BY

Jenny zhou

Leanna morinishi

Samira daswani

THREE IDEAS PRESENTATION:

BOOSTING THE BODY

THE THREE IDEAS

1. BACTERIAL INFECTIONS

2. PRIONS

3. VIRAL INFECTIONS

Introduction

Increasingdefensesofthebody!

Thethreebroadcategoriesofinfectiousagents:Bacteria,PrionsandViruses

Wechosethesetopicsbecauseregardlessoftheinfectingagent,wewanttotreatthebodytoovercomethediseaseintheearlystages

BACTERIAL INFECTION

Bacteriaareeverywhere!

Somegoodandsomebad!

Thebadonescausewidespreaddiseases!

Bacteriacauseendemic,epidemicandpandemicinfectiousdiseases!

Findthecuretoone=Findingpossiblecurestoothers!

Tackling Bacteria:Why it will help

Manyofthesicknesseswegettodayarestillbacteriarelated.

TheCentersforDiseaseControlandPreventionlistsover20bacteriarelateddiseasesthatarestillmajorconcerns.

Diseaseslikemeningitisandpneumoniastillkillpeople.

Bymakingthebodymoreabletofightoffbacterialinfections,wewouldbehelpingtoeradicateamajorhealthconcern.

ThingsWeCanTarget Flagella

Long,thinfilamentsonthecellsurfacethatenablebacteriatomove.

Spores

Dormantformthatenablebacteriatosurvivewhenenvironmentalconditionsaredifficult.

Capsules

Helpspreventwhitebloodcellsfromingestingtheseencapsulatedbacteria.

Biofilm

Asecretedsubstancethathelpsthemattachtootherbacteria,cells,orobjects.

OuterMembrane

Gram‐negativebacteriahaveanoutermembranethatprotectsthemagainstcertainantibiotics.Whenthismembraneisbreached,itreleasesendotoxins.

AntibioticResistance

Genesthatencodefordrugresistancecanbepassedtolatergenerationsorevenotherspeciesofbacteria

Streptococcus Grampositivebacteria

Highamountofpeptidoglycaninthecellwall

Lacktheoutermembraneseenaroundgramnegativebacteria

Occurinchains

Nonmotile

Nonsporeforming

Adhesins

Hyaluronicacidcapsule

MProteinshttp://www.sigmaaldrich.com/etc/medialib/life-science/biochemicals/migrationbiochemicals1/Bacterial_Cell_Lysis.Par.0001.Image.569.gif

Streptococcus

Expressesstreptolysin‐sonitssurface Whichkillsthewhitebloodcellthroughnecrosis,adeathinwhichthe

cellswellsandeventuallybursts

Causelyticgranules(lysosomes)ofthewhitebloodcelltobeemptiedintotheWBC'scytoplasminsteadofonthebacteria

• Streptococcus pyogenes (Class A) causes strep throat, rheumatic fever• Streptococcus agalactiae (Class B) causes bacterial pneumonia, meningitis

http://www.textbookofbacteriology.net/streptococcus.html

Howtosetupthebodiesdefenses

Attackadhesins

Makeantibodiesmoresensitivetothefactorsonthesurfaceofthebacteria BetteridentifytheMproteins

Defeatthehyaluronicacidcapsule Unfortunatelylookslikehostconnectivetissue

cells

Eliminatetheproductionofstreptolysin‐sbythebacteria

http://www.textbookofbacteriology.net/streptococcus_4.html

Competition

Skin,phagocytes,antibodies

Antibiotics Penicillin is still effective when diagnosis is early;

however, body notgiventhechancetodeveloppersistentantibodies

No effective vaccine M protein vaccines

Risk of autoimmunity

Increase polysaccharides Many different types of polysaccharides Normally not much of a response

http://www.textbookofbacteriology.net/streptococcus_4.html

Knownsandunknowns

Penicillinstilleffective

Antibioticresistance

AfewMproteins

Howuniquearetheproteinsandcarbohydratesthatweareidentifying? Similaritytohumancellsorbeneficialbacteria?

