Brandeis University

BIOINSPIRED SOFT MATERIALS

BIOINSPIRED SOFT MATERIALS

NEUROBIOLOGY: GENES, CHANNELS, AND BEHAVIOR

DNA DAMAGE RESPONSE AND REPAIR OF A BROKEN CHROMOSOME

MUTATIONS ARISING DURING DNA REPAIR

INSTITUTIONAL SUPPORT FROM CARES HEERF FUNDING

REPLICATION FORK REPAIR

CENTER TO IMPROVE SYSTEM PERFORMANCE OF SUBSTANCE USE DISORDER TREATMENT

CONSTRAINTS AND FRUSTRATION IN NANO-STRUCTURED AND BIO-MOLECULAR MATERIALS

NEUROMODULATION AND ROBUSTNESS OF NEURONS AND NETWORKS

REGULATION OF INTRINSIC PLASTICITY BY CAMKII

MOLECULAR AND CELLULAR MECHANISMS REGULATING ACTIN DYNAMICS

MECHANISMS AND FUNCTION OF FIRING RATE HOMEOSTASIS IN CORTICAL CIRCUITS

HEERF STUDENT AID

LONGITUDINAL STUDY OF POST-DEPLOYMENT CAM PAIN MANAGEMENT USING DOD AND VA DATA

SINGLE-MOLECULE VISUALIZATION OF TRANSCRIPTION REGULATION MECHANISMS

MECHANISMS OF SENSORY NEURON MORPHOLOGICAL DIVERSIFICATION, SIGNALING, AND FUNCTIONAL PLASTICITY

INTRINSIC PLASTICITY IN OSCILLATORY NEURAL NETWORKS

TEMPORAL CODING AND PALATABILITY IN GUSTATORY CORTEX

DOCTORAL TRAINING/HEALTH SERVICES RESEARCH ON ALCOHOL

GENETIC AND PHYSIOLOGICAL MECHANISMS OF TEMPERATURE DETECTION AND COMPENSATION

UPREGULATED NOREPINEPHRINE SYNTHESIS CAPACITY IN AGING - PROJECT SUMMARY THE LOCUS COERULEUS (LC) IS A SMALL NUCLEUS IN THE BRAINSTEM THAT IS VULNERABLE TO THE ACCUMULATION OF ABNORMAL TAU PROTEIN, A NEUROPATHOLOGICAL HALLMARK OF ALZHEIMER’S DISEASE (AD). THE LC IS STRUCTURALLY CONNECTED TO THE TEMPORAL LOBE AND MAY PLAY A ROLE IN TRANSMITTING ABNORMAL TAU THROUGH TRANS-NEURONAL SPREAD. THE LC IS THE PRIMARY PRODUCER OF THE NEUROMODULATOR NOREPINEPHRINE. NOREPINEPHRINE IS ESSENTIAL FOR NORMAL ATTENTION AND MEMORY FUNCTION. BEYOND A ROLE IN COGNITION, NOREPINEPHRINE SERVES A MYRIAD OF NEUROPROTECTIVE ROLES WHICH INCLUDE INHIBITION OF OXIDATIVE STRESS, MAINTENANCE OF THE BLOOD BRAIN BARRIER, AND ANTI-INFLAMMATORY PROCESSES. THE OCCURRENCE OF HYPERPHOSPHORYLATED TAU IN THE LC HAS BEEN LINKED WITH LOSS OF NOREPINEPHRINE-PRODUCING LC NEURONS. THE TARGETING AND NEURODEGENERATION OF LC IS PARTICULARLY INSIDIOUS DUE TO THE COMBINED LOSS OF COGNITION-ENHANCING NEUROMODULATION AND LOSS OF NEUROPROTECTIVE FUNCTIONS THUS PAVING THE WAY FOR DISEASE ACCELERATION AND PROPAGATION. DESPITE INSULTS TO THE LC, THERE IS EVIDENCE FOR UPREGULATION OF NOREPINEPHRINE METABOLISM IN HEALTHY AGING, MILD COGNITIVE IMPAIRMENT, AND AD. WE PROPOSE UPREGULATION OF NOREPINEPHRINE SYNTHESIS IN THE LC CELLS REMAINING REPRESENTS A MECHANISM OF NEUROCHEMICAL COMPENSATION THAT, IN SOME INDIVIDUALS, WARDS OFF COGNITIVE DECLINE AND PROTECTS AGAINST DISEASE SPREAD. IN HEALTHY OLDER ADULT HUMANS, WE WILL DEFINE RELATIONSHIPS BETWEEN LC STRUCTURAL INTEGRITY, AND NOREPINEPHRINE SYNTHESIS LEVELS (AIM 1). WE WILL DETERMINE THE EXTENT TO WHICH ELEVATED NOREPINEPHRINE SYNTHESIS CONFERS A BENEFIT TO MEMORY PERFORMANCE (AIM 2). FINALLY, WE WILL TEST THE HYPOTHESIS THAT ELEVATED NOREPINEPHRINE SYNTHESIS IS ASSOCIATED WITH REDUCED TAU ACCUMULATION LONGITUDINALLY (AIM 3). THIS MULTIMODAL STUDY WILL COMBINE STATE-OF-THE-ART MAGNETIC RESONANCE IMAGING (MRI) TO MEASURE LC STRUCTURAL INTEGRITY, [18F]FLUORO-M-TYROSINE POSITRON EMISSION TOMOGRAPHY (PET) TO MEASURE NOREPINEPHRINE/DOPAMINE SYNTHESIS CAPACITY, [18F]MK-6240 PET TO MEASURE TAU PATHOLOGY, AND PLASMA MEASURES OF AB42/40. IF SUCCESSFUL, THIS RESEARCH WILL PROVIDE NEW UNDERSTANDING OF THE NEUROCHEMICAL BASIS OF INDIVIDUAL DIFFERENCES IN DISEASE PROGRESSION AND WILL LAUNCH A NOVEL AVENUE OF INVESTIGATION INTO THE ROLE OF NOREPINEPHRINE IN DISEASE RESILIENCE (SUPPORTING MAINTENANCE OF COGNITIVE FUNCTION DESPITE PATHOLOGY) AND DISEASE RESISTANCE (COMBATTING DISEASE SPREAD).

MOLECULAR CODES FOR NEURONAL HOMEOSTASIS

RESEARCH IN ELEMENTARY PARTICLE PHYSICS.

ENZYME-INSTRUCTED SELF-ASSEMBLY FOR ANTICANCER NANOMEDICINE

MECHANISMS REGULATING ACTIN CYTOSKELETON DYNAMICS

NEUROSCIENCE: FROM CHANNELS TO BEHAVIOR

TIME AND THE FOREBRAIN CODING OF TASTE LEARNING.

ELUCIDATING THE FUNCTION OF CLASS 4 SEMAPHORINS IN GABAERGIC SYNAPSE FORMATION

IMPDH-TARGETED ANTIBIOTICS FOR SELECT AGENTS

RECOMBINATION MECHANISMS IN YEAST CELL DIFFERENTIATION

MOLECULAR GENETICS OF BEHAVIORAL AND NEURONAL FUNCTION

GENETIC AND BIOCHEMICAL MECHANISMS OF REGULATION

EXPERIMENTAL HIGH ENERGY PHYSICS COMPARATIVE REVIEW PROPOSAL AND PROGRESS REPORT - BRANDEIS UNIVERSITY

MACHINE LEARNING APPROACHES TO UNDERSTANDING AND CONTROLLING 3D ACTIVE MATTER

COMMUNITY LIVING POLICY CENTER

BOSTON ROYBAL CENTER FOR ACTIVE LIFESTYLE INTERVENTIONS

BRANDEIS HIGH ENERGY EXPERIMENTAL

CORE FACILITIES FOR NEUROBIOLOGY AT BRANDEIS

MECHANISMS AND REGULATION OF EXTRACELLULAR VESICLE TRAFFIC IN THE NERVOUS SYSTEM

REGULATION OF FORMINS AND CELL POLARITY IN YEAST

RATIONAL AND COMBINATORIAL DESIGN OF IMMUNOGENS TO ELICIT 2G12-LIKE ANTIBODIES

GATING OF FIRING RATE HOMEOSTASIS BY SLEEP AND WAKE STATES DURING EXPERIENCE-DEPENDENT PLASTICITY

COCHLEAR IMPLANTS AND LISTENING EFFORT: THE INTERACTION OF COGNITIVE AND SENSORY CONSTRAINTS

MOLECULAR AND CELLULAR DETERMINANTS OF DROSOPHILA LARVA THERMOTAXIS

CIRCUIT MECHANISMS UNDERLYING EXPERIENCE-DEPENDENT DEVELOPMENT

COMMUNITY LIVING EQUITY CENTER - THE COMMUNITY LIVING EQUITY CENTER (CLEC), HOUSED AT THE LURIE INSTITUTE FOR DISABILITY POLICY AT BRANDEIS UNIVERSITY IS FOCUSED ON REDUCING COMMUNITY LIVING DISPARITIES FOR PEOPLE OF COLOR AND OTHER INTERSECTING IDENTITIES. THE CLEC IS LED BY A COMMUNITY ADVISORY COMMITTEE CONSISTING OF DISABLED PEOPLE OF COLOR FROM DIVERSE BACKGROUNDS. KEY PARTNERS INCLUDE THE DISABILITY RIGHTS EDUCATION AND DEFENSE FUND, JUSTICE IN AGING, AUTISTIC SELF-ADVOCACY NETWORK, HUMAN SERVICE RESEARCH INSTITUTE, NATIONAL CENTER FOR CULTURAL COMPETENCY AT GEORGETOWN UNIVERSITY, AND NATIONAL AGING AND DISABILITY ORGANIZATIONS THAT WILL ASSIST WITH DISSEMINATION AND KNOWLEDGE TRANSLATION. THE CLEC CONSISTS OF FIVE MAJOR RESEARCH PROJECTS COORDINATED WITH KNOWLEDGE DISSEMINATION ACTIVITIES. THE MAIN OBJECTIVES ARE: 1) GENERATE DETAILED NEW KNOWLEDGE ABOUT COMMUNITY LIVING AND PARTICIPATION DISPARITIES; 2) DEVELOP NEW, OR LOCATE AVAILABLE SYSTEMS-CHANGE INITIATIVES OR OTHER PROMISING PRACTICES FOR REDUCING COMMUNITY LIVING AND PARTICIPATION DISPARITIES; AND 3) SERVE AS A NATIONAL RESOURCE FOR THE CONDUCT OF DISABILITY AND REHABILITATION RESEARCH IN THE COMMUNITY LIVING AND PARTICIPATION DOMAIN THAT IS INCLUSIVE OF PEOPLE WITH DISABILITIES FROM TRADITIONALLY UNDERSERVED COMMUNITIES. OUTCOMES INCLUDE: 1) IMPROVED POLICY AND PRACTICES THAT ADDRESS EQUITY AND 2) IMPROVED COMMUNITY LIVING OUTCOMES FOR DISABLED PEOPLE OF COLOR WITH LTSS NEEDS. PRODUCTS WILL INCLUDE A COMPREHENSIVE, ACCESSIBLE ONLINE HUB IN ENGLISH AND SPANISH, WITH A DATA DASHBOARD, TRAINING, TECHNICAL ASSISTANCE, AND WIDE RANGE OF TARGETED DISSEMINATION MATERIALS.

UBIQUITIN-INDEPENDENT TARGETED PROTEIN DEGRADATION

ASYMMETRIC REACTIONS WITH BIFUNCTIONAL ORGANOCATALYSIS

EVOLUTION OF ENZYME STRUCTURE AND FUNCTION VIEWED AT ATOMIC RESOLUTION

AHRQ MULTI-DISCIPLINARY DOCTORAL TRAINING PROGRAM

ROLE OF PHYSIOLOGICAL PATTERNS IN HIPPOCAMPAL-PREFRONTAL INTERACTIONS

STRUCTURE -FUNCTION STUDIES OF RHODOPSIN

COMBINING GENETICS, GENOMICS, AND ANATOMY TO CLASSIFY CELL TYPES ACROSS MAMMALS

UNCOVERING THE LINKS BETWEEN CIRCRNA ACCUMULATION, TRANSLATION AND AGING

ADDRESSING SEXUAL AND REPRODUCTIVE HEALTH CARE DISPARITIES AND BARRIERS AMONG ADOLESCENTS AND YOUNG ADULTS WITH DISABILITIES - PROJECT SUMMARY STUDIES TO DATE SUGGEST THAT THE SEXUAL AND REPRODUCTIVE HEALTH (SRH) CARE NEEDS OF ADOLESCENTS AND YOUNG ADULTS (AYA) WITH DISABILITIES ARE NOT WELL MET, DESPITE THE FACT THAT THIS POPULATION IS AS LIKELY TO BE SEXUALLY ACTIVE AS THEIR PEERS WITHOUT DISABILITIES. HOWEVER, RESEARCH ON SRH AND RECEIPT OF SRH-RELATED HEALTH CARE AMONG AYA WITH DISABILITIES REMAINS LIMITED. SCANT EVIDENCE INFORMS OUR UNDERSTANDING OF THE REPRODUCTIVE HEALTHCARE NEEDS OF BOTH YOUNG WOMEN AND MEN WITH DISABILITIES BY DISABILITY TYPE AND THERE IS NO RESEARCH ON REPRODUCTIVE HEALTHCARE SERVICE UTILIZATION ACROSS THE BREADTH OF THIS DIVERSE POPULATION. FURTHER, THERE ARE FEW RESOURCES TO HELP AYA WITH DISABILITIES NAVIGATE BARRIERS TO SRH CARE AND OBTAIN NEEDED SERVICES. THIS MIXED- METHODS STUDY WILL EXAMINE SRH AND HEALTHCARE UTILIZATION AND SRH-RELATED UNMET NEEDS AMONG TRANSITION AGE ADOLESCENTS AND YOUNG ADULTS WITH DISABILITIES OVERALL AND BY DISABILITY TYPE IN THE UNITED STATES. WE WILL TRIANGULATE INFORMATION FROM NATIONAL SURVEY DATA, INTERVIEWS WITH AYA WITH DISABILITIES, AND INTERVIEWS WITH PARENTS OF AYA WITH DISABILITIES. OUR ANALYSES WILL ADDRESS THREE FUNDAMENTAL QUESTIONS THAT WILL ESTABLISH A FOUNDATION FOR DEVELOPMENT AND PILOT TESTING OF A TAILORED INTERVENTION TO IMPROVE SRH CARE AND OUTCOMES FOR AYA WITH DISABILITIES, AGES 15-26: 1) WHAT DISPARITIES EXIST IN REPRODUCTIVE HEALTH CARE SERVICE UTILIZATION BY GENDER AND TYPE OF DISABILITY; 2) WHAT ARE THE BARRIERS TO SRH CARE FOR AYA WITH DISABILITIES AND HOW ARE THESE SIMILAR OR DIFFERENT BY GENDER AND DISABILITY TYPE?; AND 3) WHAT SRH INFORMATION AND RESOURCES WOULD ENHANCE KNOWLEDGE, PARTICIPATION IN CARE, AND COMMUNICATION WITH PROVIDERS FOR AYA WITH DISABILITIES? BUILDING ON THIS FOUNDATION, WE WILL COLLABORATE WITH AYA WITH DISABILITIES TO DEVELOP AN INTERVENTION TO ADDRESS THE IDENTIFIED BARRIERS AND UNMET NEEDS. OUR PROJECT DIRECTLY ADDRESSES UNMET NEEDS FOR SRH CARE IDENTIFIED BY THE NATIONAL INSTITUTES OF HEALTH, INCLUDING (1) INVESTIGATING BARRIERS TO REPRODUCTIVE HEALTH CARE FOR AYA WITH DISABILITIES, AND (2) DEVELOPING REPRODUCTIVE HEALTH EDUCATION MATERIALS FOR USE BY AYA WITH DISABILITIES. THIS PROJECT BUILDS ON THE RESEARCH TEAM’S PRIOR RESEARCH ON REPRODUCTIVE HEALTH OF TEENS AND WOMEN WITH DISABILITIES, EXPERIENCE IN DEVELOPING HEALTH EDUCATION CURRICULA AND SEXUAL HEALTH RESOURCES FOR PEOPLE WITH DEVELOPMENTAL DISABILITIES, AND CLINICAL EXPERTISE IN PROVISION OF CARE TO PEOPLE WITH DISABILITIES TRANSITIONING FROM ADOLESCENCE TO ADULTHOOD. THE EXPECTED OUTCOME OF THIS PROJECT IS AN INNOVATIVE, ACCESSIBLE, MULTI-MEDIA EDUCATIONAL TOOLKIT TO IMPROVE SRH KNOWLEDGE AND ACTIVATION AND PROVIDER COMMUNICATION. OUR PILOT TESTING WILL PROVIDE INITIAL EVIDENCE ON THE UTILITY OF THE TOOLKIT FOR OUR TARGET POPULATION, ESTABLISHING A FOUNDATION FOR FUTURE EFFICACY TESTING IN A CLINICAL TRIAL. THIS PROJECT WILL BREAK NEW GROUND BY PROVIDING A FOUNDATION OF EVIDENCE ON SRH HEALTH AND HEALTHCARE OUTCOMES, AND WILL DEVELOP AN INNOVATIVE SRH EDUCATIONAL TOOLKIT TO ADDRESS BARRIERS AND DISPARITIES AMONG AYA WITH DISABILITIES.

