Luce Inc

HEAD START: FULL YEAR PART DAYHANDICAPPED AND TECHNICAL ASSISTANCE

HEAD START AND EARLY HEAD START

HEAD START AND EARLY HEAD START

DEVELOPMENT OF A PORTABLE HIGH EFFICIENCY STERILIZER

HEAD START AND EARLY HEAD START

RAPID EVALUATION OF NEURONAL ACTIVITY IN THE INTACT WHOLE BRAIN AT SINGLE CELL RESOLUTION - PROJECT SUMMARY HERE WE SEEK TO DEVELOP A “NEURONAL ACTIVITY QUANTITATIVE DIAGNOSTIC” PLATFORM AND REAGENT KITS TO DISSEMINATE ACCESSIBLE PRODUCTS FOR MEASURING RECENT NEURAL ACTIVITY ACROSS THE ENTIRE MOUSE BRAIN TO THE NEUROSCIENCE COMMUNITY. PREVIOUSLY WE HAVE SHOWN THAT THE ACTIVITY-DEPENDENT IMMEDIATE-EARLY GENE PROTEIN PRODUCTS NPAS4 AND CFOS CAN BE CLEARLY DETECTED, IMAGED, AND QUANTIFIED USING DEVELOPMENTAL VERSIONS OF OUR PLATFORM TOOLS. IMMEDIATE EARLY GENES ARE GENES THAT ARE ACTIVATED TRANSIENTLY AND RAPIDLY IN RESPONSE TO A WIDE VARIETY OF CELLULAR STIMULI. THE THREE OVERLAPPING AIMS TO BE INVESTIGATED IN THIS PHASE II PROJECT ARE: 1) DEMONSTRATION OF THE FIDELITY OF OUR ASSAY FOR OUR CUSTOMERS. TO DEMONSTRATE THE ROBUSTNESS AND ACCURACY OF OUR NEURONAL ACTIVITY ASSAY WITH ANOTHER WELL-KNOWN ASSAY FOR ACTIVITY, WE WILL PERFORM TWO PHOTON CALCIUM FLUORESCENCE IMAGING IN THE PRIMARY VISUAL CORTEX OF MICE PRESENTED WITH REPEATED VISUAL STIMULI. WE WILL CLEAR AND STAIN THE BRAINS FOR CFOS AND NPAS4 AND DEMONSTRATE THE FIDELITY OF THESE MARKERS FOR DETECTING RECENTLY ACTIVE NEURONS. 2) DEVELOP AND BETA TEST ROBUST VERSIONS OF OUR SOFTWARE TOOLS USEABLE BY RESEARCHERS WITH NO SPECIALIZED CODING OR STATISTICS KNOWLEDGE. WE WILL DEVELOP STITCHY AND BRAINSNAP INTO ROBUST, USER-FRIENDLY SOFTWARE PRODUCTS THAT REMOVE THE CURRENT ANALYSIS BOTTLENECK FOR NEUROSCIENTISTS INTERESTED IN WHOLE-BRAIN IMAGING. STITCHY WILL BE AN IMPROVED BROWSER-BASED VERSION OF OUR INTERNAL SOFTWARE THAT SIMPLIFIES AND SPEEDS THE PROCESS OF STITCHING TOGETHER LIGHT SHEET MICROSCOPE IMAGES. BRAINSNAP SOFTWARE WILL INTEGRATE OUR HIGH-PERFORMANCE 3TK- QUANT FRAMEWORK FOR MACHINE LEARNING-ENABLED QUANTIFICATION AND OUR STATISTICAL FRAMEWORK FOR WHOLE-BRAIN ANATOMICS, 3TK-STATS, IN A BROWSER-BASED INTERFACE. WE HAVE RECRUITED END USERS WHO WILL TEST THIS SOFTWARE IN A HEAD-TO-HEAD COMPARISON WITH OUR IN-HOUSE TESTING. 3) DEVELOP AND TEST A BRAIN CLEARING AND STAINING KIT FOR NEURONAL ACTIVITY. TO HELP RESEARCHERS PRODUCE HIGH QUALITY CLEARED BRAINS STAINED WITH NEURONAL ACTIVITY MARKERS, WE WILL GENERATE NEURONAL ACTIVITY CLEARING AND STAINING REAGENTS KITS FOR CFOS AND NPAS4. THESE WILL BE TESTED BY COLLABORATORS IN HEAD-TO-HEAD COMPARISONS WITH OUR IN-HOUSE PROCEDURES ON BRAINS PREPARED IN PARALLEL. AT THE END OF PHASE II, TRANSLUCENCE WILL HAVE A MARKET-READY NEURONAL ACTIVITY QUANTITATIVE DIAGNOSTIC PLATFORM INCLUDING REAGENT KITS, USER-FRIENDLY SOFTWARE, AND SERVICE OPTIONS.

ENABLING TOXOPLASMA GONDII KINOME DIRECTED DRUG DISCOVERY - PROJECT SUMMARY TOXOPLASMA GONDII (T.GONDII), THE CAUSATIVE AGENT FOR TOXOPLASMOSIS, INVADES HOST CELLS THROUGH INGESTION OF UNCOOKED INFECTED MEAT OR CONTAMINATED WATER. T.GONDII INFECTS 30% OF THE WORLD’S POPULATION AND THE CURRENT COST OF THE DISEASE IN US ITSELF IS ESTIMATED TO BE $3B AND RISING. CURRENT TREATMENT REGIMEN IS EFFECTIVE ONLY AGAINST ACUTE INFECTION AND HAS SEVERE SIDE EFFECTS. HENCE THERE IS AN URGENT NEED FOR NEW DRUGS AND DRUG TARGETS. THE GENOME OF T.GONDII, IS PREDICTED TO ENCODE 108 ACTIVE KINASES. KINASES HAVE BEEN SHOWN TO BE INVOLVED IN EVERY ASPECT OF THE LIFE CYCLE OF T.GONDII, FROM INVASION OF HOST CELLS TO VIRULENCE. HOWEVER, THE LACK OF COMMERCIALLY AVAILABLE ROBUST KINASE ASSAYS HAS HINDERED T.GONDII KINOME-DIRECTED DRUG DISCOVERY. IN THIS APPLICATION, WE AIM TO DEVELOP AND VALIDATE ASSAYS TARGETED AGAINST THE KINASES ESSENTIAL TO THE T.GONDII PARASITE’S LIFE-CYCLE, WHICH IS RESPONSIBLE FOR TRANSMISSION AND DISEASE PATHOLOGY. THESE T.GONDII KINASE SPECIFIC ASSAYS, BASED ON OUR THREE-HYBRID SPLIT LUCIFERASE SYSTEM, WILL BE FURTHER USED FOR HIGH THROUGHPUT SCREENING OF A KINASE TARGETED INHIBITOR LIBRARY. THESE EFFORTS ARE BOTH SIGNIFICANT AND INNOVATIVE AS THE IDENTIFICATION OF TARGET SPECIFIC INHIBITORS WILL NOT ONLY PROVIDE PHARMACOPHORES FOR FURTHER DRUG DEVELOPMENT BUT ALSO IDENTIFY CHEMICAL PROBES FOR STUDYING KINASE BIOLOGY AND SIGNALING PATHWAYS TO PROVIDE NEW INTERVENTIONS.