Impact

IfwecaneffectivelytackleStreptococcus,thiswouldhelpeliminatethecommoncasesofstrepthroatseenintheschoolsystems.

Fewerdeathsduetopneumoniaandmeningitis.

Possiblytransfertreatmentideastodefeatotherbacteria.

PRIONS

Proteinsareeverywhere!

Somegoodandsomebad!

Thebadonescausebaddiseases!

Findthecuretoprionsdiseases=Saferandhappiereatingofbeef!

http://www.irbbarcelona.org/files/Image/PrP106_126_big.jpg

Prions?

WhatisaPrion?

Researchers,not100%sure Misfoldedprotein Virus HeavyMetal Combinationofmanyfactorsandcofactors

Diseaseinmammals:BSEandCreutzfeld‐Jakobdisease

AffectNeuraltissue(spongy)

Moo?

http://api.ning.com/files/wb2qI9G4S5KrG5g9GTYSKyje5LTX79nK1xICfGFbS*NwFdWUOlqf7XM7t54ObZwbJK4Pqj1XwfW-56ankdX8m4TJHMnEcspg/SpongeBobstandup.jpg

TransmissionandStructure

http://www.bioquest.org/bedrock/problem_spaces/prion/assets/prion_structure.jpg

ForBSE,whichwheningestedcausesCreutzfeld‐Jakob,normalproteinisPrPCandmutantisPrPSC(Verystable)

Mutantreplacesa‐heliceswithb‐sheetsinsecondarystructurewhichfacilitateamyloidfibers(leadtoholes/spongytissue)

Transmittedmainlythroughingestionofaffectedtissue,butalsogeneticallyinherited

Importance

Prioninfectiousdiseasescurrentlyaffect1in1millionpeoplebetweentheagesof30‐45and3in1millionundertheageof30

Whilethisisnotagreatamount,therecurrentlyisnocure

Prioninfectionisalwaysfatal

Impact

Iffullysuccessful,caneatwithoutfearofinfection

Thoughaffectedpopulationisnotwidespread,asolutionwillrelievefearsofinfectionfromafatal,untreatabledisease

http://cyber.law.harvard.edu/blogs/static/dowbrigade/BRAINsand.jpg

Competition

Recentlydevelopedvaccine,onlytestedinmice,preventsthemfromdevelopingneuralplaques

Alteringgenomeofcows/livestocksotheydon’tcarryproteinPrPC

Knowns

Prionsaremainlymisfoldedproteins Thoughsomeevidencepointstocofactors,etc.

Affectstructureofbrain/neuraltissue(createplaques,spongytissue)

Currentlyuntreatable Resistanttoprotease,heat,radiation

Mainmethodoftransmission:ingestion

Unknowns

ResearchersTHINK: Prionsmightmutateotherhealthyproteinsto

becomemutantproteins

Prionsmightnotbeproteins Viruses

HeavyMetalPoisoning

Combinationofmanyfactors

The3DstructureofPrPSC

http://dogownership.org/myPictures/MadCowMomentCommentary.jpg

PossibleSolutions

Disablethereplicationofproteins,mutantproteintransformshealthyprotein

Disabletheaggregationofmutantproteinsbyblockingtheendoftheamyloidfibersonofreeproteinscanattach

Reduceordestroytertiarystructureofmutantprotein

VIRUS INFECTIONS

Virusesareeverywhere!

Somegoodandsomebad!

Thebadonescausewidespreaddiseases!

Virusescauseendemic,epidemicandpandemicinfectiousdiseases!

Findthecuretoone=Findingpossiblecurestoothers!

HEPATITISCVIRUS

http://images.google.com/imgres?imgurl=http://secretwave101.files.wordpress.com/2007/12/blood‐virus_hcv.jpg&imgrefurl=http:/secretwave101.wordpress.com/2007/12/31/pregnant‐with‐hepatitis‐cproblem&usg=__7WWfI8gr7q0rp7r4pCmCQIaJelw=&h=598&w=600&sz=60&hl=en&start=1&sig2=vBPQKWqBBvD8XTPnGymDeg&tbnid=EG1HnA1oV20M9M:&tbnh=135&tbnw=135&ei=iN2zSbzgNOGBtgfilanEBw&prev=/images%3Fq%3Dhepatitis%2Bc%2Bvirus%26gbv%3D2%26hl%3Den%26client%3Dfirefox‐a%26rls%3Dorg.mozilla:en‐US:official%26sa%3DG>.

