Julius Adler, "My Life With Nature", Ann. Rev. Biochem 2011, 80:42-70

29 Pages·2011·1.53 MB·English

BI80CH03-Adler ARI 15May2011 14:38
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BI80CH03-Adler ARI 15May2011 14:38
My Life with Nature
Julius Adler
DepartmentsofBiochemistryandGenetics,UniversityofWisconsin,Madison,
Wisconsin53706-1544;email:[email protected]
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ev. Biochniversity Annu.Rev.Biochem.2011.80:42–70 Keywords
nu. Rby U FMirasrtchpu1b0l,is2h0e1d1onlineasaReviewinAdvanceon bacteria,behavior,chemotaxis,Drosophila,molecularbiology
n
A TheAnnualReviewofBiochemistryisonlineat Abstract
biochem.annualreviews.org
AfterachildhoodinGermanyandbeingayouthinGrandForks,North
Thisarticle’sdoi:
Dakota,IwenttoHarvardUniversity,thentograduateschoolinbio-
10.1146/annurev-biochem-121609-100316
chemistryattheUniversityofWisconsin.ThentoWashingtonUniver-
Copyright(cid:2)c 2011byAnnualReviews.
sityandStanfordUniversityforpostdoctoraltraininginbiochemistry
Allrightsreserved
andgenetics.ThenattheUniversityofWisconsin,asaprofessorinthe
0066-4154/11/0707-0042$20.00
DepartmentofBiochemistryandtheDepartmentofGenetics,Iiniti-
atedresearchonbacterialchemotaxis.Here,Ireviewthisresearchby
meandbymany,manyothersuptothepresentmoment.Duringthe
pastfewyears,Ihavebeenstudyingchemotaxisandrelatedbehaviorin
animals,namelyinDrosophilafruitflies,andsomeoftheseresultsare
presentedhere.Mycurrentthinkingisdescribed.
43
BI80CH03-Adler ARI 15May2011 14:38
1421,Cologne1426,Augsburg1439).Theyes-
Contents capedtothevillagesthatwouldacceptthem.In
thosevillagestheywerenotallowedtotakepart
1.BEGINNINGYEARS............. 44
inhusbandry,ortoparticipateinguilds,orto
2.MIDDLEYEARS.................. 46
ownland,sothatlittleremainedforthembut
2.1.EarlyResearch
pettytrades.
onChemotaxis.................. 47
By 1850, emancipation of the Jews in
2.2.TheReceptorsfor
Germanyhadstartedtotakeplace,andby1930,
Chemotaxis..................... 50
about half of them had moved back into the
2.3.ThePartBetweenReceptors
cities.Inthelargercities,manyblossomedinto
andFlagella.................... 53
professionals: businessmen, artists, musicians,
2.4.TheFlagella................... 54
andscientists.Foradescriptionofsomeofthis,
2.5.Two-ComponentSystems...... 55
seeDavidNachmansohn’sGerman-JewishPio-
2.6.ResponsestoOtherStimuli.... 57
g neersinScience1900–1933,HighlightsinAtomic
nualreviews.ornal use only. 3.L2A.7T.EElRecYtrEoAphRySsi.o.l.o.g.y............................ 5589 PbIohamoyBskiecahsg,painsaCnrihtnineoflmgfuiieistntn.rcy1e,9d3am3n,dethbBeeiocNcahueasmzeiissintmryaads(m1e)al.ilflTewhfoaayrt
no
w.aers Thesearemyteachers: GermanJewsintolerable.In1938,itwastime
wwor p thered-belliedwoodpecker for my parents, my sister, and me, now eight
om 1. F andthemuskrat yearsold,toleaveGermany.Notsofortunate
Downloaded frson on 06/29/1 wtawhnhhedeernntehdiiett-’’ajssed91wm60eilbrwaelleobewudtzteerrofl,y wlHtihveoeeryldelawmwnediyrtehwfaaiuttlhlhs,ekhrial’enlserddshi.sPutaesbursala,n,Zdwialhlnio,dwhthwaodohedsaacduagpahlewtdeartysos;
80:42-70. sin - Madi 1.BEGINNINGYEARS pYaosrOskennCgtiethyrescGwameeorereginjeutWboivlaaisenhwtin.agAstofttnhe,erahallatrwobfoo-trhdoeayfsNhtriaepiw’ns
011.scon Tome,naturehasalwaysbeenaninspiration. ride,wearrivedinGrandForks,NorthDakota,
ev. Biochem. 2niversity of Wi BnlifaoettuW.hrehtheaenrebItewhaaeustttyhhiornefgesnyatehtauarrtsehoaladnved(mdtyhoemmsionctiahetenerdcetomoldyf wMb30ohyreyhrefoeaaotrmhsd.eygrmraoonctdehreymr’sosttroherleear,tiwovpehseichnhaeddthsaeeytltilktetedlpeitnnu1ep8ig8fho0r-.
