StatementofPurpose,JeromeKu,BiomedicalEngineeringMSw/ThesisIwanttomakeadifferenceintheworld,andIwanttodothisbycreatingbiomedicaldevicesandtechnologies.Ihaveputmyheartintomanydifferentpursuitsduringmyundergraduateyears--someacademic,somenot--anditisthroughthisamalgamofexperiencesthatIhavecometorealizemylife’sambition.Researchhasmademeappreciatetherigorsofthescientificprocessandatthesametime,theexcitementoflayingthegroundworkfortechnologythatcouldone-daychangethewaywelive;foundingavolunteerorganizationhasrevealedtomemypassionforfosteringabetterworld;workingatastart-upandleadingtheEntrepreneurshipClubhasacquaintedmewithentrepreneursyoungandoldwhosemoxieandpassionhasbeentrulyinspiring;andoddlyenough,asummeronWallSt.mademerealizethatscienceismytruepassion.Throughtheseexperiences,I’velearnedwhatkindofpersonIamandwhatkindoflifeIwanttolead:IknownowthatIvaluemypassionforknowledgeanddesiretomakeadifferencethroughscience,medicine,andtechnology,aboveallelse.IknowthatIwanttodedicatemylifetobiomedicalinvention,innovation,andsomewheredowntheroad,entrepreneurship.Duringthesummerbetweenmyfreshmanandsophomoreyears,IworkedinProfessorRonWeiss’lab,applyingelectricalengineeringprinciplestocellularsystemsintheemergingfieldofsyntheticbiology.I“programmed”cellularbehaviorbyengineeringandinsertingsimplesyntheticnetworksofgeneticregulatoryelements—“logicgates”—intothemodelorganismE.Coli,asteptowardsthegoalofsomedaybeingableto“program”cellsandcellularsystemsaseasilyasweprogramcomputerstoday.Icontinuedthisresearchduringmyjuniorandsenioryears,engaginginayearandhalf-longindependentprojecttoengineertheRhlquorum-sensinggeneticcircuitfoundinthepathogenPseudomonasAeruginosa.Quorum-sensingsystemsarewell-documentedandareusedbybacteriaforcommunicationandpopulation-basedcontrolofgenes.Oneofthegoalsofthisresearchistobeabletocontrolandcoordinatecellularandpopulationbehaviorthroughsyntheticgeneticcircuitry,andquorum-sensingsystemsareanaturaljumpingoffpointforbuildingalibraryofcommunicationandcontrolcomponents.Thepurposeofmyproject,specifically,wastogenerate,usingdirectedevolution,alibraryofcircuitswitharangeofspecificitiesandsensitivitiesthatcouldbematchedwithotherquorum-sensingcircuitsforpurposesofintercellularcommunication.Basedontheresultsofmywork,wewereabletoimplementonesuchintercellularcommunicationnetworkwherebygeneexpressionisonlyactivateduponco-localizationandexchangeofsignalsbetweenmixedpopulations,asystemthatcanconceivablybeusedtotargetcancer.Theseresultsarecurrentlybeingdevelopedintoascientificpaper.Towardstheendofmysenioryearandcontinuingintothesummerof2005,Iswitchedmyresearchfocustostemcells.Here,IworkedwithoneofProfessorWeiss’graduatestudentsinconstructingsyntheticgenenetworksfororchestratinggeneticexpressionanddifferentiationatasinglecellandmulti-populationlevel.Thelong-rangeimplicationsofsuchresearchistrulyawe-inspiring,aswewillsomedaybeabletoprogramtheformationoftissuesatacellularlevel.Toachievethislong-termgoal,westartedbyconstructingbasicbuildingblocksystems:usingthetet-On,tetR/O,andlacR/Oregulatorysystemsanddevelopmentalmasterswitches(MyoD,Ppar-gamma,Nanog),wedesignedandbuilta1:2multiplexerandtoggleswitch,andalsosynthesizedanovelsignaltransductionsystembyemployingsend/receivecomponentsfromArabidopsisthalianaandS.cerevisiae(thiscrossspeciessignalrelaysystemwillminimizeeffectsofcrosstalk).MuchtimewasspentoncircuitconstructioninE.Coliandpreliminaryverificationofcircuitfunctionbytransienttransfectionof293cells(commonlyusedmammaliancellline).Mostoftheconstructswerenearingcompletiontowardstheendofmystint,andwehadbegunlarge-scaleproductionoflentivirusvectorsinpreparationfortransductionofvariousEScelllines.Thisworkshouldresultinseveralpublications.Althoughmostofmyresearchhasbeenintheareaofsyntheticbiology,IamalsoveryinterestedinthebiologicalapplicationsofmicrofabricationandaimtoexploretheareaofbioMEMS/nanotechnology/moleculardiagnosticsingraduateschool.Myundergraduateconcentrationwithinelectricalengineeringwassolidstatedevices,andIhavealsobeendoingbackgroundreading(FundamentalsofMicrofabrication,byMadou)aswellasutilizingcoursewebsitesfornotesandreferencestoscientificliteratureinthisarea.Inadditiontothisself-study,IamscheduledtotakepartinabioMEMSresearchprojectatInstituteforBioengineeringandNanotechnology(inSingapore)startingJanuary(IamcurrentlyinSingaporeonanInternationalTeachingFellowship);possibleprojectsincludeafullyintegratedbiochipforearlycancerdiagnosisanddevelopmentofplatformtechnologiesandmicrodevicesforartificialorgans.Inmyremainingtime,Ihavebeentalkingwithvariouslocalbiomedicaltechnologystart-upstolearnmoreabouthigh-techentrepreneurshipinSingapore.AsinterestedasIaminthepurescienceaspectofresearch,Icarejustasmuchaboutthehumansideofbioengineering.Thatis,inthefieldofbiomedicalengineering,wherethereissuchtremendouspotentialfortechnologiesthatwillreduceillnessandcuredisease,IamdrivenasmuchbythefactthatIamcreatingsomethingthatwillsomedaydirectlybenefithumankindasIambyincreasingscientificknowledge.OfalltheprogramsthatIhavelookedat,BM