THE MOLECULAR AND CELLULAR BASIS OF SHORT-RANGE HOST CUE SENSING IN MOSQUITO VECTORS

CAREER ADVANCEMENT AND CULTURE CHANGE IN BIOMEDICAL RESEARCH: GROUP PEER MENTORING OUTCOMES AND MECHANISMS

MECHANISM BY WHICH THE GRP94 MOLECULAR CHAPERONE FOLDS INSULIN-LIKE GROWTH FACTORS

PREDOCTORAL TRAINING IN CROSS-DISCIPLINARY MOLECULAR AND CELLULAR BIOLOGY - PROJECT SUMMARY/ABSTRACT THE GOALS OF THIS TRAINING PROGRAM ENTITLED “PREDOCTORAL TRAINING IN CROSS-DISCIPLINARY MOLECULAR AND CELLULAR BIOLOGY” (CMCB) AT BRANDEIS UNIVERSITY ARE TO PRODUCE RIGOROUS, QUANTITATIVE SCIENTISTS WITH EXPERTISE IN MULTIPLE DISCIPLINES, TO PROVIDE TRAINEES WITH THE SKILLS NEEDED TO SUCCEED IN DIVERSE SCIENCE-RELATED CAREERS, AND TO HELP TRAINEES EXPLORE AND PURSUE THEIR CAREER INTERESTS IN AN INFORMED MANNER. THIS NEW PROGRAM COMBINES THE COMPLEMENTARY STRENGTHS OF TWO PRIOR BRANDEIS T32 PROGRAMS: “GENETIC AND BIOCHEMICAL MECHANISMS OF REGULATION, T32GM007122”, EXPIRING AFTER >40 YEARS OF NIGMS SUPPORT, AND “QUANTITATIVE BIOLOGY, T32EB009419”, EXPIRING AFTER 10 YEARS OF NIBIB SUPPORT. WHILE BOTH TRAINING PROGRAMS HAD STRONG TRACK RECORDS OF STUDENT RESEARCH PRODUCTIVITY AND CAREER OUTCOMES, WE SIGNIFICANTLY RETHOUGHT AND REVISED CORE ELEMENTS OF TRAINING (BASED ON STUDENT AND FACULTY FEEDBACK) TO BETTER PREPARE STUDENTS FOR A FUTURE IN WHICH INTERDISCIPLINARY RESEARCH IS INCREASINGLY CRUCIAL. INNOVATIONS INCLUDE: (1) INCREASED QUANTITATIVE TRAINING, THROUGH COURSES AND AN ANNUAL WORKSHOP, (2) REVISING THE TIMING AND GOAL OF THE QUALIFYING EXAM, BOTH TO IMPROVE THE TRAINING VALUE AND TO BETTER SERVE STUDENTS FROM DIVERSE SCIENTIFIC AND PERSONAL BACKGROUNDS, (3) EARLIER IMPLEMENTATION OF INDIVIDUAL DEVELOPMENT PLANS AND THESIS COMMITTEE MEETINGS TO ACCELERATE TRAINEE CAREER DEVELOPMENT AND RESEARCH PROGRESS, (4) INTRODUCING A SECONDARY RESEARCH ADVISOR IN A COMPLEMENTARY DISCIPLINE TO FACILITATE INTERDISCIPLINARY TRAINING, (5) A TWO WEEK PROFESSIONAL EXTERNSHIP IN YEAR 4+, (6) NEW PROGRAM SELF-ASSESSMENT MECHANISMS, INCLUDING SEMI-ANNUAL TRAINEE FEEDBACK AND THE CREATION OF AN EXTERNAL ADVISORY COMMITTEE, AND (7) FORMAL TRAINING IN AND OVERSIGHT OF MENTORING FOR ALL TRAINING FACULTY. TRAINEE APPOINTMENTS WILL BE MADE AT THE END OF YEAR 1, AFTER STUDENTS HAVE COMPLETED ONE YEAR OF COURSEWORK, FOUR 9- WEEK LABORATORY ROTATIONS, AND CHOSEN A LAB. IN YEAR 2, TRAINEES SERVE AS TEACHING ASSISTANTS FOR ONE COURSE PER SEMESTER, TAKE A PROSEMINAR COURSE TO HELP THEM CRAFT THEIR THESIS RESEARCH PLAN AND DEFEND IT AT THEIR QUALIFYING EXAM (END OF YEAR 2), AND TO DEVELOP A CAREER INDIVIDUAL DEVELOPMENT PLAN (IDP). IN YEAR 3+, TRAINEES TAKE A FINAL ELECTIVE AND FOCUS ON THEIR RESEARCH. THEY PRESENT THEIR WORK AT ANNUAL DEPARTMENTAL TALKS, HAVE ANNUAL THESIS COMMITTEE MEETINGS FOCUSED ON CAREER PLANNING AND RESEARCH PROGRESS. IN YEAR 4+, THEY ENGAGE IN A TWO-WEEK CAREER EXTERNSHIP AND SERVE AS MENTORS AT THE ANNUAL QUANTITATIVE ANALYSIS WORKSHOP. PROGRAM OUTCOMES AND SUCCESS WILL BE MEASURED BY: (1) SUSTAINED RESEARCH IMPACT (REFLECTED IN TRAINEE PUBLICATIONS), (2) DEVELOPMENT OF INDEPENDENT SCIENTIFIC THINKING AND COMMUNICATION (ASSESSED THROUGH THESIS PROPOSALS, ANNUAL DEPARTMENTAL TALKS AND THESIS COMMITTEE MEETINGS), (3) ACTIVE TRAINEE ENGAGEMENT IN THEIR OWN CAREER DEVELOPMENT (REFLECTED IN ANNUAL IDPS, DISCUSSIONS AT THESIS COMMITTEE MEETINGS, AND THE NEW EXTERNSHIP PROGRAM), AND (4) TRAINEE PLACEMENT AND LONG-TERM SUCCESS IN SCIENCE-RELATED CAREERS. THERE ARE 29 CMCB TRAINING FACULTY, AND 12 SLOTS ARE REQUESTED (~6 TRAINEES/YEAR, WITH TRAINEES SUPPORTED IN YEARS 2 AND 3).

ADVANCING RECOVERY PATHWAYS AND SUPPORT SERVICES FOR ALCOHOL USE DISORDERS AMONG BLACK MEN AND WOMEN - BLACK AMERICANS DEMONSTRABLY SUFFER FROM A RANGE OF HEALTH DISPARITIES RISING FROM A LONG HISTORY OF STRUCTURAL INEQUITIES AND RACISM. ALTHOUGH BLACK AMERICANS ARE SLIGHTLY LESS LIKELY TO DRINK ALCOHOL THAN THE GENERAL POPULATION, THE RATE OF BLACK DRINKERS WITH ALCOHOL USE DISORDERS (AUD) IS COMPARABLE, REPRESENTING 1.5 MILLION BLACK AMERICANS WITH AUD. BLACKS SUFFER MORE NEGATIVE CONSEQUENCES DUE TO ALCOHOL USE SUCH AS ILLNESSES, INJURIES, CRIMINAL-LEGAL INVOLVEMENT, AND SOCIAL PROBLEMS. RECOVERY IS A DYNAMIC PROCESS OF BEHAVIOR CHANGE LEADING TO STABLE IMPROVEMENTS IN FUNCTIONING, PURPOSE AND WELL-BEING. NIAAA FURTHER HIGHLIGHTS RECOVERY AS REMISSION FROM AUD SYMPTOMS AS WELL AS CESSATION OF HEAVY DRINKING. RECOVERY SUPPORT SERVICES AND RECOVERY COMMUNITY ORGANIZATIONS AIM TO BUILD RECOVERY CAPITAL. YET, TO DATE LITTLE EFFORT HAS BEEN MADE TO CONSIDER RECOVERY WITHIN POPULATION GROUPS RATHER THAN ACROSS GROUPS. A “CENTERING IN THE MARGINS” APPROACH EMPHASIZES THE NEED TO EXAMINE EXPERIENCES OF RACIALIZED AND MINORITIZED POPULATIONS. THIS PROPOSED STUDY TO ADVANCE RECOVERY PATHWAYS AND SUPPORT SERVICES FOR BLACK MEN AND WOMEN HEEDS THAT CALL. IT IS DIRECTLY RESPONSIVE TO RFA-AA-21-001 IN ITS EMPHASIS ON HEALTH DISPARITIES IN AUD POPULATIONS, INTERSECTING WITH THE RFA GOALS TO ADVANCE CULTURALLY-INFORMED MEASURES AND INTERVENTIONS, INCREASE ACCESS TO AUD SERVICES, MAKE SERVICES MORE APPEALING, AND EVALUATE EVIDENCE-BASED PRACTICES. WE DO THIS WITH A FOCUS ON BLACK MEN AND WOMEN IN AUD RECOVERY. WE THUS AIM TO ITERATIVELY USE QUANTITATIVE AND QUALITATIVE METHODS TO CAPTURE AND ASSESS QUESTIONS RELATED TO AUD RECOVERY IN A HETEROGENOUS BLACK POPULATION, IN PARTNERSHIP WITH A BLACK- MAJORITY RECOVERY COMMUNITY ORGANIZATION IN DETROIT. SPECIFICALLY: (1) USE QUALITATIVE METHODS WITH A BLACK POPULATION TO (A) DEFINE AUD RECOVERY PATHWAYS; (B) ASSESS AND REFINE A MEASURE OF RECOVERY DOMAINS (E.G., RELATIONSHIPS, LIVING ENVIRONMENT); AND (C) IDENTIFY AND MAP COMMUNITY INDICATORS THAT MAY FACILITATE OR INTERFERE WITH AUD RECOVERY. (2) USE QUANTITATIVE METHODS TO DESCRIBE AND ASSESS THE PROVISION OF AUD RECOVERY SUPPORT SERVICES PROVIDED BY THE RECOVERY COMMUNITY ORGANIZATION IN TERMS OF MATCHING TO NEEDS, STAGE OF RECOVERY AND OTHER CLIENT AND COMMUNITY CHARACTERISTICS, BY RACE/ETHNICITY. (3) CONDUCT A PRAGMATIC RANDOMIZED CONTROLLED TRIAL THAT BUILDS ON AIMS 1 AND 2 WITH A BLACK AUD RECOVERY POPULATION, COMPARED TO A TREATMENT AS USUAL GROUP WITH IN-PERSON RECOVERY SUPPORT SERVICES, TO DETERMINE THE EFFECTIVENESS OF AN ADDED PHONE+DIGITAL RECOVERY SUPPORT SERVICE INTERVENTION (I.E., PROVISION OF SMARTPHONES AND GUIDANCE/SUPPORT FOR ONLINE RECOVERY ACTIVITIES). THE PROPOSED STUDY WILL ENABLE A DEEP UNDERSTANDING OF WHAT RECOVERY MEANS TO BLACK MEN AND WOMEN, HOW IT CAN BE MEASURED, AND HOW WE CAN ADVANCE RECOVERY JOURNEYS OF BLACK AMERICANS WITH AUD. THE RESULTS WILL BE MEANINGFUL TO BLACK INDIVIDUALS THEMSELVES, PROVIDERS WHO TREAT BLACKS WHO HAVE AUD, AND TO RESEARCHERS AND POLICYMAKERS WHO NEED TO BETTER UNDERSTAND THE MEANING AND NEEDS OF A HETEROGENOUS US POPULATION.

PROBING THE STRUCTURE OF THE SYNAPSE USING SUPERRESOLUTION LIGHT MICROSCOPY

BJA FY 14 HAROLD ROGERS PRESCRIPTION DRUG MONITORING NATIONAL TRAINING AND TECHNICAL ASSISTANCE PROGRAM

HOMEOSTATIC PLASTICITY IN DEVELOPING VISUAL CORTEX

SUPPORT OF FDA SAFE USE INITIATIVE AND CDC NATIONAL CENTER FOR INJURY PREVENTION AND CONTROL

INTERVENTION TO INCREASE NALOXONE ENGAGEMENT AND DISTRIBUTION IN COMMUNITY PHARMACIES: A FOUR-STATE RANDOMIZED TRIAL

HUB AND SPOKE OPIOID TREATMENT NETWORKS: 2ND GENERATION APPROACHES TO IMPROVE MEDICATION TREATMENT FOR OPIOID USE DISORDERS