RU me),Isaidinababy-talksouthernGermandi- When not helping out in the store, I at-
nu. by alect,“Mamahasbeautifulflowersinherblan- tended school. Ambition together with ability
n
A
ket.”EverySunday,myfirstgradeclasstooka ledtoachievement:editoroftheschool’snews-
hikeinthewoods.Duringoneofthesewalks, paper, debater at the state finals, and valedic-
Irememberafoxstaringatusfromitsburrow torian of my class of 203 students. My great-
and a European swallowtail gracefully gliding est interest, stimulated by my teacher Hazel
overthebranches.MygoodfriendJustinshared McMaster and her science club, was biology.
hisinterestinbutterflieswithme. Every week in the summer, Winston Jensen
Myfatherhadasmallbutchershop,which and I went out into the country to identify
washandeddownthroughgenerations,andhe prairie flowers. I put together perhaps the
was also a cattle dealer. We lived in a little largestcollectionfoundanywhereofbutterflies
village, Edelfingen, where our ancestors had of North Dakota and Minnesota. My friends
livedfor300years.Inthefifteenthcentury,the ArtHerman,RussellRhode,andImetmonthly
JewsoftheGermanlandswereforciblyexpelled to study texts by philosophers, including
from nearly all the cities (for example Vienna Nietzscheandothers.Hereisanexampleofmy
44 Adler
BI80CH03-Adler ARI 15May2011 14:38
determinationasayouth:Therewasacontest fliesandhaddozensofcatsinherhome—finally
tomakeasmanywordsaspossibleoutofthelet- convincedmetostopcollectingbutterflies.)
tersin“PepsiColahitsthespot.”Ihuntedfor I decided to go to graduate school in
threeweeksthroughtheunabridgeddictionary biochemistry at the University of Wisconsin,
inthepubliclibrary,cameupwith3,789words, whereHenryLardykindlyacceptedmeintohis
tookthemtothepostofficeat11:45PMofthe laboratory.Itwasathrillingtimeforme.Hank
daydueforpostmarking,butthemailboxdidn’t discoveredthatthecarboxylationofpropionate
getemptieduntil12:14AM,andIneverheard. formssuccinateinanimals,andItookonthis
“We’vehadagrandtime,”sangtheclassof projectforayear,workingwithratlivermito-
‘48,withaneyetoanevengranderfuture. chondria(2,3).Hank’sdiscovery,however,was
ThencameHarvardUniversity.Imajoredin taken over by Severo Ochoa’s gigantic group.
