Lake Forest College

INSTITUTIONAL PORTION OF HEERF

EMERGENCY GRANTS TO STUDENTS IMPACTED BY CORONA VIRUS

BRC-BIO: INVESTIGATION OF THE TISSUE-SPECIFIC ROLE OF THE ER MEMBRANE PROTEIN COMPLEX (EMC) IN THE DEVELOPMENT AND MAINTENANCE OF A MULTICELLULAR ORGANISM -CELLS REQUIRE MANY PROTEINS, EITHER EMBEDDED IN THE CELLULAR MEMBRANE OR MOVED OUTSIDE OF THE CELL VIA SMALL PACKAGES, FOR NUMEROUS PROCESSES. THESE PROTEINS CAN SERVE A VARIETY OF ESSENTIAL FUNCTIONS, SUCH AS RECEPTORS, TETHERS, AND SIGNALS TO OTHER CELLS. THESE PROTEINS TYPICALLY ARE PARTICULARLY CHALLENGING TO FOLD INTO THE CORRECT SHAPE. THE ENDOPLASMIC RETICULUM (ER) IS THE LOCATION WHERE THIS PROCESSING OCCURS WITH THE HELP OF SPECIALIZED PROTEIN COMPLEXES. THE PI AND UNDERGRADUATE RESEARCHERS RECENTLY FOUND THAT LOSS OF ONE COMPONENT OF AN ER MEMBRANE PROTEIN COMPLEX, EMC4, IN SPECIALIZED CELLS OF THE NERVOUS SYSTEM CALLED GLIA, LED TO A SHORTENED LIFESPAN, LOCOMOTOR DEFICITS, AND OTHER DETRIMENTAL OUTCOMES IN THE MODEL ORGANISM, THE FRUIT FLY. THE PROPOSED RESEARCH WILL INVESTIGATE NOVEL QUESTIONS REGARDING (1) WHEN DURING THE LIFE CYCLE IS THIS COMPONENT REQUIRED FOR ORGANISMAL HEALTH, (2) WHICH TYPES OF CELLS IN THE NERVOUS SYSTEM REQUIRE THIS COMPONENT TO FUNCTION NORMALLY, AND (3) WHAT IS THE ROLE OF OTHER MEMBERS OF THIS ER MEMBRANE PROTEIN COMPLEX. ANSWERING THESE QUESTIONS WILL PROVIDE INSIGHT INTO HOW THE ER PROCESSES PROTEINS AND WHETHER THIS DIFFERS BETWEEN SPECIALIZED CELL TYPES OR LIFE STAGES OF AN ORGANISM. THIS PROJECT WILL PROVIDE SCIENTIFIC TRAINING TO LAKE FOREST COLLEGE UNDERGRADUATES THROUGH MENTORED RESEARCH EXPERIENCES, IMPROVING THEIR ACCESS TO AND PREPARATION FOR STEM CAREERS. THE PROPOSED PROJECT WILL ALSO INCORPORATE A MULTI-YEAR COURSE-BASED UNDERGRADUATE