Southern Research Institute

SOUTHERN RESEARCH SPECIALIZED BIOCONTAINMENT SCREENING CENTER (SRSBSC)

BIOMASS CONVERSION TO ACRYLONITRILE MONOMER-PRECURSOR FOR PRODUCTION OF CARBON FIBERS

SOUTHERN RESEARCH MOLECULAR LIBRARIES SCREENING CENTER (SRMLSC)

DEVELOPMENT OF MU AGONIST DELTA ANTAGONIST OPIOIDS AS ANALGESICS FOR CHRONIC PAIN

ATTENUATED WEST NILE VIRUS LIVE VACCINE FOR HUMAN USE

CELLULAR MECHANISM OF SYNCHRONY IMPAIRMENTS IN SCHIZOPHRENIA

NANO-CARRIER FORMULATIONS FOR TARGETED DRUG DELIVERY AND MALARIA RADICAL CURE

TARGETING GLI-DEPENDENT TRANSCRIPTION BY GANT61 IN COLON CANCER

HOST CELL FACTORS AND AIDS PATHOGENESIS

4'-SUBSTITUTED NUCLEOSIDE ANALOGS AS ANTICANCER DRUGS

DEVELOPMENT OF SMALL MOLECULE INHIBITORS AS ANTI-INFLAMMATORY AGENTS AND ANTIDOTES FOR ARSENICALS - ARSENICALS CAUSE RAPID, SEVERE AND PAINFUL INFLAMMATORY AND BLISTERING RESPONSES IN THE SKIN. THE AVAILABLE MEDICAL COUNTERMEASURES AGAINST ARSENICAL-INDUCED TOXICITY ARE NOT EFFECTIVE DUE TO TOXICITY AND A LOW THERAPEUTIC INDEX. HENCE, THERE IS A DEMAND FOR THE DEVELOPMENT OF MORE EFFECTIVE AND LESS TOXIC ANTIDOTES FOR ARSENICALS. DEVELOPING HYBRID INHIBITORS OF BROMODOMAIN-CONTAINING PROTEIN 4 (BRD4) WHICH ARE RESPONSIBLE FOR THE REGULATION OF INFLAMMATORY GENES, RECEPTOR-INTERACTING PROTEIN KINASE-3 (RIP3, OR RIPK3), A CENTRAL PLAYER IN NECROPTOSIS, AND INTERLEUKIN-6 (IL-6) WOULD BE AN EFFECTIVE AND EFFICIENT TREATMENT TO ATTENUATE ARSENICAL-INDUCED INFLAMMATION. WE HAVE IDENTIFIED THREE POTENT INHIBITORS, SRI-43887, SRI-47362 AND SRI-47561 OF BRD4, RIPK3 AND IL6. FOR EXAMPLE, SRI-43887 EXHIBITED SIGNIFICANT ACTIVITY IN VIVO AGAINST PHENYLARSINE OXIDE (PAO) AND ARSENICALS (LEWISITE)-INDUCED MICE. CONTINUED OPTIMIZATION OF THESE COMPOUNDS WILL LEAD TO THE IDENTIFICATION OF A POTENTIAL PRECLINICAL CANDIDATE(S) FOR THE TREATMENT OF CUTANEOUS INJURIES ASSOCIATED WITH ARSENICALS. TO ACHIEVE THIS GOAL, WE WILL (I) UTILIZE MOLECULAR MODELING TO DESIGN AND SYNTHESIZE ANALOGS OF THESE THREE LEAD COMPOUNDS AND TEST IN VITRO FOR BRD4, RIPK3 AND IL6 INHIBITORY ACTIVITY; (II) EVALUATE SELECT COMPOUNDS FOR CYTOTOXICITY AND IN VITRO DRUG-LIKE PROPERTIES (SOLUBILITY, METABOLIC STABILITY, LOG D, PERMEABILITY); (III) DETERMINE THE IN VIVO PHARMACOKINETIC PROFILE (BIOAVAILABILITY AND HALF-LIFE); AND (IV) PERFORM IN VIVO STUDIES ON SELECT COMPOUNDS AGAINST PAO AND LEWISITE TO DETERMINE THE EFFICACY OF THESE COMPOUNDS. THESE GOALS WILL BE ACCOMPLISHED THROUGH A COLLABORATIVE EFFORT INVOLVING A TEAM WITH EXTENSIVE EXPERIENCE IN DRUG DESIGN, MEDICINAL CHEMISTRY, COMPUTATIONAL CHEMISTRY, BIOLOGICAL ASSAYS, PHARMACOKINETICS, MOLECULAR BIOLOGY AND DRUG DEVELOPMENT.