ACTIVITY-DEPENDENT REGULATION OF CAMKII AND SYNAPTIC PLASTICITY

TAS::89 0222::TAS RESEARCH IN ELEMENTARY PARTICLE PHYSICS

ANALYSIS OF BREAK-INDUCED REPLICATION

ARREST, RECOVERY, AND ADAPTATION FROM DNA DAMAGE

IGERT: GEOMETRY AND DYNAMICS -- INTEGRATED EDUCATION IN THE MATHEMATICAL SCIENCES

PREGNANCY OUTCOMES AND EXPERIENCES AMONG DEAF AND HARD OF HEARING WOMEN

CAPTURING THE DYNAMIC EPIGENOME USING SINGLE MOLECULE AND SINGLE CELL APPROACHES

IMPROVING PREGNANCY OUTCOMES OF WOMEN WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES

QUANTITATIVE BIOLOGY: A GRADUATE CURRICULUM LINKING THE PHYSICAL AND BIOMEDICAL S

EXAMINING OPIOID USE DISORDER TREATMENT IN MEDICAID MANAGED CARE PLANS: POLICIES AND OUTCOMES

PROVISION OF DRUG ABUSE TREATMENT SERVICES UNDER PARITY

COMPUTATIONAL MODELING OF VIRAL ASSEMBLY: ENCAPSULATION OF NUCLEIC ACIDS AND ENV

DISPARITIES IN PERINATAL CARE AND OUTCOMES AMONG BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES - PROJECT SUMMARY/ABSTRACT WOMEN WITH PHYSICAL DISABILITIES EXPERIENCE STARK DISPARITIES IN PREGNANCY CARE, COMPLICATIONS, AND OUTCOMES, COMPARED TO WOMEN WITHOUT DISABILITIES. BLACK WOMEN AND LATINAS ALSO EXPERIENCE SUBSTANTIAL DISPARITIES RELATED TO PERINATAL CARE AND OUTCOMES, COMPARED TO WHITE WOMEN. BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES, THUS, ARE PRESUMABLY AT HEIGHTENED RISK OF ADVERSE EXPERIENCES AND OUTCOMES. NONETHELESS, NO KNOWN STUDIES HAVE INVESTIGATED THE INTERSECTION OF DISABILITY AND RACE/ETHNICITY IN RELATION TO PERINATAL CARE AND DISPARITIES. PRELIMINARY FINDINGS FROM THE INVESTIGATOR TEAM DEMONSTRATE THAT BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES ARE AT SUBSTANTIAL RISK FOR ADVERSE PREGNANCY OUTCOMES. EFFORTS TO IMPROVE THEIR PREGNANCY CARE AND EXPERIENCES WHILE REDUCING COSTS REQUIRE A DEFINITIVE ASSESSMENT OF THESE WOMEN’S PREGNANCY RISKS AND OUTCOMES. THE OVERARCHING GOAL OF THIS STUDY IS TO USE A MIXED-METHODS APPROACH TO UNDERSTAND PREGNANCY EXPERIENCES, MATERNAL AND INFANT OUTCOMES, RELATED HEALTHCARE COSTS, AND UNMET PERINATAL HEALTHCARE NEEDS OF BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES AND THEIR INFANTS, AND EXAMINE THE INTERSECTING IMPACTS OF DISPARITIES FROM TWO AVENUES OF MARGINALIZATION (RACE OR ETHNICITY, AND PHYSICAL DISABILITY). THE SPECIFIC AIMS OF THIS STUDY ARE: 1) COMPARE PERINATAL CARE RECEIPT, PREGNANCY-RELATED COMPLICATIONS, HEALTH OUTCOMES, INPATIENT HEALTHCARE UTILIZATION AND COSTS AMONG COHORTS OF WOMEN BASED ON RACE, ETHNICITY, AND PHYSICAL DISABILITY STATUS, AND DETERMINE IF THE COMBINED EFFECTS OF BEING A BLACK WOMAN OR LATINA WITH PHYSICAL DISABILITIES ARE ADDITIVE OR MULTIPLICATIVE; 2) USE LINKED DATA FROM GEORGIA, CALIFORNIA, AND MASSACHUSETTS TO EXAMINE FIRST YEAR HEALTH OUTCOMES, HEALTHCARE UTILIZATION AND COSTS FOR COHORTS OF WOMEN BASED ON RACE, ETHNICITY, AND PHYSICAL DISABILITY AND THEIR INFANTS (<1 YEAR OLD), AND DETERMINE IF THE COMBINED EFFECT OF BEING A BLACK WOMAN OR LATINA WITH PHYSICAL DISABILITIES IS ADDITIVE OR MULTIPLICATIVE; AND 3) IDENTIFY UNMET NEEDS AND BARRIERS TO PERINATAL CARE FOR BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES THROUGH: (A) INTERVIEWS WITH BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES WHO ARE CURRENTLY PREGNANT OR HAVE RECENTLY GIVEN BIRTH, AND (B) FOCUS GROUPS WITH OBSTETRIC CARE PROVIDERS. THIS STUDY WILL LEAD TO A FIRST-EVER SYSTEMATIC UNDERSTANDING OF PREGNANCY AND INFANT HEALTH OUTCOMES AND PREGNANCY CARE COSTS FOR BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES, THUS ESTABLISHING A FOUNDATION FOR DEVELOPMENT AND TESTING OF FUTURE INTERVENTIONS TO IMPROVE OUTCOMES. THIS STUDY WILL FILL A CRITICAL KNOWLEDGE GAP IN UNDERSTANDING OF THE PREGNANCY-RELATED EXPERIENCES AMONG BLACK WOMEN AND LATINAS WITH PHYSICAL DISABILITIES BEFORE, DURING AND AFTER PREGNANCY.

MACROMOLECULAR STRUCTURE AND MECHANISM

COORDINATION OF THE ACTIN AND MICROTUBULE CYTOSKELETONS

COMMUNITY LIVING POLICY CENTER - GOAL: THE COMMUNITY LIVING POLICY CENTER (CLPC), HOUSED AT THE LURIE INSTITUTE FOR DISABILITY POLICY AT BRANDEIS UNIVERSITY AIMS TO IMPROVE POLICIES AND PRACTICES THAT PROMOTE COMMUNITY LIVING AND PARTICIPATION OUTCOMES FOR INDIVIDUALS WITH DISABILITIES, PARTICULARLY INDIVIDUALS WITH NEEDS FOR LONG-TERM SERVICES AND SUPPORTS. OUR PARTNERS INCLUDE DISABILITY POLICY CONSORTIUM (DPC), DISABILITY RIGHTS EDUCATION & DEFENSE FUND (DREDF), HUMAN SERVICES RESEARCH INSTITUTE (HSRI), AUTISTIC SELF-ADVOCACY NETWORK (ASAN), UNIVERSITY OF KANSAS, UNIVERSITY OF ILLINOIS AT CHICAGO, ASSOCIATION OF UNIVERSITY CENTERS ON DISABILITIES (AUCD) AND POLICY EXPERTS MIKE OXFORD AND HENRY CLAYPOOL. OBJECTIVES: THE CLPC WILL A) CONDUCT POLICY RESEARCH RELATED TO BARRIERS AND FACILITATORS TO POSITIVE COMMUNITY LIVING OUTCOMES; B) PROVIDE RAPID, TIMELY DATA AND POLICY ANALYSES TO INFORM POLICIES AND PRACTICES; C) ENSURE STUDY SAMPLES INCLUDE SUFFICIENT RACIAL AND ETHNIC DIVERSITY; D) MEANINGFULLY INVOLVE INDIVIDUALS WITH DISABILITIES IN RESEARCH; AND E) SERVE AS A NATIONAL RESOURCE FOR RESEARCH-BASED COMMUNITY LIVING POLICY. OUTCOMES: THE CLPC WILL ADVANCE COMMUNITY LIVING POLICY, PRACTICE, AND OUTCOMES IN MULTIPLE AREAS, INCLUDING ACCESS TO HOME AND COMMUNITY-BASED SERVICES AND EQUITY, IMPROVED PERSON-CENTERED PLANNING, CARE COORDINATION, AND CULTURAL COMPETENCY, STRENGTHENING THE DIRECT CARE WORKFORCE, AND IMPROVED ACCESS TO AFFORDABLE AND ACCESSIBLE HOUSING, TRANSPORTATION, DISASTER PLANNING, AND FOOD SECURITY. PRODUCTS: THE CLPC WILL COLLABORATIVELY ENGAGE IN A WIDE RANGE OF KNOWLEDGE TRANSLATION ACTIVITIES WITH PARTNERS, INCLUDING DISSEMINATION OF PRODUCTS IN MULTIPLE, ACCESSIBLE FORMATS, TRAINING AND CAPACITY BUILDING OF STUDENTS, TRAINEES, AND FELLOWS, AND TECHNICAL ASSISTANCE TARGETED TO NEEDS OF STAKEHOLDERS.

NEUROTRANSMITTER MODULATION OF NEURONAL CIRCUITS

GENETIC ANALYSIS OF SENSORY SPECIFICATION IN C.ELEGANS

IMP DEHYDROGENASE

NEUROCHEMISTRY AND GENETICS OF DROSOPHILA CAMKII

ORGANIZATION AND FUNCTION OF THE PERIACTIVE ZONE

DEVELOPMENT OF IMPDH-TARGETED DRUGS AGAINST CRYTOSPORIDIUM

PARENTS EMPOWERING PARENTS: NATIONAL RESEARCH CENTER FOR PARENTS WITH DISABILITIES

PARENTS EMPOWERING PARENTS: NATIONAL RESEARCH CENTER FOR PARENTS WITH DISABILITIES AND THEIR FAMILIES

HEARING ACUITY, COGNITIVE AGING, AND MEMORY FOR SPEECH

EFFECTS OF THE SUPPLEMENTAL NUTRITION ASSISTANCE PROGRAM ON RACIAL/ETHNIC AND DISABILITY-BASED HEALTHCARE DISPARITIES

ACTIVITY-DEPENDENT REGULATION OF MEMBRANE TRAFFIC AND GROWTH SIGNALING IN NEURONS

A NEW TOOL FOR THE CELL-SPECIFIC IDENTIFICATION OF RNA BINDING PROTEIN TARGETS

PROVISION OF ALCOHOL SERVICES IN PRIVATE HEALTH PLANS

BUILDING MECHANISTIC INSIGHT INTO EVOLVABILITY OF VIRAL CELL-ENTRY FUNCTIONS

UNRAVELING REGULATORY FUNCTIONS OF CIRCRNAS AT THE MUSCLEBLIND LOCUS

MOLECULAR AND NEURONAL MECHANISMS OF THERMOSENSORY BEHAVIOR

UNWINDING PANDEMIC-ERA SOCIAL PROGRAMS: EFFECTS ON HEALTHCARE OUTCOMES AND DISPARITIES - PROJECT SUMMARY/ABSTRACT THIS PROJECT WILL STUDY THE EFFECTS OF THE EXPIRATION OF FAMILIES FIRST CORONAVIRUS RESPONSE ACT (FFCRA) INCREASES TO SUPPLEMENTAL NUTRITION ASSISTANCE PROGRAM (SNAP) BENEFIT LEVELS ON HEALTHCARE OUTCOMES AND DISPARITIES BY DISABILITY, RACE, AND ETHNICITY. THESE GROUPS EXPERIENCE DISPARITIES IN DISEASE PREVENTION AND MANAGEMENT, UNFAVORABLE CLINICAL EVENTS, AND CARE EXPENDITURES, EACH OF WHICH ARE ASSOCIATED WITH FOOD INSECURITY. EXISTING STUDIES HAVE FOUND SNAP TO REDUCE FOOD INSECURITY AND SUGGEST SNAP MAY REDUCE UNFAVORABLE HEALTHCARE OUTCOMES, ESPECIALLY FOR VULNERABLE GROUPS, BUT THESE STUDIES SUFFERED KEY CAUSAL INFERENCE LIMITATIONS AND HAVE FOCUSED ON SNAP CHANGES SUBSTANTIALLY DIFFERENT FROM THE FFCRA UNWINDING. MEANWHILE, STATE-LEVEL VARIATION IN APPROACHES TO UNWINDING THE FFCRA SNAP INCREASES (E.G., TIMING RANGING FROM APRIL 2021 TO MARCH 2023), INDIVIDUAL-LEVEL VARIATION IN THE SIZE OF BENEFIT LOSSES (RANGING FROM $95 PER MONTH TO OVER $1,000 PER MONTH), AND A MASSACHUSETTS (MA) POLICY THAT BROKE THE STATE’S SNAP ROLLBACKS INTO TWO UNEVEN STEPS ALL CREATE NATURAL EXPERIMENTS WE CAN USE TO IDENTIFY THE CAUSAL IMPACTS OF SNAP. FURTHER, WE WILL USE ROBUST POLICY TRACKING TO IDENTIFY AND ADJUST FOR NON-SNAP POLICY UNWINDING PATTERNS, AND WE WILL LEVERAGE BOTH NATIONAL T-MSIS MEDICAID DATA AND UNIQUELY DETAILED LINKED DATA FROM MA. ULTIMATELY, THE MA AND US ANALYSES WILL COMPLEMENT EACH OTHER AND PROVIDE HIGH INTERNAL AND EXTERNAL VALIDITY. SPECIFICALLY, WE WILL CREATE A REGISTRY OF POLICIES RELATED TO THE UNWINDING OF FOOD, HOUSING, AND MEDICAID ACCESS AND THEN DEVELOP PARSIMONIOUS SETS OF POLICY UNWINDING PATTERNS TO IDENTIFY ADJUSTERS FOR LATER ANALYSES (WE WILL SIMILARLY ATTEND TO OTHER HEALTHCARE, PUBLIC HEALTH, AND ECONOMIC CONDITIONS) (AIM 1). WE WILL THEN ESTIMATE THE EFFECTS OF SNAP UNWINDING ON MEDICAID EVENT RATES (PREVENTIVE USE, UNFAVORABLE EVENT RATES, AND EXPENDITURES; AIM 2), AND WE WILL FINALLY ESTIMATE THE EFFECTS OF SNAP UNWINDING ON DISPARITIES IN THESE EVENT RATES BY DISABILITY, RACE, AND ETHNICITY (AIM 3). FOR AIMS 2 AND 3 (2020-2026), WE WILL MEASURE DIFFERENCES IN THE LEVELS AND TRENDS OF HEALTHCARE OUTCOMES AND DISPARITIES BEFORE AND AFTER UNWINDING-RELATED CHANGES USING A MULTILEVEL APPROACH TO GROWTH CURVE MODELING THAT IS FLEXIBLE AND ROBUST TO MANY VALIDITY THREATS (WHILE ALSO UTILIZING ELIGIBLE NON-PARTICIPANTS WITH PAST SNAP APPLICATIONS AS A COMPARATOR WITH NO UNWINDING EXPOSURE). CURRENT POLICY PROPOSALS WOULD REDUCE SNAP ACCESS, BUT THERE IS LITTLE DATA TO SHED LIGHT ON HOW SUCH REDUCTIONS MAY AFFECT HEALTHCARE OUTCOMES AND DISPARITIES. OUR STUDY WILL REDUCE THIS CRITICAL KNOWLEDGE GAP. STUDYING THE ONGOING SNAP UNWINDING WILL EXTEND PAST WORK THAT HAS FOCUSED ON SNAP INCREASES AND/OR CHANGES UNIFORM IN THEIR SIZE AND TIMING, AND LEARNINGS FROM THIS PROJECT WILL ALSO ADVANCE THE NIH MINORITY HEALTH AND HEALTH DISPARITIES STRATEGIC PLAN’S GOAL 3 TO ASSESS “INTERVENTIONS TO REDUCE HEALTH DISPARITIES.”

UNRAVELING THE POLYMODAL BEHAVIOR OF SENSORY TRANSDUCTION RECEPTORS

FUNCTIONAL MECHANISMS OF PROCESSIVE MOTOR ATPASES

HUB AND SPOKE MODEL TO IMPROVE PHARMACOTHERAPY USE FOR OPIOID ADDICTION AND PROMOTE RECOVERY

HIGH RESOLUTION ELECTRON CRYO-MICROSCOPE AT BRANDEIS UNIVERSITY.

INFLUENCE OF CULTURE ON LEARNING AND DECISION MAKING WITH AGE

INCENTIVES IN PUBLIC ADDICTION TREATMENT: TESTING DESIGN AND ENHANCING IMPACT

DESIGN OF IMMUNOGENS TO ELICIT PGT122 LIKE ANTIBODIES

MUSCLE STRUCTURE AND THE CONTRACTILE MECHANISM

SELECTIVE NITROGEN ATOM TRANSFER FOR APPLICATIONS IN BIOMEDICAL SCIENCES

AGING & ACCURATE FACE IMPRESSIONS: PERCEPTUAL, NEURAL & MOTIVATIONAL MECHANISMS

INROADS-A: INTERSECTING RESEARCH ON ADDICTION AND DISABILITY SERVICES - ALCOHOL - ABSTRACT PEOPLE WITH DISABILITIES (PWD) ARE AN OVERLOOKED HEALTH DISPARITY POPULATION WHO ROUTINELY EXPERIENCE STIGMA, DISCRIMINATION, ABLEISM, AND LOWER SOCIOECONOMIC STATUS. BARRIERS TO HEALTH CARE ARE GENERALLY HIGH FOR PWD, AND DESPITE OVER THREE DECADES OF THE AMERICANS WITH DISABILITIES ACT, MANY HEALTH CARE SETTINGS INCLUDING ADDICTION TREATMENT ARE NOT FULLY ACCESSIBLE FOR PWD. RECENT STUDIES HAVE FOUND THAT PWD ABSTAIN FROM ALCOHOL MORE FREQUENTLY THAN PEOPLE WITHOUT DISABILITIES (PWOD); HOWEVER, AMONG CURRENT DRINKERS, PWD HAVE ELEVATED RATES OF AT-RISK ALCOHOL USE. FURTHERMORE, PWD HAVE GREATER RISK FOR ADDICTION, GIVEN HIGHER RATES OF MENTAL AND PHYSICAL HEALTH COMORBIDITIES, SOCIAL ISOLATION, TRAUMA HISTORY AND ADVERSE SOCIAL DETERMINANTS OF HEALTH. DESPITE THIS CONSTELLATION OF RISK FACTORS, VERY LITTLE IS KNOWN ABOUT RISK FOR ALCOHOL USE DISORDER (AUD) OR ALCOHOL-RELATED MORBIDITY OR CONSEQUENCES AMONG PWD, OR WHETHER DISPARITIES EXIST FOR PWD IN ACCESSING OR ENGAGING IN AUD TREATMENT COMPARED TO PWOD. WE WILL USE RIGOROUS QUASI-EXPERIMENTAL METHODS TO COMPARE PWD TO PWOD, USING HOUSEHOLD SURVEY DATA (NATIONAL SURVEY ON DRUG USE AND HEALTH) AND COMPLEMENTARY MEDICAL CLAIMS DATASETS (MEDICAID IN 13 STATES; COMMERCIAL INSURANCE IN MARKETSCAN) TO EXAMINE ALCOHOL USE, AUD INDICATORS, MORBIDITY AND CONSEQUENCES, AUD TREATMENT SERVICES, QUALITY MEASURES AND OUTCOMES BY DISABILITY STATUS. DISABILITY STATUS IS DEFINED BY FUNCTIONAL LIMITATIONS IN SURVEY DATA AND BY DIAGNOSES OF DISABLING CONDITIONS IN CLAIMS. BECAUSE DISABILITY IS NOT HOMOGENEOUS, ANALYSES WILL CONSIDER ANY DISABILITY AND TYPES OF DISABILITY. ANALYSES WILL BE REPLICATED TO INVESTIGATE OUTCOMES FOR WOMEN WITH DISABILITIES, AN UNDERSTUDIED AND FURTHER STIGMATIZED POPULATION. OUR APPROACH IS ORGANIZED BY THE CASCADE OF CARE FRAMEWORK, AND INFORMED BY INTERSECTIONALITY, CRITICAL DISABILITY THEORY, AND THE INSTITUTE OF MEDICINE DEFINITION OF HEALTH CARE DISPARITIES THAT SEPARATES NEEDS-RELATED DIFFERENCES FROM TRUE DISPARITIES. THE PROPOSED SPECIFIC AIMS ARE TO: 1) IDENTIFY DIFFERENCES IN ALCOHOL USE, ALCOHOL-RELATED MORBIDITY, AND AUD DIAGNOSES, BY DISABILITY STATUS; 2) AMONG PEOPLE WITH AUD, INVESTIGATE DISPARITIES BY DISABILITY STATUS IN ALCOHOL-RELATED MORBIDITY, CONSEQUENCES, AND ACCESS TO AUD TREATMENT; AND 3) AMONG PEOPLE RECEIVING AUD TREATMENT, ASSESS DISPARITIES BY DISABILITY STATUS IN RECEIVING QUALITY-ALIGNED AUD TREATMENT AND EXPERIENCING ACUTE ALCOHOL-RELATED OUTCOMES. OUR MULTIFACETED APPROACH TO DATA SOURCE SELECTION AND FOCUS ON DISPARITIES BETWEEN PWD AND PWOD WILL ALLOW A MORE COMPREHENSIVE PICTURE OF HOW THE DISABILITY COMMUNITY IS AFFECTED BY ALCOHOL PROBLEMS. FINDINGS ARE EXPECTED TO PROVIDE POLICY MAKERS, RESEARCHERS, AND CLINICIANS WITH CRITICAL INFORMATION TO ADDRESS DISPARITIES IN ACCESS TO, ENGAGEMENT IN, AND OUTCOMES OF AUD TREATMENT FOR PWD, HELPING TO REDUCE ALCOHOL-RELATED MORBIDITY AND IMPROVE THE HEALTH OF THIS COMMONLY OVERLOOKED HEALTH DISPARITY POPULATION.