biochemicalsciences,whichincludedamixture Atthatpoint,inresponse,Idecidedtoworkon
of courses in biology, chemistry, and physics. themostobscureproblemIcouldpossiblyfind,
g The most influential teachers were George themechanismofitaconicacidmetabolismin
nualreviews.ornal use only. WcaohngedyamldCoi(sfloytrdftyhre,heKLoAdoluoumcpikseshriFniocihfeaasnnme,rIewno)h,dnwoiaohntroasgulaegonchfittcutarhcenhedtehomSrnooisubpttiorhoyl---, rtthiaoteuWslsiisvlyheinridleim1d9iim5tno7yc(hHfi4or,asnn5td)ks.r’tisuad,lytahboeofrsbauetbohjraeyvc,itoorI.fWsmuyrerPwephetrDie-
no
w.aers west.Themostimportantexperiencewaspro- raisingbiotin-deficientratstofindoutifthecar-
wwor p videdbymybiochemistrytutorDavidNovelli; boxylationofpropionaterequiresbiotin,which
om 1. F I was allowed to do research in his and Fritz itturnedoutitdid.Ifaithfullyraisedsuchde-
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80:42-70. sin - Madi stoicxviyeedsnatnaissfi.”cGAprrotowHdtauhrcvtSa,tr“idmN,uIiclmaontaitdnseicfmoAracAnidycenatonebwdacDftreierernsiuvdabs--, smivaedFleyromfmroemHthatihnnekk,baIbioloetuainrtn-pceoodsnsttihabeilnevianmlgueeccuhopafnb(i6rso)m.aTsd.hina-t
011.scon includingTomEisner,nowstudyinginsectbe- terests,toleranceofindividualdifferences,and
ev. Biochem. 2niversity of Wi hfCeaosvslDioloerurgroeaiftnobgCfrPoathrihnneyesssliculci,imeaannnmcsdeeaEranstrdibCcSeoKutlwraugnemeedonbenila,cso.nUlolnewgiveaeprasrcioaty-- tp1h9oe5sBt7gdelototawcrktyeoienorngaflfCrrseeotecureddnioiveemilsnis,ginvIamrnsepysNeenaPirtehclD’htsh.ecaonsuudrmsesmtianerrtminoig-f
RU demicyears,Iworkedinmyparents’store,but crobiology at the Hopkins Marine Station in
nu. by inaddition,IgottoknowWilliamCornatzer, PacificGrove,California.Unforgettableinspi-
n
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chaiman of the Department of Biochemistry rationwasgeneratedbyVanNiel,aswellasby
at the University of North Dakota in Grand thebeautyofthelocalseashorewithitsabun-
Forks. Pursuing my interest in butterflies and dance of fabulous inhabitants. Also attending
putting that together with my newly discov- thisclasswasTetsuoIino,whohadjustgotten
eredknowledgeoforganicchemistry,Idecided hisPhDwithJoshuaLederberginMadisonand
Iwouldtry,withhelpfromDr.Cornatzer,to wastobecomeafounderoftheJapaneseschool
identifytheorangepigmentonthewingsofthe ofstudyofbacterialflagella.TetsuoandIhad
orange-sulfurbutterfly.Ispentmuchofseveral greattimestogethercollectingbutterfliesinPa-
summerscatchingthousandsofthesebutterflies cific Grove. But my greatest accomplishment
but never got enough to isolate the pigment. there was to make a decision on my research
Nevertheless,Ithinkitwasagoodprojectfor subjectasanindependentscientist.Iwantedto
justanundergraduate.(Thedesperateappeals study behavior, but which behavior of which
bythe“catlady”—theladywholovedbutter- organism? The Marine Station has a grand
www.annualreviews.org • MyLifewithNature 45
BI80CH03-Adler ARI 15May2011 14:38
librarywithjournalsdatingbacktonearlythe I moved to Stanford with the Kornberg
beginning.ThereIfoundthe“ancient”(1880s) groupinthefallof1959tolearngeneticsfrom
publicationsofWilhelmPfefferonthechemo- Dale Kaiser. He taught me how to study the
tactic behavior of bacteria. I decided that was geneticsofgalactosemetabolisminE.coli(11).
it! Daleisamarvelousteacher,agreatexperimen-
MyfirstpostdoctoralstudywaswithArthur talist, and one of the kindest people. In re-
KornbergatWashingtonUniversityfrom1957 centyears,hehasbeenstudyinghowbacteria
to1959.IhadheardaseminarbyArthuratthe formafruitingbody.AlsoatStanford,Ilearned
MassachusettsInstituteofTechnologywhenI muchfromtheenthusiasticEstherLederberg,
wasanundergraduateatHarvard,andIdecided who was continuing her research on bacterial
thenandtherethatIwouldliketolearnfrom genetics.