SOUTHERN RESEARCH INSTITUTE TINA - NUCLEAR CONTROL NUMBER 1953-1539

TRANSCRIPTIONAL REGULATION OF METABOLISM IN NEURONS

PILOT SCALE DEMONSTRATION OF FULLY INTEGRATED COMMERCIAL PROCESSES FOR CONVERTING WOODY BIOMASS INTO CLEAN BIOMASS DIESEL FUEL

COMBINED SORBENT/WGS-BASED CO2 CAPTURE PROCESS WITH INTEGRATED HEAT MANAGEMENT FOR IGCC SYSTEMS

WNT CO-RECEPTOR LRP6 TURNOVER AND CANCER

PILOT-SCALE LIBRARIES BASED ON NUCLEOSIDE TEMPLATES FOR THE ML INITIATIVE

NEW AWARD NO. DE-FE0031531 TITLED, ''SMALL-SCALE ENGINEERED HIGH FLEXIBILITY GASIFIER''

DEMONSTRATION OF HIGH-TEMPERATURE CALCIUM-BASED THERMOCHEMICAL ENERGY STORAGE SYSTEM FOR USE WITH CONCENTRATING SOLAR POWER FACILITIES

SMALL SCALE COAL BIOMASS LIQUIDS PRODUCTION USING HIGHLY SELECTIVE FISCHER TROPSCH CATALYST

DE-FE0031713, FIELD SCALE TESTING OF THE THERMOCATALYTIC ETHYLENE PRODUCTION PROCESS USING ETHANE AND ACTUAL COAL FIRED FLUE GAS CARBON DIOXIDE (CO2)