RESEARCH EXPERIENCE (CURE) TO SIGNIFICANTLY INCREASE THE NUMBER OF STUDENTS THAT GAIN VALUABLE RESEARCH TRAINING. THE RECENTLY DISCOVERED ER MEMBRANE PROTEIN COMPLEX (EMC) CONSISTS OF 8-10 CONSERVED SUBUNITS, AND IS THOUGHT TO BE INVOLVED IN INSERTION, FOLDING, AND PROTECTION FROM DEGRADATION OF MEMBRANE PROTEINS. HOWEVER, UNDERSTANDING OF EMC FUNCTION IS LIMITED BY THE FACT THAT MOST PRIOR WORK HAS BEEN CONDUCTED IN SINGLE-CELL SYSTEMS. A MULTICELLULAR ORGANISM IS REQUIRED TO INVESTIGATE THE CELL TYPE-SPECIFIC ROLES OF EMC SUBUNITS OR THE IMPACT OF EMC FUNCTION ON DIFFERENT LIFE STAGES. DROSOPHILA REPRESENT A POWERFUL MODEL SYSTEM TO ANSWER QUESTIONS THAT INTEGRATE THE MOLECULAR AND CELLULAR FUNCTION OF EMC WITH ITS IMPACT ON THE ORGANISM. THE PI AND UNDERGRADUATE RESEARCHERS RECENTLY DISCOVERED THAT GLIA-SPECIFIC RNAI KNOCKDOWN (KD) OF THE FLY HOMOLOG OF AN EMC SUBUNIT, EMC4, SEVERELY REDUCES ADULT SURVIVAL. FLIES LACKING GLIAL EXPRESSION OF EMC4 ALSO DISPLAY A MILD DEVELOPMENTAL DELAY, BUT NO SIGNIFICANT DECREASE IN DEVELOPMENTAL VIABILITY. EMC4 GLIAL KD FLIES ALSO DISPLAY SEVERE LOCOMOTOR DEFECTS AND INCREASED PROTEIN AGGREGATION. THIS RESEARCH PROPOSES TO INVESTIGATE (1) THE ROLE THAT GLIAL EMC4 PLAYS IN DIFFERENT LIFE STAGES, SPECIFICALLY DURING DEVELOPMENT VS. DURING MAINTENANCE OF AN ADULT ORGANISM, (2) THE CELL-SPECIFIC FUNCTION OF EMC4 IN SPECIALIZED CELL TYPES OF THE NERVOUS SYSTEM, AND (3) THE SPECIFICITY OF ANY OF THESE PHENOTYPES TO EMC4 VS. OTHER EMC SUBUNITS. THIS RESEARCH WILL ADVANCE UNDERSTANDING OF THE ROLE OF EMC IN MEMBRANE PROTEIN BIOGENESIS BY TAKING AN INTEGRATIVE APPROACH EXAMINING SURVIVAL, BEHAVIOR, AND DEVELOPMENT ALONGSIDE MOLECULAR AND CELLULAR FUNCTION. 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.