SBIR PHASE II: AI-BASED AUTOMATED, PORTABLE, AND HIGH-THROUGHPUT PLATFORM FOR EARLY IDENTIFICATION AND CHARACTERIZATION OF POTENTIALLY HARMFUL MICROORGANISMS IN AQUACULTURE

KINASE TARGETED ANTIMALARIAL AGENTS

FLUORESCENT IRE SENSOR FOR SYNUCLEINOPATHY DRUG DISCOVERY - ABSTRACT THE GOAL OF THIS PHASE II PROPOSAL IS TO ADVANCE SYNUCLEINOPATHY DISEASE DRUG DISCOVERY BY VALIDATING A HIGH- THROUGHPUT SCREENING (HTS)-READY ASSAY AND ESTABLISH A RNA STRUCTURE SENSOR PLATFORM FOR RNA-TARGETED DRUG DISCOVERY. DEMENTIA WITH LEWY BODIES IS THE SECOND MOST COMMON FORM OF DEGENERATIVE DEMENTIA IN THE ELDERLY POPULATION AFTER ALZHEIMER’S DISEASE; AND IT IS CHARACTERIZED BY ABNORMAL ACCUMULATION OF ALPHA-SYNUCLEIN (SNCA) AGGREGATES. DISEASES FEATURING PATHOGENIC SNCA PROTEINS ARE COLLECTIVELY KNOWN AS SYNUCLEINOPATHIES, WHICH ALSO INCLUDE PARKINSON’S DISEASE, MULTIPLE SYSTEM ATROPHY, AND ALZHEIMER’S DISEASE WITH AMYGDALA RESTRICTED LEWY BODIES. THERE IS CURRENTLY NO DISEASE-MODIFYING CURE AVAILABLE FOR ANY OF THE SYNUCLEINOPATHIES. IT IS KNOWN THAT SNCA GENE DUPLICATION INCREASES SNCA LEVELS AND IS CORRELATED WITH DISEASE PROGRESSION AND SEVERITY, LEADING TO EARLY PARKINSONISM AND DEMENTIA. STUDIES SHOWED REDUCTIONS IN SNCA LEVELS CAN REDUCE AGGREGATION, PREVENT LEWY BODY FORMATION, AND CONFER NEUROPROTECTION. THUS, INHIBITING SNCA EXPRESSION DURING DISEASE PRODROMAL PHASE HAS THE POTENTIAL TO SLOW DISEASE PROGRESSION OR HALT DISEASE ONSET. SNCA TRANSLATION IS CONTROLLED BY AN IRON-RESPONSE ELEMENT (IRE) IN THE 5’UTR OF THE MRNA. TO DEMONSTRATE FEASIBILITY, WE DEVELOPED PROOF-OF-CONCEPT RNA STRUCTURE SENSORS THAT WERE RESPONSIVE TO THE BINDING OF SMALL MOLECULES AND ANTISENSE OLIGONUCLEOTIDES, AND DEMONSTRATED FEASIBILITY FOR HTS USE. TO ACCOMPLISH THE GOAL OF THIS PROPOSAL, WE WILL COMPLETE THE FOLLOWING SPECIFIC AIMS: 1) FINALIZE HTS OPTIMIZATION OF THE SNCA-SPECIFIC RNA SENSOR AND PERFORM A PILOT SCREEN, 2) ESTABLISH THE GENERALIZABILITY OF THE RNA STRUCTURE SENSOR PLATFORM BY DEVELOPING HTS- COMPATIBLE SENSORS TARGETING ANOTHER PATHOGENIC RNA STRUCTURE, 3) DEVELOP A STANDARD OPERATING PROCEDURE FOR THE COMMERCIALIZATION OF CUSTOM RNA SENSOR SERVICES, 4) PERFORM A PRIMARY SCREEN TO IDENTIFY INHIBITORS OF SNCA PROTEIN TRANSLATION. IF SUCCESSFUL, WE WILL HAVE A VALIDATED HTS ASSAY FOR SYNUCLEINOPATHY DRUG DISCOVERY AND A RNA STRUCTURE SENSOR PLATFORM THAT AIMED TO ACCELERATE THE CURRENT PACE IN RNA STRUCTURE-BASED DRUG DISCOVERY AND TO ENABLE MORE RNA-TARGETED DRUG DEVELOPMENT PROGRAMS TARGETING DISEASE-CAUSING RNA STRUCTURES.

LOW-COST, PORTABLE AND AUTOMATED SEMEN ANALYSIS USING COMPUTATIONAL MICROSCOPY FOR HOME-BASED TESTING OF MALE WELLNESS AND FERTILITY

RAPID KINASE PROFILING WITH LUMINESCENT REPORTERS

ARRA IND PK EXPANSION

KINOME-WIDE CELL-BASED ASSAYS

SPLICE SENSORS FOR CANCER DRUG DISCOVERY

TOOLS FOR ACCELERATING R&D FOR HISTORICALLY UNDERSTUDIED PROTEIN KINASES

BRAIN-WIDE QUANTIFICATION OF BLOOD-BRAIN BARRIER PENETRATING ANTIBODY THERAPEUTICS - THE PROCESS OF DELIVERING ANTIBODY-BASED THERAPEUTICS DRUGS TO THE BRAIN IS COMPLICATED BY THE NEED TO PENETRATE THE BLOOD-BRAIN BARRIER (BBB), PROMPTING INTEREST IN BBB-PENETRATING STRATEGIES FOR ANTIBODY THERAPEUTICS. HOWEVER, THE METHODS TO TEST BRAIN PENETRATION OF THESE DRUGS ARE INADEQUATE DUE TO THE INTERMINGLING OF BLOOD VESSELS AND BRAIN TISSUE, WHICH CONFOUNDS THE SIGNAL OF DRUG PENETRATION. CURRENT METHODS FOR MEASURING THE DISTRIBUTION OF ANTIBODY DRUGS IN THE BRAIN ARE INADEQUATE, LACKING IN ACCURACY, RELIABILITY AND THE CAPACITY FOR THREE-DIMENSIONAL, HIGH-RESOLUTION, QUANTITATIVE ANALYSIS. ADDRESSING THIS TECHNOLOGICAL SHORTFALL, TRANSLUCENCE BIOSYSTEMS IS ENHANCING ITS PROPRIETARY 3D BRAIN IMAGING AND ANALYSIS PLATFORM TO CREATE A SPECIALIZED VASCULATURE SUBTRACTION PARENCHYMAL QUANTIFICATION (VSPQ) WORKFLOW. THIS TOOL AIMS TO ISOLATE AND MEASURE ONLY THE THERAPEUTICALLY RELEVANT ANTIBODY DRUG WITHIN THE BRAIN PARENCHYMA. THE PHASE II GOAL IS TO REFINE THIS APPROACH TO ENSURE PRECISE MEASUREMENT, LEVERAGING THE COMPANY’S EXPERIENCE AND EXPERTISE IN NEUROSCIENCE, ARTIFICIAL INTELLIGENCE (AI), AND TECHNOLOGY COMMERCIALIZATION. THE SPECIFIC AIMS OF THE PROJECT ARE TO DEVELOP AND QUALIFY THE VSPQ WORKFLOW USING MACHINE LEARNING ALGORITHMS TO DISTINGUISH BETWEEN VASCULATURE AND PARENCHYMA SIGNALS, TARGETING 95% SENSITIVITY AND SPECIFICITY RELATIVE TO HUMAN ASSESSMENTS; INTEGRATE THE VSPQ WORKFLOW INTO THE EXISTING 3D IMAGING PLATFORM, ENSURING THAT THE AI-GENERATED DATA CORRELATES STRONGLY WITH MANUALLY PARTITIONED REGIONAL DATA; VALIDATE THE UTILITY OF THE SOFTWARE THROUGH BLIND ANALYSIS OF DATA PROVIDED BY STRATEGIC PARTNERS, DEMONSTRATING ITS ROBUSTNESS AND ACCURACY IN REAL-WORLD CONDITIONS; AND VALIDATE A CLOUD- BASED VERSION OF THE PIPELINE, ENSURING THAT IT IS STABLE, RELIABLE, AND PERFORMS CONSISTENTLY WITH THE LOCAL VERSION. THE IMPACT OF THIS RESEARCH IS POISED TO BE SIGNIFICANT, PROVIDING A VITAL TOOL FOR ALZHEIMER'S DISEASE DRUG DISCOVERY AND POTENTIALLY IMPROVING THE RATE OF SUCCESSFUL TREATMENT DEVELOPMENT. BY OFFERING THE VSPQ WORKFLOW AS A CLOUD-BASED SOFTWARE-AS-A-SERVICE, TRANSLUCENCE BIOSYSTEMS IS AIMING TO MAKE THIS INNOVATIVE TECHNOLOGY WIDELY ACCESSIBLE, THEREBY STREAMLINING THE DRUG DEVELOPMENT PIPELINE AND BRINGING NEW THERAPIES TO PATIENTS MORE EFFICIENTLY.