SYNAPTIC HOMEOSTASIS IN NEOCORTICAL NEURONS

INCENTIVES AND ALERTS FOR IMPROVING PERFORMANCE IN WASHINGTON STATE

THALAMIC MECHANISMS FOR GENERATING ABNORMAL LOW FREQUENCY OSCILLATIONS RELEVANT TO SCHIZOPHRENIA

MULTIPLE MECHANISMS OF NEURAL COORDINATION FOR ASSOCIATIVE MEMORY PROCESSES

UNDERGRADUATE AND GRADUATE TRAINING IN COMPUTATIONAL NEUROSCIENCE

A GENETIC AND GENOMIC RESOURCE FOR MOUSE VISION RESEARCH

NEUROTRANSMITTER PLASTICITY AND REGULATION OF BEHAVIOR - PROJECT SUMMARY NEURONS HAVE CLASSICALLY BEEN DEFINED BY THE NEUROTRANSMITTER THEY RELEASE. THIS “IDENTITY” HAS BEEN CONSIDERED TO BE BOTH SINGULAR (I.E. ONE TRANSMITTER) AND IMMUTABLE (I.E. GENETICALLY HARDWIRED). WHILE THE ASTONISHING PREVALENCE OF COTRANSMISSION HAS CHANGED THINKING ABOUT THE SINGULARITY OF NEUROTRANSMITTER IDENTITY THERE HAS BEEN CONSIDERABLY LESS APPRECIATION OF THE ABILITY OF NEURONS TO EXHIBIT PLASTICITY IN THEIR EXPRESSION. RECENTLY, WE DISCOVERED THAT THE MICRORNA MIR-190 IS A POTENT REGULATOR OF ADULT SLEEP. SPATIAL AND TEMPORAL MAPPING OF ITS SITE OF ACTION DEMONSTRATES THAT IT IS REQUIRED DURING PUPATION IN A POPULATION OF CELLS THAT TRANSCRIBES BOTH CHOLINERGIC AND GLUTAMATERGIC GENES BUT DIFFERENTIATES TO BECOME A SMALL SUBSET OF THE ADULT GLUTAMATERGIC NEURONS. THIS SUBSET INCLUDES COMPONENTS OF THE CORE SLEEP HOMEOSTASIS CIRCUIT. WE WILL TEST THE HYPOTHESIS THAT A NEUROTRANSMITTER PLASTICITY EVENT IS CRITICAL TO FUNCTION OF THE MATURE CIRCUIT AND THAT IT PROVIDES A NOVEL MECHANISM FOR ESTABLISHING, AND POTENTIALLY MODIFYING, THE SLEEP SET-POINT OF THE HOMEOSTATIC MACHINERY. AIM 1 WILL DETERMINE THE ROLE OF NEUROTRANSMITTER PLASTICITY IN THE CONTROL OF ADULT SLEEP, WITH A FOCUS ON UNDERSTANDING THE CIRCUIT-LEVEL CHANGES. AIM 2 WILL INVESTIGATE THE ROLE OF NEURONAL ACTIVITY IN TRANSMITTER SWITCHING AND HOMEOSTAT PLASTICITY, WITH A FOCUS ON UNDERSTANDING THE MOLECULAR EVENTS. IN THIS PROPOSAL, WE BRING THE POWER OF DROSOPHILA GENETICS TO BEAR ON THIS NOVEL AND IMPORTANT TYPE OF PLASTICITY. WE DEMONSTRATE THAT PROGRAMMED TRANSMITTER PLASTICITY DURING PUPAL LIFE IS CRUCIAL TO ADULT FUNCTION OF THE SLEEP CIRCUITRY. THE GENETIC REAGENTS WE HAVE DEVELOPED WILL ALLOW US TO ADDRESS BASIC MECHANISMS UNDERLYING TRANSMITTER PLASTICITY IN THE CONTEXT OF BOTH THE DEVELOPING AND MATURE NERVOUS SYSTEMS AND, FOR THE FIRST TIME, LINK THIS TYPE OF PLASTICITY TO SLEEP.

ROLE OF NMDA RECEPTORS IN AWAKE-STATE THALAMOCORTICAL SLOW WAVES

MECHANISMS OF ENZYMIC AND HYDRIDE TRANSFERS

GROWTH AND DECLINE IN SNAP GENEROSITY: OUTCOME AND EQUITY IMPLICATIONS - PROJECT SUMMARY/ABSTRACT THIS PROJECT WILL EXAMINE THE EFFECTS OF ADDED SUPPLEMENTAL NUTRITION ASSISTANCE PROGRAM (SNAP) BENEFITS ON HEALTHCARE OUTCOMES AND DISPARITIES BY RACE/ETHNICITY AND DISABILITY. SNAP HAS BEEN FOUND TO ALLEVIATE FOOD INSECURITY (ALBEIT NOT FULLY), AND IS DISPROPORTIONATELY UTILIZED BY RACIAL/ETHNIC MINORITIES AND PEOPLE WITH DISABILITIES, WHO HAVE GREATER SENSITIVITIES TO FOOD INSECURITY (GIVEN “THINNER MARGINS OF HEALTH” STEMMING FROM EXPOSURES TO OTHER INEQUITIES). SNAP POLICY CHANGES COULD THEREFORE AFFECT HEALTHCARE OUTCOMES FOR RACIAL/ETHNIC MINORITIES AND PEOPLE WITH DISABILITIES IN DIFFERENT WAYS THAN FOR THEIR COUNTERPARTS. FURTHER, THESE GROUPS EXPERIENCE HEALTHCARE DISPARITIES (E.G., IN DISEASE PREVENTION AND MANAGEMENT, UNFAVORABLE CLINICAL EVENTS, AND EXPENDITURES) THAT ARE LIKELY AFFECTED BY FOOD INSECURITY: INDIVIDUALS EXPOSED TO FOOD INSECURITY MISS NEEDED CARE AND MEDICATIONS, USE EMERGENCY AND INPATIENT CARE, AND REQUIRE EXPENDITURES ALL AT HIGHER RATES THAN UNEXPOSED INDIVIDUALS, AND EFFECTS ARE ELEVATED AMONG PEOPLE WITH CHRONIC CONDITIONS. WE WILL USE BOTH NATIONAL MEDICAID DATA AND A NOVEL SET OF LINKED CLAIMS, PUBLIC HEALTH, AND ADMINISTRATIVE SNAP DATA FROM MASSACHUSETTS TO EXPLOIT A STAGGERED SET OF NATURAL EXPERIMENTS CREATED BY THE FAMILIES FIRST CORONAVIRUS RESPONSE ACT: (I) APRIL 2020: ~60% OF SNAP HOUSEHOLDS WERE GIVEN VARIABLE AMOUNTS OF ADDED MONTHLY BENEFITS (UP TO OVER $1,000/MONTH, WITH AN AVERAGE OF $161/UNIT/MONTH OVER THE FIRST YEAR), (II) MAY 2021: THOSE WITH NO/SMALL BOOSTS WERE GIVEN UP TO $95/MONTH IN ADDED BENEFITS, AND (III) SINCE APRIL 2021: 18 STATES HAVE ENDED THE NEW BENEFITS, WHICH WILL END FOR REMAINING STATES IN MARCH 2023. IN MA, SNAP-LINKED DATA WILL ALLOW US TO USE THESE CHANGES TO MODEL DOSE-RESPONSES AND TREATMENT REMOVAL PRECISELY. T-MSIS MEDICAID DATA AND STATE VARIABILITY WILL BROADEN INSIGHTS AND IMPROVE THE GENERALIZABILITY OF OUR FINDINGS. AS THESE SNAP CHANGES OCCURRED, MULTIPLE CONTEMPORANEOUS DISRUPTIONS TO HEALTHCARE, PUBLIC HEALTH, SOCIAL WELFARE POLICIES, AND ECONOMIC CONDITIONS WERE OCCURRING AS WELL. TO ADDRESS THIS ISSUE, WE WILL LEVERAGE THE SIGNIFICANT HETEROGENEITY IN THE GEOGRAPHY AND TIMING OF THE DISRUPTIONS, IN ADDITION TO THE ROBUST EFFORTS THAT HAVE TAKEN PLACE DURING THE PANDEMIC TO PROVIDE DETAILED, PUBLICALLY AVAILABLE DATA ON THESE DISRUPTIONS. WE WILL USE CONFIRMATORY FACTOR ANALYSIS, MACHINE LEARNING TECHNIQUES, AND AN EXPERT PANEL TO GUIDE OUR UNDERSTANDING OF AND ADJUSTMENT FOR THESE FACTORS (AIM 1). WE WILL THEN USE GROWTH CURVE MODELS TO MEASURE THE EFFECTS OF EACH SNAP CHANGE ON HEALTHCARE OUTCOMES (I.E., PREVENTIVE USE, UNFAVORABLE EVENTS, AND EXPENDITURES) (AIM 2) AND ON HEALTHCARE DISPARITIES BASED ON RACE/ETHNICITY AND DISABILITY STATUS (AIM 3) IN MA AND THE US. CHANGES TO SNAP’S FUNDING AND ADMINISTRATION ARE ROUTINELY DEBATED. THIS STUDY WILL INFORM THESE DEBATES BY OFFERING RIGOROUS, ACTIONABLE EVIDENCE ON THE POTENTIAL PUBLIC HEALTH IMPACT OF THESE POLICY CHOICES.

FIRST LONGITUDINAL STUDY OF MISSED TREATMENT OPPORTUNITIES USING DOD AND VA DATA

PRESCRIPTION DRUG MONITORING PROGRAM NATIONAL TRAINING AND TECHNICAL ASSISTANCE CENTER

A NEW FAMILY OF VOLTAGE-GATED POTASSIUM CHANNEL REGULAORY SUBUNITS

CRCNS: EVIDENCE-BASED MODELING OF NEUROMODULATORY ACTION ON NETWORK PROPERTIES

IGERT: TIME, SPACE, AND STRUCTURE: PHYSICS AND CHEMISTRY OF BIOLOGICAL SYSTEMS

CIRCUITRY, PLASTICITY AND GENE EXPRESSION IN A MOUSE MODEL OF RETT SYNDROME

HOW DOES A METALLOCOFACTOR IN THE HEPATITIS B VIRAL PROTEIN X ORCHESTRATE PATHOGENESIS AND LIVER CANCER?

BRANDEIS UNIVERSITY STUDENT SUPPORT SERVICES PROGRAM (SSSP)

EQUIPMENT: MRI: TRACK 2 ACQUISITION OF A TUNDRA CRYO-ELECTRON MICROSCOPE -AN AWARD IS MADE TO BRANDEIS UNIVERSITY TO ACQUIRE A THERMO-FISHER TUNDRA CRYO-ELECTRON MICROSCOPE. THIS MICROSCOPE WILL ENABLE VISUALIZATION AND ANALYSIS OF COMPLEX STRUCTURES AT THE MACROMOLECULAR LEVEL, AND WILL BRING TOGETHER RESEARCHERS FROM DIVERSE FIELDS, RANGING FROM MATERIALS SCIENCE AND CHEMISTRY TO CELL, MOLECULAR, AND STRUCTURAL BIOLOGY, THUS FOSTERING INTERDISCIPLINARY COLLABORATION. IT WILL BE AVAILABLE TO RESEARCHERS AT BRANDEIS AND IN THE LOCAL REGION. THE MICROSCOPE WILL ALSO HAVE A SIGNIFICANT IMPACT ON EDUCATION, TRAINING, AND OUTREACH. IT WILL HELP TRAIN THE NEXT GENERATION OF SCIENTISTS, INCLUDING THOSE FROM UNDERREPRESENTED GROUPS, THROUGH HAND-ON COURSES AND WORKSHOPS FOR UNDERGRADUATES, GRADUATE STUDENTS, AND POSTDOCTORAL SCHOLARS. IN ADDITION, OUTREACH PROGRAMS FOR HIGH SCHOOL STUDENTS WILL INCREASE SCIENTIFIC KNOWLEDGE AND UNDERSTANDING AMONG THE PUBLIC. THE RESEARCH PROJECTS ENABLED BY THE TUNDRA CRYO-ELECTRON MICROSCOPE SPAN DIFFERENT SCIENTIFIC FIELDS INCLUDING THE STUDY OF BIOMATERIALS, CELLS, AND BIOLOGICAL STRUCTURES. FOR EXAMPLE, SEVERAL GROUPS OF RESEARCHERS WILL USE CRYO-ELECTRON MICROSCOPY TO UNDERSTAND HOW MOLECULES SELF-ASSEMBLE INTO LARGER STRUCTURES, AS WELL AS HOW THOSE SAME DESIGN PRINCIPLES COULD BE USED TO CREATE NEW SYNTHETIC NANOMATERIALS. OTHER GROUPS WILL USE THE INSTRUMENT TO INVESTIGATE THE SHAPES AND FUNCTIONS OF CELL MEMBRANES AND PROTEINS. THE TUNDRA MICROSCOPE WILL BE ESSENTIAL FOR CAPTURING DETAILED IMAGES AND DETERMINING THE STRUCTURES OF THESE MOLECULES. OVERALL, THE MICROSCOPE WILL ADVANCE KNOWLEDGE OF HOW BIOLOGICAL MOLECULES ARE STRUCTURED AND HOW THEY FUNCTION, WHICH HAS IMPORTANT IMPLICATIONS FOR UNDERSTANDING OF HOW LIFE WORKS, AND FOR TAKING INSPIRATION FROM BIOLOGY TO CREATE THE NEXT GENERATION OF MATERIALS FOR HUMAN USE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