WhatisHepatitis?

Hepatitisisaninflammationoftheliver.

Causedbyviruses.

ThemostimportanttypesofviralhepatitisarehepatitisA,hepatitisB,andhepatitisC.NewlydiscoveredformsofviralhepatitisalsoincludehepatitisD,E,andG.

WhatisHepatitisC?

HepatitisC,adiseasecausingcirrhosisoftheliverbroughtbytheattackofanRNAvirus,HCV.

Inmid‐1995thehepatitisCviruswasseenforthefirsttime.

Thevirusisalinearsingle‐strandRNAvirus40‐50nanometersinsize.Itiscoveredwithalipidenvelopeandisencasedwithglycoproteinpeplomersor"spikes".

Thisvirusbringsaboutthecirrhosisoftheliver:wherenormallivercellsaredamagedandreplacedbyscartissue,decreasingtheamountofnormallivertissue

McInnis,Vikki."WhatisHCV?"HepatitsCInformationCenter.8Aug.2002.8Mar.2009<http://www.hepatitis‐central.com/hcv/whatis/whatishcv.html>.

ProbableoutcomeofcontactwithHCV

If100peoplecontractHCVatthesametime

Between80to85peoplehavechronichepatitisCinfection

15to20peoplegetridoftheviruswithin2to3months(butcarryantibodiesforsometime)

Around20peoplewillneverdevelopanyliverdamage

Between60to65peoplewilldevelopsomelevelofliverdamage(afteranaverageof15years)

Between20to25peoplewilldevelopcirrhosisoftheliver(afterabout20years)

Between5to10ofthosepeoplewithcirrhosiswillexperienceliverfailureorcancer(after25to30years)

Importanceoftheproblem

Theliveristhemostimportantorganofourbody.

Itisourbodiesfiltersystem.

Itnotonlyhelpsremovertoxins,drugsandwastematerial,butalsohelpsproducebile,essentialtothedigestionoffats.

BUT:theliverinfected,HCV,cancausemildproblemslikejaundice,nausea,fever,diarrheaormoreseriousillnesssuchascancer.

Importanceoftheproblemcontd. TheWorldHealthOrganizationconsidersHepatitisCan

epidemic.

BecauseapatientlivingwithHepatitisCcanbeinfectedfordecadesbeforebeingdiscovered,itisoftencalledthe"silent"epidemic.

HepatitisCisthemostcommonblood‐borneinfectionintheUnitedStates.Itaffectsatleast4millionpeopleintheU.S.and175millionpeopleworldwide.

Itistheleadingcauseforlivercancer!

Currenttreatment

Combinationtherapywithpegylatedinterferonandribavirinisthetreatmentofchoiceresultinginsustainedresponseratesof40%‐80%.

Interferonmonotherapyisgenerallyreservedforpatientsinwhomribaviriniscontraindicated.

Ribavirin,whenusedalone,doesnotwork.

Interferon,reducestheamountofliverenzymestonormallimits.Withliverenzymesattheoptimumamount,thenormallivercellsfunctionbetter.

Ribavirinmaysuppressviralreplication,butdoesnotappeartoeradicatethevirus.Hence,theliverenzymesdropwiththeviralloadremainingthesame.

Problemsofthecurrenttreatment

Mostpersonshaveflu‐likesymptoms(fever,chills,headache,muscleandjointaches,fastheartrate)earlyintreatment.Latersideeffectsmayincludetiredness,hairloss,lowbloodcount,troublewiththinking,moodiness,anddepression.

Severesideeffectsincludethyroiddisease,depressionwithsuicidalandhomicidalthoughts,seizures,acuteheartorkidneyfailure,eyeandlungproblems,hearingloss,andbloodinfection.

