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PartIIIBiologicalPhysicscourse- 2020Lecturer: Dr DianaFuscodf390
Prof.PietroCicuta
Supervisions:NikhilKrishnannpk28
Guestlectures:
Dr.JamieBlundell(Oncology)Dr.Somenath Bakshi (Engineering)Prof.BenSimons(DAMTP)Dr.JamesLocke(SainsburyLab)
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PhysicalBiologyoftheCell- 2nd ed.,Garland2013Phillips,Kondev,Theriot,GarciaReadinglist:
ModelsofLife- CUP2014&freee-bookKimSneppen
PhysicsinMolecularBiology- CUP2005KimSneppenandGiovanniZocchi
PartIIThermalStatisticalPartIISoftCondensedMatter[orselfstudy]
Pre-requisites:
AnIntroductiontoSystemsBiology- ChapmanandHall2007+2nd ed 2020UriAlon
PhysicalModelsofLivingSystems- Freeman2015
BiologicalPhysics- :Energy,Information,Life- Freeman2007
PhilNelson
MolecularBiologyoftheCell- Garland(manyeditions,updatedalmostyearly)BruceAlbertsetal.
Warning,thisisabiologybook
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UsefulInformation:Website,linkedfromTiS:http://people.bss.phy.cam.ac.uk/courses/biolectures/
Sendcomments&errorstodf390.Alistofknownerrorsismaintainedonthewebsite.
SupervisionsavailableforstudentsinPartIIIandMASt(3supervisions, 1or2largegroups,SmallLectureTheatre).
Times(TBD,butapproximatelyevery2-3modules)
Wewillprovidewrittenanswerstothequestionsheetattheendofthecourse.
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Structureofthecourse:24lectures,in7modules:
A- context/overview/intro/basics,networksB- evolutionandgrowthofpopulationsC- dynamicsinthecellD- elementsofneuro-physicsE- patternformationinbiologyF- proteinproductionandregulationofgeneexpressionG- dynamicalsystems,switchesandoscillations
4lectureswillbegivenbyotherCambridgecolleaguesactiveonthebiology/physicsinterface:materialclosertoactiveresearch(detailsnotexaminable)
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Lengthscales
BiologicalsystemshaveahierarchicalorganizationacrossmanylengthscalesLengthscaleßà Timescale…hence“emergence”.Non-equilibrium(butconsideringseparationoftimescales,equilibriumoftenvalid)Selfassemblyandselfreplication
Wefocusinthiscourseonscaleswherethermalnoiseandsmallnumbernoiseareatplay- classicalstatisticalmechanics.
e.g.photosynthesis e.g.ecologicalsystemsandevolution
Ourcourse
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Whyisitagoodtimeto“deploy&develop”physicshere?
Fantasticdetailedknowledgeofthemoleculesthatmakeuplivingsystemsfromdecadesof“structuralbiology”.Precisegeneticcode.Thebroadlycorrectunderstandingofmechanismsofactionofmanyoftheseconstituents.Quantitativedatasetsresolvedonrelevantlengths×.Uniquepowerofphysics (statmech,dynamicalsystems,softmatter)inlinkingupscalesàmodelsthathavethe“correct”mechanism,andthatrepresentanunderstanding. Physicsisrequired.
e.g.photosynthesis e.g.ecologicalsystemsandevolution
Ourcourse
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Physicsisrequired.Asinotherfields(condensedmatter,etc),whatisourapproach?
• Understandcontext- here,cellbiologycontext.• Makeorderofmagnitudeestimates.• Becomefamiliarwithtoolsformodelbuilding.• Criticalanalysistodeterminelimitations,andsuggestrefinement
tomodels.
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Crick’slegacy- PolymerLanguages
Hierarchyofscales:bothInformationandStructure. 8lecture 1
Structure
Spaceof“Genotypes”
Spaceof“Phenotypes”
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Generegulation:the“centraldogma”Crick1953-1957
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NucleotidesandDNA
10lecture 1
AdenineThymineGuanineCytosine
ReplacedbyUracilinRNA
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Thegeneticcode
11lecture 1
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ManywaystoseeaDNAdoublehelix
12lecture 1
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Manywaystoseeaprotein
13lecture 1
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Manywaystoseealipidmembrane
14lecture 1
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Tocells:Manywaystoseeabacterium
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Whatis“right”levelofdescription?
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Whatdowewanttoavoid?
Exampleofpopulationgrowthdata
f(t)=a1/[a2– (t/1yr)]a1=10000,a2=2050worksverywellorf(t)=a1exp(a2t)
PhysicalModelsneedtoreflectamechanism,andcanpointustofurtherkeyinsights. 17lecture 1
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Asuccessinquantitativebiology(andstillongoing):TheLacrepressorWhereStatmech andPolymerphysicsmeetthebiologyofgeneregulation
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Anexampleof“importantquestion”thatcanbeaddressedinverydifferentways:Howdocellsregulatedivisiontohaveameansize?
Inprinciple,controlcouldbethrough“sizer”,“timer”orsomecombination.
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E.colibacteriaImagedinfluorescencemicroscopy.
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FromS.Jun, S.Taheri-Araghi,TrendsinMicrobiology4,23(2015)
Dataonregulationofdivision
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Howdocellsregulatedivisiontohaveameansize?Onecanalsotrytoestablishthegeneralcontroltheory,lookingatthedata.
Onecansearchforthemolecularmechanism,butcertainlymorecomplexthan“thegene”!Notsosimpletocomeupwithsizermechanisms:plausiblescenarioputforwardinyeastmightinvolvesensingsizethroughthebalancebetweenaspeciesthathasconstantconcentrationinthecellvolumeasmonomers,anadsorptionequilibriumwiththemembrane(hence#proptoarea),andapolymerisation“sink”.Concentrationatthesinkisthenamembraneareasensor,triggeringdivision.23
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Recap:- Spiritandremitofthiscourse.- Howphysicscontributestothis
areaofscience.- Afirstoverviewofcellmachinery.- Confidenceindevelopingmodels
anddeterminingtherightlevelofdescription.
- Nexttwolecturesare“intro”tonetworks.