Alberta Investment, Global Impact.

2013-14 ANNUAL REPORTALBERTA PRION RESEARCH INSTITUTE

When the first case of bovine spongiform encephalopathy (BSE) in a domestic animal was confirmed on an Alberta farm in May 2003, the socioeconomic impacts were immediate and devastating. Dozens of countries around the world closed their borders to Canadian beef. Amid the uncertainty and economic losses, the Government of Alberta received international praise for its focus on public interest and its transparent and effective response.

A lasting legacy of Alberta’s response to the 2003 BSE crisis is an investment in research. The Government of Alberta created the Alberta Prion Research Institute in April 2005 to fund research on BSE and other prion and protein misfolding diseases. The province invested $35 million over seven years and renewed its commitment to prion research in 2012 with an investment of $15 million over three years.

The impact of the Alberta investment is substantial. Alberta is now home to some of the best prion researchers in the world. Alberta universities house some of the best prion research facilities in the world. Alberta researchers have made and continue to make significant contributions to advances in prion science.

Today, Alberta is a global leader in prion and protein misfolding research.

Alberta Investment

Global Impact

Winnipeg

Toronto

Montreal

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In 2005... When the Alberta Prion Research Institute was created in April 2005, there were very few researchers in Canada studying bovine spongiform encephalopathy and other prion diseases. None of these researchers were based in Alberta, home to Canada’s largest beef and cattle industries. �e Government of Alberta created the Alberta Prion Research Institute with a mandate to build the scienti�c capacity in the province.

Alberta has gone from not having any prion researchers to being internationally recognized as a leading research location in prion and protein misfolding diseases because of the Government of Alberta’s investment. Internationally-renowned scientists have taken note of Alberta’s excellence in prion science. Eleven world-class researchers have moved to Alberta since the formation of the Alberta Prion Research Institute. Hundreds of students and postdoctoral fellows, many from outside of Canada, have been trained in Alberta labs.

The creation of the Alberta Prion Research Institute has significantly increased Alberta’s and Canada’s scientific standing internationally. This research investment clearly demonstrates that Alberta is committed to addressing prion and prion-like diseases in humans and animals. The investment in research and state-of-the-art equipment has allowed researchers in Alberta to make important contributions to the prion and protein misfolding fields. Their research findings have had an impact on the research of other scientists around the world.

By 2014... �ere are now dozens of researchers in Alberta focused on prion diseases such as bovine spongiform encephalopathy and chronic wasting disease and prion-like protein misfolding diseases such as Alzheimer’s and Lou Gehrig’s. �ese researchers collaborate with scientists and institutions around the world, expanding the reach and global impact of the Alberta investment. �e creation of the Alberta Prion Research Institute has led to Alberta becoming a global leader in prion and protein misfolding research.

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VictoriaCalgary

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Edmonton

TexasColorado

TaiwanJapan

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WisconsinMississippi

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GermanySpain

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Alberta Prion Research Institute Connections

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INTERNATIONAL

Message from the Executive DirectorThe Alberta Prion Research Institute, a part of Alberta Innovates Bio Solutions, has supported 48 researchers, three industry partners and over 360 research technicians, postdoctoral fellows and graduate students since its inception in April 2005. The scientific capacity that has been built in our province over the last nine years is impressive.

Our funded researchers have made significant contributions to the prion and protein misfolding fields. They have made key findings in the structure and behaviour of prion proteins. They have published papers in leading scientific journals. The innovative researchers and state-of-the-art research facilities at Alberta universities are the reason Alberta is now internationally recognized as a leading research location for prion science.

As we enter the last year of our current 10-year commitment from the Government of Alberta, we will continue to work closely with researchers, post-secondary institutions and partners to fund new and inventive prion and protein misfolding research. We are committed to fundamental and applied research on diagnostics and treatments of prion diseases for the benefit of Albertans and industry.