HIGH-THROUGHPUT, COST EFFECTIVE AND AUTOMATED PLATFORM FOR LABEL FREE MONITORING AND CHARACTERIZATION OF ALGAE, THEIR LIPID CONTENT, AND OTHER MICRO-OBJECTS

NEW TOOLKIT TO VISUALIZE RNAS IN LIVING CELLS

SBIR PHASE II: FOUNDRY-COMPATIBLE SILICON-INTEGRATED EPITAXIAL BARIUM TITANATE WAFERS FOR SILICON PHOTONICS -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE II PROJECT IS TO ENABLE INNOVATORS IN THE AREA OF INTEGRATED SILICON PHOTONICS TO EXPERIMENT WITH A SUPERIOR OPTICAL MATERIAL THE WILL RESULT IN NEW APPROACHES, NEW DEVICE ARCHITECTURES, AND HIGH DENSITY NETWORKS THAT WILL CREATE TECHNOLOGIES THAT DO NOT EXIST TODAY AS MATERIALS AVAILABLE NOW CAN?T SUPPORT SUCH IDEAS DUE TO CURRENT PHYSICAL LIMITATIONS. THIS WILL BE ACHIEVED THROUGH MAKING AVAILABLE SEMICONDUCTOR FABRICATION SERVICES FOR SPECIAL TYPE OF MATERIALS USED IN ULTRA-LOW POWER, ULTRA-FAST AND ULTRA-SMALL COMPONENTS AT A REASONABLE COST, WITH IMPROVED MANUFACTURING YIELDS, AND REDUCED DEVELOPMENT CYCLE TIME. THE MATERIAL CALLED BARIUM TITANATE (BATIO3) CAN POTENTIALLY DOMINATE THE MARKET FOR DATA CENTERS. THE BATIO3-BASED COMPONENTS ARE ULTRA-LOW POWER AND THUS MAY SIGNIFICANTLY REDUCE THE POWER CONSUMPTION OF EXISTING DATA CENTERS. THE WORK WILL ALSO SUPPORT THE ENTIRELY NEW MARKETS OF QUANTUM AND NEUROMORPHIC COMPUTING. THE PROPOSED PROJECT WILL RESULT IN THE INTRODUCTION TO THE MARKET OF 200-MM WAFERS OF BATIO3 ON SI FOR SILICON PHOTONICS. BATIO3 ALTERS THE SPEED OF LIGHT WHEN SUBJECTED TO ELECTRIC FIELD MORE EFFICIENTLY THAN ALMOST ANY OTHER MATERIAL. THE COMPANY WILL DEVELOP CHEMICAL MECHANICAL POLISHING AND WAFER BONDING PROCESSES, INCLUDING THE NECESSARY PROCESS DESIGN KITS (PDKS) COMPATIBLE WITH A STANDARD SILICON PHOTONIC FOUNDRY. THIS WILL ENABLE HUNDREDS OF SMALL TO MEDIUM PHOTONIC COMPANIES TO INNOVATE WITH SUPERIOR MODULATOR MATERIAL AND NEW AUTOMATION TOOLS. THE CHARACTERISTICS OF BATIO3 WILL QUALITATIVELY CHANGE WHAT IS POSSIBLE WITH INTEGRATED, ON-CHIP OPTICAL NETWORKS. THE WORK WILL FOCUS ON TRANSFERRING THE 50-MM PROCESS DEVELOPED IN PHASE I TO A 200-MM WAFER. THE INNOVATIVE DEPOSITION TECHNIQUE WILL ENABLE MASS PRODUCTION OF SUCH WAFERS. THE COMPANY THEN WILL WORK WITH A SUBCONTRACTOR TO UNDERSTAND THE CHEMISTRY, PARTICLE SIZE OF THE SLURRY AND VELOCITY AND PRESSURE OF THE PROCESS TO PRODUCE BATIO3 WAFERS WITH LESS THAN 0.5 NM ROUGHNESS NECESSARY FOR WAFER BONDING. THIS WILL ENABLE THE DEVICE BUILDERS TO USE ALREADY EXISTING DEVICE ARCHITECTURE FABRICATED IN SI OR SIN IN HETEROGENEOUS INTEGRATION WITH BTO. 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.

RURAL COMMUNITIES OPIOID RESPONSE-IMPLEMENTATION

RURAL COMMUNITIES OPIOID RESPONSE PROGRAM ? NEONATAL ABSTINENCE SYNDROME - RURAL COMMUNITIES OPIOID RESPONSE PROGRAM – NEONATAL ABSTINENCE SYNDROME

THE CHIPPEWA/LUCE/MACKINAC CONSERVATION DISTRICT WILL IMPLEMENT MANURE MANAGEMENT PRACTICES AT HIGH PRIORITY SITES IN THE MUNUSCONG RIVER AND THE LITTLE MUNUCONG RIVER WATERSHEDS, WHICH ARE SUB-BASINS WITHIN THE ST. MARY'S RIVER WATERSHED (CONNECTING THE CHANNEL BETWEEN LAKE SUPERIOR AND LAKE HURON AND MICHIGAN).

CLEARBOT: A SYSTEM FOR FULLY AUTOMATED, HIGH-THROUGHPUT TISSUE CLEARING AND IMMUNOSTAINING - SUMMARY TISSUE CLEARING IS A POWERFUL TECHNIQUE THAT RENDERS LARGE BIOLOGICAL SAMPLES OPTICALLY TRANSPARENT AND ALLOWS 3D VISUALIZATION OF WIDE-BRAIN MOLECULAR ANATOMY. TO HELP DISSEMINATE THIS TECHNOLOGY, TRANSLUCENCE BIOSYSTEMS DEVELOPED A MESOSCALE IMAGING SYSTEM™ AND, USING PREVIOUS SBIR NIH SUPPORT, AN ANALYTICAL SOFTWARE PACKAGE FOR ADVANCED ANALYSIS OF BRAIN SAMPLES, 3TKTM. WHILE COMPLETE SOLUTIONS EXIST FOR IMAGING AND ANALYSIS OF CLEARED SAMPLES, NO COMPLETE SOLUTION EXISTS FOR THE HIGHLY LABOR INTENSIVE AND ERROR PRONE TISSUE CLEARING PROCESS. HERE TRANSLUCENCE BIOSYSTEMS INTRODUCE CLEARBOT™, AN AUTOMATED SYSTEM FOR SAMPLE CLEARING AND IMMUNOSTAINING THAT WILL COMPLEMENT PREVIOUS TRANSLUCENCE DEVICES AND COMPLETE A PIPELINE FOR RELIABLE BRAIN- WIDE MOLECULAR ANATOMY OF INTACT RODENT AND HUMAN TISSUES. IN THIS PHASE I PROPOSAL, TRANSLUCENCE BIOSYSTEMS WILL BUILD A PROTOTYPE OF CLEARBOT™ AND DEMONSTRATE AUTOMATED BRAIN TISSUE CLEARING FOR WHOLE-BRAIN ANALYSIS. SPECIFIC AIMS: AIM 1: ASSEMBLE AND EVALUATE A CLEARBOT PROTOTYPE: THE BASIC FUNCTIONALITY OF THE PROTOTYPE DEVELOPED BY AN ENGINEERING CONSULTANT WILL BE EVALUATED FOR FUNCTIONALITY, ROBUSTNESS, ENERGY CONSUMPTION, AND OVERALL RELIABILITY. AIM 2: EVALUATE THE UTILITY OF CLEARBOT FOR AUTOMATED CLEARING AND IMMUNOSTAINING OF INTACT BRAINS: QUALITY AND REPEATABILITY OF TISSUE CLEARING WILL BE EVALUATED USING THE PROTOTYPE ASSEMBLED IN AIM 1. MULTIPLE MOUSE BRAINS WILL BE CLEARED AND IMMUNOSTAINED WITH CLEARBOT AND BENCHMARKED TO MANUAL PROCESSING DONE IN PARALLEL. THIS PHASE I PROJECT WILL DEMONSTRATE THE FEASIBILITY OF DEVELOPING AN AUTOMATED DEVICE THAT IS COMPARABLE TO OR BETTER THAN MANUAL CLEARING. FOLLOWING SUCCESS OF THIS PHASE I FEASIBILITY TESTING, FUTURE DEVELOPMENTS WILL ADVANCE THE PROTOTYPE TO A FLEXIBLE, COMMERCIAL-GRADE SYSTEM WITH A ROBUST AND SIMPLE USER-INTERFACE, HELPING RESEARCHERS APPLY THIS GAME-CHANGING TECHNOLOGY TO THEIR RESEARCH QUESTIONS.

