy Transfer;Freezing;Goals;Human;Human body;innovation;insight;knowledge base;Label;Life;Measurement;Measures;Membrane Proteins;Methodology;Methods;millisecond;Modeling;Molecular;Molecular Conformation;Motion;nanoscale;novel therapeutics;Process;protein complex;Protein Conformation;Proteins;Reproducibility;Research Personnel;Spectrum Analysis;Structure;Techniques;Time;tool;X-Ray Crystallography

PROJECT_TITLE: Equipment Supplement: DEER spectroscopy tools for probing protein conformational dynamics


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Narrative Concerns of permanent undesirable off-target DNA edits has hampered acceptance of genomic editing tools to treat genetic disorders. The long-term goal of this proposal aims to treat these disorders by selectively editing the RNA transcripts to produce functional protein. Guide oligonucleotides will be screened and optimized to target mRNA mutations that can be repaired by the cell’s RNA editing enzymes.

PI_NAMEs: FISHER, ANDREW J (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: ADAR1;Adenosine;Amino Acids;analog;base;Binding;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Codon Nucleotides;Complex;Cryoelectron Microscopy;Data;Deaminase;Deamination;design;Disease;DNA;Double-Stranded RNA;DRADA2b protein;dsRNA adenosine deaminase;Enzymes;experience;experimental study;Future;Genetic Diseases;genome editing;Goals;Guanosine;Guide RNA;high throughput screening;improved;innovation;Inosine;insight;Knowledge;Lead;lead optimization;Length;Location;Messenger RNA;Metabolic;Methods;Microfluidics;Minor;Molds;Mutation;Nonsense Mutation;novel;nucleobase;nucleotide analog;Nucleotides;Oligonucleotides;Point Mutation;Positioning Attribute;pressure;Principal Investigator;Proteins;rational design;Reaction;repaired;Reporting;Resolution;RNA;RNA Editing;Sequence Analysis;Site;Structure;Techniques;Terminator Codon;tool;Transcript;Translations;X-Ray Crystallography

PROJECT_TITLE: Supplement:High-throughput screening and structure-guided optimization of oligonucleotides for site-directed RNA editing by ADARs

STUDY_SECTION: SBCB

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


ADMINISTERING_IC: DP

IC_NAME: NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION

ORG_CITY: LA JOLLA

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE We propose to follow and expand our previously created cohorts of veterans and non-veterans with IC to understand treatment patterns, clinical characteristics, and lifestyle factors. We will also validate previously identified urinary biomarkers for IC. Finally, we will work with the IC Network (ICN) to continue educating the larger IC community as well as providing a forum for disseminating our research.

PI_NAMEs: ANGER, JENNIFER TASH (contact);FREEDLAND, STEPHEN JAY

PROGRAM_OFFICER_NAME: BROWN, NATALIE

PROJECT_TITLE: RFA-DP-24-031: Longitudinal Follow-up of a Nationwide Multiethnic Cohort of Veterans and Non-Veterans with Interstitial Cystitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZDP1 OHI (01)]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: BOZEMAN

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: MONTANA STATE UNIVERSITY - BOZEMAN

ORG_STATE: MT

PHR: Project Narrative Each of our cells inactivates many of its available genes to perform a unique function. Failure to properly inactivate genes underlies developmental disorders and devastating pediatric brain and blood cancers. This project investigates how cells inactivate the correct genes at the correct time during development to understand how defective gene inactivation can cause disease.

PI_NAMEs: DELUCA, STEVEN  (contact)

PROJECT_TERMS: Binding;Biological Models;Cell Culture Techniques;Cell Differentiation process;Cells;Chemicals;Childhood Malignant Brain Tumor;ChIP-seq;Chromatin;Communities;Cultured Cells;Development;developmental disease;Disease;Drosophila genus;embryonic cell culture;Embryonic Development;Engineering;Epigenetic Process;Failure;gene correction;Gene Expression;Gene Silencing;Genes;Genetic;Genetic Transcription;Genome;Genome engineering;Genomics;Hematopoietic Neoplasms;Human;Maintenance;Malignant Neoplasms;Molecular;mutant;Nurses;Organism;Polycomb;prevent;programs;Proteins;Research;Time;tool;transcription factor

PROJECT_TITLE: Developmental control of gene silencing


ORG_CITY: LOGAN

ORG_NAME: UTAH STATE UNIVERSITY

ORG_STATE: UT

PHR: Project Narrative PRMT1 is a human protein that plays a critical role in the ability of cells to communicate and organize chemical reactions in the cell. In this project we will investigate how grouping PRMT1 molecules together and how stress damage of PRMT1 affects the ability of the protein to function. Additionally, we will test a new way of controlling the activity of PRMT1 using designed small molecules.