Dr. Kevin KeoughE X E C U T I V E D I R E C T O R

2013-14 Annual ReportT A B L E O F C O N T E N T S

3 For Albertans and Industry

4 Innovation and Collaboration

9 Pursuit of Knowledge

11 Investment and Impact

12 Novel Ideas and New Directions

14 Alberta: Contributing to Global Knowledge

24 CJD Awareness and Support

25 Expanding Horizons: The Next Generation

27 Awards, Honours and Publications

30 International Research Advisory Council

31 Prion 101

32 Where Are We Today?

A timeline of research achievements funded by the Alberta Prion Research Institute can be found inside the back cover.

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For Albertans and Industry

The Alberta Prion Research Institute was borne out of the 2003 BSE crisis. It supports top researchers working on solutions to the serious scientific and socioeconomic challenges associated with prion diseases in animals and prion and prion-like diseases in humans. Today, the Alberta Prion Research Institute is the only research funding agency in North America with a mandate focused on BSE and other prion and prion-like protein misfolding diseases.

It has supported researchers who have developed new methods to turn specified risk materials from cattle into products that have potential commercial and industrial applications. It has supported researchers studying compounds that could ultimately detect, treat or stop the spread of prion diseases in animals and humans. It has supported researchers looking into methods to decontaminate infectious prion proteins.

Alberta-based scientists are conducting innovative research that will one day lead to more effective diagnoses, treatments and interventions of prion and protein misfolding diseases in animals and humans. The prion research being done in Alberta labs has benefited and will continue to benefit Albertans and industry.

The Government of Alberta committed hundreds of millions of dollars towards the BSE recovery plan for the benefit of Albertans and industry. Estimated losses from the 2003 BSE crisis are as high as $11 billion.

The BSE crisis helped shape the evolution of Canada’s food safety systems: enhancing the livestock traceability system; strengthening regulations and livestock disease control methods; and increasing research capacity.

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Innovation and CollaborationResearch and innovation are driven by talent, ideas and collaboration.

The Alberta Prion Research Institute and its funded researchers have built strong partnerships since 2005 with researchers, post-secondary institutions, research centres, scientific journals and government agencies in Canada and around the world. Most of these partnerships are ongoing today. These partnerships have led to research collaborations, scientific workshops, exchange of research knowledge and discoveries in prion and protein misfolding research.

Alberta• AlbertaInnovatesBioSolutions• AlbertaInnovatesHealthSolutions• AlbertaInnovatesTechnologyFutures• AlbertaLivestockandMeatAgency• AlzheimerSocietyofAlbertaandNorthwestTerritories• CampusAlbertaNeuroscience• CentreforPrionsandProteinFoldingDiseases• ChemRoutesCorporation• GenomeAlberta• GovernmentofAlberta• HighmarkRenewableResearchInc.• HotchkissBrainInstitute• KeyanoCollege• LakelandCollege• LethbridgeCollege• OldsCollege• UniversityofAlberta• UniversityofCalgary

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Canada• AgricultureandAgri-FoodCanada• BiogenIdec• BiosphereTechnologiesInc.• BordenLadnerGervais• BMGLabtech• CanadaFoundationforInnovation• CanadaResearchChairs• CanadianCooperativeWildlifeHealthCentre• CanadianFoodInspectionAgency• CanadianInstitutesofHealthResearch• GEHealthcare• HealthCanada• HospitalforSickChildren• NationalInstituteforNanotechnology• NationalMicrobiologyLaboratory, Prion Diseases Program• NationalResearchCouncil• NaturalSciencesandEngineeringResearch

Council of Canada• PREVENT• PrioNetCanada• PrometicBiosciences• PublicHealthAgencyofCanada• Sanimax• UniversityofBritishColumbia• UniversityofGuelph• UniversityofManitoba• UniversityofOttawa• UniversityofSaskatchewan• UniversityofToronto• UniversityofVictoria• VIDO-InterVac• TheWoodbridgeGroup

International• A.C.CamargoHospital,Brazil• AtomicEnergyCommission,France• CaseWesternReserveUniversity,UnitedStates• CentralVeterinaryInstituteofWageningen