him.IworkedwithArthur,hiswifeSylvy,Ernie My best companion at Stanford was Buzz
Simms, Bob Lehman, and Maurice Bessman Baldwin.HeandIwentforahikenearlyevery
g to discover more about DNA synthesis in Es- weekendtodiscussscience,people,andnature.
nualreviews.ornal use only. carhonewdrFiacrihdnoivmtaeiscrooeAlrsi.rt(ts7h,–ui1nr0,t)e.InBsloeebadrrneeedmdicaaitnthiseomnvyatloculoeosneolffyrinoeannrde- AtthhlaethtyoIeuhagrahsvekadipnohdnyleysiicenanltchboeiuorbcaihogeelomdgiiasctna,dlBscucrizieztnichciaezsse.dovaelrl
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w.aers subject,andtheneedforobjectiveandsimple
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011.scon Fred and I were particularly close because he KhoranaandImetforthefirsttime,eachhik-
ev. Biochem. 2niversity of Wi attHoolsiolmtdhceieanmWeg.ieroBflrhewoly,mhownoadhlwoiatotlclluealtdmGhaeestor,tmooFnartnebhdveeicilnloUatmgrnoeeit,devmudecyreSydwtnaimetfeaeers, iGspniatogrybtsoieonfpfdBatrrhhiaatetideshlEayrnCrazionvyldemudmeerxbeIpcineaescntttioittnluybgteefcrt,oooammnmdetehdeIetirhUenacondtoiovrjneuores-tf.
RU fromNurembergin1941.Hildehasbeenmy arrived from Stanford. Arthur had told both
nu. by wife for over 45 years. She is my greatest ad- Gobindandmethatwemustgettogetherbe-
n
A
mirerandmybestcritic.Wehaveamusician causeofsimilarinterests.Itwas“love”atfirst
son,David,andanartistdaughter,Jeane. sight.Wehadsomuchincommonintermsof
Betweenthispostdoctoralstudyandmynext science,philosophy,andpersonality.
one,inthesummerof1959,Itooktwocourses Gobind and I did research together for
atColdSpringHarborthatinfluencedmylife. aboutayear.Acatalystforthiswasthevisitof
Onewasonbacterialgenetics,andtheotherwas ArturoFalaschifromItalytobeapostdoctoral
onphagegenetics.Amongourinspiringteach- fellow with me for a brief period until space
ers were Milislav Demerec, Evelyn Witkin, opened up at Stanford in Arthur’s laboratory.
GeorgeStreissinger,FrankStahl,andSalvador Arturo, Gobind, and I then worked together
Luria. There, I started many lasting friend- on the chemical synthesis of polynucleotides
shipswithothersjustbeginningtheirscientific (12). However, my greatest interest was not
careers: Masayasu Nomura with wife Junko, there. Gobind and I discussed this often.
MarshallNirenberg,andmore. Gobind kindly encouraged me to work more
46 Adler
BI80CH03-Adler ARI 15May2011 14:38
fullyonwhatIreallydreamedabout—thebe-
haviorofbacteria.
Apartofmyjobwasteachingcourses.This
not only informed and inspired students, but
it also kept me up to date on the latest de-
velopments. For 15 years, I taught one of the
world’s first molecular genetics courses, to-
gether with Hatch Echols, also a new assis-
tantprofessorintheBiochemistryDepartment
(and a close friend of mine, here until 1969
and then in Berkeley until his untimely death
in1993),andwithErnstFreese,alsoanewas-
sistant professor in the Genetics Department
g (hereuntil1963,thenhewenttoNIHtobe-
nualreviews.ornal use only. coPloolrogmoiggceyaralcamhnDideiafsdteoiartfshetecehsteoNarLnaoadtfbiooStnhrtaarelotoBkIrneays;sitochitfeuNMtdeeouieolredofcsuNpcliraeeerunmrBcoeai---s flFEailgegcuetlrrleaon(14m1)i.crographofEscherichiacolishowing
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om 1. F Nomura. After that, I taught a course on chemicalcomingoutofacapillary(Figure2),
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ev. Biochem. 2niversity of Wi Ch(oaonvlidtohrSebpmyriBonalglrurHsycaGArbapnolyers,tizaIk),tyaa(unogdnhflmtiaeesc()oo,EnurrbsicaecKoteanrnibade)e.-l taellchfunritchiaenrwwohrokminanmaygeladbaollrathtoisryanfodrsu1p7eyrevaisres.d)
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nu. by 2.1.EarlyResearchonChemotaxis
n
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When I arrived in Madison, 50 years ago, I
started behavioral work on E. coli. It was first
necessarytodevelopanobjectiveassayforbac-
terialmotility(13);todeviseasimple,chemi-
callydefinedmediumformotility;andtofind
agrowthmediumthatwasbestforthesynthe-
sis of flagella (Figure 1) (14). Then I needed
todeviseanobjectiveassayforchemotaxis(15).
