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iSci AnISCI2A18

ResearchProject

DrugDiscovery

iSCI2A18ProjectPack(Fall2018)

ProjectLeader:Dr.RosadaSilva AdministrativeLead:RussEllis

INTEGRATEDSCIENCE2A18 DRUGDISCOVERYPROJECTPACK Dr.daSilva’sInformationEmail:rosa.dasilva@mcmaster.caOffice:LSB540OfficeHours:Fridays;1:00-2:00pm

Introduction&BackgroundMacromolecules such as nucleic acids and proteins are essential elements of life. They areresponsiblefortheproperexecutionofvariousbiochemicalprocesseswithinthe livingorganism.The conformational states and chemical stability of these macromolecules are often preciselytunedforachievingtheiroptimal(normal)functions.Assuch,diseasestatescanoccurwhenthesemacromolecules are structurallymodified. Wewill develop an understanding ofwhat principlesandstrategiesareconsideredduringdrugdiscovery,designanddevelopmentandhowexternallyintroducedmedicinaldrugscan interactwithmacromoleculestofacilitatethetreatmentofmanysymptoms and the overall progression of many disorders. This will be accomplished throughstudying the chemical and conformational properties of these target molecules and theirinteractionswithmedicinaldrugs.Objectives

Thisprojectwillintroduceyoutoabroadunderstandingofthebiochemicalinteractionsthatoccurwithin cells, and how medicinal drugs can help correct any inappropriate interactions that canoccur indisease states. Thiswill be facilitated throughanunderstandingof theprocessofdrugdiscoveryanddevelopment.

SkillsDevelopment Theprojectwillintroduceyoutotheprinciplesofnucleicacidandproteinstructureandfunction,drug development, and how drugs exert their effects through interactions with thesemacromolecules. You will learn key vocabulary of biochemistry, the fundamentals of molecularstructureandfunction,andhowdrugsinteractwiththeirtargets.

Resources RecommendedTextbook:AnIntroductiontoMedicinalChemistry,6thedition.Author:GrahamL.PatrickISBN:978-0198749691

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Assessment In-ClassTest1,FridayNovember16 (Individual) 7pointsIn-ClassTest2,WednesdayNovember28 (Individual) 7pointsDrugDiscoveryShowcaseVideo(Group) 8pointsDrugDiscoveryShowcasePresentation(Group) 3pointsDrugDiscoveryReview(Individual) 10points NotesonAssessment1. Tests(IndividualAssessment)-14pointstotal:Therewillbe2in-classtestsintheiSci2A18Drug

DiscoveryResearchProjectthatwilltestmaterialpresentedduringlecturesgivenbyDr.daSilvaandanyguestlecturer(s)alongwithanyprovidedreadings/lecturenotespostedonAvenuetoLearn. Termtestscan includemultiplechoice,shortanswer, labelingfigures,definitions,andcan include compare and contrast short answer questions. Term tests are scheduled duringregular class time. The scheduled term testswill not be changed, and youmustwrite bothtests.

Test1:FridayNovember16,3:30-5:30pm(worth7pointsofyourfinalgrade)Test2:WednesdayNovember28,7:00-9:00pm(worth7pointsofyourfinalgrade)

*Note:ThereisnofinalexamintheDrugDiscoveryProjectforiSci2A18*

2. DrugDiscoveryShowcase(GroupAssessment)-11pointstotal:

Students in iSci2A18 will break into groups of 5 (for a total of 12 groups) and will create aunique5-minutevideothatwillbepresentedattheend-of-termDrugDiscoveryShowcase.ThefocusofthisShowcasewillbeonthe“off-label”usesandeffectsofmedicinaldrugs.Thisisacommonpracticeinthefieldofmedicinetoday.Throughthisvideoprojectandin-classgrouppresentation,eachgroupwillpresentthemannerinwhichyourselectedmedicinaldrugisabletotargetandalleviatethesymptomsofamedicalconditionforwhichithasnotbeenapproved.Eachgroup in the classmust selectauniquemedical conditionandaccompanyingoff-labeldrugtherapeutic.Sign-upwillbeonafirst-come-firstservebasiswithDr.daSilva.