COLLABORATIVE RESEARCH: RUI - EMERGENT PROPERTIES OF BIOMASS PULSES: UNCOVERING THE ANT-MEDIATED EFFECTS OF PERIODICAL CICADAS ON FOREST ECOSYSTEMS -IN NATURE, POPULATIONS OF PLANTS AND ANIMALS OCCASIONALLY EXPLODE IN NUMBERS, PROVIDING A TEMPORARY SURPLUS OF NUTRITIOUS FOOD FOR CONSUMERS. WHEN THESE NUTRITIONAL ?PULSES? OCCUR, THEY CAN INITIATE CHAIN REACTIONS IN FOOD WEBS, AS CONSUMERS SWITCH FROM THEIR NORMAL DIETS TO FEAST INSTEAD ON THE ABUNDANT NEW FOOD ITEMS. UNDERSTANDING THE CONSEQUENCES OF THESE FOOD PULSES FOR NATURAL COMMUNITIES ? WHICH ORGANISMS ARE AFFECTED, FOR HOW LONG, AND IF THEY STOP PERFORMING THEIR NORMAL ?JOBS? TO TAKE ADVANTAGE OF THE NEW RESOURCE ? CAN PROVIDE INSIGHTS INTO HOW ECOLOGICAL SYSTEMS FUNCTION AND RESPOND TO CHANGE. THE SYNCHRONIZED EMERGENCE OF BILLIONS OF PERIODICAL CICADAS EVERY 13 OR 17 YEARS IN THE EASTERN U.S. PROVIDES AN ENORMOUS PULSE OF INSECT FOOD FOR A VARIETY OF GENERALIST CONSUMERS. THE ASSEMBLED RESEARCH TEAM WILL BE THE FIRST TO DOCUMENT THE IMPACTS OF CICADA PULSES ON THE FORAGING BEHAVIORS AND POPULATION DYNAMICS OF ONE OF THE MOST ABUNDANT ANIMALS ON THE PLANET: ANTS. RESULTS OF THE STUDY WILL ADVANCE OUR UNDERSTANDING OF HOW NUTRIENT PULSES ALTER THE VARIED ECOSYSTEM SERVICES THAT ANTS ROUTINELY PROVIDE, MANY OF WHICH ARE RELEVANT FOR BOTH THE FORESTRY AND AGRICULTURE SECTORS. IN ADDITION TO TRAINING UNDERGRADUATE RESEARCHERS IN FIELD BIOLOGY, THE RESEARCH TEAM HAS CREATED A FREE DIGITAL EDUCATION PROGRAM, ?FRIEND TO CICADAS,? THE GOAL OF WHICH IS TO TRAIN AND EMPOWER TEACHERS THROUGHOUT THE ENTIRE RANGE OF PERIODICAL CICADAS TO PROVIDE ACTIVITIES THAT SPARK WONDER AND CURIOSITY IN THEIR STUDENTS. IN THIS STUDY, THE RESEARCHERS TEST THE HYPOTHESIS THAT MOST ANTS WILL OPPORTUNISTICALLY ADJUST THEIR FORAGING TO CAPITALIZE ON ABUNDANT CICADA PREY, BOTH DURING THE DRAMATIC SPRING EMERGENCE AND AGAIN WHEN THE NEXT GENERATION OF CICADAS HATCHES LATER IN THE SUMMER. FURTHER, THEY PREDICT THAT CHANGES IN ANT FORAGING WILL ALTER THE STRENGTH OF THEIR COMPETITIVE AND MUTUALISTIC INTERACTIONS, INITIATING CHAINS OF INDIRECT EFFECTS IN THE FOREST COMMUNITY. USING A COMBINATION OF DIRECT FORAGING OBSERVATIONS, NUTRIENT BAITING, ANT EXCLUSION EXPERIMENTS, PITFALL TRAPPING, AND ISOTOPIC ANALYSES, THE RESEARCHERS WILL QUANTIFY THE IMPACTS OF THESE BIOMASS PULSES ON ANT FORAGING AT BOTH THE POPULATION AND COMMUNITY LEVELS. WITHIN- AND BETWEEN-YEARS COMPARISONS WILL ENABLE THE TEAM TO GAUGE THE IMPACTS OF CICADA PULSES ON ANT-MEDIATED ECOSYSTEM FUNCTIONS, FORAGING DYNAMICS, AND ANT-ANT INTERACTIONS. SPECIFICALLY, THE TEAM WILL DOCUMENT THE INDIRECT EFFECTS THAT ARE LIKELY TO OCCUR IF SHIFTS IN FORAGING ALTER SEED DISPERSAL, SCAVENGING, AND PROTECTIVE SERVICES PROVIDED TO APHIDS. USING STABLE ISOTOPES TO QUANTIFY THE TROPHIC POSITION OF ANT FORAGERS IN BOTH EMERGENCE AND NON-EMERGENCE YEARS WILL ALLOW THE TEAM TO TEST WHETHER ANTS INITIALLY OCCUPYING A RANGE OF TROPHIC POSITIONS CONVERGE WHEN FED A COMMON DIET. MOREOVER, THESE BIOMASS PULSES PRESENT A UNIQUE OPPORTUNITY TO EXAMINE THE CONTEXT-DEPENDENCY OF SPECIES INTERACTIONS IN BOTH MUTUALISTIC AND COMPETITIVE SETTINGS. TAKEN TOGETHER, THESE FINDINGS WILL CONTRIBUTE TO THE VERY LIMITED LITERATURE DESCRIBING THE IMPACTS OF RESOURCE PULSES ON TERRESTRIAL INVERTEBRATES AND PROVIDE IMPORTANT INSIGHTS INTO HOW TROPHIC ECOLOGY IS ALTERED DURING, AND SUBSEQUENT TO, NUTRIENT PULSES. 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.