PI_NAMEs: HEVEL, JOAN M (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Active Sites;Adenosine;Administrative Supplement;Affect;anti-cancer therapeutic;Area;Arginine;Binding;Biochemical;Biochemistry;Biological;Biomedical Research;biophysical techniques;carcinogenesis;Cardiovascular Diseases;Cardiovascular Pathology;career;Catalysis;Cell Culture Techniques;Cell Cycle Regulation;Cell Extracts;Cell Physiology;Cells;chemical reaction;Chemistry;Chronic Disease;Communication;Cysteine;design;Development;dimer;dimethylarginine;Disease;Disease Progression;DNA Repair;drug development;Enzymes;epigenetic regulation;equipment acquisition;Estrogen Receptors;Eukaryotic Cell;Event;experimental analysis;Experimental Designs;Family;Fluorescence;Future;Goals;graduate student;Grouping;Health;Histone H4;Histones;Homeostasis;Human;In Vitro;in vivo;Inflammatory;inhibitor;interest;Intervention;Kidney;Kidney Diseases;Kinetics;Lung;Lung Diseases;Mammalian Cell;Mediating;Mediator;Medicine;Methylation;Modification;molecular recognition;monomer;N,N-dimethylarginine;Nerve Degeneration;Neurodegenerative Disorders;non-histone protein;novel;oxidation;Oxidative Stress;Pharmaceutical Preparations;Pharmacologic Substance;Play;Post-Translational Protein Processing;Progesterone Receptors;programs;Protein Dynamics;protein function;Protein Inhibition;Protein Isoforms;Protein Methylation;Protein-Arginine N-Methyltransferase;Proteins;Regulation;Research;Research Personnel;Role;Signal Transduction;Site;small molecule;Specificity;Spectrum Analysis;Stress;supportive environment;Testing;therapeutic target;tool;Training;Transcriptional Regulation;Translations;Treatment Protocols;undergraduate research;undergraduate student;United States National Institutes of Health;Universities;Utah;Variant;Viral Pathogenesis;Work;Writing