(Ihaddesertedenzymology,ArthurKornberg’s
onlylove,andIamsurehemusthavefeltaban-
doned by my study of the wildest of subjects,
Figure2
behavior. Yet, I feel he must have approved
Escherichiacoliattractedbytryptonecomingoutofa
of my quantitative, simple assay of chemo- capillary(46).
www.annualreviews.org • MyLifewithNature 47
BI80CH03-Adler ARI 15May2011 14:38
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w.aers nonchemotacticmutantsspreadlittle(topright),and
wwor p nonmotilemutantsdonotspreadatall(lowerright)
om 1. F (18).
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011.scon needed for chemotaxis, the che genes (cheA,
ev. Biochem. 2niversity of Wi cgPloheawenrBkef,isrnaonosmodnn1ct,h9hwe7eCh0)Eot(.o1wc71ao)9ls,i7ahc2nehdrarenothdmaestonhasewopnmoewsmetedan(o1ptc8pot)eon.drStatoalhnfbeedeslye--
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Escherichiacoliaredepositedinthecenterofa researchmuchfurther(19–21),andhecontin-
semisolidagarplatecontainingtryptone,wherethey ues the use of genetics to discover molecular
grow,useupthelocalL-serine,andsearchfor
mechanisms of behavior (22). Mel (now sec-
L-serine,movingtotheoutermost,L-serine,ring.
tion chief, National Institute of Child Health
Thensomeofthosebacterialeftbehindinthe
centeruseupthelocalL-aspartate,thensearchfor &HumanDevelopment,NIH)succeededfor
L-aspartate,movingtothesecond,L-aspartate, the first time in purifying intact flagella from
ring.Andsomebacterialeftbehinduseupthelocal E.coliandalsofromBacillussubtilis(23);thenhe
L-threonine,searchforL-threonine,andmoveinto
determinedtheirstructurebymeansoftheelec-
thethird,L-threonine,ring(42).
tron microscope (24). Subsequently, he found
EveryyeartheDepartmentofBiochemistry out how the flagellar hook–basal body com-
accepted ∼20 talented graduate students, and plexisattachedtothevariouspartsofthecell
right away, I had some of these assigned to envelope (25). At the same time at the Uni-
me: John Armstrong, Mel DePamphilis, and versityofCalifornia,SanDiego,MelSimon’s
48 Adler
BI80CH03-Adler ARI 15May2011 14:38
laboratoryreportedthepurificationandstudy theseyearstomakemanydiscoveriesinbacte-
ofintactflagella(26)andhooks(27)fromB.sub- rialchemotaxis.)WolfgangEpsteinandI(34)
tilis.Thispioneeringworkwascontinuedlater thenfoundoutthatphosphotransferasesugars
in E. coli and Salmonella by others, so that we wereattractantsandthatmutantslackingtheir
now have a good understanding of the struc- enzymesIIfailedtobeattractedbythem.
