Important)Informa+on!Review!Session!1:!Thursday!Dec.!10th,!6-8PM!TLS!154!!Review!Session!2!(Last!Day!of!Class):!Friday!Dec.!11th,!1:25PM!Normal!Class!IF!YOU!HAVE!QUESTIONS!ABOUT!THE!EXAMS,!ASK!THEM!BEFORE!THE!END!OF!CLASS!!!If!you!have!“bunched”!final!exams!or!“extenua]ng!circumstances”!requiring!an!alternate!Final!Exam!]me,!contact!the!Dean!of!Students!office-!ASAP)–)Deadline)TODAY.!!!!Scheduled)Final)Exam:)Wednesday)December)16,)Arjona)Hall;)8:00-10:00;)10:00-12:00;)12:00-2:00,)2:00-4:00.))See)Exam)Registra+on)Link-)You)must)be)registered)and)show)up)at)the)correct)+me!)!!Early/Late!Final!Exam:!TBA!!!Our!HuskyCT!site!is!usually!taken!down!shortly!following!the!end!of!the!semester,!so!you!should!save!or!print!all!course!material!before!then!!!The!professor!and!TA!will!not!have!contact!with!Cell!Biology!students!ader!Dec!11th,!and!you!may!not!discuss!Exam!content!with!any!other!students!during!finals!week!!Pathogen-infected)Cells)))Last)class:))Stem)Cells!J.Gurdon!a.)Induced)pluripotency.!The!expression!of!4!transcrip]on!factors!Oct4,)Sox2,)Klf4,)and)c-Myc)(OSKM)!can!reprogram!soma]c!cells!to!a!state!that!is!similar!to!that!of!embryonic!stem!(ES)!cells.!These!cells!are!called!induced)pluripotent)stem)(iPS))cells.!b.)Nuclear)transfer)to)eggs.!A!single!Xenopus(laevis((or!mammalian)!soma]c!cell!nucleus!is!transplanted!to!an!enucleated!X.laevis((or!mammalian)!egg.!Upon!expansion!in!culture,!this!technique!can!give!rise!to!gene]cally!matched!embryonic!stem!(ES)!cells.!Alterna]vely,!upon!transfer!into!a!surrogate!mother,!it!can!give!rise!to!a!clone!(‘‘reproduc]ve!cloning’’).!Thus,!new!cell!types!and!new!organisms!can!be!generated.!or!new!ES!cells!Molecular Biology of the Cell Today!we!will!focus!on!how!viruses!and!bacteria!take!over!some!of!the!normal!cellular!processes!that!we!have!discussed!throughout!the!course,!including!cytoskeletal!dynamics,!cell!adhesion,!signal!transduc]on,!etc.!!These!types!of!studies!fall!into!the!fields!of!!host-pathogen!interac]ons,!cellular!microbiology,!and!microbial!pathogenesis.!Today:))How)pathogens)exploit)cells!1000nm)Most!bacteria!are!free-living!organisms.!!Viruses!are!not!‘alive’;!they!require!living!cells!for!replica]on.!Virus)transport)relies)on)microtubules)a\er)entry!Depending!on!the!virus!and!the!cell!type,!viruses!enter!by!(A)!directly!fusing!with!the!plasma!membrane!or!(B)!via!endocy]c-based!mechanisms.!Regardless!of!the!mode!of!entry,!viruses!within!endosomes!or!as!non-enveloped!capsids!probably!recruit!both!kinesin!and!dynein!even!though!they!move!in!net!minus-end!directed!direc]on!along!microtubules!towards!the!nucleus.!!cytoplasmic!dynein!kinesin!M.Way!Figure 24-35a Molecular Biology of the Cell (© Garland Science 2008) Some!virus!nucleocapsids!including!Herpes!viruses!assemble!in!the!nucleus!and!then!bud!through!the!inner!nuclear!membrane!into!the!space!between!the!inner!and!outer!nuclear!membranes,!acquiring!a!membrane!coat.!The!virus!par]cles!then!apparently!lose!this!coat!when!they!fuse!with!the!ER!membrane!to!escape!into!the!cytosol.!Subsequently,!the!nucleocapsids!enter!the!Golgi!apparatus!and!bud!out!again!on!the!other!side,!acquiring!two!new!membrane!coats.!The!virus!then!buds!from!the!cell!with!a!single!membrane!when!its!outer!membrane!fuses!with!the!plasma!membrane!