PROJECT_TITLE: Administrative Supplement for Equipment Purchase


NIH_SPENDING_CATS: Contraception/Reproduction

ORG_CITY: HADLEY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

ORG_STATE: MA

PHR: Request Justification  The parent award (R01GM147548-01A1) has a heavy reliance on microscopy. Our overall research goal has not changed and our access to high-end microscopy (point-scanning, high-resolution, multi-photon) in our campus’ Light Microscopy Core Facility (LMCF) has not changed. The Supplemental request is for a replacement of our 27-year-old microscope (a NIKON E800, purchased in 1996 on NIH GH52953). The E800 has been a workhorse and contributed heavily to my entire portfolio of publications with a cell biological orientation (the most relevant to the project is listed in my Biosketch), including a new paper in Cell, listed as the last entry in my Biosketch. There have been many generations of microscopes marketed by NIKON since the E800. While we coped the best we could with out-dated technology, the functionality of our microscope has been on a slow decline over the past decade due to increasing difficulty in acquiring replacement parts. In the last service call (January 2023), I was warned the E800’s capability would continue to decline to below the limits of operational needs (such as moving shutters in and out, filter turrents etc.; yes these are all in manual mode).  The requested microscope will provide hours of access for training and pilot experiments prior to using the LMCF facility, which charges by the hours on all microscopes. Our original budget has depended on the E800 (located just steps from my office and lab). Declining ability to do so translates to a full reliance on the LMCF (hourly users-fees are set between $22.05–$26.25 for point-scanning confocals, and $33.60 for multi- photon). The added costs will be unsustainable. It will also incur extraordinary hardship for the many hours of on-hand training (typically provided by the PI and a senior trained personnel, to postdoc) needed to initiate each new trainee. Research strategy  The goal is to achieve the originally planned research using the requested microscope (a NIKON Ti2-E microscope with CREST V2 spinning disc components). The new microscope will be many generations advanced from the NIKON E800 and the added spinning confocal capability will provide an enhanced imaging capability before advancing to the microscopes in the LMCF. Proposed activities: A. Pollen and pollen-derived molecular trigger-induced stigmatic cell responses to initiate pollen hydration and germination. Figs. 1, 2 are examples of how we shall meet our imaging needs.  • Typically (Fig. 1A), we monitor hydration for 10-30 minutes (Wildtype completes in 10, mutants take longer). We use epifluorescence to monitor the rise or fall in nitric oxide (NO) or ROS (not shown), which do not require the resolution of confocal imaging, but extended time on the microscope. The next is pollen tube emergence and penetration of the stigmatic papilla cell (Fig. 1B). This relies on confocal imaging. Fig. 1B shows one hr after pollination, when a pollen tube is seen attached to a papilla cell. The goal is to monitor pollen hydration and tube germination with papilla cell responses [revealed by, e.g., Ca2+, water channel (see Fig. 2) cell wall quality reporters] over the time course. The requested microscope will provide on-hand training for students and collect preliminary observations for the optimal time frame for each response to guide the more refined imaging needs at the LMCF. Fig. 1A. (upper) Wide-field imaging  of stigmatic NO response upon  pollination. (Lower) Bright-field, time  course of wildtype pollen hydration  from time of deposition to full  hydration (published). Fig. 1B. Point-  confocal scanning image of a  germinating pollen tube (acquired in  LMCF). New student acquired images.  • Fig. 2 (next page) shows how we shall examine stigmatic cell responses to pollen-derived molecular trigger (pollen coat protein-Bγ, PCP-Bγ) partially on the requested microscope (Fig. 2A) and partially at the LMCF (Fig. 1B). Typically, and using Ca2+ dynamics as an example, we screen the efficacy of recombinant molecules by bright-field (top) and epifluorescence (bottom) (Fig. 2A, the green fluorescence shows extracellular Ca2+, reflecting efflux from the papilla).  The determined optimum reagent, dosage and time frame (requiring  considerable microscope time) will inform on experimental conditions used for confocal microscopy to acquire refined data (Fig. 2B,  acquired by point-scanning confocal at the LMCF).  • Fig. 2C shows how the trigger PCP-Bγ had impacted the activation (reflected by higher plasma-membrane intensity of the probe aquaporin- Cherry). The images were acquired on a Crest V2 demo session. The proof of principle experiment provides solid support and justification to move forward to higher spatial resolution point-scanning confocal or high-resolution STORM microscope at the LMCF. The savings based on using the requested microscope will allow higher qualitative and quantitative achievements.  Fig. 2A (legend). Pollen trigger PCP-Bg induced Ca2+ efflux from papilla cells. Co-imaging (upper, bright-field; lower, epifluorescence). Pilot experiments to  establish MBP-PCP-Bg has higher efficacy. Fig. 2B. Point-scanning confocal  image of MBP-PCP-Bg-triggered papilla cell Ca2+ efflux, permitting considerably higher resolution details. Fig. 2C. PCP-Bγ-induced enhance membrane  association of aquaporin, facilitating water transfer to hydrate deposited pollen  grains. Acquired by a demo on CREST V2. B. Another goal of the parent grant is to reveal how the target female cells respond when pollen tubes approach, arrive, penetrate and burst to release sperm for fertilization. We can refine the temporal and spatial windows (e.g., see Fig. 3A,B, under semi-in vivo condition where access to imaging is easier), which takes a lot of time, on the requested microscope. The we migrate to the LMCF to monitor detailed dynamics of ovule responses. Fully in vivo experiments are even more challenging. Fig. 3C shows a typical time course for in-vivo pollination. Typically, we establish the pollen tube front (arrow) migration rate using the requested microscope. The information will inform on how to set up higher-resolution experiments that monitor the female cell dynamics during pollen tube entry and burst with the microscopes in the LMCF.  Fig. 3. (A) Pollen tube growth and  targeting under semi-in vivo conditions.  (B) Monitoring the process over three to  four hours from the start of observation  till completion of pollen tube burst and  sperm release in our basic set up for  these experiments. these were acquired  by the E800 a couple of years ago. (C)  typical preliminary experiments to define  the pollen tube front achievable in the  E800 and will be done on the requested microscopes. C. Training and maintenance plan. Four frequent users (currently one senior research associate, 3 graduate students) and 3-4 new trainees (1 new graduate student, 3 undergrads) will be initiated on the microscope. The PI and senior research associate (Dr. Mingche Liu) will be responsible for training; Dr. Liu will be charged with upkeep duties and training of students on general equipment care after each use. The proximity of the requested microscope to the lab and PI’s office allows close supervision at the beginning and drop-in help and consultations as needed. We will also have access to consultation with the LMCF staff as needed and for transition to use the facility there. After the initial warranty (five years on the microscope, 1 year on electrical and third-party parts), service contracts will be financed partially by a budget allocation from the parent grant and partially from departmental contribution based on the lab’s research activities. We anticipate a low level of sharing (< 10%) from departmental colleagues’ labs; their use will be prorated towards a contribution for service expenses.