BRAIN-WIDE QUANTITATIVE MAPPING OF MICROGLIA ACTIVATION

AMERICAN RESCUE PLAN

THE 92ND DISTRICT COMMUNITY COURT PROGRAM WILL BE A COURT ORDERED, AND COMMUNITY-BASED RESOURCE FOR THOSE WITH LOW-LEVEL MISDEMEANOR CRIMES. OUR MAIN FOCUS IS COMMUNITY ENGAGEMENT, INTRODUCING RESOURCES TO FURTHER EDUCATION, JOB-TRAINING OR EMPLOYMENT DEPENDING ON THE NEEDS OF OUR PARTICIPANTS. ALSO, ENSURING EQUAL ACCESS TO SUD AND MENTAL HEALTH TREATMENT, RELATIONSHIP BUILDING AND REDUCING RECIDIVISM IN LOCAL AND OUTLYING COMMUNITIES. THE PROGRAM WILL WORK WITH THE LOCAL AND SURROUNDING COMMUNITIES TO COMBINE RESOURCES AND JOIN EFFORTS TO MINIMIZE DUPLICATE EFFORTS, ENHANCE CONSISTENCY, AND INCREASE OUTCOMES.             BEING ON THE CUSP OF A “HIGH-PRIORITY” AREA, WITH AN INCREASE IN POVERTY EVERY YEAR, OUR TWO VERY RURAL COMMUNITIES HAVE BEEN LEFT TO FEND FOR OURSELVES. WITH THE LIMITED ACCESS TO INTERNET SERVICES AND TRANSPORTATION BARRIERS OUR ENTIRE COMMUNITIES HAVE SUFFERED. THE COMMUNITIES HAVE FAILED TO THRIVE IN THIS INCREASINGLY DIGITAL WORLD, CAUSING NEGATIVE REPERCUSSIONS THAT HAS AFFECTED US ALL. AN INCREASE IN CRIME AND REDUCTION IN RELIABLE RESOURCES MAKE THE NEED FOR FUNDING DIRE.             WITH THE INCREASE IN MISDEMEANOR CRIMES IN SMALL COMMUNITIES, DUPLICATE EFFORTS AND INCONSISTENT PROCESSES ONLY REDUCE THE CHANCE THAT INDIVIDUALS WILL GET AND MAINTAIN HEALTHY AND PRODUCTIVE LIFESTYLES. BY MAPPING OUT GUIDELINES AND PROTOCOLS FOR ALL AGENCIES TO UTILIZE THE EFFORTS AND RESOURCES BECOME MORE RELIABLE AND EFFICIENT AT OVERALL PROGRAM AND INDIVIDUAL SUCCESS. ALONG WITH COMPLIANCE MONITORING WE CAN IMPROVE ACCOUNTABILITY FOR THE PARTICIPANTS.             AFTER COLLABORATION WITHIN THE COMMUNITY AND OUT-LYING COMMUNITIES THE PROGRAM WILL BE ACCESSIBLE TO ALL. DURING THE PRE-TRIAL PHASE OF THE COURT PROCEEDINGS, CLIENTS ARE SCREENED USING EVIDENCE BASED SCREENING TOOL TO ADDRESS RISK AND NEEDS. WITH THESE PRACTICES IN PLACE, THE INDIVIDUAL WILL BE ASSESSED AND TRANSITION INTO THE PROGRAM, WITH CONSISTENT MONITORING AND SUPPORT TO ENSURE SUCCESS.             WITH DATA COLLECTION AND PROCESSING THROUGHOUT THE PROGRAM LIFE WE CAN MAP OUR SUCCESS AND SEEK OUT DOWNFALLS TO CORRECT ANY ERRORS AND FURTHER FUTURE SUCCESSES. THE REQUESTED FUNDING FOR THE PROGRAM IS A TOTAL OF $597685.00  TO EXPAND OVER THE FOUR-YEAR FUNDING PERIOD. WITH COMBINED SUPPORT FROM LOCAL AGENCIES AND PROGRAM SUSTAINABILITY EFFORTS IN PLACE THE PROGRAM WILL FAR SURPASS THE PROPOSED PROGRAM LENGTH.             THANK YOU FOR YOUR CONSIDERATION IN THE 92ND DISTRICT COMMUNITY COURT PROGRAM.