ROLE OF CAMKII IN MEMORY STORAGE

SI2-SSI: THE LANGUAGE APPLICATION GRID: A FRAMEWORK FOR RAPID ADAPTATION AND REUSE

REGULATION OF INTRINSIC PLASTICITY IN NEURAL CIRCUITS - PROJECT SUMMARY THE PUBLIC HEALTH AND ECONOMIC IMPACT OF CHRONIC SLEEP DEPRIVATION (SD) HAVE GROWN ENORMOUSLY WITH THE INCREASINGLY GLOBAL AND 24-HOUR NATURE OF OUR SOCIETY. THE HUMAN COSTS ARE ALSO HIGH; SD IS AN EXACERBATING FACTOR IN MANY MENTAL ILLNESSES. IN SPITE OF THIS, HOWEVER, WE KNOW VERY LITTLE ABOUT THE MECHANISMS BY WHICH SD ALTERS MEMORY CIRCUITS. MEMORY FORMATION IS BIDIRECTIONALLY SENSITIVE TO SLEEP LEVELS. SD HAS NEGATIVE EFFECTS ON ITS FORMATION, WHILE LEARNING HAS BEEN SHOWN TO ENHANCE SLEEP DRIVE, SUGGESTING THAT THERE ARE CIRCUIT INTERACTIONS BINDING MEMORY AND SLEEP CENTERS. IN DROSOPHILA, WE HAVE A VERY DETAILED UNDERSTANDING BOTH OF THE COMPUTATIONS THAT UNDERLIE MEMORY FORMATION AND THE STRUCTURE OF SLEEP CIRCUITS. THIS PROPOSAL LEVERAGES THIS KNOWLEDGE TO UNDERSTAND, FOR THE FIRST TIME AT A CIRCUIT AND MOLECULAR LEVEL, HOW SD DYSREGULATES BOTH SHORT-TERM AND LONG-TERM MEMORY FORMATION. IN AIM 1 WE INVESTIGATE THE EFFECTS OF SLEEP DEPRIVATION ON SHORT-TERM MEMORY FORMATION. BASED ON PRELIMINARY DATA, WE HYPOTHESIZE THAT SD-DEPENDENT CHANGES IN DOPAMINE DYNAMICS DEGRADE COINCIDENCE DETECTION. WE TEST SPECIFIC CIRCUIT AND MOLECULAR MECHANISMS AND PROPOSE STRATEGIES TO AMELIORATE SD PATHOLOGY. IN AIM 2 WE PROBE THE EFFECT OF SD ON PROTEIN SYNTHESIS-DEPENDENT LONG-TERM MEMORY. PRELIMINARY DATA DEMONSTRATE THAT PRE-TRAINING SD BLOCKS ACTIVITY-DEPENDENT LOCAL PROTEIN SYNTHESIS AND THAT LOCAL SYNTHESIS IS SENSITIVE TO INHIBITION OF MAPK PATHWAYS. WE WILL UNCOVER THE MOLECULAR MECHANISMS OF HOW SPACED TRAINING PROMOTES THIS CRITICAL STEP IN INITIATION OF STABLE MEMORY FORMATION AND WE WILL DETERMINE HOW SD DISRUPTS THE PROCESS. LOOKING AT SD THROUGH A LENS OF PLASTICITY DYSFUNCTION WILL PROVIDE A STRONG MOLECULAR UNDERSTANDING OF HOW MEMORY FORMATION IS ADVERSELY AFFECTED BY LACK OF SLEEP. IMPORTANTLY, THESE STUDIES ALSO WILL DEEPEN OUR KNOWLEDGE OF HOW MEMORY IS FORMED IN WELL-RESTED BRAINS AND GIVE US INSIGHT INTO WHAT PARTS OF THE PROCESS ARE VULNERABLE TO DISRUPTION, MAKING THIS WORK RELEVANT TO UNDERSTANDING A WIDE RANGE OF OTHER PATHOLOGIES.

A DATABASE OF MAMMALIAN NEURONAL CELL TYPES

MACROMOLECULAR STRUCTURE AND MECHANISM

NMR STUDIES OF BIOLOGICAL MEMBRANES

CRCNS: QUANTITATIVE DESCRIPTION OF INITIAL BIOCHEMICAL STEPS IN LTP

CHARACTERIZING A NEW ROLE FOR TIMELESS IN THE GENERATION OF ROBUST AND PLASTIC CIRCADIAN RHYTHMS

SYNAPTIC HOMEOSTASIS IN NEOCORTICAL NEURONS AND CIRCUITS

UNDERGRADUATE AND GRADUATE TRAINING IN COMPUTATIONAL NEUROSCIENCE

A HIERARCHY OF TIMESCALES FOR SWITCHING BETWEEN STATES OF NEURAL ACTIVITY DURING CONSUMPTION DECISIONS

STRUCTURE AND DYNAMICS OF METAL-CONTAINING PROTEINS

ADDRESSING PROTEIN SYNTHESIS REGULATION WITHIN SMALL NUMBERS OF DISCRETE NEURONS - PROJECT SUMMARY/ABSTRACT TRANSCRIPTION DOMINATES THE GENE EXPRESSION LANDSCAPE OF CIRCADIAN RHYTHMS AND A NUMBER OF NEUROSCIENCE AREAS. YET POST-TRANSCRIPTIONAL REGULATION, INCLUDING TRANSLATIONAL REGULATION AND THE ROLE OF RNA BINDING PROTEINS (RBPS), HAS BECOME INCREASINGLY RECOGNIZED AS IMPORTANT IN RECENT YEARS. MOREOVER, UNDERSTANDING THE ROLES OF RBPS IN DIVERSE CELL TYPES AND DISEASES AND ULTIMATELY THERAPEUTIC INTERVENTION REQUIRES IDENTIFYING THE RNA TARGETS OF RBPS. THE RIBOSOME CAN BE CONSIDERED A RBP, SO THIS FOCUS ON POST-TRANSCRIPTIONAL REGULATION AND RBP TARGETS INCLUDES IDENTIFYING RIBOSOME-ASSOCIATED TRANSCRIPTS, NAMELY RNAS THAT CHANGE THEIR TRANSLATIONAL STATUS UNDER DEFINED CIRCUMSTANCES. RBP IDENTIFICATION IS PARTICULARLY CHALLENGING FROM SMALL NUMBERS OF CELLS, E.G., CANCER STEM CELLS WITHIN A LARGE, HETEROGENEOUS SOLID TUMOR OR DISCRETE NEURONAL SUBTYPES. THESE SETTINGS PRECLUDE TRADITIONAL BIOCHEMISTRY AND THEREFORE REQUIRE NEW APPROACHES. TWO NEW METHODS RECENTLY APPEARED, TRIBE AND STAMP, WHICH EXPLOIT THE RNA EDITING ENZYMES ADAR AND APOBEC, RESPECTIVELY. THEIR RIBOSOME VERSIONS, RIBO-STAMP AND RIBO-TRIBE, ARE EVEN MORE RECENT AND FUSE A RIBOSOMAL PROTEIN TO THE EDITING ENZYMES. THIS IS SO THAT THE ENZYME WILL BE NEAR RNAS THAT ARE BEING TRANSLATED AND WILL “MARK” THEM BY CHANGING THEIR SEQUENCE. THESE EDITS ARE IDENTIFIED BY MRNA SEQUENCING AND STRAIGHTFORWARD COMPUTATIONAL METHODS, EVEN FROM SINGLE CELLS. WE PROPOSE TO COMPARE RIBO-STAMP AND RIBO-TRIBE SIDE-BY-SIDE IN MAMMALIAN CELL CULTURE SYSTEMS, TO ASSESS THEIR EFFICACY AND TO DETERMINE THE OPTIMAL CONFIGURATION OF RIBOSOME-EDITING ENZYME FUSIONS. WE ALSO PROPOSE TO DEVELOP RIBO-TRIBE FOR USE IN DROSOPHILA; WE RECENTLY DISCOVERED THAT STAMP DOES NOT WORK IN THIS ORGANISM, WHICH LIMITS US TO TRIBE. WE WILL THEN EXTEND THESE METHODS TO THE MORE BIOLOGICAL CONTEXT OF NEURONS, FROM DROSOPHILA AS WELL AS FROM MOUSE BRAINS. TO COMPLEMENT THESE EFFORTS, WE WILL DEVELOP AN EXTENSION OF THE TRIBE/STAMP THEME CALLED NANOBODY-EDITING. IT CONSISTS OF FUSING THE EDITING ENZYME, ADAR OR APOBEC, TO A GFP-NANOBODY, WHICH WILL THEN DELIVER THE EDITING ENZYME TO ANY GFP-TAGGED RNA BINDING PROTEIN OR GFP-TAGGED RIBOSOME. THE CHIMERIC, RECOMBINANT PROTEIN WILL BE USED IN VITRO AS A RECOMBINANT PROTEIN OR EXPRESSED IN VIVO. NANOBODY- EDITING WILL FACILITATE IDENTIFYING RBP AND RIBOSOME TARGETS, BECAUSE ALREADY EXISTING GFP-TAGGED RBP OR RIBOSOMES CAN SERVE AS SUBSTRATES. MOREOVER, IN VITRO EDITING WILL IN MANY CASES OBVIATE THE NEED TO GENERATE NEW TRANSGENES AND TRANSGENIC ANIMALS. LASTLY, TRIBE AND AS WELL AS RIBO-TRIBE WILL BE USED TO CHARACTERIZE TRANSLATIONAL REGULATION “AROUND THE CLOCK” WITHIN A FEW KEY DROSOPHILA CIRCADIAN NEURONS. THESE EFFORTS WILL DEEPEN OUR UNDERSTANDING OF CIRCADIAN GENE EXPRESSION REGULATION AS WELL AS PROVIDE THE COMMUNITY WITH NEW TOOLS WITH WHICH TO STUDY TRANSLATION IN IMPORTANT BUT CHALLENGING BIOLOGICAL SYSTEMS.

MALADAPTIVE COMPENSATORY PLASTICITY IN DEVELOPING CORTICAL CIRCUITS

STUDENT SUPPORT SERVICES PROGRAM

MECHANISMS OF VISUAL SIGNALING

TEMPERATURE COMPENSATION OF NEURONAL AND NETWORK FUNCTION

MECHANISM OF THE TRANSCRIPTIONAL RESPONSE TO TRANSITION METALS

HIERARCHICAL ACTIVE MATTER: FROM EXTENSILE BUNDLES TO FLOWING GELS, STREAMING LIQUID CRYSTALS AND MOTILE EMULSIONS

CHANNELS WITH KCNE SUBUNITS: CONFORMATIONAL DYNAMICS

CENTER FOR DISABILITY AND PREGNANCY RESEARCH - THE LURIE INSTITUTE FOR DISABILITY POLICY PROPOSES THE CENTER FOR DISABILITY AND PREGNANCY RESEARCH (CDPR), A CROSS-DISABILITY INITIATIVE TO ADDRESS GAPS IN KNOWLEDGE ABOUT PREGNANCY AND DISABILITY, ENHANCE THE EXPERIENCE OF PREGNANCY IN WOMEN WITH DISABILITIES AND PROMOTE OPTIMAL PREGNANCY-RELATED OUTCOMES FOR PREGNANT PEOPLE WITH DISABILITIES. THE CDPR?S PROPOSED WORK: 1) LEVERAGES EXISTING AND NEW DATA SOURCES TO EXAMINE RACIAL AND ETHNIC DISPARITIES IN PERINATAL CARE, COMPLICATIONS, AND OUTCOMES; 2) DEVELOPS AND TESTS THE EFFICACY OF A PRECONCEPTION EDUCATION CURRICULA FOR WOMEN WITH MOBILITY DISABILITIES; 3) ADAPTS AND PILOTS THE USE OF AN ACCESSIBLE PREGNANCY ACTION PLAN FOR WOMEN WITH DIVERSE DISABILITIES; 4) TESTS THE EFFICACY OF A DISABILITY ACCOMMODATION FIELD IN THE ELECTRONIC HEALTH RECORD ACROSS A NETWORK OF HOSPITAL-BASED OBSTETRIC CLINICS AND; 5) ADAPTS AND VALIDATES A SCREENING TOOL FOR THE DETECTION OF PERINATAL DEPRESSION IN WOMEN WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES. OUTCOMES INCLUDE: RIGOROUS, EVIDENCE-BASED RESEARCH THAT HELPS SHAPE OPTIMAL PERINATAL POLICY AND PRACTICE GUIDELINES, AND PROVIDES TARGETED, TAILORED, EFFECTIVE SUPPORTS FOR PREGNANT PEOPLE WITH DISABILITIES. KNOWLEDGE TRANSLATION ACTIVITIES EMPLOYING STATE-OF-THE-ART TECHNOLOGIES WILL BE GUIDED AND INFORMED BY THE CDPR COMMUNITY ADVISORY BOARD AND SUPPORTED BY NATIONAL PARTNERS COMPRISED OF DISABILITY ORGANIZATIONS AND MATERNAL AND CHILD HEALTH ORGANIZATIONS. PRODUCTS WILL INCLUDE A COMPREHENSIVE, ACCESSIBLE ONLINE PORTAL WITH LINKS TO RESEARCH, PRACTICE AND ADVOCACY SUPPORTS, TRAINING FOR PRACTITIONERS AND INDIVIDUALS, AND DISSEMINATION MATERIALS DESCRIBING OUR FINDINGS AND THEIR IMPLICATIONS FOR CLINICAL PRACTICE, POLICY, FAMILIES AND PREGNANT PEOPLE WITH DISABILITIES.