PI_NAMEs: CHEUNG, ALICE Y. (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Achievement;Address;Agriculture;Alkalinization;Angiosperms;Binding;Biochemical Process;Biological;Budgets;Capsid Proteins;Caring;Cell Communication;Cell membrane;Cell Wall;Cells;Charge;confocal imaging;Confocal Microscopy;Consultations;Contract Services;coping;Core Facility;cost;Cytoplasm;Data;Deposition;DISC components;Disease;Dissection;dosage;Drops;egg;Ensure;Equipment;Event;experimental study;extracellular;falls;Fees;Female;Fertilization;Fluorescence;food security;Generations;Germination;Goals;graduate student;Grain;Growth;Hand;Health;Homologous Gene;Hour;Human Resources;Hydration status;Image;Image Enhancement;imaging capabilities;in vivo;Ligands;light microscopy;Location;Maintenance;male;Manuals;Marketing;Mediating;Membrane;Microscope;Microscopy;migration;Molecular;Monitor;multi-photon;mutant;Nitric Oxide;Nutritional;Paper;parent grant;parent project;Partner in relationship;Penetration;Peptide Receptor;Phase;Phosphotransferases;Pistil;Plants;Pollen;Pollen Tube;Positioning Attribute;Postdoctoral Fellow;prevent;Process;Production;Proliferating;Proteins;Publications;Publishing;rational design;Reagent;receptor;Recombinants;Reporter;Reproduction;reproductive success;Research;Research Activity;Resolution;response;Savings;Scanning;Services;Signal Transduction;social stigma;Solid;sperm cell;student training;Students;success;Supervision;Surface;Technology;Time;Tissues;tongue papilla;Training;Transcription Factor AP-1;Translating;transmission process;Tube;undergraduate student;United States National Institutes of Health;ward;Water;water channel

PROJECT_TITLE: Deciphering Male- and Female-coordinated Gating Mechanisms that Ensure Plant Reproductive Success

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: We are responding to the NINDS Diversity Training Team’s email of January 12, 2024 to request supplemental funding of $521 for Dr. Ramesh Raghupathi’s travel costs to attend the NINDS R25/T32 Workshop, "Sustaining a Neural Network: Fostering an Inclusive Research Culture.”

PI_NAMEs: BAAS, PETER W. (contact)

PROGRAM_OFFICER_NAME: KORN, STEPHEN J

PROJECT_TERMS: innovation;Spinal cord injury;Training Programs

PROJECT_TITLE: Training Program on Innovative Approaches to Spinal Cord Injury


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative: Increasing the research infrastructure of the Resendiz lab, with the purchase of an isothermal titration calorimeter (ITC), will expedite the characterization/identification of RNA-based aptamers with potential biomedical applications. Importantly, this will improve the quality of the training that is being carried out within the PI's group, and potentially attract students to embark in the research enterprise. The data that will be obtained with this instrument will be important to accomplish the goals of the proposal that is associated with this supplement request.