University&ResearchCentre,TheNetherlands• CJDFoundation,UnitedStates• ColoradoStateUniversity,UnitedStates• GermanCenterforNeurodegenerative Diseases, Germany• GermanPrimateCentre,Germany• TheHelmholtzAssociation,Germany• ImperialCollegeofLondon,UnitedKingdom• KineticsFoundation,UnitedStates• LandesBioscience,UnitedStates• L’Écoledeshautesétudesensciences sociales, France• NationalEngineeringLaboratoryforAnti-

Tumor Protein Therapeutics, China• NationalInstituteofAnimalHealth,Japan• NationalInstitutesofAllergyandInfectious

Diseases,UnitedStates• NeuroPrion,France• PrionicsAG,Switzerland• RiodeJaneiroResearchFederation,Brazil• Robert-Koch-InstituteBerlin,Germany• SãoPauloResearchFederation,Brazil• Taylor&FrancisGroup,UnitedKingdom• TechnicalUniversityofMunich,Germany• TokyoUniversity,Japan• UniversidadeFederaldoRiodeJaneiro,Brazil• UniversityHospitalZurich,Switzerland• UniversityofCalifornia,SanFrancisco, UnitedStates• UniversityofGöttingen,Germany• UniversityofSussex,UnitedKingdom• UniversityofWisconsin,UnitedStates• WildlifeResearchCenter,UnitedStates

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PARTNER HIGHLIGHTS

TheAlbertaLivestockandMeatAgency(ALMA)isa longstanding partner of the Alberta Prion Research Institute.ALMAisaGovernmentofAlbertaagency that funds research that drives innovation in the meat and livestock industry with the aim to enhance competitiveness and increase profitability for industry. Together, the two agencies funded nine research projects in 2013-14 for almost $3 million. These projects focus on research related to bovine spongiform encephalopathy, specified risk materials and chronic wasting disease. The two agencies have also hosted industry meetings and workshops to highlight the research being doing in Alberta for the benefit of the meat and livestock industry.

The Alberta Prion Research Institute and the Alzheimer Society of Alberta and Northwest Territories formed a partnership in 2012 to create the Alberta Alzheimer Research Program. This program has provided six Alberta-based researchers with almost $1.1 million for research related to understanding the fundamental mechanisms of Alzheimer’sdiseaseandimprovingthequalityoflife for those with the disease. This partnership encouragesresearcherstolookatAlzheimer’sdiseaseinadifferentway.LookingatAlzheimer’sfromaprion perspective presents a new avenue for scholars to share approaches and discoveries between the prion and neurodegenerative disease communities.

The Alberta Prion Research Institute has funded 15UniversityofCalgaryresearcherssince2005.ManyofthefundedresearchersareaffiliatedwiththeFacultyofVeterinaryMedicineand/orthe Hotchkiss Brain Institute. The Alberta Prion Research Institute has also committed funding for operational support of a new prion research facility attheUniversityofCalgaryFoothillscampus.The facility will be completed in 2014. This new state-of-the-art facility is one of the reasons Sabine Gilch and Hermann Schätzl, the two most recent researchers recruited from outside of Alberta, moved their research labs from Wyoming. The dedicated prion research facility and cell culture labs will have asignificantimpactontheirresearch.Dr.Gilch’sresearch focuses on investigating prion-host cell interactions, developing new therapeutic approaches and improving diagnosis of chronic wasting disease. Dr.Schätzl’sresearchfocusesondevelopingavaccine approach against chronic wasting disease and on understanding the molecular and cellular biology of prions in general.

Sabine Gilch and Hermann Schätzl

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The Alberta Prion Research Institute hasfunded31UniversityofAlbertaresearchers since 2005. Its largest infrastructure investment is the Centre for Prions and Protein Folding Diseases(PrionCentre).WhenDavidWestaway, a leading prion researcher attheUniversityofToronto,wasfirstapproached in 2005 to lead the Prion Centre,itwasavirtualcentrewithnophysicalspace.ThatquicklychangedwhentheUniversityofAlbertadonatedtheBrainandAgingResearchBuilding(formerlytheEnvironmentalEngineeringBuilding)and contributed significant funding for design and refurbishing to create the Prion Centre.