Whencreatingandstoryboardingthisvideo,youwillwanttoconsiderthefollowing:

• Abriefintroductiontothediseaseyourgrouphaschosenandthecellularmechanismthatisdrivingdiseasesymptoms

• Themanner inwhichthemedicationyouhaveselected isable to interactwith thecellularmechanismsthataredefective

• Theeffectsofthemedicationondiseasesymptomsandprogression• Anywarningsthatshouldbeconsidered• Whoisyourtargetaudienceandwhy?Isitprofessionals?Alayaudience?Pickone.

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TheDrugDiscoveryShowcaseVideocanbeinanyformat.Becreative!Someoptionsincludebut are not limited to: white board videos; claymation or stopmotion; interviews with anexpert; amovie style “trailer”etc. Thereexistsanarrayofdifferent (and free) videoeditingsoftwareoptionsthatyoucanuse.Theseinclude:• Animaker• Lightworks• Avidemux• Shotcut• Hitfilmexpress• Biteable• iMovie(Maconly)

Whileweencouragecreativityduringthevideostoryboardingandcreationprocess,feelfreetouse the 5-minuteVideoGuidelines document that is posted in our iSci2A18 Drug DiscoveryContentAreasonAvenuetoLearn.Theseguidelineswillhelpyouwiththeprojectplanningandprovidesuggestedtimemanagementstrategies.

Be sure toalsovisitMcMaster’s LyonsNewMediaCentre (LNMC) locatedatMills Library (L-411) for any technical assistance as you create you Drug Discovery Showcase videos.https://library.mcmaster.ca/lyons

5-minuteDrugDiscoveryShowcaseVideoSubmission:Once your group has completed its 5-minute Drug Discovery Showcase video, you will thenuploadittoYouTubeforfinalsubmission.WhenuploadingyourvideotoYouTube,besuretosetprivacysettingsto“UNLISTED”. ThiswillensureyourvideosareonlyvisibletothosewhohaveitsURL(webaddress).Onceyouhaveuploadedthevideo,youwillthensubmityourvideoURL(bycopyingandpastingyourYouTubevideolink),andnameofallyourgroupmembersasa singlepagePDF toadesignateAvenue to Learn submission folder. The iSci2A185-minuteDrugDiscoveryShowcasevideoisduebyNovember23at11:59pm.

In addition to McMaster’s Code of Student Rights and Responsibilities(https://www.mcmaster.ca/policy/Students-AcademicStudies/Code_of_Student_Rights_and_Responsibilities.pdf), please also note thatYouTube also has it’s own Policies and Safety Guidelines(https://www.youtube.com/yt/about/policies/#community-guidelines). Please be sure tothoroughly read and abide by these guidelines as you create your 5-minutes DrugDiscoveryShowcasevideos.

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TheDrugDiscoveryShowcase:TheDrugDiscoveryShowcasewill takeplaceonNovember30andDecember5duringourregularlyscheduledclasstime,inourregularlyscheduledclassroom(ABB136).Allgroupswillhave the opportunity to present their 5-minute Drug Discovery Showcase videos. Duringeachgroup’spresentation,allgroupswillstartwitha10-minutetotaloraldescriptionof:1. whytheychosethisspecificdrugandtheoff-labelconditionthatitisusedfor2. whytheybelievethatthisdrugshouldorshouldnotcontinuetobeutilizedforoff-label

purposes3. theirtargetaudience4. the rationale behind their creative approach, and why they believe their video is

beneficialfortheirtargetaudience

Each groups’ 10-minute Drug Discovery Showcase Presentation Introduction is worth 3pointsofyourgroups’finalgrade.Thegroupvideowillthenbeplayedfortheentireclasstoadjudicate(thevideoisworth8pointsofyourgroups’finalgrade).Ascheduleandsign-upforpresentationdateswillbemadeavailablelateronintheterm.

DrugDiscoveryShowcaseAdjudicationThe5-minuteDrugDiscoveryShowcaseVideoswillbeadjudicatedinthreeways.

1. ByDr.daSilva(thiswillcounttowardsyourDrugDiscoveryShowcasegrade-worth8points your final gradeasdescribed in the sectionabove, inaddition to your rankacrossallgroupsintheclass)

2. By your peers (this will contribute to the overall rank of your Drug DiscoveryShowcasevideoacrossthewholeclass).

3. The top 5 ranking videos (as adjudicated by Dr. da Silva, and your peers) will befurther ranked. The group that creates the top ranked videowill received a DrugDiscoveryShowcaseExperienceAward.AdditionaldetailsontheExperienceAwardwillfollowthroughoutthesemester.

