idemalab.tudelft.nl

Idemagroup-overviewBiologyisoftenhighlynonlinear,whichisgoodnewsforlife:manyactorstogethercan accomplishwhat a few cannot, not just for lackof individual strength, butbecausethewholereallyismorethanthesumofitsparts.Inourgroup,westudyhow collective dynamics of many particles, from protein inclusions in themembrane to growing and dividing cells in colonies, affect the function andbehaviourofthelivingsystemtheyarepartof.

FromsingletomulticellularbehaviourIndividual cells and animals behavedifferently ontheirownthaninagroup.Beingpartofagroupisoftenuseful, forprotectionagainstoutside factorsliketheweatherorpredators,orbecausetogethercells can achievemore than any single one couldalone. We study the collective behaviour of self-propelledsoftparticlesasamodelforthesesystems,lookingforaminimalsetofrulesthatallowsthecellstocreatecomplexpatterns.

Developmentanddefectsinbacterialcoloniesandeukaryotictissues

Manybacteriahaverod-likeshapes,whichextendastheygrow, and are halved when they divide. Due to thiscombination of geometry and growth, a bacterial colonybecomes an active material with interesting topologicalproperties,includingsuchfeaturesasorientationalregionsand defects. Similarly, growing and dividing eukaryoticcellsformtissues,bothhealthyandtumourcells.Westudythedevelopmentofboththesesystemsinsimulations.

Membrane-mediatedinteractionsWhen you put two balls on a mattress, they attract,because they deform the mattress. Two (or more)proteinsinamembraneexperiencesimilarinteractionsbecause of the deformations they impose. Unlikeelectrostatic interactions, these membrane-mediatedinteractionsarenotadditive,andcanevenchangesignduetothepresenceofmultipleproteins.Moreover,manymembranes in livingsystemsarenaturallycurved,creatinganontrivialenergylandscape that depends on the relative curvature of the membrane and theimposed curvature of the protein. We study the patterns and shapes thesemembrane/proteincompoundsform,usingbothanalyticalandnumericaltools.

idemalab.tudelft.nl

Project1:Dynamicsofself-propellingrod-shapedparticlesA(verysimple)modelforthecollectivedynamicsofagroupofbacteriaistomodelthemaselongatedparticlesthatself-propelandinteractwhentheytouch.Suchmodelshavebeenstudiedextensivelyfordiskandsphere-shapedparticles,whichhaveverysimpleinteractions,butalsoastrongrestriction:theforcesalwaysactbetweentheparticlecentres,sothereareneveranytorques.Analternativeistouse ellipticalparticles, forwhich the interactions can still be calculated fromasingle potential (though not as easily as for spherical particles) andwhich doexperience torques. Bacteria however typically have rod-like shapes, and inearlier projects we’ve found that the difference between rods and ellipses isimportantforthewaytheparticlespacktogether.Inthisproject,we’llstudytheinteraction between self-propelling rod-shaped bacteria to get a betterunderstanding of their collective dynamics. The bacteria will be modelled asspherocylinders: cylindrical bodies with spherical caps. Their interactions aresoft:bacteriacandeformabit,whichgeneratesarepulsiveforceandtorque.Theirself-propulsioncanbeeitherunidirectionaloruptorandomswitching,andwe’llinvestigateifabiasinswitchingcanbeusedtokeepagroupofbacteriatogether.

Project2:DevelopmentofabacterialcolonyNexttoself-propelling,bacteriacanalsogrowanddivide.In this project, we’ll study that process, again for rod-shaped bacteria. These bacteria do not moveautonomously,butcanbepushedawayduetothegrowthoftheirneighbours.Ontheotherhand,theycanalsoadheretothoseneighbours.Wewill investigatehowthebalancebetween adhesion and repulsion affects colonymorphology and topology, for both homogeneous andheterogeneouscolonies.

Project3:Getout(fast)Whenself-propellingparticlesoffinitesize(rangingfrombacteriatopeople)trytogothroughasmallopening(sayadoor)inlargenumbersquickly,theytendtoget jammed, causing a significant slowdown.The jamusually resolves throughrearrangements,butispotentiallyhazardousifthepressuresinthegroupbecometoohigh.Experimentalresultssuggestthatthestrategicplacementofobstaclesinfrontoftheopeningmayhelpstreamlinetheflow.Inthisproject,we’llinvestigatethis effect for soft self-propelling particles as a function of opening size, self-propulsionspeed,andobstacleshapeandposition.

idemalab.tudelft.nl

Project4:CellulardemixinginembryoidbodiesEmbryoidbodies(EBs)arethree-dimensionalaggregatesofstemcells,mimickingtheveryearlystagesofembryodevelopment.Thestemcellscanbeinducedtodifferentiate, and differentiated cells can be tracked through time. Oneparticularlyinterestingexperimentalobservationisthatifthefirstdifferentiationstep(intoectodermandXENcells)happensinarandomway,theresultingcellsspontaneously rearrange such that the ectoderm cells locate at the top. Thisdemixing can be stopped by inhibiting the formation of integrin-beta, whichmeansthatthecellscannolongerspecificallyadheretoothercellsofthesametype.We’llinvestigatethisdemixingbybuildingamodelthatincludesdifferentialadhesionandself-propulsionofsimplesphericalcells.