ture of the flagellum and what each part of it Wung-Wai Tso studied repellents of
does(seebelow).Sylvia(whowentontowork E.colibytesting164chemicals(35).Thesewere
attheUniversityofIllinoisMedicalCenterat grouped into at least nine classes, presumably
Chicago)purifiedbacteriophagechiforthefirst eachforadifferentchemoreceptor.Themost
time(28),andshefoundthatitrequiresbacte- potentrepellentswereshort-chainfattyacids,
rial motility to attach to moving flagella and hydrophobic amino acids, indole, skatol, ben-
that chi-resistant bacteria were not motile, so zoate, salicylate, Co2+, Ni2+, H+, OH−. Mu-
wewereabletoisolatemotilitymutantsinthat tantslackinghydrophobicaminoacidtaxisand
g way(29). a mutant lacking salicylate taxis were isolated
nualreviews.ornal use only. tHchhaeezAmgefleotbentaraeuxreiwasrlelyt&ofntoaoBulnlnoycdbh(eiMtm.hee.eo,stiabJmcootuhvictna’(nms3t0usc)htaetdnhitasmsct)ou,fvtJaaeeinrlreetrsddy, asooonffrdsHpodeofernsbmcgiroaiKtcboheozednom(ga3.,i)5swtI)r.nhy(Waeadrtedutinhhtigeeo-nWsCt,uhtahdiinieieesmssnetuohtwUeannamtipvforeootrrifsleaiittstyy--
no
w.aers “specifically nonchemotactic mutants,” those tractiontoL-serine(seeabove)wasfoundtonot
wwor p that failed chemotaxis to only a single attrac- berepulsedbyanumberoftheserepellentssuch
om 1. F tantanditscloserelatives,namelyonemutant asacetateandL-leucine(32,35),andthemu-
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011.scon ferent chemoreceptors were involved, one for Tisa and coworkers (37–39) explored the role
ev. Biochem. 2niversity of Wi Ltathhs-paasttaerfrfataianiillteeeeddrrieiennppLrrLee-s-saesesennprtatieenrddteabtbteayyxtaiaasx,mimsan(uu3dtt1aaan,nn3tto2wwt).hee(eSiirssooofoollnaarttaLeefdd-- onawtfootwrChkeasa2Uo+pnnriomiovfneeicssrrssooiintbryiboaolaffpcNmtheieyrcwsiraioolHblociahogmelyom.p)gsDoyhtiaaarvxneii,ddsw.Rg(heLeenporeaeutsihkcieess
RU tergettinghisPhDwithmein1971,Bobtook foundthatcertainattractantsandrepellentsare
nu. by offforTasmaniatobecomeanapplepickerand not detected by specific chemoreceptors but
n
A
eventuallytocompile“MillipedesofAustralia” ratherbyprotonmovementacrossthecytoplas-
and“TasmanianCentipedes.”) micmembrane,causingachangeintheinternal
JerryHazelbauer&MargeDahl(33)tested pH(40).(DaveisnowdirectorintheDepart-
all the common sugars and related chemicals, mentofPediatricsattheNationwideChildren’s
altogether 85 of them. The best attractants HospitalofOhioStateUniversity.)
were D-ribose, D-galactose, D-glucose, D- The news of our studies of chemotaxis
mannitol, D-sorbitol, maltose, and trehalose. spreadfast,anditwasMaxDelbru¨ckwhoper-
Ninedifferentchemoreceptorswereinvolved. hapsappreciatedthesethemost.Oncehehad
Mutants lacking the D-galactose receptor, or completed his work on E. coli bacteriophage,
the D-mannitol receptor, or the maltose re- heswitchedtothebehaviorof“simple”organ-
ceptorwereisolated(33).(Jerryisnowchair- isms:Heworkedonphototropisminthemold
manoftheDepartmentofBiochemistryatthe Phycomyces,andhisstudentRodClaytonstud-
University of Missouri and has continued all iedphototaxisinpurplebacteria.Thathisown
www.annualreviews.org • MyLifewithNature 49
BI80CH03-Adler ARI 15May2011 14:38
E.colicoulditselfbeusedtostudybehaviorblew AtHarvard,HowardBerginventedatrack-
hismind. ingmicroscopetofollowthebehaviorofbac-
Max invited me to speak at the 1965 Cold teria(43).In1970he,togetherwithMaryand
SpringHarborsymposiumon“SensoryRecep- children,cametoMadisonforfourmonthsto
tors,”wherethe“orthodox”neurobiologistsde- learn about E. coli and about our assays for
scribedtheirresultsonthebehaviorofanimals. chemotaxis.Then,heandDouglasBrown(44)
Iaddressedthemeeting(41): describedhowtotrackbacteriathatcarryout
chemotaxis.Howardwenton,andcontinues,to
Verylittleisknownaboutthemechanismof makemanyadvancesinthestudyofthebehav-
behaviorinbacteria.Onewouldliketoknow iorofbacteriawithhiscolleagues(45).