***Pleasenote that ranking for theExperienceAwardswill nothaveany influenceonanycoursegrades. Specifically, the top rankedgroup in the classwillNOThaveanyacademicadvantageovertheirpeers.

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DrugDiscoveryShowcasePeerReviewAdjudicationThe Drug Discovery Showcase video project is an incredible opportunity for students toharnesstheirskillstowardscreativelyconveyingtheirscientificknowledgetowardsatargetaudience. We will celebrate this creativity and knowledge by respecting each other’spresentationsandassistingintheadjudicationprocess.Asaresult,attendanceisrequiredbyallgroupsatbothDrugDiscoveryShowcasedates.

Aspartof thePeerReviewAdjudication,youandyourgroupwillberequiredtosubmitanevaluationforyourtop2choicevideosduringeachDrugDiscoveryShowcasedate(Nov30andDec5).ResponsestothefollowingDrugDiscoveryShowcasePeerReviewAdjudicationquestionsmustbesubmittedwithin24hoursaftereachDrugDiscoveryShowcasedate:

1. Whatarethetop2videosthatyouhavechosenduringthisDrugDiscoverShowcasedate?

2. Whichofthe2videoshadthebestcreativeapproachandwhy?3. Whichofyourtop2chosenvideosonthisDrugDiscoverShowcasedatedoyouthink

aremostappropriateforthegroup’stargetaudienceandwhy?3. DrugDiscoveryReview(IndividualAssessment)-10pointstotal:Theprocessofdrugdiscovery

anddevelopmenthasmarkedlychangedtheworldofmedicinesuch that likeexpectancyhasnearlydoubledinCanadaoverthelast100years.ThroughtheDrugDiscoveryReview,studentsiniSci2A18willselectONEmedicinaldrugfromalistofoptionsandwillinvestigatetheprocessofdrugdiscoveryanddevelopmentthatoccurredforthatspecificdrug,and inturnhowthatdrughasmadealargeimpactintreatingordealingwithdiseasesymptoms.

EachstudentiniSci2A18willsign-upforONEofthefollowingmedicinaldrugsasthefocusfortheirDrugDiscoveryReview.Sign-upwillbedoneonAvenuetoLearnonMondayOctober29at6pmonafirst-come-firstservebasis.

1. Gefitinib2. Nitrolingual3. Gemfibrozil4. Codeine5. Ventolin

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TheDrugDiscoveryReviewOutline:Students will utilize informational search engines (including PubMed, Medline, or GoogleScholar)tofindrecentandrelevantarticlespertainingtotheirtopic,andtoaddressallofthefollowingquestionsintheirreview:

1. Drugdiscovery:Howwasitdiscovered?Whodiscoveredthedrug?Whatisthedrug

targetand itsmechanismsofactiononcells?Howdoes thismedicinaldrugcorrectany cellular or systemic malfunction, and ultimately alleviate symptoms? Whatpatentingprocesswasinvolved?(ifany)?

2. Preclinical Research: How was dosage determined? Is there any potential drug

toxicity?Whoconductedtheinvitroandinvivoresearch?

3. ClinicalResearch:Howmanypeople/phaseswereinvolved?Whatweretheselectioncriteria?Whoreviewedandanalysedthedata(whatkindofprofessionalscontributetothereviewpanel)?Whatphaseisthedrugcurrentlyin?Werethereanyadditionaltoxicitiesoroff-targeteffectsseeninhumans?

4. A)FoodandDrugAdministrationApproval:Whatandwhodeterminedtheproposed

labeling,safetyadvisories,drugabuseinformationanddirectionsforuseofthedrug?IsthisdrugusedelsewherearoundtheworldwithoutFDAapproval?

