Contents - Max-Planck-Institut für Physik komplexer Systeme
Contents - Max-Planck-Institut für Physik komplexer Systeme
Contents - Max-Planck-Institut für Physik komplexer Systeme
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thatupregulatesactivestress,cangeneratesteadyflowandconcentrationpatterns.Thisworkdescribes<br />
anovelmechanismofpatterngeneration. ItextendstheoriginalworkofAlanTuringdescribinghow<br />
twochemicalspeciesdiffuseandreactwithoneanothertogeneratespatialpatterns,toincludeactive<br />
mechanicalstresses,deformationandtransportofthematerialinwhichthechemicalspeciesdiffuse.<br />
Weapplythisgeneralapproachtounderstandhowmechanicsandbiochemistryinteractintheprocess<br />
ofpolarizationoftheC.elegansembryo. Weuseopticaltechniquestocharacterizethemotilityof<br />
specificproteinsthatarepartoftheassociatedregulatorybiochemicalpathways. Weinvestigatetheir<br />
abilitiestoformpatternsintheframeworkofreaction-diffusion. Wefindthatthismass-conserved<br />
systemcanselforganizeandswitchfromastableunpolarizedstateintoapolarizedstateinresponseto<br />
stimuli. Importantly,flowsoftheactomyosincortexgenerateperturbationsinthespatialdistributions<br />
oftheproteinsthatarepartoftheregulatorypathways.Ifsufficientlylarge,theseperturbationstrigger<br />
polarizationofanotherwisestableunpolarizedstate. Thesefindingsdescribeanovelmechanismby<br />
whichcorticalflowsareabletolocalizethecomponentsthatspecifyanaxiswithinthecell,whichisan<br />
essentialprocessinthedevelopmentofeachandeveryanimal.<br />
TranscriptionalSystems. RNApolymeraseisthemolecularmachineresponsibleforreadingoutthe<br />
geneticcodestoredwithinDNAintheformofanRNAtranscript.Thistranscriptislaterusedfortranslationintothepreciseaminoacidsequencethatformstheproteinproduct,whichisofcourseencoded<br />
bythesequenceofDNAthatwasoriginallyreadout.Sincetheproductionofeachandeveryproteinin<br />
acellcommenceswiththisprocessofinformationtransfer,RNApolymeraserepresentsacentralcontrol<br />
pointforallcellularfunctionsandbehaviors. WeinvestigatehowthismachinemovesalongtheDNA<br />
template,andhowitensuresthataminimumnumberofcopymistakesismade.Weaskifalargepartof<br />
theirregularbehaviorobservedintranscriptionisadirectconsequenceoftheneedforrapidproduction<br />
oflonghigh-fidelitytranscripts. Byextendingestablishedtheoreticalproofreadingschemestoinclude<br />
transcriptshortening,webuildaquantitativestochasticmodelcouplingtranscriptionalproofreadingand<br />
chainelongation.Throughthisweelucidatethepreciseinterplaybetweentranscriptionalpauses,fidelity,<br />
polymerizationrate,andnucleotideconsumption.Thisrevealsamechanismwherebyslowandirregular<br />
transcriptionatthelevelofindividualpolymerasesleadstoastronomicalgainsintheproductionrateand<br />
nucleotideefficiencywithwhichlongandhigh-fidelitytranscriptscanbeproduced. Thesetheoretical<br />
investigationsarecomplementedbytheconstructionofahigh-resolutiondual-trapopticaltweezerapparatus,whichiscomplete.Wecurrentlyutilizethismicroscopetotesttheoreticalpredictionsregarding<br />
thetranscriptionalprogressofpolymerasemolecules,bymonitoringandmanipulatingonemoleculeata<br />
time.<br />
ThegroupisjointlyappointedtotheMPI-CBGand mpipks,wasstartedin2006,andhasgrowntofull<br />
sizeoverthepastcoupleofyears.StephanGrillreceivedtheARCHESPrizeoftheGermanMinistryof<br />
EducationandResearchin2009,theEuropeanMolecularBiologyOrganization(EMBO)younginvestigatorawardin2010,andthePaulEhrlich-undLudwigDarmstaedter-Nachwuchspreisforbiomedical<br />
researchin2011.<br />
Cooperations<br />
OhadMedalia,UniversityofZurich:Ultrastuctureoftheactomyosincortex<br />
A.A.Hyman,MPI-CBG:CorticalpolarizationinC.elegans<br />
J.Howard,MPI-CPfS:Singlecellperturbationexperiments<br />
F.Jülicher, mpipks,Dresden:ActivePolarGels<br />
C.Müller,EuropeanMolecularBiologyLaboratory,GrenobleOustation,France:TranscriptionbyRNA<br />
PolymeraseIII<br />
J.M.R.Parrondo,UniversidadComplutensedeMadrid,Spain: Irregulardynamicsfortranscriptional<br />
proofreading<br />
34 ScientificWorkanditsOrganizationatthe<strong>Institut</strong>e–anOverview