Project5:DevelopmentofconfluenttissuesIninsects,afertilizedeggcellfirstundergoesanumberof nuclear divisions, after which the resulting(proto)cells migrate to the egg’s surface, where theydivide a couple more times, eventually forming aconfluent layer. We found earlier that this confluentlayer corresponds very closely to the Voronoitessellation of the nuclei of the cells. To model thissystem, we couple internal and external cellularmechanicsthroughacombinationofadhesionbetweencells and a cytoskeletal network (with actin andmicrotubules) inside the cell.Initiallywe only included compressional forces, but themicrotubules can alsobend,soweshouldincludetorquesonthemaswell.Thispresentsbothachallengeandanopportunityformodellingcelldivision,whichistheaimofthisproject.Ifsuccessful,wewillalsousethemodelforstudyingtheformationoftumoursinotherwisehealthytissues.

idemalab.tudelft.nl

Project6:Membrane-mediatedinteractionsintubesManycellularorganelles, including theERandmitochondrialnetworks,haveatubularshapeor tube-shapedregions.Such tubularmembranescanbe formedeasily by the application of a force on a flatmembrane. It can also be formedthroughtheactionofbanana-shapedproteins,whichinturncanactascurvaturesensorsaswell.We’verecentlybeguntoinvestigatethedynamicsofsuchbanana-shapedproteinsontubularnetworks(seeeLife6:e30292(2017)).WearealsocollaboratingwiththeexperimentalAubin-TamgroupinBNtostudythissysteminamicrofluidicchip.Inthisproject,we’llstudytheinteractionbetweendifferentkindsofproteininclusions,andpossiblythedistributionofinclusionsonatubularY-junction(thebasicbuildingblockofatubularnetwork).

idemalab.tudelft.nl

AfewnotesonworkingintheIdemagroupAsaBEPorMEPstudentinanygroup,you’llgetyourownspecificprojectwhichis usually a part of a larger research line going on in the group. Your directsupervisor can eitherbe a “junior scientist” (aPhD student orpostdoc) or thegroup’sPI, dependingon theproject. Sincewe’re a theorygroup,ourmethodsdiffersomewhatfromthoseoftheexperimentalgroups:ratherthangoingintothelab, most of the projects we have involve building and running simulations,sometimescomplementedwithanalyticalwork.We’llgiveyousometraininginhowtodothis,butyouprobablyalreadyknowthebasicidea(therearethingslike“for loops”and“ifstatements”).Theresultsof thesimulationsyouanalyseandinterpretjustlikeyouwouldexperimentaldata.Also,you’resupposedtoputyourresultsintocontext,whichmeansthatyou(withsomehelp)havetolookforandreadtherelevantliteratureanddiscussyourresultscomparedtothoseofothers.Forourspecificcase,whenpossiblecomparisonstoexperimentsareespeciallyvaluable.Attheendofyourproject,youwriteathesisandgiveapresentation.Onboth of these, we’ll give you feedback on the initial version, which you canincorporate in the final version thatwill go to the thesis committee and yourfriendsandparents.Intheevaluation,welookatthepresentationandthesis,butalso at the quality of the work, your level of independence, creativity,communication,andunderstandingofyourtopic.Nobodyinscienceworksalone–eventhougheveryonehastheirownproject,itisveryusefultodiscussthemwithothers.Infact,youcanonlyclaimyouunderstandsomethingifyoucanexplainit,andbyexplaining,youoftenrealizenewthings(orthatyoudidn’tunderstandsomething).Tothatend,Iencouragepeopletomakeuseoftheofficespacewehaveandtalktotheotherstudentsthere,andwehaveaweeklygroupmeetingtowhichIexpecteverybodytoattendifpossible.Duringgroup meeting, everybody gives a brief update on their project, especiallyfocussing on the things you are working on or struggling with right then; ithappens frequently that someone else in the room has encountered the sameproblem and can help you out - or you can help out someone else. In thedepartment,we have forummeetings everyMonday. In evenweeks, this is atlunch(provided)withthewholedepartment(bigforum),inoddweekswithjustthetheorists(theoryforum).Inadditiontotheseplannedmeetings,youcanhaveone-on-onemeetingswithmetodiscussyourprojectindetailwhenneeded(thisvarieswidely).We’retheretohelp, so please don’t hesitate to ask for it when necessary. Most importantlythough,pickaprojectthatappealstoyou,andmakesureyouhaveagoodtimeworkingonit!