B)Distribution and Post-Market SafetyMonitoring:What process was involved inadvertising,thedevelopmentofgenericdrugs,andsurveillanceofdrugsafety?Whichcountrieshaveaccesstothisdrug?Arethereanysourcesofillegalproductionofthisdrug? Are there any additional post-market safety concerns that have recentlyemerged?Note:TheDrugDiscoveryReviewisworth10pointsofyourfinalgradeandisdue

byDecember5,2018at11:59pm*

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Absences AbsencefromiConS: If you are absent from any scheduled ISCI2A18 session, it is your responsibility to make upmissedworkandobtainnotesfromAvenueand/orotherstudentsinthecourse. Procedureforauthorizedabsence: PleasereviewISCI2A18CourseOutlinefordetailsonsubmittinganMSAFtoaccountforabsencesandmissedwork.

MissedDeadlines Any late submission forAssignmentswithout appropriate documentation to account for themisseddeadline(eg.MSAF)willresultinapenaltyof20%perday.Thisholdsforbothgroupand individual assignments. Anymissed tests or presentationswill be graded 0% unless theabsenceisauthorized(seeabove).

Discipline-SpecificLearningSpecifications Thematerial covered in this projectwill prepare you for additional Biochemistry courses availablethroughtheDepartmentofBiochemistryandBiomedicalSciences,andCellBiologycoursesavailablethroughtheDepartmentofBiologyatMcMasterUniversity.

AcademicIntegrity In this project we will be using a web-based service (Turnitin.com) to reveal plagiarism. TheindividualDrugDiscoveryReviewfoldersonAvenuewillautomaticallysubmitworktoTurnitin.comsothat itcanbechecked foracademicdishonesty.Studentsorgroupswhodonotwish tosubmittheir work to Turnitin.commust still submit a copy to Dr. da Silva through an alternate Avenuesubmissionfolderthat isnotassociatedwithTurnitin.com.Nopenaltywillbeassignedtostudentswhodonotsubmitwork toTurnitin.com.All submittedwork is subject tonormalverificationthatstandardsofacademicintegrityhavebeenupheld(e.g.,on-linesearch,etc.).ToseetheTurnitin.comPolicy,pleasegotohttps://www.mcmaster.ca/academicintegrity/turnitin/students/index.html

TheinstructorsandtheuniversityreservetherighttoalterthisoutlineifnecessaryThe instructors anduniversity reserve the right tomodifyelementsof the courseduring the term.Theuniversitymaychangethedatesanddeadlinesforanyorallcoursesinextremecircumstances.Ifeither type of modification becomes necessary, reasonable notice and communication with thestudents will be given with explanation and the opportunity to comment on changes. It is theresponsibility of the student to check theirMcMaster email and course Avenue to Learnwebsitesweeklyduringthetermandtonoteanychanges.

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iSci2A18DrugDiscoveryProjectScheduleFall2018

Date Topic Tests Drug Discovery Group Presentation

Drug Discovery Report

All Grades

Week 7 Oct 24, 26 Introduction to Drug Discovery Module 1: Drug Targets

Week 8 (LAB 1) Molecular Modeling

Nov 2

Module 2: Principles & Strategies of Drug Discovery and Development

Week 9 (LAB 2) In vitro Enzyme Assay

Nov 7, 9 Module 2: Principles & Strategies of Drug Discovery and Development Module 3: Pharmacodynamics and Pharmacokinetics

Week 10 Nov 14, 16

Module 3: Pharmacodynamics and Pharmacokinetics & Test 1

Test 1 (Covering Modules 1 & 2)

Fri November 16

Week 11 LAB 3 In vivo Planaria and Inhibitors

Nov 21, 23 Module 4: The Evolving Field of Drug Discovery

Drug Discovery Showcase Videos Due by Nov 23 at

11:59pm

Week 12 November 28, 30 Test 2 & Drug Discovery Showcase -Group Presentations Day 1

Test 2 (Covering Modules 3 & 4)

Wed November 28

Drug Discovery Showcase

Day 1 Fri November 30

Week 13 December 5 Drug Discovery Showcase -Group Presentations Day 2

Drug Discovery Showcase Day 2

Wed December 5

Drug Discovery Final Report Due Wed December 5

EVALUATION: Tests (2x20%) = 14 points

Drug Discovery Showcase Video

= 8 points Group Presentation:

= 3 points

Drug Discovery Review:

= 10 points * Lectures for iSci2A18 are Wednesdays 7-10pm and Fridays from 3:30-5:30pm in ABB 136 as noted in the above schedule. There will also be special guest lectures scheduled throughout the term.