CELL-BASED RNA DEGRADATION ASSAY FOR C9ALS/FTD DRUG DISCOVERY - PROJECT SUMMARY TO OVERCOME THE “UNDRUGGABLE” PROTEIN PROBLEM, RESEARCHERS HAVE TURN TO DRUGGING MRNAS THAT TRANSLATE INTO THESE UNDRUGGABLE PROTEINS OR NON-CODING RNAS THAT REGULATE THE BIOGENESIS OF THESE PROTEINS. AVENUES OF CONTROLLING RNA DEGRADATION INCLUDE INDUCED PROXIMITY DEGRADATION OR SPLICING MODULATED NONSENSE-MEDIATED DECAY (NMD). INDUCED PROXIMITY DEGRADATION IS A STRATEGY WHERE A BIFUNCTIONAL DRUG BINDS A TARGET RNA VIA A SMALL MOLECULE (SM) ENTITY ON ONE ARM AND INDUCES SELECTIVE RNA DEGRADATION VIA A RIBONUCLEASE ON THE OTHER ARM. THERAPEUTIC MODULATION OF NMD VIA RNA SPLICING IS ANOTHER STRATEGY TO SELECTIVELY CONTROL RNA DEGRADATION. EARLY-STAGE RNA DEGRADATION DRUG DISCOVERY HAS BEEN HINDERED BY CURRENT HIGH-THROUGHPUT SCREENING (HTS) ASSAY TECHNOLOGIES DESIGNED FOR PROTEIN TARGETS. SPECIFICALLY, CELL-BASED DRUG SCREENS USE MINIGENE REPORTERS THAT RELY ON LUCIFERASE OR FLUORESCENT PROTEIN SIGNALS FOR ASSAY READ-OUT. MINIGENE REPORTER DESIGN IS STRAIGHTFORWARD BUT MINIGENE REPORTER REQUIRES MRNA EXPORT TO THE CYTOSOL AND PROTEIN TRANSLATION. THIS SIGNIFICANTLY INCREASES THE RATE OF FALSE HITS PER SCREEN SINCE COMPOUNDS THAT INHIBIT GLOBAL PROTEIN TRANSLATION MACHINERY OR RNA EXPORT WILL ALSO IMPACT REPORTER READ-OUT. FURTHER, PROTEIN-BASED REPORTERS CANNOT BE USED TO STUDY NUCLEAR RNA OR NON- CODING RNA TURNOVER, AND IN DISEASES WITH NUCLEAR EXPORT DEFECTS. THUS, THERE IS AN UNMET NEED FOR A CELL-BASED HTS ASSAY PLATFORM THAT MONITORS SELECTED RNA TURNOVER DIRECTLY, REFLECTS REAL- TIME RNA DYNAMICS, AND COMPATIBLE FOR DIFFERENT TYPES OF RNA. A PRIME EXAMPLE WHERE A PREVIOUSLY INTRACTABLE DISEASE CAN BE UNLOCKED BY RNA DEGRADING DRUGS IS THE G4C2 HEXANUCLEOTIDE REPEAT EXPANSION IN THE C9ORF72 GENE – THE MOST FREQUENT GENETIC CAUSE OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) AND FRONTOTEMPORAL DEMENTIA (FTD). IT IS NOW KNOWN THAT THE TOXIC GAIN-OF-FUNCTION FROM THE EXPANDED G4C2 REPEATS INDUCES ALS/FTD PATHOLOGY. ANTISENSE OLIGONUCLEOTIDES (ASOS) DESIGNED TO BIND EITHER THE G4C2 SEQUENCES OR INTRONIC REGIONS DOWNSTREAM OF THE REPEAT SEQUENCES SHOWED REDUCTION IN DISEASE PHENOTYPES IN C9ORF72 MODELS. HOWEVER, ASOS CAN TRIGGER IMMUNE RESPONSES AND SUFFER FROM TISSUE DELIVERY ISSUES. A CELL- BASED ASSAY THAT CAN REPORT EXPANDED TRANSCRIPT TURNOVER TO IDENTIFY EFFECTIVE C9ORF72 RNA GAIN- OF-FUNCTION SM INHIBITORS WILL HAVE HIGH COMMERCIAL POTENTIAL. THE GOALS OF THIS PHASE I SBIR APPLICATION WILL BE CELL-BASED RNA DEGRADATION REPORTERS FOR VALIDATED RNA TARGETS IN NEURODEGENERATIVE DISEASES. THE RESULTS WILL FORM THE FOUNDATION OF AN HTS ASSAY PLATFORM FOR EARLY-STAGE DISCOVERY SMS THAT MODULATE RNA STABILITY.

EDI SPECIAL PROJECTS

CLOZAPINE SENSORS FOR IMPROVING THERAPEUTIC TREATMENTS OF SCHIZOPHRENIA

DESCRIPTION:CHIPPEWA LUCE MACKINAC CONSERVATION DISTRICT WILL IMPLEMENT CONSERVATION PRACTICES ON HIGH PRIORITY AGRICULTURAL SITES THAT WILL REDUCE NUTRIENT LOADING INTO THE WAISHKEY RIVER WATERSHED.ACTIVITIES:ACTIVITIES INCLUDE WORKING WITH LANDOWNERS TO IMPLEMENT AGRICULTURAL BEST MANAGEMENT PRACTICES INCLUDING EXCLUSION FENCING, MANURE MANAGEMENT PLANS, RIPARIAN BUFFERS, AND ROTATIONAL GRAZING SYSTEMS.SUBRECIPIENT:LAKE SUPERIOR STATE UNIVERSITY'S CENTER FOR FRESHWATER RESEARCH AND EDUCATION WILL CONDUCT LAB ANALYSIS OF E. COLI AND TOTAL COLIFORM LEVELS.OUTCOMES:DELIVERABLES REDUCTION OF 400 LBS/YEAR OF PHOSPHOROUS IN THE WAISHKEY RIVER WATERSHED, BEST MANAGEMENT PRACTICES IMPLEMENTATION ON 2-4 HIGH PRIORITY LIVESTOCK SITES ON AT LEAST 350 ACRES, PROTECTION OF 1,320 FT OF STREAM BANK, AND PRE AND POST PROJECT SAMPLING TO MEASURE TOTAL E. COLI CONCENTRATIONS. THIS PROJECT AIMS TO REDUCE PHOSPHOROUS AND OTHER NUTRIENT LOADING INTO THE RIVER AND IMPROVE THE ECOSYSTEM HEALTH OF THE WAISHKEY RIVER WATERSHED. BENEFICIARIES INCLUDE THE BAY MILLS INDIAN COMMUNITY WHO WILL BENEFIT FROM THE IMPROVED WATER AND ECOSYSTEM QUALITY AS WELL AS INCREASED CLIMATE RESILIENCY.

NEW TOOLKIT TO VISUALIZE RNAS IN LIVING CELLS

IN VIVO IMAGING PLATFORM FOR DM1 DRUG DISCOVERY - PROJECT ABSTRACT/SUMMARY MYOTONIC DYSTROPHY TYPE 1 (DM1) IS A MULTISYSTEMIC DISORDER CAUSED BY CUG REPEAT EXPANSION IN THE 3’ UTR OF THE DMPK GENE. DM1 PATIENTS CAN HAVE BETWEEN 50 TO 5,000 CUG REPEATS, LEADING TO DMPK MRNA AGGREGATION WITHIN THE NUCLEUS. THESE RIBONUCLEAR CLUSTERS, TERMED FOCI, SEQUESTER SEVERAL SPLICING FACTORS, SUCH AS MUSCLEBLIND-LIKE (MBNL) PROTEINS, AND TRANSCRIPTION FACTORS, LEADING TO DYSREGULATION OF SPLICING, MIRNA AND CIRCRNA FORMATION, AND MRNA LOCATION AND STABILITY. DM1 IS THE MOST COMMON ADULT FORM OF MUSCULAR DYSTROPHY AND AFFECTS 1 IN 8,000 PEOPLE WORLDWIDE. THERE IS CURRENTLY NO CURE FOR DM1 AND TREATMENT CONSISTS OF SYMPTOM MANAGEMENT. RECENT ADVANCES IN RNA-FOCUSED DRUG LIBRARY DESIGN AND SCREENING TOOLS NOW ALLOW BETTER, MORE BIOLOGICALLY RELEVANT HIT SCREENING THAT OVERCOME TRADITIONAL PROTEIN-BASED DRUG DISCOVERY APPROACHES. HOWEVER, APPROPRIATE ANIMAL MODELS FOR EFFICIENT PRECLINICAL TESTING OF RNA-FOCUSED DRUG CANDIDATES REMAINED LACKING. PHARMACOKINETIC AND TARGET ENGAGEMENT STUDIES FOR EVERY NEW DRUG CANDIDATE STILL RELY ON BIOCHEMICAL MEASUREMENTS IN HARVESTED TISSUES, WHICH IS EXPENSIVE, TIME CONSUMING, AND REQUIRES LARGE NUMBERS OF ANIMAL SACRIFICE. THERE IS CURRENTLY NO IN VIVO MODEL CAPABLE OF MONITORING TOXIC FOCI AND MBNL SEQUESTRATION, THE TRIGGER OF DM1 DISEASE PHENOTYPE, IN REAL TIME HIGH-THROUGHPUT FORMAT, AND IN A NON-INVASIVE MANNER TO LIMIT THE NUMBER OF ANIMALS NEEDED. THE GOAL OF THIS SBIR PHASE I PROJECT TO DEVELOP AN IN VIVO REPORTER PLATFORM THAT ALLOWS MORE EFFICIENT EVALUATION OF TRIAGED DRUGS AND LEAD COMPOUNDS FOR TARGET ENGAGEMENT AND OTHER PK METRICS. WE WILL USE OUR PROPRIETARY FLUOROGENIC RNA APTAMER TECHNOLOGY TO DEVELOP IN VIVO REPORTERS THAT CAN DETECT DRUG-INDUCED CHANGES IN TOXIC FOCI FORMATION AND CUG-MBNL INTERACTION. IN PHASE, I WE WILL DEMONSTRATE THE FEASIBILITY OF THE IN VIVO REPORTER SYSTEM IN DM1 MODEL CELL LINES AND ANIMAL MODEL AND IN PHASE II, WE WILL GENERATE TRANSGENIC REPORTER ANIMALS, PERFORM PRECLINICAL TESTING WITH COLLABORATOR LEAD COMPOUNDS, AND EXPAND THE PLATFORM CAPABILITY TOWARD OTHER MICROSATELLITE DISEASES.