BRAIN-BODY-BEHAVIOR INTERFACE IN LEARNING AND DEVELOPMENT ACROSS THE LIFESPAN

INROADS: INTERSECTING RESEARCH ON OPIOID MISUSE, ADDICTION, AND DISABILITY SERVICES

HAROLD ROGERS PRESCRIPTION DRUG MONITORING PROGRAM TRAINING AND TECHNICAL ASSISTANCE

STUDENT SUPPORT SERVICES PROGRAM

A NOVEL APPROACH TO CHEMICAL COMMUNICATIONS

CONTROL BELIEFS, MEMORY, AND AGING

BAYESIAN ANALYSIS OF STRUCTURAL SHAPE AND CONFORMATION

UNRAVELING THE SYNAPTIC AND CIRCUIT MECHANISMS UNDERLYING A PLASTICITY-DRIVING INSTRUCTIVE SIGNAL - PROJECT SUMMARY LEARNING, FUNDAMENTAL TO COGNITION, REQUIRES STORING OF INFORMATION IN FLEXIBLE NEURAL ACTIVATION PATTERNS AND SYNAPTIC WEIGHT CHANGES (I.E., PLASTICITY) WITHIN NEURONAL ENSEMBLES. THESE REPRESENTATIONS ARE MODIFIED WITH EXPERIENCE ON THE TIMESCALE OF SECONDS TO MINUTES AND EVEN LIFETIMES. ALTHOUGH RECENT PIVOTAL WORK HAS PROVIDED INSIGHTS INTO HOW POPULATION ACTIVITY DRIVES MEMORY-GUIDED BEHAVIORS, MANY FUNDAMENTAL QUESTIONS REMAIN ABOUT THE NEURAL PLASTICITY MECHANISMS THAT UNDERLIE THE FORMATION OF THESE REPRESENTATIONS IN RESPONSE TO NEW EXPERIENCES. THE STANDARD SYNAPTIC PLASTICITY RULE (I.E., SPIKE TIMING- DEPENDENT PLASTICITY, STDP) REQUIRES PRECISELY TIMED AND REPETITIVE PRE- AND POSTSYNAPTIC ACTIVATION, WHICH IS INCONGRUENT WITH THE SEEMINGLY CHAOTIC ACTIVITY OF NETWORKS IN AWAKE BEHAVING ANIMALS. IN CONTRAST, BEHAVIORAL TIMESCALE SYNAPTIC PLASTICITY (BTSP), A LEARNING RULE I RECENTLY CO-DISCOVERED TO UNDERLIE THE DEVELOPMENT OF EXPERIENCE-DEPENDENT SPATIAL REPRESENTATIONS IN HIPPOCAMPAL CA1, REQUIRES ONLY A SINGLE INDUCTION TRIAL AND OPERATES ON THE COGNITIVELY RELEVANT TIMESCALE OF SECONDS. THUS, BTSP PROVIDES ONE OF THE FIRST BIOLOGICALLY PLAUSIBLE MECHANISMS FOR HOW A SINGLE EXPERIENCE CAN PRODUCE LEARNING-RELATED CHANGES IN BRAIN ACTIVITY. THIS PREVIOUS RESEARCH HAS POSITIONED MY LABORATORY TO ADDRESS FUNDAMENTAL QUESTIONS REGARDING THE CIRCUIT AND SYNAPTIC MECHANISMS UNDERLYING LEARNING. BUILDING UPON MY PUBLISHED WORK, THIS PROPOSAL WILL TEST THE MODEL THAT THE MEDIAL ENTORHINAL CORTEX LAYER 3 (MEC3) SERVES AS AN INSTRUCTOR, PROVIDING A CONTEXT-SPECIFIC TARGET SIGNAL TO CA1 NEURONS VIA THEIR TUFT DENDRITES, THEREBY DRIVING BTSP AND DIRECTING THE CA1 NETWORK IN HOW TO FORM A LEARNING-RELATED REPRESENTATION. SPECIFICALLY, WE WILL DETERMINE HOW THE MEC3 PRODUCES THIS TARGET SIGNAL. WE WILL FIRST USE EXTRACELLULAR RECORDINGS WITH NEUROPIXELS PROBES TO MONITOR THE NEURAL ACTIVITY FROM LARGE POPULATIONS OF MEDIAL ENTORHINAL CORTEX (MEC) NEURONS IN AWAKE MICE DURING A FLEXIBLE SPATIAL MEMORY PARADIGM THAT ALLOWS CONTROL OVER THE LEARNING TIME COURSE. USING THIS APPROACH, WE WILL DETERMINE THE FLOW OF INFORMATION THROUGH THE MEC NETWORK. SECOND, WE WILL USE IN VIVO WHOLE-CELL RECORDINGS OF MEC3 NEURONS DURING THE SAME LEARNING TASK TO PINPOINT THE SINGLE-CELL COMPUTATIONS UNDERLYING THE INSTRUCTIVE SIGNAL. WE WILL IDENTIFY THE PROCESSES INVOLVED, WHICH MAY INCLUDE CHANGES IN EXCITABILITY, SYNAPTIC INPUT INTEGRATION, AND PLASTICITY. THIRD, WE WILL COMBINE ACTIVITY RECORDING TECHNIQUES AND OPTOGENETICS TO DETERMINE THE EXTENT TO WHICH THE INSTRUCTIVE SIGNAL IS PRODUCED BY LOCAL COMPUTATION OR INHERITED FROM UPSTREAM CORTICAL REGIONS. THIS PROPOSAL WILL HAVE A FAR-REACHING INFLUENCE ON CELLULAR, SYSTEMS, AND COGNITIVE NEUROSCIENCE. AS LEARNING IS A FUNDAMENTAL COMPONENT OF VIRTUALLY ALL MAJOR BRAIN FUNCTIONS, UNDERSTANDING THE NEURAL ALGORITHMS OF LEARNING, FROM SYNAPTIC TO POPULATION LEVEL NEURAL CODING, WILL PROVIDE A BASIS FOR UNDERSTANDING HOW THE BRAIN PERFORMS ALL COMPLEX TASKS THAT DEPEND UPON LEARNING.

A CONTINUING EDUCATION INTERVENTION TO ADDRESS ABLEISM AMONG OBSTETRIC CLINICIANS PROVIDING PERINATAL CARE - PROJECT SUMMARY THE NOTION THAT DISABLED PEOPLE WOULD SEEK PREGNANCY AND MOTHERHOOD DEFIES LONG-HELD SOCIAL NORMS AND IS FRAUGHT WITH ECHOES OF THE EUGENICS MOVEMENT OF EARLY 20TH CENTURY AMERICA. NEVERTHELESS, PREGNANCY AND PARENTHOOD ARE INCREASINGLY COMMON AMONG DISABLED PEOPLE. DESPITE THE INCREASING NUMBERS OF DISABLED WOMEN HAVING BABIES, OBSTETRICIANS OFTEN HAVE LITTLE TRAINING IN HOW BEST TO PROVIDE HIGH QUALITY CARE TO THIS DIVERSE POPULATION, DOCUMENTED THROUGH PERSPECTIVES OF BOTH OBSTETRIC CLINICIANS THEMSELVES AND WOMEN WITH DISABILITIES. DISABLED WOMEN OFTEN EXPERIENCE WORSE MATERNAL AND CHILD HEALTH OUTCOMES THAN THEIR NONDISABLED PEERS. BARRIERS TO OPTIMAL CARE INCLUDE LACK OF TRAINING AND DISABILITY KNOWLEDGE OF OBSTETRIC CLINICIANS; LACK OF PROFESSIONAL GUIDELINES FOR PROVIDERS; PROVIDER UNWILLINGNESS TO CARE FOR WOMEN WITH DISABILITIES; INACCESSIBLE EQUIPMENT AND FACILITIES, POOR COMMUNICATION, AND ABLEIST ATTITUDES AND PRACTICES AMONG OBSTETRIC HEALTH CARE PROVIDERS AND STAFF. FURTHERMORE, EMERGING RESEARCH SUGGESTS THAT ABLEIST AND DISCRIMINATORY EXPERIENCES IN REPRODUCTIVE CARE MAY DISPROPORTIONATELY AFFECT DISABLED WOMEN OF COLOR. RESEARCH, BOTH WITH DISABLED WOMEN AND OBSTETRICIANS, HAS IDENTIFIED RECOMMENDATIONS FOR IMPROVING CARE, HOWEVER, THE CRITICAL NEXT STEP HAVE YET TO BE TAKEN – DESIGNING AN EDUCATIONAL INTERVENTION TO ADDRESS THESE CONCERNS AND PREPARE OBSTETRICIANS TO PROVIDE INCLUSIVE CARE. THIS STUDY WILL DEVELOP AN ONLINE CONTINUING EDUCATION PROGRAM FOR PRACTICING OBSTETRICIANS THAT ADDRESSES ABLEISM AND STRUCTURAL ABLEISM IN PERINATAL AND POSTPARTUM CARE. THE STUDY WILL FIRST CONDUCT FOCUS GROUPS AND KEY INFORMANT INTERVIEWS TO IDENTIFY ESSENTIAL CONTENT AND OPTIMAL APPROACHES FOR EDUCATING PROVIDERS ABOUT MITIGATING ABLEIST ATTITUDES, PRACTICES, AND POLICIES, STRUCTURAL ACCESS BARRIERS, AND PROVIDING PERINATAL CARE TO A DIVERSE POPULATION OF DISABLED PATIENTS. BASED ON THESE FINDINGS, THE STUDY TEAM WILL DESIGN AN ONLINE CONTINUING MEDICAL EDUCATION PROGRAM AND CONDUCT A RANDOMIZED CONTROLLED TRIAL WITH 200 OBSTETRIC PROVIDERS. PARTICIPANTS WILL COMPLETE ASSESSMENTS PRIOR TO TRAINING, AND AT THREE- AND 9-MONTHS FOLLOWING COMPLETION. THE STUDY WILL MEASURE CHANGE IN ABLEIST ATTITUDES AND CLINICAL POLICIES AND PRACTICES. KNOWLEDGE ACQUISITION, SATISFACTION WITH COURSE CONTENT, AND USABILITY WILL SIMILARLY BE EVALUATED. WE WILL ALSO INTERVIEW 20 PARTICIPANTS ABOUT THEIR EXPERIENCES AND REVISE THE PROGRAM ACCORDINGLY. WE WILL COLLABORATE WITH THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG) TO DISSEMINATE THE FINAL PROGRAM TO PRACTICING OBSTETRICIANS. THIS PROJECT DIRECTLY ADDRESSES PRIORITIES IDENTIFIED BY THE FUNDING AGENCY TO DEVELOP AND TEST INTERVENTIONS AT A COMMUNITY OR HEALTH SYSTEMS LEVEL TO MITIGATE ADVERSE HEALTH EFFECTS OF ABLEISM AND STRUCTURAL ABLEISM. THE EXPECTED OUTCOME OF THIS PROJECT IS AN INNOVATIVE EDUCATIONAL INTERVENTION TO IMPROVE PROVIDER KNOWLEDGE TO MITIGATE ABLEISM IN PERINATAL CARE.

PHYSIOLOGICAL GENOMICS OF NEURONAL CELL TYPES IN SENSORY AND MOTOR CORTEX

PROBING MOLECULAR AND GENETIC MECHANISMS OF INVERTEBRATE SUGAR DETECTION - PROJECT SUMMARY/ABSTRACT GUSTATORY RECEPTORS (GRS) ARE A LARGE FAMILY OF LIGAND-GATED ION CHANNELS IMPORTANT FOR INVERTEBRATE CHEMOSENSATION. WHILE THE FUNCTIONAL IMPORTANCE OF GRS IN INVERTEBRATE CHEMOSENSATION IS WELL-ESTABLISHED, LITTLE HAS BEEN KNOWN ABOUT GR STRUCTURE AND FUNCTION, INCLUDING HOW GRS RECOGNIZE LIGANDS AND HOW LIGAND BINDING IMPACTS GR ACTIVITY. THIS PROPOSAL ADDRESSES THE MECHANISMS OF GR ACTION BY FOCUSING ON THE GR43A FAMILY OF SUGAR RECEPTORS, COMBINING HIGH-RESOLUTION STRUCTURAL DETERMINATION WITH MUTATIONAL ANALYSIS, ION CHANNEL PHYSIOLOGY, AND MOLECULAR GENETICS AND BEHAVIOR IN DROSOPHILA. AIM 1) PROBE THE MECHANISMS THAT CONTROL LIGAND SENSITIVITY AND SPECIFICITY IN THE GR43A FAMILY: STRUCTURE-GUIDED MUTATIONAL AND FUNCTIONAL ANALYSIS WILL BE USED TO PROBE MECHANISMS OF LIGAND RECOGNITION AND CHANNEL ACTIVATION. IN ADDITION, AS GR43A HAS MULTIPLE ALTERNATIVE ISOFORMS IN DIPTERANS, THEIR IMPACT ON LIGAND SENSITIVITY AND SPECIFICITY WILL BE EXAMINED. AIM 2) ASSESS HOW ALTERNATIVE ISOFORMS OF D. MELANOGASTER GR43A IMPACT ITS FUNCTION: GR43A PERFORMS MULTIPLE SENSORY FUNCTIONS IN VIVO, ACTING BOTH AS A PERIPHERAL GUSTATORY RECEPTOR AND AN INTERNAL NUTRIENT SENSOR. USING TRANSGENIC AND GENOME EDITED DROSOPHILA, THE HYPOTHESIS THAT DIFFERENT GR43A ISOFORMS SERVE DISTINCT IN VIVO FUNCTIONS WILL BE TESTED. AIM 3) EXAMINE THE IMPACT OF ACTIVITY-ALTERING MUTATIONS AND ISOFORM VARIATION USING CRYO-EM: HIGH-RESOLUTION CRYO-EM-BASED STRUCTURES AND CONFORMATIONAL ENSEMBLES WILL BE DETERMINED TO EXAMINE HOW ALTERNATIVE ISOFORMS OF WILD TYPE GR43A AND SELECT MUTANT GR43A FAMILY MEMBERS IMPACT LIGAND AND CHANNEL OPENING AT A MECHANISTIC LEVEL. THIS BASIC SCIENCE INVESTIGATION WILL PROVIDE A DETAILED UNDERSTANDING OF THE STRUCTURAL AND FUNCTIONAL ASPECTS OF LIGAND-BINDING AND CHANNEL ACTIVATION WITHIN THE LARGE AND, TO DATE, POORLY UNDERSTOOD GR FAMILY. UNDERSTANDING GR ACTIVATION BY LIGANDS IS OF POTENTIAL VALUE FOR DISEASE VECTOR CONTROL. GRS PLAY IMPORTANT ROLES IN SENSORY-DRIVEN BEHAVIORS IN ARTHROPOD DISEASE VECTORS, AND GR-EXPRESSING NEURONS ARE OFTEN ACCESSIBLE TO ENVIRONMENTAL CHEMICALS, MAKING GRS PROMISING TARGETS FOR CONTROL AGENTS.

DYNAMICAL MAINTENANCE OF LEFT-RIGHT SYMMETRY DURING VERTEBRATE DEVELOPMENT - BROAD OBJECTIVE: MAINTAINING ANATOMICAL SYMMETRY IN VERTEBRATES IS ESSENTIAL FOR PROPER PHYSIOLOGICAL FUNCTION, AND LOSS OF SYMMETRY IN RIBS AND VERTEBRAE CAN LEAD TO SERIOUS CONDITIONS SUCH AS SCOLIOSIS AND IMPAIRMENTS OF APPROPRIATE BREATHING AND POSTURE. THIS PROJECT WILL EXPLORE THE DEVELOPMENTAL EMERGENCE OF LEFT-RIGHT SYMMETRY, COMBINING BIOLOGICAL EXPERIMENTS ON WILD-TYPE MICE AND A MODEL OF EARLY LOSS OF SYMMETRY WITH MATHEMATICAL MODELS OF GENE EXPRESSION AND MOLECULE DISTRIBUTIONS. THROUGH THESE STUDIES, THE PROJECT WILL PROVIDE NEW IMPORTANT INSIGHT INTO THE DETERMINANTS OF BODY (A)SYMMETRY. SPECIFIC AIMS AND RESEARCH DESIGN: THE SOMITES ARE THE EMBRYONIC STRUCTURES GIVING RISE TO THE VERTEBRAE AND RIB CAGE. THEY ARE FORMED AT EARLY PHASES OF EMBRYONIC DEVELOPMENT AND EMERGE PROGRESSIVELY IN PAIRS OF PARAXIAL MESODERM BLOCKS ON BOTH SIDES OF THE MIDLINE IN A HIGHLY SYMMETRIC MANNER. THE SYMMETRY OF THE SOMITES IS ACTIVELY MAINTAINED THROUGH MECHANISMS CONTROLLED BY RETINOIC ACID (RA) SIGNALING. INDEED, ANIMALS DEFICIENT IN RA EXHIBIT AN ASYMMETRIC SOMITE FORMATION. THIS PROPOSAL WILL INVESTIGATE THIS RA-MEDIATED SYMMETRY MAINTENANCE MECHANISMS BY COMBINING EXPERIMENTS ON RA-DEFICIENT MICE WITH MATHEMATICAL MODELS OF SOMITOGENESIS. IN AIM 1, TO INVESTIGATE THE DYNAMICAL MECHANISM OF SOMITE FORMATION IN WILD-TYPE AND RA-DEFICIENT EMBRYOS, WE WILL CHARACTERIZE FINELY THE SOMITE FORMATION TIMING, PERIOD, AND POSITIONS IN MOUSE EMBRYOS THROUGH LIVE IMAGING TECHNIQUES COUPLED WITH AND TOPOLOGICAL DATA ANALYSIS. IN AIM 2, TO STUDY THE GENETIC MECHANISM INVOLVED IN THE SEGMENTATION CLOCK, WHICH CONTROLS THE SPATIO-TEMPORAL FORMATION OF SOMITES, THE SAME LIVE-IMAGING SETUP WILL BE LEVERAGED TO EXTRACT THE DYNAMICS OF THE SEGMENTATION CLOCK IN MOUSE EMBRYOS. THIS DATA WILL BE USED TO DEVELOP AND SPECIFY A THEORETICAL MODEL OF SOMITOGENESIS WHICH WILL IN TURN ALLOW EXPLORING THE DETERMINANTS OF SYMMETRY MAINTENANCE AND ITS BREAKDOWN. TO EXPLORE HOW ASYMMETRY MAY ARISE AND BE BUFFERED BY RA, AIM 3 PROPOSES TO STUDY THE ORIGIN OF ASYMMETRY IN RA-DEFICIENT MOUSE. IT WILL RELY ON THE DEVELOPMENT OF COMPUTATIONAL FLUID DYNAMICS SIMULATIONS TO ANALYZE THE GLOBAL DISTRIBUTION OF KEY SIGNALING MOLECULES AS THEY ARE TRANSPORTED IN FLUIDS DRIVEN BY CILIA MOVEMENTS. THIS WILL BE COUPLED TO REACTION-DIFFUSION SYSTEMS AND THEIR DYNAMICS WILL BE EXPLORED TO INVESTIGATE HOW RA-MEDIATED MECHANISM CAN BUFFER ANY INITIAL ASYMMETRY IN MOLECULAR CONCENTRATIONS.