PI_NAMEs: RESENDIZ, MARINO JE (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TITLE: 8-Oxo-7,8-dihydroguanosine in aptamer development and its impact on RNA structure Supplement


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Schizophrenia

ORG_NAME: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

ORG_STATE: NY

PHR: PROJECT NARRATIVE Reversal learning, a form of cognitive flexibility, is impaired in schizophrenia, substance use disorders, and other psychiatric and neurologic conditions, but we lack adequate treatments for these debilitating impairments. This proposal will investigate the role of the thalamus in regulating acetylcholine release in the striatum during reversal learning. This research will provide insight into brain circuit specific control of neuromodulation and learning that will influence future development of treatments for impaired cognitive flexibility.

PI_NAMEs: LOWES, DANIEL CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Academic Medical Centers;Acceleration;Acetylcholine;Address;Affect;Association Learning;Behavior;Behavioral;Biosensor;Brain;career;cholinergic;Cognitive;Communication;Computer Models;Consumption;Corpus striatum structure;Data;density;Development;Disease;Dorsal;Electrophysiology (science);Exhibits;experimental study;Fiber;flexibility;Future;Genetic;Goals;Grant;Halorhodopsins;Impaired cognition;Impairment;improved;in vivo;innovation;insight;Institution;Interneurons;Jaw;K-Series Research Career Programs;Knock-out;Knowledge;Leadership;Learning;Measures;Medical center;Mental disorders;Mentored Research Scientist Development Award;Modeling;Modernization;Mus;Nervous System Disorder;neural;neural circuit;Neurologic;Neurons;neuroregulation;Neurosciences;New York;Obsessive-Compulsive Disorder;optogenetics;Outcome;Photometry;Population;Psychiatry;Psychological reinforcement;rate of change;redshift;Regulation;Research;Research Personnel;Reversal Learning;Rewards;Risk Factors;Role;Schizophrenia;schizophrenia risk;Science;Scientist;Silicon;skills;Substance Use Disorder;success;Teaching Hospitals;Testing;Thalamic structure;therapeutic target;therapy design;therapy development;Training;Universities;Update;Viral;Virus;Work;Writing

PROJECT_TITLE: Thalamostriatal regulation of acetylcholine during reversal learning

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


PHR: PROJECT NARRATIVE Molecular communication across cell types is central to life—communication between cell types in a human organ is critical to normal function, and microbe-host or microbe-microbe communication drives microbial ecosystems. This proposal will study signaling between human immune cells and fibroblasts and signaling between microbes relevant for human health (e.g., commensal and pathogenic bacteria and fungi). We will develop a suite of microfluidic tools to broaden the scope of mechanistic questions that can be addressed, ultimately enabling the development of therapies to target dysfunctional signaling and inflammation in human disease.

PI_NAMEs: THEBERGE, ASHLEIGH BROOKS (contact)

PROJECT_TERMS: Address;Affect;Area;B-Lymphocytes;Bacteria;Biological Assay;Biological Process;Biomedical Engineering;Biomimetics;Blood capillaries;cell type;Cells;Chemical Stimulation;Chemicals;commensal bacteria;commensal microbes;Communication;Complex;cost effective;Development;Disease;Ecosystem;Engineering;eosinophil;Equipment;experimental study;Fiber;Fibroblasts;fungus;Future;Health;Home;Human;human disease;Immune;Immune response;Inflammation;Inflammatory;innovation;Investigation;Life;Mass Fragmentography;Mediating;Methods;Microbe;microbial;microbial community;Microfluidics;Molecular;monocyte;neutrophil;novel;novel strategies;Organ;paracrine;Paracrine Communication;pathogen;pathogenic bacteria;Phase;Positioning Attribute;Production;Role;sample collection;Sampling;Signal Transduction;Signaling Molecule;Signaling Protein;small molecule;Solid;System;therapy development;Time;tool;Translating;user-friendly;Vocabulary;volatile organic compound;Volatilization;Work

PROJECT_TITLE: Deciphering the role of chemical signals in inflammation with open microfluidic functional assays - Equipment Supplement


NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Eye Disease and Disorders of Vision;Fibromyalgia;Neurosciences;Pain Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Chronic musculoskeletal pain is a significant public health problem that is often refractory to available pain management strategies, and new, non-opioid treatments are urgently needed. Increasing evidence shows that colored light delivered to the retina can relieve pain. This proposal will elucidate the neural mechanisms of pain relief driven by light by recording from neurons in the retina, tracing retinal inputs throughout the brain in rodent pain models, and identifying central targets in humans using functional neuroimaging.