RH&ED-INNOV ACTIVITY

TARGETED RNA DEGRADATION ASSAY FOR NEW ANTIVIRAL DRUG DISCOVERY - PROJECT SUMMARY THERE ARE CURRENTLY NO EFFECTIVE VACCINES OR ANTIVIRAL DRUGS FOR MOST OF THE VIRAL DISEASES AFFLICTING HUMAN. DEVELOPMENT OF NEW THERAPY IS CHALLENGING AND EXPENSIVE, AND OFTEN COMPLICATED BY DRUG RESISTANCE. IT IS NOW KNOWN THAT VIRAL TRANSCRIPTS CONTAIN MANY HIGHLY STRUCTURED RNA ELEMENTS IN BOTH THE CODING AND NONCODING REGIONS, AND THEY PLAY KEY ROLES IN THE VIRAL LIFE CYCLE. MANY OF THESE ELEMENTS ARE HIGHLY CONSERVED AND, THUS, THEY ARE ATTRACTIVE NEW TARGETS THAT POTENTIALLY HAVE LOWER LIKELIHOODS OF VIRAL RESISTANCE DEVELOPMENT. TARGETED RNA DEGRADATION (TRD) IS AN EMERGING STRATEGY IN RECENT EFFORTS TO FURTHER DISCOVER NEW ANTIVIRAL SMALL MOLECULES WITH PRIVILEGED SCAFFOLDS AND BETTER RESISTANCE PROFILES. HOWEVER, EARLY-STAGE TRD DRUG DISCOVERY HAS BEEN HINDERED BY CURRENT HIGH-THROUGHPUT SCREENING (HTS) ASSAY TECHNOLOGIES DESIGNED FOR PROTEIN TARGETS. VIRTUALLY ALL CELL-BASED DRUG SCREENS USED MINIGENE REPORTERS THAT RELY ON LUCIFERASE OR FLUORESCENT PROTEIN SIGNALS FOR ASSAY READ-OUT. MINIGENE REPORTER DESIGN IS STRAIGHTFORWARD BUT MINIGENE REPORTER REQUIRES MRNA EXPORT TO THE CYTOSOL AND PROTEIN TRANSLATION. THIS SIGNIFICANTLY INCREASES THE RATE OF FALSE HITS PER SCREEN SINCE COMPOUNDS THAT INHIBIT GLOBAL PROTEIN TRANSLATION MACHINERY OR RNA EXPORT WILL ALSO IMPACT REPORTER READ-OUT. ASSAYS THAT MONITOR ENDOGENOUS RNA LEVELS ARE LOW-THROUGHPUT OR TIME-CONSUMING, INVOLVE MULTIPLE STEPS, AND NOT READILY ADAPTABLE FOR HIGH-THROUGHPUT SM SCREENING. THUS, THERE IS AN UNMET NEED FOR A NEW CELL-BASED HTS ASSAY PLATFORM THAT MONITORS TARGET RNA TURNOVER DIRECTLY, REFLECTS REAL-TIME RNA DYNAMICS, AND COMPATIBLE FOR DIFFERENT TYPES OF RNA AND DIFFERENT TRD APPROACHES. FOR PROOF-OF-CONCEPT, THIS PROJECT AIMS TO DEVELOP HTS-COMPATIBLE REPORTERS THAT CAN MEASURE DRUG- INDUCED CHANGES OF RNA LEVELS OF DENGUE AND INFLUENZA VIRUSES, TWO GLOBAL PATHOGENS WITH DIFFERENT GENOMIC STRUCTURES AND LIFE CYCLES. THE ULTIMATE PRODUCT OF THIS SBIR PROJECT WILL BE A CELL-BASED HTS ASSAY PLATFORM THAT CAN ACCELERATE THE EARLY-STAGE DISCOVERY OF TRD DRUGS TOWARD PREVIOUSLY INTRACTABLE VIRAL DISEASES.

HOMOGENOUS NAD ASSAY FOR ARDT ACTIVITY MEASUREMENT

A POLY(ADP-RIBOSE) DETECTION ASSAY ENABLING DRUG DISCOVERY AND DEVELOPMENT

STTR PHASE I: SILICON-INTEGRATED EPITAXIAL BARIUM TITANATE (BATIO3) CHIPS FOR PHOTONICS APPLICATIONS -THE BROADER / COMMERCIAL IMPACT OF THIS SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PHASE I PROJECT IS MASS PRODUCTION OF A STANDARDIZED, LARGE-AREA, SILICON-BASED MATERIALS PLATFORM (WAFER) FOR PHOTONIC INTEGRATED CIRCUITS. PHOTONICS IS THE NEXT STEP IN INFORMATION PROCESSING, USING LIGHT SIGNALS INSTEAD OF ELECTRONS. SUCH A MATERIALS PLATFORM IS EXPECTED TO REVOLUTIONIZE THE SILICON PHOTONICS MARKET MUCH LIKE THE INTRODUCTION OF SILICON CHIPS DID FOR THE MICROELECTRONICS INDUSTRY. THE FIRST STEP TO SUCCESSFULLY PRODUCE SUCH WAFERS IS TO MANAGE THE EXTREME THERMAL STRESS ARISING FROM THE COMBINATION OF TWO MATERIALS (THE OPTICAL MATERIAL BARIUM TITANATE (BATIO3) AND THE SILICON CARRIER CHIPS) WITH VERY DIFFERENT RATES OF THERMAL EXPANSION. VARIOUS PROCESSING TECHNIQUES WILL BE INVESTIGATED TO DETERMINE HOW SUCH THERMAL STRESS CAN BE MITIGATED. IF SUCCESSFUL, THIS NEW MATERIALS PLATFORM WILL USED BY TELECOM AND DATA COMPANIES, AND MAY ENABLE NEW KINDS OF COMPUTING, SUCH AS PHOTONIC QUANTUM COMPUTING. THE TOTAL OF THESE INDUSTRIES IS EXPECTED TO EXCEED $100 BILLION IN COMBINED MARKET SIZE BY 2030. THIS STTR PHASE I PROJECT WILL ADDRESS ONE OF THE CRITICAL ISSUES OF SCALING UP BARIUM TITANATE ON SILICON TECHNOLOGY TO THICKER AND LARGER AREA WAFERS. BARIUM TITANATE AND SILICON HAVE VERY DIFFERENT THERMAL EXPANSIONS AND SINCE THE INTEGRATION IS ACHIEVED BY DEPOSITION AT ELEVATED TEMPERATURE, COOLING CAUSES LARGE STRESSES TO DEVELOP. THE RESULTING STRESS MAY RESULT IN CRACKS IN THE FILM OR EVEN IN SHATTERING THE WAFER. STRESS ALSO AFFECTS THE OPTICAL PERFORMANCE OF THE MATERIAL AND THEREFORE, ITS MANAGEMENT IS CRUCIAL FOR SUBSEQUENT DEVICE FABRICATION. THE COMPANY IS DEVELOPING A PROCESS THAT MITIGATES THIS PROBLEM (E.G., PROGRAMMED COOLING) WHICH WILL AFFECT WAFER PRODUCTION THROUGHPUT. IN ADDITION, THE COMPANY MUST CONTROL THE DIRECTION OF FERROELECTRIC POLARIZATION, AN IMPORTANT CUSTOMER REQUIREMENT FOR MAKING DEVICES. SOLVING THESE TWO ISSUES IS CRUCIAL TO SUCCESSFUL COMMERCIALIZATION OF THIS TECHNOLOGY. BARIUM TITANATE FILMS OF THICKNESSES RANGING FROM 0.2 TO 2 MICROMETERS WILL BE INTEGRATED ON SILICON AND SUBJECT TO DIFFERENT THERMAL HISTORIES. RESIDUAL STRESS WILL BE MEASURED BY X-RAY DIFFRACTION AND CORROBORATED WITH POLARIZED RAMAN SPECTROSCOPY. THE RESULTING CRYSTAL STRUCTURE, MORPHOLOGY, POLARIZATION DISTRIBUTION, AND ELECTRO-OPTIC PERFORMANCE WILL BE USED AS METRICS FOR DETERMINING IF THE THERMAL PROCESSING WAS SUCCESSFUL. 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.