MECHANISMS OF MITOTIC ACTIVATION OF THE ATM KINASE

DEVELOPMENT OF DOPAMINE D3 LIGANDS AS MEDICATIONS FOR PSYCHOSTIMULANT ADDICTION

TARGETED LIBRARY SYNTHESIS AND SCREENING: ALLOSTERIC MODULATORS OF TRANSPORTERS

STRUCTURE OF M. TUBERCULOSIS ADENOSINE KINASE AND DESIGN OF ANTIMICROBIAL NUCLE

AN AUTOMATED COMPOUND MANAGEMENT SYSTEM FOR SMALL MOLECULE DRUG DISCOVERY - ABSTRACT SOUTHERN RESEARCH (SR) IS REQUESTING FUNDS FOR THE PURCHASE OF A HAMILTON VERSO M3 (“VERSO”) TO ASSIST IN THE EXECUTION OF DRUG DISCOVERY AND CHEMICAL BIOLOGY PROJECTS. THE VERSO WILL SERVE AS THE SMALL MOLECULE REPOSITORY FOR SR, UAB, AND SEVERAL INSTITUTIONS IN THE REGION, REPLACING THE CURRENT DE-CENTRALIZED MODEL. THIS WILL COMPLEMENT THE ROLE OF SR AS THE PROVIDER OF HIGH-THROUGHPUT SCREENING, CHEMISTRY, AND OTHER DOWNSTREAM DRUG DISCOVERY ACTIVITIES TO THE PARTICIPATING INSTITUTIONS. THE VERSO WILL STORE SAMPLES IN A -20 ºC DRY ENVIRONMENT, ENABLE SINGLE CONTAINER RETRIEVAL (“CHERRY-PICKING”), ALLOW ACTIVE THAWING WITHIN THE SYSTEM, PROVIDE AN UP-TO-DATE INVENTORY OF THE CONTENTS, AND PROVIDE REAL-TIME MONITORING OF THE SYSTEM STATUS. THESE PRIMARY FEATURES OF THE SYSTEM WILL SERVE TO PROTECT THE SAMPLES’ INTEGRITY, REPLACE THE CURRENT MANUAL STEPS OF RETRIEVAL AND STORAGE, AND IMPROVE THE PROCESSES THAT TRACK SAMPLES FROM SOURCE CONTAINER TO EXPERIMENTAL RESULTS. ACTIVITIES THAT THE VERSO SERVICE WILL SUPPORT INCLUDE PRIMARY SCREENING TO IDENTIFY ACTIVE COMPOUNDS, CONFIRMATION AND COUNTER-SCREENING OF PRIMARY AND VIRTUAL SCREENING HITS, IN VITRO POTENCY DETERMINATIONS DURING HIT-TO-LEAD AND LEAD OPTIMIZATION STAGES, DRUG REPURPOSING SCREENING, AND FUNDAMENTAL CHEMICAL BIOLOGY STUDIES. THE PROJECTS THAT WILL BENEFIT FROM THE VERSO REPRESENT MULTIPLE STAGES ALONG THE DISCOVERY PIPELINE RANGING FROM EARLY TARGET IDENTIFICATION AND VALIDATION STUDIES TO THOSE AT THE THRESHOLD OF CLINICAL TRIALS. AS SOUTHERN RESEARCH CHARTS A PATH OF GROWTH, THE NEED FOR SMALL MOLECULE DRUG DISCOVERY WILL GROW AS WELL. CURRENTLY, SR’S COLLECTION IS COMPRISED OF OVER 4000 PLATES (CONTAINING 320 COMPOUNDS EACH) AND OVER 66,000 SINGLE CONTAINERS (TUBES AND VIALS) MANAGED ACROSS GROUPS WITH SUBOPTIMAL MANUAL PROCESSES. ESTIMATED GROWTH IS EXPECTED TO CONSIST OF APPROXIMATELY 1600 INDIVIDUAL SAMPLES PER YEAR AND THE ACQUISITION OF A NEW 100,000 COMPOUND LIBRARY IN MULTIPLE FORMATS TO SERVE THE NEEDS OF THE USERS. THE USER BASE WILL GROW BY PROGRESSING EARLY-STAGE PROJECTS FROM PILOT SCREEN TO A FULL SCREENING CAMPAIGN AND BY IDENTIFYING PROMISING NEW TARGETS AND APPROACHES TO FUND THROUGH THE ALABAMA DRUG DISCOVERY ALLIANCE (ADDA). THE IMPLEMENTATION OF AN AUTOMATED COMPOUND MANAGEMENT SYSTEM WILL BE CRITICAL FOR SUPPORTING THIS GROWTH AND CONTRIBUTING TO ONGOING NIH-FUNDED PROJECTS AND NEWLY EMERGING DRUG DISCOVERY PROGRAMS.

TARGETING MDR-TB

THIS AMERICAN RECOVERY & REINVESTMENT ACT OF 2009 FUNDING IS PROVIDED FOR THE IMPLEMENTATION OF EMERGING TECHNOLOGIES THAT ACHIEVE DIESEL EMISSIONS