PI_NAMEs: KUCHENBECKER, JAMES A;MAUCK, MATTHEW CHRISTOPHER (contact);NEITZ, JAY ;TAYLOR, NORMAN

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Absence of pain sensation;Affect;alertness;Analgesics;antinociception;Area;Behavioral;Biological Models;Brain;Brain region;Calcium;Cell Nucleus;Cells;Central Nervous System;Chemicals;Chronic;Chronic low back pain;chronic musculoskeletal pain;chronic widespread pain;circadian;Circadian Rhythms;Clinical Treatment;Clinical Trials;Color;Color Visions;Cone;design;detector;disability;Electrical Engineering;Electrophysiology (science);experimental study;extracellular;Failure;Fibromyalgia;Frequencies;Functional Imaging;Future;gain of function;ganglion cell;Genetic;Geniculate body structure;Health;Human;Image;Immunohistochemistry;improved;innovation;insight;Knowledge;Light;light effects;Link;loss of function;Maps;Mediating;Mediator;Modeling;Moods;multidisciplinary;neural;neural circuit;Neural Pathways;neuroimaging;neuromechanism;Neurons;Neurosciences;Nociception;non-opioid analgesic;Nonpharmacologic Therapy;Opioid;Pain;Pain management;pain model;pain processing;pain relief;Pain Research;Pathway interactions;Patients;pharmacologic;Phototherapy;Population;pre-clinical;Primates;Property;Public Health;Rattus;Recording of previous events;Refractory;Research;Research Personnel;response;Retina;Retinal Cone;Retinal Ganglion Cells;Risk;Rodent;Rodent Model;Role;Series;Signal Transduction;Stimulus;Structure;success;Talents;Testing;Time;Translating;Translations;Viral;Vision;Visual Pathways;Visual System;voltage clamp

PROJECT_TITLE: Neural Mechanisms of Colored Light Driven Analgeisa

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-R (21)]


NIH_SPENDING_CATS: Complementary and Integrative Health

ORG_CITY: SAN JOSE

ORG_NAME: SAN JOSE STATE UNIVERSITY

PHR: NOT-GM-24-021 Narrative Ningkun Wang Narrative This proposal requests funding for an OpenSPR to support the project that project proposes to understand the nuanced nature of SIRT1 regulation by small molecules and by its own regulatory domains. The findings enabled by the requested equipment will provide crucial information to clarify regulation of SIRT1 within the cell. The knowledge gained here can also shed light on the mechanism for regulation of other multidomain post-translational modification enzymes, many of which are integral to human health.

PI_NAMEs: WANG, NINGKUN  (contact)

PROGRAM_OFFICER_NAME: NANDA, JAGPREET SINGH

PROJECT_TERMS: Affect;Affinity;Allosteric Regulation;Alzheimer's Disease;Binding;Binding Sites;Biochemical;Biochemistry;Biological;Biological Assay;C-terminal;Catalytic Domain;Cell Culture Techniques;Cells;Complex;design;Disease;Dissociation;Distal;enzyme activity;Enzymes;Equilibrium;Equipment;Event;Funding;Goals;Health;Human;In Vitro;inhibitor;instrument;insulin secretion;Knowledge;Light;lipid metabolism;Measures;Methods;Molecular;Molecular Conformation;molecular dynamics;N-terminal;Nature;Nerve Degeneration;Non-Insulin-Dependent Diabetes Mellitus;Pathway interactions;Phosphorylation;Phosphorylation Site;Piceatannol;Play;Post-Translational Protein Processing;Property;Proteins;Regulation;Request for Proposals;Research;Rest;Resveratrol;Role;Sir2-like Deacetylases;SIRT1 gene;Sirtuins;small molecule;Structure;Therapeutic;therapeutic target;tumor;Work