howthebacteriasensethegradientsofchemi- How do bacteria sense the chemicals that
calsthatstimulateachemotacticresponse.Are attract them? One way would be by metabo-
theresensoryreceptorsinbacteria?Inaddi- lizingthemsothatenergy(ATP)isproduced,
g tiononewouldliketoknowhowthesensed and then that energy tells the flagella what to
nualreviews.ornal use only. dotcrharydteatimonaoagrtteeiantxtgarisnasnsyiwnsslteaeErtmssecdthtoehirtnaihcttheodsiaiearceqctocuiltoiesnswtt.hiaoIessnflusta,hngaederseletrluatada?kycTeoono-f dheelnoalvae.erAwgcnyihtphearolmtoueodtrruneacanctteiyiovpnemto.werTtsaa,hybweomhsleiiisccgmhohntiadnbnswedtratuwyhcaiittsththbhooauecwtflteaaarnngiya--
no
w.aers inthislaboratory.Thisorganismwaschosen imalsdoit.Idecidedearlythat,ifthefirstway
wwor p becausethevastknowledgeofitsbiochemistry werecorrect,Iwouldstoptheworkonchemo-
om 1. F andgeneticscouldbebroughttobearonthe taxisandgoontoadifferentsubject.Itturned
Downloaded frson on 06/29/1 Mcoynptrewosbtoelredkm.bwyasothweerlsl. rSeocoeniveadftebry, Isopmubel,ishanedd oipnue“rtIiCtmhpheauentbmttlshiospehreresecedseceptonhtnotidesrdspwitinavhyoBetrwaaeclattsecerocllionatrc”hrl(aeu4tcs6,tio.e).vnMeinnanin1y9te6hx9e-
80:42-70. sin - Madi wBahcatterwiae”k(n4e2w). at that time in “Chemotaxis in abifbaascetcenhrceieamcoiacfnaalsnctayilnlmbbeeetamatbterotalacibstmeodlizotoefdiataacnnhddecmtohiuacltad,l,etvhtehunes
ev. Biochem. 2011.niversity of Wiscon Greaclaecpttoosre rGelcuecpotsoer reRcibeopstoer Arespceaprttaotre reSceerpinteor (ryt4reiae6scelA)dt,aasranAcntthTod.oFPionti,tgihibsutearrrwceetaoee6luraliyrlwadllytahcnssheotpeutbrmdeansseoeientscnateostxsefissdoaa.frliilnlcyshuthebbmaesteoaqptnuaapexainetsr-t,
RU Galactose taxis Serine taxis thereweretwo.MelSimonwithhisgroupwas
nu. by mutant mutant highlyinstrumentalinworkingoutthemech-
n
A
anismofE.colichemotaxis,especially,butnot
exclusively, using genetic approaches; he and
Generally nonchemotactic mutants Michael Silverman (47) started reporting this
work in 1972 with a study of E. coli flagella.
Dan Koshland, with his group of largely but
notexclusivelybiochemists,wasalsohighlyin-
Response
strumental. He started reporting research on
Figure6
chemotaxisin1972withRickDahlquistandPe-
Specificallynonchemotacticmutantsfailinaspecificresponseowingtoa
ter Lovely (48), Bob Macnab (49) and Robert
receptordefect;forexample,thegalactosetaxismutantisdeficientinthe
Aksamit (50); they studied the closely related
galactosereceptor,andtheserinetaxismutantisdeficientintheserine
receptor.Bycontrast,generallynonchemotacticmutantsfailinallofthe Salmonellatyphimurium(nowcalledSalmonella
chemotacticresponsesowingtoadefectinthefinalcommonpathwaythattells entericaserovarTyphimurium);andlater,they
flagellahowtorespond(46). alsostudiedE.coli.