(Figure).!Some)viruses)transit)through)the)secretory)pathway)on)their)way)to)exi+ng)the)cell!Other!viruses,!including!Vaccinia!virus!(which!is!closely!related!to!the!virus!that!causes!smallpox)!assembles!in!“replica]on!factories”!within!the!cytosol,!acquires!membranes!from!the!Golgi!apparatus!by!a!poorly!defined!wrapping!mechanism,!and!eventually!fuses!with!the!plasma!membrane.!!How!do!the!viruses!get!to!the!plasma!membrane?!Following!their!exit!from!the!nucleus,!many!viruses!recruit!kinesin-1!and!cytoplasmic!dynein!to!facilitate!their!bidirec]onal!transport!on!microtubules.!They!will!move!along!microtubules!un]l!they!encounter!membrane!compartments!into!which!they!can!bud!to!form!enveloped!virions!(G).!The!loca]on!of!these!membrane!compartments!will!vary!depending!on!the!posi]on!of!the!MTOC!and!organiza]on!of!the!microtubule!cytoskeleton,!which!will!be!cell-type!dependent.!!Viruses)rely)on)microtubules)during)egress!Consequently,!viral!movements!towards!these!membrane!compartments!may!require!a!net!minus-end!(dynein)!or!plus-end!(kinesin-1)!driven!transport!depending!on!the!site!of!envelopment!with!respect!to!the!MTOC.!Some!viruses,!however,!may!never!encounter!the!right!membrane!compartment!and!will!con]nue!to!move!as!non-enveloped!capsids!throughout!the!cell!(H).!Ader!envelopment,!viruses!within!vesicular!compartments!(I)!will!be!transported!in!a!net!anterograde!manner,!possibly!by!kinesin-1,!towards!the!plasma!membrane,!where!they!fuse!and!are!released.!M.Way!The!human!body!is!a!complex!ecosystem!that!contains!about!1013!human!cells!and!about!1014!microbial!cells!(bacteria,!fungi,!and!protozoa),!which!represent!thousands!of!microbial!species.!These!commensal!microbes,!called!the!normal)flora,!are!usually!beneficial!to!our!existence!and!are!found!in!various!parts!of!our!bodies,!including!the!skin,!mouth,!and!intes]nes.!Pathogens!!are!organisms!that!can!cause!overt!disease!in!healthy!people,!and!are!dis]nct!from!the!normal!flora.!They!differ!from!commensal!organisms!in!their!abili]es!to!breach!barriers!and!survive!in!host!loca]ons!where!other!microorganisms!cannot.!Pathogens!(bacteria,!fungi,!parasites,!as!well!as!viruses)!are!the!agents!that!cause!infec]ous!diseases.!Infec]ous!diseases!currently!cause!about!one-third!of!all!human!deaths!in!the!world,!more!than!all!forms!of!cancer!combined.!!A!rela]vely!small!number!of!genes!can!cause!the!significant!differences!between!a!virulent!pathogenic!bacterium!and!its!closest!nonpathogenic!rela]ve.!Proteins!that!contribute!to!the!ability!of!an!organism!to!cause!disease!are!called!virulence)factors.!Genes!encoding!these!proteins!are!frequently!clustered!together,!either!in!groups!on!the!bacterial!chromosome!called!“pathogenicity!islands”!or!on!extra-chromosomal!plasmids.!These!genes!may!also!be!carried!on!mobile!bacteriophages!(bacterial!viruses).!A!new!pathogen!may!arise!when!groups!of!virulence!genes!are!transferred!together!into!a!previously-nonvirulent!bacterium.!An)introduc+on)to)bacterial)pathogens)and)virulence)factors!Figure 24-5 Molecular Biology of the Cell (© Garland Science 2008)
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