RESEARCH CENTER ON MANAGED CARE AND DRUG ABUSE TREATMENT

RESEARCH IN QUANTUM FIELD THEORY, COSMOLOGY, AND STRING THEORY

EMPIRICALLY TESTING THE ACCURACY AND BIAS OF ANCESTRAL PROTEIN RESURRECTION METHODS

TRAINING IN COGNITIVE AGING IN A SOCIAL CONTEXT

STUDY OF CAREER ADVANCEMENT AND QUALITY JOBS IN HEALTH CARE

TAS::89 0227::TAS RECOVERY;NEW-EARLY CAREER:RECOVERY ACT- EARLY-LATE HETEROBIMETALLIC COMPLEXES LINKED BY PHOSPHINOAMIDE LIGANDS: TUNING REDOX POTENT

CRCNS: CORTICAL NETWORK MODELS OF TASTE PROCESSING: DYNAMICS AND PLASTICITY

UNCOVERING THE FUNCTIONS OF CIRCRNAS IN AGING - PROJECT SUMMARY AGING CAN BE DESCRIBED AS THE PROGRESSIVE LOSS OF CELLULAR HOMEOSTASIS AND AN INCREASE IN DYSFUNCTION OVER TIME. ONE SYSTEM THAT SEEMS ESPECIALLY SUSCEPTIBLE TO THE RAVAGES OF TIME IS THE CENTRAL NERVOUS SYSTEM. BRAIN FUNCTION REQUIRES MULTILEVEL CONTROL OF GENE EXPRESSION. IN PARTICULAR, REGULATION OF RNA METABOLISM IS A MAJOR HUB FOR REGULATION AND RECENT RESEARCH HAS SHOWN A STRONG LINK BETWEEN PERTURBATION OF RNA METABOLISM AND A NUMBER OF NEUROLOGICAL AND NEURODEGENERATIVE DISEASES FOR WHICH AGING IS THE MAIN RISK FACTOR AND DRIVING FORCE. HOWEVER, WE STILL DON’T KNOW THE EXACT LINKS BETWEEN RNA METABOLISM AND AGING. CIRCULAR RNAS (CIRCRNAS) ARE HIGHLY ABUNDANT RNAS PRODUCED BY CIRCULARIZATION OF SPECIFIC EXONS. AS CIRCRNA PRODUCTION COMPETES WITH RNA SPLICING, THEIR BIOGENESIS IS PER SE A CIS REGULATOR OF GENE EXPRESSION. MOREOVER, SEVERAL CIRCRNAS ALSO HAVE FUNCTIONS IN TRANS IN TISSUES LIKE THE MUSCLE AND THE BRAIN WHERE SOME OF THEM ARE TRANSLATED. INTERESTINGLY, CIRCRNAS HAVE BEEN SHOWN TO ACCUMULATE IN AN AGE DEPENDENT MANNER, SUGGESTING THAT THEY MIGHT BE RELEVANT FOR AGE-RELATED HOMEOSTASIS AND/OR PATHOGENESIS. WE RECENTLY DEVELOPED NEW BIOCHEMICAL AND GENETIC TOOLS THAT ALLOW US TO DETERMINE THAT A SUBSET OF CIRCRNAS REGULATE LIFESPAN. BRIEFLY, WE GENERATED A RESOURCE TO KNOCKDOWN (KD) CIRCRNAS AND IDENTIFIED 24 CIRCRNAS THAT ALTER LIFESPAN WHEN KNOCKED DOWN (KD). INTERESTINGLY MANY OF THE PROTECTIVE-CIRCRNAS (THOSE THAT DIMINISH LIFETIME WHEN KD) ARE TRANSLATED AND ARE HOSTED BY GENES BOUND BY FOXO, A KEY REGULATOR OF AGING AND TRANSLATION, SUGGESTING A STRONG CONNECTION BETWEEN CIRCRNA TRANSLATION, AGING AND FOXO. IN ADDITION, WE FOUND THAT KD OF CIRCKLG AND CIRCSIDEIII RESULT IN STRONG AND CONSISTENT LIFESPAN EXTENSIONS, INCREASED HEALTH SPANS AS WELL AS “YOUNGER TRANSCRIPTOMES” DEMONSTRATING A DIRECT IMPACT OF THESE CIRCRNAS ON AGING. THIS PROPOSAL AIMS TO EXPAND THESE EXCITING RESULTS AND MECHANISTICALLY DISSECT THE INTERPLAY BETWEEN CIRCRNAS AND AGING PATHWAYS. FOR DOING SO, WE WILL: 1) DETERMINE THE MECHANISM BEHIND THE AGING- PROMOTING CIRCRNAS; 2) DETERMINE THE EXTENT AND REQUIREMENTS FOR CIRCRNA TRANSLATION AND RELATIONSHIP TO AGING AND 3) DEFINE THE RELATIONSHIP BETWEEN THE FOXO REGULON AND CIRCRNAS IN AGING. IN SUM, THIS PROJECT WILL ILLUMINATE KEY REGULATORY MECHANISMS OF CIRCRNA TRANSLATION AND THE RELATIONSHIP OF THESE RNAS WITH AGING. IN ADDITION, THIS PROJECT IS HIGHLY INNOVATIVE IN ITS ANALYSIS OF THE GENERAL FUNCTIONS OF CIRCRNAS, BUILDS ON STRONG PRELIMINARY RESULTS AND THE UNIQUE AND CONSTANTLY EVOLVING EXPERTISE OF OUR GROUPS.

MULTISCALE MODELING OF MECHANISMS FOR VIRAL CAPSID ASSEMBLY AND POLYMORPHISM

WASHINGTON CIRCLE PERFORMANCE MEASURES AND CRIMINAL JUSTICE OUTCOMES

PREDOCTORAL RESEARCH TRAINING AT THE INTERFACE OF BRAIN, BODY, AND BEHAVIOR

JOINT BAYESIAN ANALYSIS OF SINGLE-MOLECULE COLOCALIZATION IMAGES AND KINETICS

MECHANISMS OF LONG-TERM POTENTIATION

FOXO REGULON AND TRANSLATION CONTROL

STUDY OF EMPLOYMENT AND ADVANCEMENT OF RACIAL, ETHNIC AND LINGUISTIC MINORITIES FOR NEW HAMPSHIRE HEALTH PROFESSION OPPO

DYNAMIC CONTROL OF MITOCHONDRIAL FUNCTION BY THE PROTEIN UNFOLDASE CLPX - ABSTRACT MITOCHONDRIA MUST MAINTAIN AND REGULATE THEIR PROTEOME TO MEET THE VARIED NEEDS OF THE CELL THROUGHOUT GROWTH AND DEVELOPMENT. MITOCHONDRIA EMPLOY SEVERAL AAA+ FAMILY PROTEIN UNFOLDASES AS AN IMPORTANT TOOL IN ACCOMPLISHING THIS CONTROL. WE HERE FOCUS ON THE AAA+ PROTEIN UNFOLDASE CLPX, WHICH CAN ACT ON ITS OWN OR UNFOLD PROTEINS FOR COUPLED DEGRADATION BY ITS PARTNER PROTEASE CLPP. LOSS OF CLPX IS LETHAL IN MICE, MUTATIONS IN CLPX AND CLPP CAUSE MITOCHONDRIOPATHIES, AND CLPXP DRIVES CANCER PROGRESSION AND IS TARGETED BY DRUGS IN CLINICAL TRIALS IN A DIVERSE RANGE OF CANCERS. THESE PHENOTYPES INDICATE THE CRUCIAL CONTRIBUTIONS OF CLPX AND CLPP TO MITOCHONDRIAL PHYSIOLOGY. THE OVERALL GOAL OF THIS PROJECT IS TO REVEAL THE MECHANISMS BY WHICH CLPX SELECTS SUBSTRATES AT THE APPROPRIATE TIME, THUS TAILORING THEIR FUNCTION TO MITOCHONDRIAL AND CELLULAR NEEDS. PROTEOMIC STUDIES HAVE LINKED CLPX TO MULTIPLE LIKELY SUBSTRATES THAT CONTROL CORE MITOCHONDRIAL PROCESSES, ALTHOUGH ONLY A FEW HAVE BEEN FURTHER CHARACTERIZED, AND MECHANISMS FOR CONDITIONAL SUBSTRATE SELECTION REMAIN LARGELY UNDETERMINED. ONE OF THE BEST-CHARACTERIZED FUNCTIONS FOR CLPX IS TO REGULATE HEME BIOSYNTHESIS, A CRUCIAL MITOCHONDRIAL FUNCTION, BY ACTING ON THE FIRST ENZYME IN THIS PATHWAY, ALA SYNTHASE (ALAS). CLPX ACTIVATES ALAS BY PARTIAL UNFOLDING TO FACILITATE COFACTOR INCORPORATION. WHEN HEME LEVELS ARE HIGH, CLPX (WITH ITS PARTNER PROTEASE CLPP) ALSO APPEARS TO INACTIVATE ALAS BY COMPLETE UNFOLDING AND DEGRADATION, SIGNALED BY A HEME-BINDING SITE IN ALAS. IN PRELIMINARY RESULTS, WE HAVE BIOCHEMICALLY RECONSTITUTED HEME-INDUCED DEGRADATION OF ALAS BY CLPXP, CONFIRMING THE DIRECT NATURE OF THIS ACTIVITY. WE ADDITIONALLY DISCOVERED THAT DEGRADATION STRONGLY DEPENDS ON A HEME-SENSITIVE ADAPTOR PROTEIN. THE PROJECT PROPOSED HERE WILL (1) ELUCIDATE THE MECHANISM BY WHICH HEME DRIVES ASSEMBLY AND LICENSING OF A DEGRADATION COMPLEX FOR ALAS, USING OUR RECONSTITUTED SYSTEM WITH EQUILIBRIUM-BINDING AND KINETIC ANALYSES OF COMPLEX ASSEMBLY AND ALAS DEGRADATION IN PARALLEL WITH OBSERVATIONS IN CELLS. (2) WE WILL DETERMINE HOW HEME IS DIRECTLY SENSED WITHIN THE COMPLEX USING SPECTROSCOPIC AND STRUCTURAL METHODS AND TEST HOW THE HEME-RESPONSIVENESS OF THIS SYSTEM IS TUNED TO SUIT DIFFERENT CELLULAR PROGRAMS. (3) WE WILL DETERMINE HOW A HEME-SENSITIVE ADAPTOR IN THE CLPXP DEGRADATION COMPLEX TUNES SUBSTRATE SELECTION BY CLPX BEYOND ALAS, USING A CANDIDATE-BASED APPROACH AND AN UNBIASED PROTEOMIC APPROACH IN PARALLEL. THIS STUDY WILL REVEAL FUNDAMENTAL MECHANISMS FOR THE CONDITIONAL CONTROL OF MITOCHONDRIAL FUNCTIONS AND WILL PROVIDE DETAILED MOLECULAR TARGETS FOR THE DEVELOPMENT OF THERAPY FOR MULTIPLE DISEASES WITH A BASIS IN MITOCHONDRIAL FUNCTION, INCLUDING DISORDERS OF HEME BIOSYNTHESIS AND CANCER.

SIGNIFICANT STATIC & DYNAMIC STRUCTURES IN NATURAL SCENES FOR VISUAL RECOGNITION

REGULATION OF SYMPATHETIC NEURON SYNAPTIC ACTIVITY

THERMOGENETIC TOOLS FOR MANIPULATING NEURONAL ACTIVITY IN MAMMALS

STRUCTURE AND MECHANISM OF A VIRTUAL PROTON PUMP

ABBERIOR 3D-STED MICROSCOPE FOR SUPER-RESOLUTION IMAGING - PROJECT SUMMARY WE ARE REQUESTING FUNDS TO PURCHASE AN ABBERIOR INSTRUMENTS FACILITY LINE 3D STED MICROSCOPE TO BE MAINTAINED IN THE BRANDEIS UNIVERSITY CONFOCAL IMAGING CORE FACILITY. THIS MICROSCOPE WILL SERVE A PRIMARY USER GROUP OF 10 NIH FUNDED INVESTIGATORS, AND TWO JUNIOR FACULTY WHO WILL BE APPLYING FOR NIH FUNDING, AND WE WELCOME ADDITIONAL USERS FROM THE BIOMEDICAL SCIENCES AT BRANDEIS AND THE REGION. OUR GROUPS PURSUE A WIDE VARIETY OF PROJECTS RELEVANT TO HUMAN HEALTH INCLUDING AGING, CANCER BIOLOGY, NEURODEGENERATION, EPILEPSY, LEARNING AND MEMORY, AND THE ORIGINS OF MULTICELLULAR ORGANISMS. A COMMON FEATURE OF THESE DIVERSE STUDIES IS A DEEP RELIANCE ON OPTICAL MICROSCOPY AND AN OVERARCHING INTEREST IN UNDERSTANDING HOW MOLECULAR-SCALE STRUCTURES (TENS OF NANOMETERS IN SIZE) CONTROL CELL AND TISSUE-SCALE BIOLOGICAL PROCESSES. A MAJOR BARRIER TO OUR PROGRESS IN THESE AREAS IS THE LACK OF AN IMAGING SYSTEM AT OUR INSTITUTION THAT CAN RESOLVE THESE TINY STRUCTURES OF INTEREST. AMONG THE MANY STRATEGIES TO OVERCOME THIS RESOLUTION BARRIER (SUCH AS STORM, SOFI, AND EXPANSION MICROSCOPY), A STED MICROSCOPE IS THE IDEAL SOLUTION FOR OUR RESEARCH COMMUNITY: IT IS FUNDAMENTALLY A CONFOCAL MICROSCOPE, AND OUR USER BASE HAS EXCEPTIONALLY BROAD AND DEEP EXPERTISE IN ALL ASPECTS OF CONFOCAL MICROSCOPY INCLUDING SAMPLE PREPARATION, IMAGING, AND RIGOROUS QUANTITATIVE IMAGE ANALYSIS. A STED MICROSCOPE WOULD REPRESENT A FIVE-FOLD IMPROVEMENT IN RESOLUTION OVER OUR CURRENT CAPABILITIES AND WOULD OPEN UP AVENUES OF BIOLOGY THAT ARE COMPLETELY INVISIBLE TO US NOW. DATA COLLECTED ON THE INSTRUMENT WILL HELP ANSWER MANY OPEN QUESTIONS: HOW DO NOVEL THERAPEUTIC NANOPARTICLES TARGET SUBCELLULAR ORGANELLES TO FIGHT CANCER? HOW DO SIGNAL SENDING AND RECEIVING STRUCTURES AT NEURONAL SYNAPSES ASSEMBLE TOGETHER TO CONTROL LEARNING AND MEMORY OR PREVENT EPILEPSY? HOW DO MOLECULES IMPORTANT TO AGING AND NEURODEGENERATION LOCALIZE AND FUNCTION AT THESE SYNAPSES? BECAUSE OF THE SMALL SIZE OF EACH OF THESE STRUCTURES, THESE ARE QUESTIONS WE CANNOT ANSWER WITH OUR CURRENT TECHNOLOGY. BEYOND THE INCREASE IN RESOLUTION THIS SYSTEM PROVIDES, IT IS EQUIPPED WITH FEATURES THAT FACILITATE DEEP VOLUMETRIC IMAGING AND LIVE IMAGING, WHICH WILL ALLOW US TO PERFORM EXPERIMENTS IN VIVO IN LIVING TISSUES. TOGETHER, THE ABBERIOR STED SYSTEM WOULD PROFOUNDLY IMPROVE OUR ABILITY TO DISCOVER HOW NANOSCALE MOLECULAR AND CELLULAR STRUCTURES CONTROL CELL AND TISSUE BIOLOGY THAT IS RELEVANT TO HUMAN HEALTH AND DISEASE.