HIGH HYDROGEN, LOW METHANE SYNGAS FROM LOW RANK COALS FOR COAL-TO-LIQUIDS PRODUCTION

PURINE ANALOG ANTI-MYCOBACTERIAL DRUG DEVELOPMENT

PILOT-SCALE DEMONSTRATION OF FULLY INTEGRATED COMMERCIAL PROCESSES FOR CONVERTING WOODY BIOMASS INTO

PLASMA ARC GASIFICATION BASED RARE EARTH ELEMENT RECOVERY FROM COAL FLY ASH

OXYGEN-FIRED CO2 RECYCLE FOR APPLICATION TO DIRECT CO2 CAPTURE CO2 CAPTURE FROM COAL-FIRED POWER PLANTS

REGENERATIVE CARBONATE-BASED THERMOCHEMICAL ENERGY STORAGE SYSTEM FOR CONCENTRATING SOLAR POWER

DE-FE0029570, LOW TEMPERATURE PROCESS UTILIZING NON-ENGINEERED CATALYST FOR OLEFIN PRODUCTION FROM COAL DERIVED FLUE GAS

RANK SIGNALING INHIBITORS FOR TREATING BREAST CANCER BONE METASTASIS

TARGETED LIBRARY SYNTHESIS AND SCREENING: ALLOSTERIC MODULATORS OF TRANSPORTERS

MILD BIOMASS LIQUEFACTION PROCESS FOR ECONOMIC PRODUCTION OF STABILIZED REFINERY-READY BIO-OILS

SYNTHETIC GYPSOGENIN SAPONINS AS SYNERGISTIC VACCINE ADJUVANTS

MECHANISM OF METHYLTHIOADENOSINE NUCLEOSIDASE-MEDIATED INHIBITION OF BIOFILM FORM

NEW DRUG LEADS FOR RESISTANT VISCERAL LEISHMANIASIS

SMALL MOLECULE FZD7 INHIBITORS FOR CANCER THERAPY

DESIGN OF MULTI-TARGET D-ALA-D-ALA LIGASE LIGANDS

DEVELOPMENT OF OPIOID RECEPTOR MODELS FOR RATIONAL DESIGN OF BIFUNCTIONAL LIGANDS

ALLIANCE FOR INNOVATIVE MEDICAL TECHNOLOGY PROOF OF CONCEPT CENTER

GEOTHERMAL THERMOELECTRIC GENERATION (G-TEG) WITH INTEGRATED TEMPERATURE DRIVEN MEMBRANE DISTILLATION AND NOVEL MANGANESE OXIDE LITHIUM EXTRACTION

TREATMENT OF PRODUCED WATER FROM CARBON SEQUESTRATION SITES FOR WATER REUSE, MINERAL RECOVERY AND CARBON UTILIZATION

DESCRIPTION:THIS ACTION APPROVES AN AWARD IN THE AMOUNT OF $437,545 TO SUPPORT SOUTHERN RESEARCH INSTITUTE TO CONDUCT AMBIENT AIR MONITORING OF POLLUTANTS OF GREATEST CONCERN IN COMMUNITIES WITH ENVIRONMENTAL AND HEALTH OUTCOME DISPARITIES STEMMING FROM POLLUTION AND THE COVID-19 PANDEMIC. THIS PROJECT WILL MONITOR CRITERIA AIR POLLUTANT CONCENTRATIONS IN TWO UNDERSERVED NEIGHBORHOODS IN BIRMINGHAM, AL AS WELL AS MONITOR CONCENTRATIONS OF KEY VOLATILE ORGANIC COMPOUNDS INCLUDING NAPHTHALENE AND BENZENE. ACTIVITIES TO BE PERFORMED: WILL BE USED TO SUPPORT COMMUNITY AND LOCAL EFFORTS TO MONITOR THEIR OWN AIR QUALITY AND TO PROMOTE AIR QUALITY MONITORING PARTNERSHIPS BETWEEN COMMUNITIES AND LOCAL GOVERNMENTS AND A RESEARCH GROUP THAT: LEVERAGE EXISTING AIR QUALITY EXPERTISE, EXPAND USE OF COMMUNITY MONITORING GROUPS AND OTHER APPROACHES THAT GIVE THE COMMUNITY A VOICE IN THE MONITORING OF THE AIR QUALITY, AND BUILD A FOUNDATION OF TRUSTING RELATIONSHIPS AND ENHANCED UNDERSTANDING FROM WHICH SUSTAINABLE SOLUTIONS TO COMMUNITY AIR POLLUTION PROBLEMS CAN BE FOUND. THE ANTICIPATED DELIVERABLES INCLUDE: A PROJECT SPECIFIC QAPP; MEASUREMENTS OF PARTICULATE MATTER, GASEOUS POLLUTANTS, AND VOCS IN IDENTIFIED STUDY AREAS, DATA ACCESS TO CLOUD STORED AIR QUALITY DATA, REGULAR PRESENTATIONS OF ANALYZED AIR QUALITY DATA AS WELL AS TRAINING SESSIONS ON HOW CONSTITUENTS CAN ACCESS DATA VIA THE CLOUD; PROGRESS REPORTS; AND A FINAL ASSESSMENT REPORT. THE EXPECTED OUTCOMES INCLUDE: COMMUNITY AWARENESS AND KNOWLEDGE ABOUT PARTICULATE MATTER, CRITERIA POLLUTANT, AND OTHER KEY ORGANICS; GREATER ACCESS TO INFORMATION ABOUT POTENTIAL ENVIRONMENTAL AND HUMAN HEALTH RISKS; INFORMATION TO SUPPLEMENT EXISTING MONITORING SITES AND POTENTIALLY IDENTIFY LOCATIONS WHERE ADDITIONAL PROTECTIVE ACTIONS MAY BE NEEDED. THE INTENDED BENEFICIARIES INCLUDE: THE NORTH BIRMINGHAM AND WEST END COMMUNITIES; BIRMINGHAM RESIDENTS AND STUDENTS; THE CITY OF BIRMINGHAM, AL; THE COUNTY DEPARTMENT OF HEALTH; AND OTHER COMMUNITY PARTNERS.ACTIVITIES:.SUBRECIPIENT:NO SUBAWARDS ARE INCLUDED IN THIS ASSISTANCE AGREEMENT.OUTCOMES:.

