31Laboratory of Animal PhysiologyShinichiYONEKURAProfessor,Ph.D./Skeletalmuscle/Mammarygland/Neurodegenerativedisease/Cellbiology/MolecularBiologyCurrentresearchinourlabfocusesonunderstandinggrowthanddevelopmentatthecellularleveltoidentifymethodstoimproveefficiencyofanimalproduction.Regardingtheanimalproduction,currentlytherearetwomajorfocusesinthelaboratory.Thefirstistounderstandthemolecularmechanismofskeletalmuscledevelopment.Thesecondfocusinthelaboratoryistodeterminethemolecularmechanismofmammaryglanddevelopment.Inaddition,weareinvestigatingthemolecularmechanismofneurodegenerativediseaseandtryingtofindoutthepreventionfactorsforthesediseases.Molecular mechanisms of skeletal muscle developmentABCDABCMice and Drosophilaas a model for studying about the molecular mechanism of mammary gland development and neurodegeneration.Tissue culture experiments are necessary for understanding at molecular basis. Right picture indicates myotube formation after myogenic stimuli. Biotechnology DivisionMolecular mechanisms of mammary gland developmentMolecular mechanisms of neurodegenerative disease and explore the prevention factorsMammaryglandNeuron（写真一枚or複数枚組み合わせ）活性ありDay 0Day 4Tissue culture experimentin vivo experiment (Mice, Drosophila)Laboratory of Applied and Molecular MicrobiologyTakeshiHOSAKAAssociateProfessor,Ph.D.Actinomycetes, Antibiotic, Secondary metabolism, Ribosome engineering, Antibiotic hormesisActinomycetesproduceabundantamountsofnumerousbioactivemetabolites,includingantibiotics,immunosuppressants,andantitumoragents.Whole-genomesequencingstudiesofactinomyceteshaveshownthateachspeciescouldproducemanymoresecondarymetabolitesthanwereexpected.Thisindicatesthatthevastmajorityofsecondarymetabolitesremainunexpressedorbarelyexpressedunderstandardlaboratoryconditions.Thus,thereisconsiderableinterestinexploringpracticalmeanstoinducethisgeneticpotentialinactinomycetes,whichcouldresultinisolationofnovelbioactivemetabolites.Ourlaboratoryaimstounderstandthemolecularmechanismsactivatingsecondarymetabolismandtoestablisheffectivemethodsfordevelopingcrypticgeneclustersforsecondarymetabolicpathwaysinmicroorganisms.Biotechnology Division Originally,anantibioticisdefinedasachemicalcompoundthatisproducedbyamicroorganism,suppressesthegrowthofothermicroorganisms,andhaslittletoxicitytoanimals.Speakingofantibiotics,almosteveryonecanimaginethiseffect.Meanwhile,itremainsaprofoundmysterywhatrolesantibioticsplayinthenaturalworld.Withmulti-drugresistantbacteriaemergingoneafteranother,thediscoveryofnovelantibioticsandthedevelopmentofalternativestoantibioticsarebecomingincreasinglycrucial.Thenumberofnewlydiscoveredantibiotics,usuallyisolatedfromsecondarymetabolitesofmicroorganismsincludingactinomycetes,havebeendeclining.Tosolvethispredicament,inadditiontocontinuingthedevelopmentofnovelantibioticsandalternativestoantibiotics,itwouldbeofutmostimportanttounderstandthefundamentalworkingsofantibioticsthemselves,antibiotic-producingmicroorganism,andantibioticresistance.Ourlatestfindingsdemonstratethatribosome-targetingantibioticsnotonlyfunctionsasanantimicrobialbutalsocanactasanactivatorforsecondarymetabolismofactinomycetes.Giventhisphysiologicalfact,ourlaboratoryhasbeenanalyzingtheconcentration-dependentactivitiesofantibioticsatthemolecularlevelwiththehopeofuncoveringmysteriessuchasmechanismsforsecondarymetabolisminactinomycetesandtherolesofantibioticsinthenaturalworld.Concentration-dependent effects of lincomycin on secondary metabolism in S. coelciolor A3(2)Life cycle of actinomycetesSecondary metabolite productionSporesSubstrate mycelium formationAerial mycelium formationSpore maturationSporulationOHOHOOHOOOOOOHOHH104to107CFU ofactinomycetesin1 gram soil（in most soils（Spore germination01050Lincomycin(µg/mL)
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