COLLABORATIVE EXPERIMENTAL & COMPUTATIONAL STUDIES OF CONFORMATIONAL TRANSITIONS

TECHNOLOGIES FOR DIRECTED EVOLUTION OF GLYCOAPTAMERS - PROJECT SUMMARY/ABSTRACT THE GOAL OF THIS FOCUSED TECHNOLOGY R01 PROJECT IS TO DEVELOP TECHNOLOGIES FOR RAPID DISCOVERY OF INHIBITORS OF CARBOHYDRATE-BINDING PROTEINS (CBPS). CARBOHYDRATE-PROTEIN INTERACTIONS ARE CRITICAL IN NUMEROUS PROCESSES INCLUDING HOST-PATHOGEN RECOGNITION, CELL ADHESION AND CELL SIGNALING, CANCER ANGIOGENESIS, IMMUNE SUPPRESSION, HEART/LIVER/LUNG/EYE FIBROSIS, ATHEROSCLEROSIS, DIABETES, AND RHEUMATOID ARTHRITIS, TO NAME A FEW EXAMPLES. HOWEVER, SELECTIVE DISRUPTION OF SPECIFIC CBP INTERACTIONS IS CHALLENGING IN VIVO. CBPS GENERALLY BIND WEAKLY TO INDIVIDUAL GLYCANS, WITH HIGHER AFFINITY (AVIDITY) OR SPECIFICITY COMING FROM MULTIVALENT INTERACTIONS TO CLUSTERED GLYCANS OR INTERACTIONS WITH NEARBY NON-CARBOHYDRATE ELEMENTS. A GIVEN CBP ALSO USUALLY BINDS TO VARIOUS GLYCANS. TO UNTANGLE THE COMPLEX WEB OF CBP FUNCTIONS, IT IS IMPORTANT TO HAVE A WAY TO RAPIDLY DEVELOP A SPECIFIC AND POTENT INHIBITOR OF A CBP THAT CAN BE USED IN THE RELEVANT IN VIVO CONTEXT. TO THIS END, WE PROPOSE TWO AIMS: 1) TO DEVELOP MULTIVALENT GLYCO-F-RNA APTAMERS, IN WHICH A NUCLEASE-RESISTANT, F-RNA BACKBONE IS EVOLVED TO PRESENT SIMPLE GLYCANS IN A MANNER THAT IS SELECTIVELY RECOGNIZED BY A CBP OF INTEREST; 2) TO DEVELOP MONOVALENT GLYCO- F-RNA APTAMERS, IN WHICH A SIMPLE GLYCAN PROVIDES A BINDING “FOOTHOLD” FOR THE CBP OF INTEREST, WHICH THE EVOLVED F-RNA COMPONENT CONFERS ADDITIONAL BINDING AFFINITY AND SPECIFICITY THROUGH INTERACTIONS AUXILIARY TO THE GLYCAN-BINDING POCKET.

HIPPOCAMPAL - GUSTATORY CORTICAL INTERACTIONS UNDERLYING FORMATION OF TASTE-SPACE COGNITIVE MAPS - PROJECT SUMMARY/ ABSTRACT ANIMALS NEED TO LEARN AND REMEMBER THE LOCATIONS OF NOURISHING AND TOXIC FOOD SOURCES FOR SURVIVAL AND FOR ADAPTING TO CHANGES IN THE EXTERNAL ENVIRONMENT. IT IS THEREFORE NECESSARY TO ASSOCIATE LOCATIONS WITH REWARDING AND AVERSIVE TASTE EXPERIENCES IN SPATIAL CONTEXTS – THESE ARE ESSENTIALLY EPISODIC EXPERIENCES THAT FORM ASSOCIATIVE MEMORIES OF TASTES AND SPATIAL LOCATIONS. IT IS KNOWN THAT THE HIPPOCAMPUS IS NECESSARY FOR EPISODIC MEMORIES AND FORMATION OF SPATIAL COGNITIVE MAPS, AND THE GUSTATORY CORTEX (GC) PLAYS A CENTRAL ROLE IN TASTE PERCEPTION AS WELL AS FOR PALATABILITY AND VALENCE CODING. BUT HOW NETWORKS OF NEURONS IN THESE TWO REGIONS INTERACT TO ASSOCIATE TASTE PALATABILITY INFORMATION WITH THE SPATIAL CONTEXTS IN WHICH THEY OCCUR, AND HOW SUCH INTERACTIONS DRIVE SUBSEQUENT BEHAVIORAL EXPLORATION TO APPROACH POTENTIAL FOOD SOURCES, IS LARGELY UNKNOWN. WE HAVE RECENTLY DISCOVERED A SUBSET OF HIPPOCAMPAL CA1 PLACE CELLS IN RATS THAT DISCRIMINATE TASTES BASED ON PALATABILITY, PROVIDING A FOUNDATION FOR ADDRESSING THESE QUESTIONS. WE FOUND THAT TASTE RESPONSIVE CA1 CELLS ENCODE TASTE PALATABILITY ON A SLOW TIMESCALE IN RESPONSE TO TASTE STIMULI, AND THESE TASTE RESPONSES ARE GATED BY THE SPATIAL RESPONSES OF INDIVIDUAL CELLS. FURTHER, WE ALSO SHOWED THAT SPATIAL CODING OF THIS TASTE-RESPONSIVE CA1 SUB-NETWORK IS REFINED THROUGH OFFLINE REACTIVATION DURING SHARP-WAVE RIPPLES (SWRS). HERE, WE WILL USE A COMBINATION OF MULTISITE ELECTROPHYSIOLOGY, ANALYSES OF BEHAVIOR, AND OPTOGENETIC MANIPULATION OF INTER-REGIONAL CONNECTIVITY TO INVESTIGATE THE ROLE OF HIPPOCAMPAL-GUSTATORY CORTICAL INTERACTIONS IN FORMING A SPATIAL COGNITIVE MAP OF ECOLOGICALLY RELEVANT FOOD STIMULI. IN PARTICULAR, WE HYPOTHESIZE THAT NETWORKS IN CA1 AND GC INTERACT FOR LEARNING, FORMATION, AND RECALL OF MEMORIES OF LOCATIONS ASSOCIATED WITH SPECIFIC TASTE EXPERIENCES. WE WILL FIRST USE SIMULTANEOUS RECORDINGS FROM NEURAL ENSEMBLES IN GC AND CA1 REGIONS AS RATS LEARN TO ASSOCIATE APPETITIVE AND AVERSIVE TASTES WITH SPECIFIC LOCATIONS IN AN ADAPTABLE MAZE, QUANTIFYING HOW EXPLORATION PATHS CHANGE WITH TASTE EXPERIENCE. WE WILL INVESTIGATE THE DEVELOPMENT OF TASTE-LOCATION CODING IN CA1 AND THE COORDINATION OF GC AND CA1 ACTIVITY IN SERVICE OF PALATABILITY CODING AT FOOD SOURCE LOCATIONS. NEXT, WE WILL TEST IF SWRS IN HIPPOCAMPUS AT FOOD SOURCES ARE ASSOCIATED WITH TASTE-SPECIFIC REACTIVATION SIMULTANEOUSLY IN CA1 AND GC, AND WHETHER THERE IS COORDINATION OF REACTIVATION OF TASTE AND LOCATION INFORMATION THAT CAN SUPPORT TASTE-LOCATION ASSOCIATIONS. FINALLY, WE WILL USE OPTOGENETIC PERTURBATION OF THE INPUT FROM THE TASTE SYSTEM TO THE HIPPOCAMPUS DURING FOOD SAMPLING TO TEST IF THIS WILL DISRUPT FORMATION OF DISCRIMINATIVE MEMORIES FOR SPATIAL LOCATIONS OF PREFERRED TASTES. TOGETHER, THESE AIMS WILL PROVIDE CRUCIAL INSIGHT INTO HOW NETWORKS IN THE HIPPOCAMPUS INTERACT WITH PRIMARY SENSORY CORTICAL NETWORKS THAT MEDIATE TASTE PERCEPTION, IN ORDER TO EMBED ETHOLOGICALLY RELEVANT FOOD INFORMATION IN THE SPATIAL COGNITIVE MAP, THUS ENABLING ANIMALS TO SUCCESSFULLY NAVIGATE A TASTE-SPACE COGNITIVE MAP.

INHIBITOR MEDIATED PROTEIN DEGRADATION

UROL: EPIGENETICS 2: ROBUSTNESS AND ADAPTABILITY OF THE DYNAMIC EPIGENOME: A MULTISCALE APPROACH -CELLS EXPERIENCE A WIDE RANGE OF UNFORESEEN CHALLENGES IN THEIR NATURAL ENVIRONMENT. UNDER THESE CIRCUMSTANCES, CHANGE IS OFTEN NOT A CHOICE. CELLS INEVITABLY FIND NEW WAYS TO ADAPT AND SURVIVE UPON EXPOSURE TO ACUTE STRESS. BACTERIAL CELLS THAT ARE EXPOSED TO ANTIBIOTICS ACQUIRE RESISTANCE THROUGH CHANGES TO THEIR DNA SEQUENCE. PLANTS MAKE DECISIONS ABOUT THEIR FLOWERING TIMES BASED ON THEIR TIME OF EXPOSURE TO COLD CONDITIONS. CANCER CELLS, WHEN EXPOSED TO CHEMOTHERAPEUTIC AGENTS, CAN BECOME RESISTANT, POSING A SIGNIFICANT CHALLENGE TO TREATMENT AND WORSENING PATIENT OUTCOMES. IN MANY CASES, THESE ADAPTIVE CHANGES ARE EPIGENETIC - THEY RESULT IN GENE EXPRESSION CHANGES WITHOUT ANY ALTERATIONS TO THE GENETIC BLUEPRINT. IN CONTRAST TO GENETIC MUTATIONS, EPIGENETIC CHANGES CAN BE TRANSIENT, HERITABLE AND REVERSIBLE PROVIDING DIVERSE PATHWAYS FOR CELLULAR INNOVATION. THE THOUSANDS OF GENES WITHIN THE NUCLEUS OF EACH CELL SERVE AS TUNABLE KNOBS THAT CAN ALTER CELL FITNESS. WE DO NOT UNDERSTAND HOW CELLS CHOOSE WHICH KNOBS TO TURN, AND MAKING THE WRONG CHOICE COULD PROVE CATASTROPHIC. THIS NSF-FUNDED RESEARCH PROGRAM AIMS TO UNDERSTAND THE FUNDAMENTAL RULES THAT SHAPE THE INNER WORKINGS OF THE CELL. THIS RESEARCH PROGRAM CAPTURES THE CHAOTIC COLLISIONS BETWEEN MOLECULES WITHIN A CELL WHICH CAN WORK IN UNISON TO HELP CELLS MAKE ACCURATE, ADAPTIVE DECISIONS. THIS PROJECT ALSO SEEKS TO BROADLY IMPACT HIGH SCHOOL AND UNDERGRADUATE EDUCATION IN MICHIGAN THROUGH A UNIQUE EMPHASIS ON INTERDISCIPLINARY RESEARCH AND LEARNING. UNDERSTANDING THE FUNDAMENTAL RULES OF LIFE THAT GUIDE CELLS TO MAKE ADAPTIVE DECISIONS REQUIRES INTERDISCIPLINARY TOOLS THAT CAPTURE CELLULAR PROCESSES ACROSS DIFFERENT TIME AND LENGTH SCALES. BECAUSE EPIGENETIC CHANGES CAN OCCUR EVEN WITHOUT CELL DIVISION AND ARE NOT PERMANENT, THEY LEAD TO A RAPID, REVERSIBLE, AND ADAPTIVE CELLULAR RESPONSE THAT HAS PROFOUND CONSEQUENCES FOR CELL GROWTH AND SURVIVAL. THIS RESEARCH USES HIGH-RESOLUTION IMAGING TO VISUALIZE SINGLE MOLECULES IN CELLS, MICROFLUIDIC PLATFORMS TO REVEAL DECISION MAKING EVENTS WITHIN INDIVIDUAL CELLS, AND AUTOMATED CONTINUOUS CULTURE METHODS TO INVESTIGATE THE DYNAMICS OF CELL POPULATIONS. THE SYNTHESIS AND INTEGRATION OF THESE MULTI-DIMENSIONAL VIEWPOINTS WILL ENABLE THE DEVELOPMENT OF MATHEMATICAL MODELS WITH THE POTENTIAL TO PREDICT EMERGENT PROPERTIES OF THESE COMPLEX REGULATORY NETWORKS. ULTIMATELY, THE OUTCOME OF THESE STUDIES WILL BE A SET OF RULES THAT DEFINE HOW ADAPTIVE EPIGENETIC STATES, MUCH LIKE GENETIC MUTATIONS, REPRESENT EVOLVABLE TRAITS IN EUKARYOTIC GENOMES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

PRESCRIPTION DRUG MONITORING PROGRAM CLEARINGHOUSE / CENTER OF EXCELLENCE

DMREF: PROGRAMMABLE CHEMOMECHANICAL MATERIALS

TRIO - STUDENT SUPPORT SERVICES - STUDENT SUPPORT SERVICES PROGRAM

MULTISCALE MODELING OF ENZYMATIC REACTIONS AND BIOIMAGING PROBES - MULTISCALE MODELING OF ENZYMATIC REACTIONS AND BIOIMAGING PROBES ABSTRACT THIS PROJECT ADDRESSES A CRITICAL TECHNOLOGY/SOFTWARE GAP — THE ACCESSIBILITY OF AB INITIO QUANTUM MECHAN- ICAL MOLECULAR MECHANICAL (QM/MM) MULTISCALE MODELING TOOLS IN THE ENZYMOLOGY AND BIOIMAGING FIELDS — BY DEVELOPING MACHINE-LEARNING-BASED AND PHYSICS-BASED ELECTRONIC STRUCTURE AND MOLECULAR SIMULATION METHODS. IN OUR R01 FUNDING PERIOD, WE MADE SEVERAL METHODOLOGICAL ADVANCES, ESPECIALLY (A) THE FIRST !-LEARNING POTEN- TIAL FOR SIMULATING THE ENZYME REACTION FREE ENERGY (AS DEMONSTRATED WITH THE MODELING OF CHORISMATE MUTASE CATALYSIS), (B) AN ADVANCE TO THE MULTIPLE TIME-STEP FREE ENERGY SIMULATION METHODOLOGY, AND (C) AN ANALYSIS TOOL FOR INTERPRETING/PREDICTING THE SUBSTITUTION EFFECT ON CHROMOPHORE EMISSION WAVELENGTH BASED ON CHROMOPHORE- SUBSTITUENT ORBITAL INTERACTIONS. BUILDING ON THESE METHOD DEVELOPMENTS, WE WILL FURTHER DEVELOP ROBUST ACTIVE-LEARNING PROTOCOLS FOR TRAINING !-LEARNING POTENTIALS FOR GROUND AND EXCITED ELECTRONIC STATES FOR SYSTEMS IN THE MACROMOLECULAR OR SOLVENT EN- VIRONMENTS. THESE !-LEARNING POTENTIALS, WHEN VALIDATED AGAINST ADVANCED PHYSICS-BASED MODELS, WILL ENABLE ROUTINE (A) ENZYME REACTION SIMULATIONS AND (B) OPTOACOUSTIC AND OTHER BIOIMAGING PROBE MODELING IN OUR LAB AND THE LARGER COMMUNITY. CRISPR-CAS PROTEINS WILL BE USED AS OUR PRIMARY TEST ENZYME SYSTEMS. WE WILL EMPLOY THE !-LEARNING POTENTIALS IN MOLECULAR DYNAMICS SIMULATIONS AND SEEK AN ATOMISTIC UNDERSTANDING OF (A) THE EFFECT OF SPYCAS9 CONFORMATIONAL CHANGES ON HNH- AND RUVC-DOMAIN CATALYZED DNA CLEAVAGE ACTIVITY, AND (B) THE MECHANISM OF ASCAS12A AND FNCAS12A RUVC-DOMAIN CATALYZED NON-TARGET STRAND DNA CLEAVAGE. FOR BIOIMAGING PROBES, WE WILL SEEK GENERAL GUIDING PRINCIPLES FOR DESIGNING OPTOACOUSTIC IMAGING PROBES. IT WILL BE ACHIEVED BY PERFORMING AB INITIO-QM/MM-QUALITY MULTISCALE MODELING TO EXPLORE THE IMPACT OF STRUC- TURAL MODIFICATIONS (ESPECIALLY THE ATTACHMENT OF HALOGEN ATOMS AND FLEXIBLE ALKANE CHAINS) ON THE MOLECULAR ABSORBANCE AND NONRADIATIVE DECAY RATE, BOTH KEY FACTORS IN THE OPTOACOUSTIC SIGNAL GENERATION.

CATALYSIS, DYNAMICS AND STABILITY OF ENZYMES UNDER EXTREME CONDITIONS

MECHANISMS OF BIOLOGICAL FLUORIDE RESISTANCE EXPORTERS

"MODELS AND MECHANISMS FOR ENHANCED SENSORY-MOTOR CONTROL"

BRANDEIS UNIVERSITY AND WALTHAM HIGH SCHOOL UPWARD BOUND PROPOSAL

INTERACTION TORQUES IN VOLUNTARY TURNING AND REACHING

BACTERIAL CELL CYCLE CONTROL

CATALYSIS, DYNAMICS AS STABILITY OF ENZYME UNDER EXTREME CONDITIONS