NOVEL UP-REGULATORS OF NF-KB ACTIVITY: EFFECT ON MNSOD AND TBI IN VITRO MODELS

DIETARY MODULATION OF MAMMARY TUMORIGENESIS IN THE PYMT MODEL

TESTING OF MERCURY CONTROL WITH CALCIUM-BASED SORBENTS AND OXIDIZING AGENTS

DEVELOPEMENT AND VALIDATION OF A HIGH THROUGHPUT SCREEN FOR COMPOUNDS WITH ANTIVIRAL ACTIVITY AGAINST ENCEPHALITIC ALPHAVIRUSES

CHOLERA PATHOGENESIS, MUCINASE ACTIVITY AND MOTILITY

THIS CENTER VERIFIES PROMISING GHG (GREENHOUSE GAS) MITIGATION TECHNOLOGIES AS WELL AS ENERGY EFFICIENT ALTERNATIVES, SUBJECTS THEM TO INDEPENDENT T

A FULLY VALIDATED ASSAY TO IDENTIFY ACTIVATORS OF ERSR IN HUMAN GLIOMA CELLS: IDE

DISCOVERY OF SMALL MOLECULE INHIBITORS OF THE ONCOGENIC AND CYTOKINETIC PROTEIN M

OMIC PROFILING OF VULNERABLE SYNAPSES IN AGE-RELATED NEURODEGENERATION

DEMONSTRATION OF A PISTON DRIVEN PLUG FEED SYSTEM FOR FEEDING COAL/BIOMASS MIXTURE ACROSS A PRESSURE GRADIENT FOR APPLICATION TO COMMERCIAL CBTL

A HTS ASSAY FOR IDENTIFYING ANTI-VIRAL DRUGS AGAINST ARBOVIRUS INFECTIONS

A CELL BASED ASSAY FOR THE IDENTIFICATION OF LEAD COMPOUNDS WITH ANTI-VIRAL ACTIV

DEVELOPMENT OF A LOW MAINTENANCE, FIELD REGGEDIZED SO3 CEM SUITABLE FOR UNATTENDED PLANT USE

INDIRECT LIQUEFACTION OF COAL-BIOMASS MIXTURES FOR PRODUCTION OF JET FUEL WITH HIGH PRODUCTIVITY AND SELECTIVITY

OXYGEN-FIRED CO2 RECYCLE FOR APPLICATION TO DIRECT CO2 CAPTURE CO2 CAPTURE FROM COAL-FIRED POWER PLA

BUILDING EXPANSION

DEV OF A VALIDATED MODEL FOR USE IN MINIMIZING NOX EMISSIONS AND MAXIMIZING CARBON UTILIZATION WHEN COFIRING BIOMASS WITH COAL