RAPID HISTONE METHYLTRANSFERASE PROFILING WITH LUMINESCENT REPORTERS

SPLIT-LUCIFERASE EPIGENETIC ASSAYS FOR DRUG DISCOVERY - PROJECT SUMMARY EPIGENETIC CONTROL IS ESSENTIAL FOR MAINTAINING TRANSCRIPTIONAL INTEGRITY. REGULATION OF THE DYNAMIC EPIGENOME IS MEDIATED THROUGH A RANGE OF POST TRANSLATIONAL MODIFICATIONS ON DNA AND HISTONE TAILS. HISTONE MODIFICATIONS ARE MEDIATED BY ENZYMES WHICH CAN BE BROADLY CLASSIFIED INTO “WRITERS” THAT CATALYZE THE ADDITION OF CHEMICAL MODIFICATIONS, “ERASERS” THAT REMOVE THE MODIFICATIONS, AND “READERS” THAT CAN RECOGNIZE CHEMICAL MODIFICATIONS THROUGH SPECIFIC PROTEIN DOMAINS. THE WRITING AND ERASING OF HISTONE MARKS BY ENZYMES IS A DYNAMIC PROCESS, AND WHEN DYSREGULATED IS ASSOCIATED WITH CANCER, INFLAMMATORY AND NEUROLOGICAL DISEASES. IN THIS APPLICATION WE FOCUS ON THE TWO CLASSES OF HISTONE MODIFYING ENZYMES, LYSINE METHYL TRANSFERASES (KMTS) AND LYSINE DEMETHYLASES (KDMS), AND AIM TO DEVELOP AND VALIDATE CELL- BASED ASSAYS TARGETING BOTH KMTS AND KDMS. THESE ASSAYS, BASED ON A THREE-HYBRID SPLIT LUCIFERASE SYSTEM, ARE REVERSIBLE ALLOWING DOSE DEPENDENT QUANTIFICATION OF INHIBITOR BINDING. THESE EFFORTS ARE BOTH SIGNIFICANT AND INNOVATIVE AS THEY CAN REPORT ON THE DIRECT BINDING OF A DRUG TO THE TARGET PROTEIN AT ITS INTENDED SITE OF ACTION, THEREBY FACILITATING THE GENERATION OF LEAD THERAPEUTIC CANDIDATES AND IDENTIFICATION OF CHEMICAL PROBES FOR STUDYING HISTONE BIOLOGY AND PATHWAYS.

KINOME-WIDE CELL-BASED ASSAYS

GREAT LAKES RESTORATION INITIATIVE ST MARYS RIVER STORMWATER REDUCTION INITIATIVE

ENABLING TOXOPLASMA GONDII KINOME DIRECTED DRUG DISCOVERY

RAPID EVALUATION OF NEURONAL ACTIVITY IN THE INTACT WHOLE-BRAIN AT SINGLE CELL RESOLUTION

NEW HIGH-THROUGHPUT SCREENING TECHNOLOGIES TO IMPROVE CANNABINOID PRODUCTION IN YEAST.

SBIR PHASE I: COST-EFFECTIVE, PORTABLE AND FAST PLATFORM FOR AUTOMATED CHARACTERIZATION OF AQUATIC MICROORGANISMS AND OTHER PARTICLES FOR AQUACULTURE, PUBLIC HEALTH AND MARINE RES

CELL-BASED VIRAL HELICASE ASSAY FOR DENGUE DRUG DISCOVERY

CELL-BASED ASSAY DIRECTLY MONITORING VIRAL POLYMERASE ACTIVITY FOR DRUG DISCOVERY.

ENABLING MALARIAL KINOME DIRECTED DRUG DISCOVERY

SPLICE SENSORS FOR CANCER DRUG DISCOVERY

CELL-BASED ASSAY DIRECTLY MONITORING RNA POLYMERASE I ACTIVITY FOR CANCER DRUG DISCOVERY

FLUORESCENT IRE SENSOR FOR PD DRUG DISCOVERY

SEC. 9007 REAP-RENEW ENERGY SYS GRANTS (MAN)

ASSAY CLASSIFIER ENGINE (ACE) FOR ENHANCING SPLICE SENSOR ASSAY PERFORMANCE

METHYLTRANSFEREASE SENSORS FOR HOMOGENOUS HTS ASSAYS

HEAD START: FULL YEAR PART DAYHANDICAPPED AND TECHNICAL ASSISTANCE

FLUORESCENT RNA FOCI ASSAY FOR FXTAS DRUG DISCOVERY

OPTIMIZATION OF NOVEL RYANODINE RECEPTOR MODULATORY COMPOUNDS FOR ALZHEIMER'S DISEASE

RURAL COMMUNITIES OPIOID RESPONSE (PLANNING)