Althoughrare,deathshaveoccurredduetoliverfailureorbloodinfection,mostlyinpersonswithcirrhosis.

Animportantsideeffectofinterferonisworseningofliverdiseasewithtreatment,whichcanbesevereandevenfatal,becauseoncetheinterferonhasbeenremovedfromthebodytheliverenzymesonceagainincreaseinproduction

Reasonsbehindtheproblem:TheUnknowns

SixsubtypesofhepC,plusvariations,allofwhichrespondtotreatmentsdifferently.

Exactlyhowthevirusattacksthecellsoftheliverandwhatitdoestothecells

Generalmethodstokillvirusesinsidethehumanbody

Howtopreventthevirusfrommultiplyingwithinthebody

Theknown’s

ItisknownthatHCVreplicatesbyhijackingthenucleotidesofitshostcell.Itisthelivercellsthatstillhaveavailablenucleotidesinsufficientsuppliesevenafterthecellshavestoppeddividing.

StudieshaveshownthatifthenucleotidesinthecellsarereplacedbynucleosidestheHCVareinhibitedfromreplication.

Tang‐NelsonstudyatFSU,2006.

FirstPossiblesolution!

KILLINGTHEVIRUSBEFOREITATTACKSMULTIPLECELLS

Viruseshaveproteincapsids.

IncreasetheproductionofHydrogenPeroxideintheperoxisomesofcells,andshutoffitsconversiontowater.

Directittotheproteinaceouscapsidofthevirusanddestroyit,releasingtheRNA/DNAintothebloodstream.

Byincreasingtheproductionofexo‐nucleases,theRNAandDNAcouldbedestroyed.

OtherPossibleSolutions!

2.PREVENTINGTHEREPLICATIONOFVIRUSES:ReengineertheDNAofthehostcellsoastopreventthereplicationofviruses,byconvertingtheexistingnucleotidestonucleosides.

3.HELPHEALTHYCELLSFROMVIRUSATTACKS:ReengineertheDNAofthelivercellssoastoproducemoreinterferonfasterthantheviruscanreplicate.

4.HELPHEALTHYPEOPLEFROMTHEINFECTION:DiscoveringavaccineagainstHCV.

Impactofsolution

Thus,comingupwithasolutiontohelpHepatitisCpatients,wouldhelppeoplefromaroundtheworld.

SincethereisnocurrentvaccineagainstHepatitisC,creatinganefficientvaccinemayevenleadtotheeradicationofthisdisease.

Moreover,sinceitisavirusinfection,acuretothisdiseasemayevenleadtoagenericcuretoallviralinfections.

SUMMARY

Infectiousagents,eitherbacteria,prionsorviruses,bringaboutprolongeddegradationofourbody.

Iftheseagentscanbestoppedattheearlystagesoftheirattackbyboostingourhumanbodies,thenanumberofhumansaroundtheworldcanbesavedfromalifetimeofillness.

Takealookatthehandouts!!!

SURVEY!

Couldyoupleasetakeamomenttolookatthehandoutswepassedaroundandfilloutthesurveysheet!

Thankyou!!!

BIBLIOGRAPHY

http://ghr.nlm.nih.gov/condition=priondisease

"WhatisHepatitis?"WhatisHepatitis?<http://www.hepcprimer.com/what.html>.

AmericanAcademyofPediatrics(2006).HepatitisC.InLKPickering,ed.,RedBook:2006ReportoftheCommitteeonInfectiousDiseases,27thed.,pp.355–359.ElkGrove,IL:AmericanAcademyofPediatrics.

McInnis,Vikki."WhatisHCV?"HepatitsCInformationCenter.8Aug.2002.8Mar.2009<http://www.hepatitis‐central.com/hcv/whatis/whatishcv.html>.

http://www.sciencedaily.com/releases/2009/02/090223221427.htm

http://www.merck.com/mmhe/sec17/ch190/ch190a.html

http://www.textbookofbacteriology.net/streptococcus.html

http://www.sciencedaily.com/releases/2007/05/070503135420.htm

http://www.washingtonpost.com/wp‐dyn/content/article/2006/12/31/AR2006123100672.html