RUI - AN INTEGRATIVE STUDY OF COVARIANCES BETWEEN BEHAVIORAL AND MORPHOLOGICAL LIFE-HISTORY TRAITS

COLLABORATIVE RESEARCH: THE PROXIMATE BASIS OF INDIVIDUAL VARIATION IN PHENOTYPIC PLASTICITY

COLLABORATIVE RESEARCH: IS HYPOXIA A CRITICAL CUE FOR MOLTING IN DROSOPHILA?

RUI: EXCEPTIONALLY SHORT TELOMERES IN FILAMENTOUS FUNGI AND THE RNA THAT MAKES THEM

CHARACTERIZING THE REQUIREMENT OF THE MYCOBACTERIAL BRKB ORTHOLOG IN TB PATHOGENESIS - PROJECT SUMMARY / ABSTRACT: DUE TO THE RISE OF ANTIBIOTIC RESISTANT TUBERCULOSIS AND THE LONG TREATMENT TIME OF CURRENT ANTI-TUBERCULOSIS THERAPIES, THERE IS AN IMMEDIATE NEED FOR NEW DRUG TARGETS AGAINST TUBERCULOSIS. MY LAB HAS IDENTIFIED THE MYCOBACTERIAL BRKB ORTHOLOG AS A LIKELY DRUG TARGET. WE HAVE ALREADY OBSERVED THAT MUTATION OF MYCOBACTERIAL BRKB GREATLY ATTENUATES GROWTH OF OUR MODEL ORGANISM MYCOBACTERIUM MARINUM IN ITS NATURAL HOST, THE ZEBRAFISH. FURTHERMORE, WE HAVE OBSERVED THAT THIS ORGANISM IS ATTENUATED FOR GROWTH IN BOTH INTRACELLULAR AND EXTRACELLULAR SPACES, MAKING IT PARTICULARLY ATTRACTIVE BECAUSE EXTRACELLULAR MYCOBACTERIA ARE ESPECIALLY PRESENT IN LATE-STAGE TB AND CONTRIBUTE TO TB TRANSMISSION, AND BECAUSE THERE IS A SPECIFIC NEED TO TARGET MYCOBACTERIA IN THE EXTRACELLULAR NICHE. WHILE BRKB IS FOUND THROUGHOUT THE BACTERIAL KINGDOM, THE FUNCTION OF BRKB REMAINS ELUSIVE. I PROPOSE TO CHARACTERIZE THE BIOCHEMICAL FUNCTION OF MYCOBACTERIAL BRKB AND RESOLVE ITS ROLE IN VIRULENCE BY COMPLETING THE FOLLOWING THREE SPECIFIC AIMS: (1) IDENTIFY MYCOBACTERIAL BRKB CHANNEL SUBSTRATE(S) AND TEST FOR PROTEIN INTERACTIONS, (2) IDENTIFY MECHANISM OF BRKB EXTRACELLULAR GROWTH REQUIREMENT, AND (3) MEASURE MYCOBACTERIAL BRKB GROWTH UNDER LATE-STAGE INFECTION CONDITIONS. TOWARDS THIS END, I HAVE PURIFIED RECOMBINANT TUBERCULOSIS BRKB FROM E. COLI. IN COLLABORATION WITH DR. PAUL DECAEN (NORTHWESTERN UNIV.), MY STUDENTS AND I WILL TEST BRKB FOR CHANNEL FUNCTION. MY LAB HAS EXTENSIVE EXPERIENCE WITH THE BIOCHEMISTRY, MICROBIOLOGY, AND ORGANISMAL BIOLOGY REQUIRED TO COMPLETE AIMS 1,2, AND 3 RESPECTIVELY. WITH THE BIOPHYSICAL EXPERTISE OF THE DECAEN LAB, WE COLLECTIVELY SHARE THE EXPERTISE TO SOLVE THE ROLE OF BRKB IN THE MYCOBACTERIAL CELL AND IN THE CONTEXT OF INFECTION. THIS PROJECT WILL SERVE AS THE FOUNDATION OF A SUSTAINABLE RESEARCH PLATFORM THAT WILL EMPOWER UNDERGRADUATES TO TEST INDEPENDENT HYPOTHESES ABOUT MYCOBACTERIAL VIRULENCE FACTORS AND HOST SUSCEPTIBILITY FACTORS. STUDENTS WILL HAVE THE TOOLS NECESSARY TO INVESTIGATE THE BIOCHEMICAL FUNCTIONS OF THESE FUNCTIONS, TO WORK AT BIOSAFETY LEVEL 2 TO INVESTIGATE MYCOBACTERIAL CELLULAR BIOLOGY, AND TO TEST THEIR MOLECULAR HYPOTHESES AT THE ORGANISMAL LEVEL USING THE ZEBRAFISH MYCOBACTERIUM MARINUM MODEL OF INFECTION.

MOLECULAR REGULATION OF ALPHA-SYNUCLEIN MISFOLDING AND TOXICITY IN TWO YEAST MODE

COLLABORATIVE RESEARCH/RUI: BEHAVIORAL AND GENETIC MECHANISMS FOR FREQUENCY-DEPENDENT SURVIVAL AND MATING ADVANTAGE IN GUPPIES

NATIONAL CENTER FOR EDUCATION RESEARCH