SOLUTION-PHASE AUTOMATED SYNTHESIS OF OLIGOSACCHARIDES

SBIR PHASE I: LOW-COST PRINTABLE PHOTOVOLTAICS ON FLEXIBLE PLASTICS

RAPID KINASE PROFILING WITH LUMINESCENT REPORTERS

FLUORESCENT REPORTERS FOR REAL-TIME SINGLE-CELL POL III TRANSCRIPTION MEASUREMENT

SBIR PHASE I: LIVE-CELL METABOLITE SENSORS FOR IMPROVING BIOFUEL PRODUCTION

GREAT LAKES RESTORATION INITIATIVE: MUNUSCONG RIVER WATERSHED GREEN INFRASTRUCTURE AND TREE/SHRUB MANAGEMENT PROJECT

EUROPEAN FROG-BIT IS A PLANT THAT CAN CAUSE NEGATIVE IMPACTS ON WETLAND ECOSYSTEMS. THE DENSE FLOATING MATS FORMED BY EUROPEAN FROG-BIT CHANGE THE WATER COLUMN IN A WAY THAT AFFECTS FOOD WEBS, MACROINVERTEBRATE COMMUNITIES, AND THE GROWTH OF SUBMERGENT PLANTS WHILE LIMITING HUMAN RECREATION ACTIVITY OPPORTUNITIES. ITS BEEN HYPOTHESIZED THAT THE EFFECTS OF EUROPEAN FROG-BIT EXPAND INTO ALTERING WATERFOWL AND MARSH BIRD COMMUNITIES, LEADING TO A NEED TO INVESTIGATE THE QUESTION ARE WATERFOWL AND MARSH BIRD COMMUNITIES AFFECTED BY EUROPEAN FROG-BIT INFESTATIONS? THROUGH THIS PROJECT PROPOSAL, WE HOPE TO INVESTIGATE THIS QUESTION FURTHER, WHILE ALSO TAKING ACTIVE MANAGEMENT ACTIONS TO PREVENT THE FURTHER SPREAD OF EUROPEAN FROG-BIT IN THE STRAITS OF MACKINAC.THE MICHIGAN ENVIRONMENT GREAT LAKES AND ENERGY MIEJ SCREEN TECHNICAL REPORT (KRUSE ET AL. 2022), REVEALS THAT THE PROJECT FOCAL AREA FALLS WITHIN THE 71ST PERCENTILE FOR SOCIOECONOMIC FACTORS RELATING TO LOW INCOME, TYPICALLY RESULTING IN UNDERSERVED POPULATIONS THAT FACE UNEMPLOYMENT AND HOUSING BURDENS. ONE PRIMARY CAUSE MAY BE THE RELATION THAT THE REGION IS HIGHLY DEPENDENT ON TOURIST SPENDING. MACKINAC COUNTY, LOCATED IN THE PROJECT FOCAL REGION, IS THE HIGHEST TOURIST SPENDING REGION IN THE ENTIRE UPPER PENINSULA OF MICHIGAN (TOURISM ECONOMIC IMPACT REPORT 2021), AND TOURISTS FROM ACROSS THE COUNTRY VISIT MACKINAC COUNTY TO ENJOY ITS DIVERSE RECREATIONAL OPPORTUNITIES, RANGING FROM DIVERSE WILDLIFE VIEWING, VAST HUNTING OPPORTUNITIES, AND MILES OF PRISTINE SHORELINE FOR KAYAKING OPPORTUNITIES. HOWEVER, THE SPREAD OF EUROPEAN FROG-BIT THROUGHOUT THE REGION IS ADVERSELY AFFECTING THESE RECREATIONAL OPPORTUNITIES AND CHANGING THE NATURAL, PRISTINE LANDSCAPE. THIS INVASIVE SPECIES THREATENS AQUATIC BIODIVERSITY, AND CHANGING GLOBAL CLIMATE FACTORS SUCH AS LONGER GROWING SEASONS INCREASE THE RISK OF ITS SPREAD. BY TREATING EUROPEAN FROG-BIT AND OTHER HIGH-PRIORITY INVASIVE SPECIES IN THIS PROJECT, WE AIM TO PROTECT AND ENHANCE COASTAL WETLANDS FOR HABITAT RESILIENCY, BENEFITING HUNDREDS OF SPECIES AND CREATING RECREATIONAL OPPORTUNITIES FOR THOUSANDS OF TOURISTS UPON WHOM THE UNDERSERVED COMMUNITY OF MACKINAC COUNTY RELIES UPON. FURTHERMORE, OUR PROJECT AIMS TO EVALUATE THE EFFECT OF EUROPEAN FROG-BIT INFESTATIONS ON WATERFOWL AND MARSH BIRD POPULATIONS, WHICH WILL AID WILDLIFE MANAGERS IN TAKING ACTION TO INCREASE WATERFOWL HUNTING OPPORTUNITIES FOR UNDERSERVED COMMUNITIES.PROJECT ACTIVITIES WILL OCCUR ACROSS 30 COASTAL WETLANDS WITHIN THE EASTERN UPPER PENINSULA SECTION OF THE STRAITS OF MACKINAC FOCAL REGION. THE PROJECT WILL FOCUS ON WETLANDS BETWEEN THE MACKINAC BRIDGE (45.847277, -84.744518) AND THE DETOUR PENINSULA (45.955101, -83.916817). EACH SITE MONITORED AND MANAGED WILL CONSIST OF EMERGENT COASTAL WETLANDS OCCURRING ON THE SHORELINE OF LAKE HURON. PRIMARY ACTIVITIES WILL INCLUDE CONDUCTING WATERFOWL AND MARSHBIRD SURVEYS, CONDUCTING ENVIRONMENTAL SURVEYS AT MONITORED COASTAL WETLANDS AND RESPONDING TO NEW INVASIVE SPECIES THREATS FOUND DURING MONITORING ACTIVITIES, CONDUCTING EUROPEAN FROG-BIT MANAGEMENT AND PREVENTION OF NEW INFESTATIONS AND SPREADING, AND PROVIDING EDUCATION THROUGH PUBLIC OUTREACH EVENTS TO PREVENT THE ACCIDENTAL SPREAD OF EUROPEAN FROG-BIT AND OTHER AQUATIC INVASIVE SPECIES. EXPECTED PROJECT RESULTS INCLUDE ENHANCING 20 ACRES OF WETLANDS THROUGH INVASIVE SPECIES REMOVAL, PROTECTING 700 ACRES OF WETLANDS THROUGH MONITORING ACTIVITIES, CONDUCTING 8 OUTREACH AND EDUCATION EVENTS TO EDUCATE AT LEAST 200 INDIVIDUALS. THIS WORK WILL ALSO LAY THE FOUNDATION FOR A FUTURE PEER-REVIEWED RESEARCH ARTICLE OR REPORT.

COMMUNITY FACILITY GRANTS - COMMUNITY FACILITY

COMMUNITY FACILITY GRANTS

TO PROVIDE PSYCHOLOGICAL GUIDANCE AND EMOTIONAL SUPPORT TO THE LGBTQ+ YOUTH COMMUNITY IN PERU.

ENERGY EFFICIENCY GRANTS

THIS EDA INVESTMENT SUPPORTS THE ECONOMIC DEVELOPMENT CORPORATION OF LUCE COUNTY, MICHIGAN, WITH COMPLETING A COMPREHENSIVE STRATEGIC PLAN FOR THE AREA, INCLUDING A FEASIBILITY STUDY FOR THEIR INDUSTRIAL PARK. THE PROJECT WILL UPDATE THE CURRENT COMPREHENSIVE ECONOMIC DEVELOPMENT PLAN IN LIGHT OF CHANGES TO THE REGION, INCLUDING THOSE CAUSED BY THE COVID-19 PANDEMIC. ONCE COMPLETED, THE STUDY WILL IDENTIFY AN OPPORTUNITY TO INCREASE ECONOMIC RESILIENCY AND STABILITY IN THE REGION, WHICH WILL BOOST JOB CREATION AND STRENGTHEN THE LOCAL ECONOMY.

COMMUNITY FACILITY GRANTS

COMMUNITY FACILITY GRANTS

COMMUNITY FACILITIES - ECONOMIC IMPACT INITIATIVE GRANTS

SRSA APPLICATION

SEC. 9007 REAP-ENERGY EFFICIENCY IMPROVEMENTS GRANTS (MAN)

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT $20K AND LESS

COMMUNITY FACILITY GRANTS - COMMUNITY FACILITY

COMMUNITY FACILITIES - ECONOMIC IMPACT INITIATIVE GRANTS

APPLICATION FOR SMALL RURAL SCHOOL ACHIEVEMENT PROGRAM

APPLICATION FOR SMALL RURAL SCHOOL ACHIEVEMENT PROGRAM

COMMUNITY FACILITY GRANTS

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

COMMUNITY FACILITY GRANTS

COMMUNITY FACILITY GRANTS

APPLICATION FOR SMALL, RURAL SCHOOL ACHIEVEMENT PROGRAM

TOOLS FOR CIRCULAR RNA RESEARCH AND DRUG DISCOVERY

SEC. 9007 REAP-RENEW ENERGY SYS GRANTS (MAN)