50 Adler
BI80CH03-Adler ARI 15May2011 14:38
2.2.TheReceptorsforChemotaxis 60
Whatarethechemoreceptors?WhenIarrived
in Madison in 1960, I asked Hatch Echols to
P 50
give me a strain of E. coli to study. Hatch, by MC
justgoodluckforme,gavemeB275.Itturned of Parent
n
outthatthisstrainrequiredL-methioninefor o 40
growth. I found that it would do chemotaxis ylati
only when provided with L-methionine, but Meth 30 Mutant
not when deprived of it (13). Somehow L-
methionine was required for chemotaxis. But
how?
20
It was the team of Ed Kort, Michael Goy,
Steve Larsen, and me that discovered the an- 0 0 2 4 6 8 10 12
org swer. A graduate student in the Genetics De- Time after addition (min)
www.annualreviews.or personal use only. pbmEminaivoeercettcthnhhmhetiieooumemnnnaoltiiilnn,tsyateeE,rxyIdtirso,c.ewsolq(oeEanuashdvirrhieneniismgschtpehoueedlwndyrhthiermaiedmopsefisttshthttcoehaihoneugentsmmeietnnoooeertsatdatfidoucxbisiinorsncoiagltcf(lii5taotai1nhvnn)yeest. FEmmlikifeugfeettuhactrhntyeleto-i7fapscaadcdreeedpfnietttciino(t5ingv2eco).hfineLmL-so-estreairxniienseporntoaxttheisie,nbm(uMetthCoytPhla)e.triTwonihseeof
om 1. F personIhaveevermet,butafterhereceivedhis Waldhaddiscoveredrhodopsinasthesensory
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011.80:42-70. sconsin - Madi itptnhhaiernstUemsutneruiondvsteycr.oisef(inHtCyceeeo,lfilhsNaanndoodrtwthMheaCohlapiegrrcohoulefilesnatsraseoaPntrhtChyinushisaotipahloseemglHDyfoeoilr-fl (t(Rn5he3oes)wec.ayTretcoxhhepeclnLausatiminbvoie1cr9adm7tior7eer,miceMtbso)rCr,aMnPoefIiIcbrhweyasaeMesalrdaGcrihstoycyoa,StvapeMnrriednedgrmceinker
em. 2of Wi andworksonanendocrinepeptidethatcoordi- (53) and by Michael Silverman & Mel Simon
ev. Biochniversity naaapgtrreaosdfeeulsaestcoetrrsoitnulydttheeenbtDailneapnBacireotmcinheeanmntiiomsftarMyls..i)(cHrSotebeviisoelnowogawys (rta5er4ce).(pttaMoxriCsPotrIoITaissapraa,lrstaoantedknaoitnwsdngoeatnsheetrhweraesapsepnlalaermtnatetsde)
RU
nu. by andImmunologyatIndianaUniversitySchool (53). Another cytoplasmic membrane protein
An ofMedicineandworksonthegeneticsofdis- MCPIII, serving D-ribose and D-galactose,
eases caused by Chlamydia.) In 1975, we dis- was discovered by Hisato Kondoh, Carl Ball,
coveredthatthemethylgroupofmethionineis and me (55). (Hisato is now project director
incorporatedintoanovelprotein,themethyl- of the Institute for Molecular and Cellular
accepting chemotaxis protein (MCP), located Biology at Osaka University, where he works
inthecytoplasmicmembrane,thatattractants onthedevelopmentoffish.Carlischairofthe
such as L-serine bring about its methylation, DepartmentofBiologyatAlvernoCollegeand
and that some of the chemotaxis mutants we studies yeast physiology.) The gene is called
isolated were not methylated (Figure 7) (52). trg (taxis to ribose and galactose); mutants
In short, MCP was found to be the receptor defective in trg were already known owing to
forbacterialchemotaxis.Thisrepresentedthe theworkofGeorgeOrdalandme(56),Strange
first time that a sensory chemoreceptor was &Koshland(57),andHazelbauer&Harayama
everchemicallyidentified;previously,George (58). (George is now a professor in the
www.annualreviews.org • MyLifewithNature 51