The Alberta Prion Research Institute invested $2.1 million for infrastructureandequipmentandcontinuestoprovideoperationalsupport of the facility and funding to the seven researchers with labs in the Prion Centre. Dr. Westaway and the other Prion Centre researchers leveraged the initial investments from the Alberta Prion Research InstituteandtheUniversityofAlbertaforanadditional$19.2million from other government programs and funding agencies. The Government of Alberta invested in the refurbishing of the building and labspacethroughtheMinistryofAdvancedEducationandTechnology(nowtheMinistryofInnovationandAdvancedEducation)andtheAlberta Science and Research Investments Program.

Whatusedtobeabuildingwithofficesandroutineteachinglabspace was transformed into a state-of-the-art facility and one of the fewresearchcentresintheworldthatiscertifiedandwell-equippedto analyze all types of infectious prion proteins, including those thatinfecthumans.ThePrionCentretotals27,000squarefeetofcustomizedlabspaceandhouses$12millionofspecializedequipment,much of it inside three enhanced biosafety level 2+ laboratory areas thattotal9,000squarefeet.

David Westaway (right), Director of the Centre for Prions and Protein Folding Diseases, with PhD student Robert MercerPhoto courtesy of Judd Aiken

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At the heart of research is the pursuit of knowledge. By learning how things work at their core, we often uncover new avenues of application and translation that we cannot possibly predict ahead of time. Only with knowledge can we hope to react to prion diseases and other prion-like diseases and prevent the significant problems they cause from getting bigger.

VA L E R I E S I MAssistantProfessor,UniversityofAlberta,andAHFMRClinicalInvestigator

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Pursuit of KnowledgeThe Alberta Prion Research Institute has funded 48 researchers and three industry partners since its inception in 2005. With support from government and industry, the Alberta Prion Research Institute has provided funding to help the University of Alberta and the University of Calgary recruit 11 world-class researchers from outside of Alberta.

UniversityofAlbertaVicAdamowiczJudd Aiken*Ted Allison*Burim AmetajMiodragBelosevicDavid BresslerDavid Coltman*Debra DavidsonEllen GoddardLeluoGuanCharles HolmesMichaelJamesJack JhamandasSatyabrata KarNat KavAndriy KovalenkoDebbieMcKenzie*EvelynMerrillStephenMooreNorman NeumannBrenda ParleeLuisSchangValerieSim*MariaStepanovaBrian SykesFrederick WestDavid Westaway*Holger Wille*David WishartMichaelWoodsideHoward Young

UniversityofCalgaryJanice BraunMarkusCzub*Stefanie Czub*Carmen FuentealbaSabine Gilch*Frank JirikChristophMuellingHermann Schätzl* Christoph SensenJosephine Smart Peter StysRoger ThompsonWilfreda ThurstonShigeki TsutsuiGeraldZamponi

UniversityofSaskatchewanScott Napper

Agriculture and Agri-Food CanadaTimMcAllister

Canadian Food Inspection AgencyStefanie Czub*

Industry Partners AubreyMendonca,ChemRoutesCorporation

Tiejun Gao, Highmark Renewable Research Inc.

Tony Galasso, Sanimax

* Recruited from outside of Alberta

09Pictured to the left: Valerie Sim with postdoctoral fellow Jitendra Kumar

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Investment and Impact

Since its formation by the Government of Alberta in April 2005, the Alberta Prion Research Institute has funded 97 research projects for a total of $37,241,116. In addition, the Alberta Prion Research Institute has provided Alberta universities with $1,128,000 to recruit 11 world-class researchers to Alberta and $4,099,826 in infrastructure and equipment funding to build and equip state-of-the-art prion research facilities.