PROJECT_TITLE: Elucidating the Mechanism for Allosteric Regulation of SIRT1 through the N-Terminal Region


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Drug Abuse (NIDA only);Harm Reduction for Substance Misuse;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Opioid Misuse and Addiction;Opioids;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Rural Health;Social Determinants of Health;Substance Misuse;Substance Misuse Prevention

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Rural legally involved youth have high substance use rates yet cannot access needed prevention resources. We will codesign a multilevel substance/overdose prevention intervention with diverse multisector partners and input from a broad advisory board. We will use a stepped wedge hybrid 2 design to evaluate implementation success/effectiveness in 15 rural county courts and 470 youth (360 complete cases).

PI_NAMEs: AHRENS, KYM R (contact);MC CARTY, CAROLYN A

PROGRAM_OFFICER_NAME: LEE-WINN, ANGELA EUNJI

PROJECT_TERMS: Academy;Address;Adolescent;Adoption;Alcohols;Assertiveness;Awareness;Behavioral;behavioral outcome;Benzodiazepines;Caregivers;Caring;Child;Communities;Complex;contingency management;Country;County;court;court personnel;Crime;Data;design;disorder prevention;Drug usage;Education;Educational Curriculum;Effectiveness;effectiveness outcome;effectiveness testing;effectiveness/implementation trial;Elements;Eligibility Determination;evidence base;experience;Family;Feedback;Frequencies;Goals;Grant;Harm Reduction;Health;high risk;Hybrids;implementation evaluation;implementation fidelity;implementation outcomes;implementation process;implementation strategy;Imprisonment;innovation;interest;Intervention;intervention refinement;juvenile justice system;Knowledge;Legal;Legal system;Letters;Life;Lived experience;Local Government;Medicine;Modeling;motivational enhancement therapy;Naloxone;naloxone dispensing;Opioid;opioid use disorder;Outcome;Overdose;overdose death;overdose prevention;overdose risk;Parents;Persons;Pharmaceutical Preparations;Phase;Population;Positioning Attribute;prevent;Prevention;Prevention education;prevention service;Prevention strategy;Prevention trial;preventive intervention;probation;Procedures;programs;Protocols documentation;Psychological reinforcement;recruit;Rehabilitation therapy;Reporting;Reproducibility;Resources;Rewards;Rural;rural area;rural counties;Rural Population;Schools;Services;skills;social;State Government;Stimulant;substance use;Substance Use Disorder;substance use prevention;success;Surveys;synthetic opioid;System;Telephone;Testing;Text;tool;Trauma;Videoconferencing;Visit;Washington;Youth

PROJECT_TITLE: Multilevel SUD and Overdose Prevention for Rural Youth Involved in County Legal Systems

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


NIH_SPENDING_CATS: Microbiome

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project description  Sterols are critical for the structure of eukaryotic cells and serve as important signaling molecules. Some bacteria also engage with these lipids, but the molecular mechanisms of these engagements are not known. Inspired by our recent discovery of bacterial proteins that transport sterols, we seek to uncover the molecular determinants of sterol recognition and transport in other bacteria, including pathogens and the gut microbiome.

PI_NAMEs: DASSAMA, LAURA  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Acceleration;Affinity;Archaea;Bacteria;Bacterial Proteins;Binding;Bioinformatics;Biological;Borrelia burgdorferi;Cardiometabolic Disease;cell envelope;Cell Physiology;Chlamydia;Cholesterol;Development;Dyslipidemias;Eukaryota;Eukaryotic Cell;Event;Family;fluidity;Genomic approach;Genus Mycobacterium;gut microbes;gut microbiome;gut microbiota;Homologous Gene;Homologous Protein;hydrophilicity;Hydrophobicity;insight;instrument;Knowledge;Ligand Binding;Ligands;Lipid Binding;lipid metabolism;lipid transport;Lipids;Lipoproteins;Mammalian Cell;member;Membrane;Metabolism;Methylococcus capsulatus;microorganism interaction;Molecular;new therapeutic target;novel;Order Spirochaetales;pathogen;Pathogenicity;Periplasmic Binding Proteins;phosphonate;protein transport;Proteins;Proteome;Regulation;Reporting;Research;Resistance;Rickettsia;Signal Transduction;Signaling Molecule;Site;Sterol Biosynthesis Pathway;Sterols;stress tolerance;structural genomics;Structure;Therapeutic Intervention;trafficking;Treponema pallidum;Validation;Work

PROJECT_TITLE: Deciphering the molecular mechanisms of sterol lipid trafficking in bacteria


PHR: Project Narrative Mitochondria are essential for cellular function and maintain their health through dynamic properties including fusion, division and transport on microtubules. Mitochondrial dysfunction is associated with neurodegeneration and mitochondrial fusion is protective against declining function. This proposal seeks to understand the molecular machinery that mediates mitochondrial fusion.

PI_NAMEs: HOPPINS, SUZANNE C (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Address;age-related disease;Aging;Allosteric Regulation;Apoptotic;Ataxia;Biochemical;Biochemistry;Biological Assay;Biology;Cell Physiology;Cells;Cellular biology;Collection;Compensation;Complement;Complex;Defect;Development;Dynamin;Event;Family;Genes;Guanosine Triphosphate Phosphohydrolases;Health;insight;Knowledge;Link;Mediating;Membrane;Membrane Fusion;Metabolic;Microtubules;Mitochondria;mitochondrial dysfunction;Molecular;Molecular Conformation;Mutation;Myopathy;Nerve Degeneration;novel strategies;Optic Atrophy;Organelles;Outer Mitochondrial Membrane;Peripheral Nervous System Diseases;Production;programs;Property;Proteins;reconstitution;Regulation;Research;self assembly;Shapes;Stimulus;Stress;tool;Variant;Work

PROJECT_TITLE: Determining the mechanism of mitochondrial outer membrane fusion

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


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

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: As the human population ages, the ability to maintain cognitive function with a brain accumulating tau pathology relies on the preservation and maintenance of synaptic networks. Therefore, understanding the mechanism by which tau contributes to network and synapse dysfunction is critical for developing preventative therapeutics. This proposal aims to determine the cellular mechanisms(s) by which pathologic tau drives neuronal network dysfunction and propose a training plan catered to the applicant that will promote success as an independent researcher in the field of aging research.

PI_NAMEs: WEBER, AUDREY  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Action Potentials;Affect;Affinity;Age;age related;age related neurodegeneration;Aging;aging brain;aging related;Alzheimer's Disease;Axon;Biochemical;Biochemistry;Biological;Biological Models;Brain;Brain region;Cell model;cell type;Cells;Cellular biology;cognitive function;cohort;Communities;Data;Dendrites;Dendritic Spines;density;Disease;disease model;Electrophysiology (science);entorhinal cortex;Event;Exhibits;Experimental Designs;Experimental Models;experimental study;Exposure to;Functional disorder;Glutamate Receptor;Goals;Human;human data;human disease;human model;Impaired cognition;interest;Link;Maintenance;MAPT gene;Mass Spectrum Analysis;Mediating;Memory;Methods;Microscopy;Microtubules;Modeling;Molecular;morphometry;mouse model;multi-electrode arrays;Nerve Degeneration;network dysfunction;Neurofibrillary Tangles;neuronal cell body;Neurons;new therapeutic target;normal aging;novel;Pathologic;Pathology;Pathway interactions;Patients;Phase;Phenotype;Population;Positioning Attribute;Postdoctoral Fellow;postsynaptic;pre-clinical;preservation;Process;Proteins;Proteome;Proteomics;religious order study;Research;Research Personnel;Sampling;Severities;Signal Pathway;skills;Specificity;Structure;success;Synapses;tau aggregation;tau mutation;tau Proteins;Tauopathies;Techniques;Temporal Lobe;Testing;Therapeutic;therapeutic target;Tissues;Training;Universities;Validation;Vertebral column;Work

PROJECT_TITLE: Tau-mediated synaptic dysfunction in age-related neurodegenerative diseases