The research investment of $42,468,942 to date has built scientific capacity, created jobs, trained young scientists and led to research discoveries – all right here in Alberta.

RESEARCH FOCUS AREAS

Note: the Alberta Prion Research Institute funds research projects that have more than one focus area related to prions and misfolded proteins.

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SCIENTIFIC THEMES OF FUNDED PROJECTS

BOVINE SPONGIFORM ENCEPHALOPATHY

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CHRONIC WASTING DISEASE

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OTHER NEUROLOGICAL DISEASES

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SPECIFIED RISK MATERIALS

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SOCIAL SCIENCES

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PATHOBIOLOGY OF TSEs

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SURVEILLANCE AND CONTROL

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PROTEIN FOLDING & MISFOLDING

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TSEs & SOCIETY

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Novel Ideas and New Directions

Much is still unknown about prions and prion diseases. There are still many questions to answer. Novel ideas and new directions are necessary to unlock the prion mystery. The Alberta Prion Research Institute funds some of the best prion researchers in the world. They are conducting new and inventive research to look for more effective ways to diagnose, treat and eventually cure prion and protein misfolding diseases.

In 2013-14, 20 research projects received $4,622,887 in funding.

APRI/ALMATargeted Areas Program(Partnership with Alberta Livestock and Meat Agency)

Judd Aiken: Environmental chronic wasting disease infectivity

Tiejun Gao: Exploring the nutrient value of specified risk materials from thermophilic anaerobic digestion

Sabine Gilch: Defining a relationship between biochemical properties of chronic wasting disease prions and prion shedding

David Westaway: Biological destruction of prion proteins

David Wishart: Developing a vaccine for chronic wasting disease using synthetic, stabilized PrP oligomers

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Alberta Alzheimer Research Program (Partnership with Alzheimer Society of Alberta and Northwest Territories)

Jack Jhamandas: Glycolytic modulation of amyloid-astrocyte interactions: implications forAlzheimer’sdiseasepathogenesis

Research Team Program

Andriy Kovalenko: Targeting prion-like propagated misfolding ofSOD1forALSimmunotherapy

Holger Wille: Human prions – distinguishing sporadic from familial forms via structure and function

Explorations Program

Stefanie Czub: Discrimination of classical and atypical BSE by a distinct PrPSc profile(funding partnership with ALMA)

Stefanie Czub: Oral challenge of classical and atypical BSE to determine transmissibility, age-related susceptibility and agent distribution (funding partnership with ALMA)

Sabine Gilch: Peptide aptamers as therapeutic and analytic tools in prion research

Sabine Gilch: Prion-host cell interaction: importance of prion interference with host cell cholesterol metabolism for persistent prion propagation

Michael James: Structure-guided design and biological validation of PrPC stabilization by small compounds using a novel multi-site targeting approach

Debbie McKenzie: Cell tropism of prion strains

Debbie McKenzie: Determining the diversity of chronic wasting disease agents

Brenda Parlee: Tracking changes in wildlife health - traditional knowledge and Aboriginal peoples

Hermann Schätzl: A new anti-prion strategy: modulation of Prnp transcriptional activity (funding partnership with ALMA)

Hermann Schätzl: Between propagation and clearance: the dual role of autophagy in prion infection

Hermann Schätzl: Limitingzoonoticpotentialand spread of chronic wasting disease by wild-life vaccination

Valerie Sim: Prion disease therapies trial (funding partnership with ALMA)

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Pictured to the right: Satyabrata Kar (right) with graduate student Jiyun Chung

Alberta: Contributing to Global Knowledge

The Alberta Prion Research Institute hosts and attends local and international events to facilitate the exchange of knowledge about prion research between Albertans and the scientific community. The Alberta Prion Research Institute also supports its researchers and students to attend scientific, public and industry meetings to discuss their research findings.

It is important to keep Albertans informed about the research being done in Alberta to diagnose, treat and prevent prion and prion-like diseases that have posed and continue to pose serious socioeconomic challenges in Alberta. It is equally important to keep the international research community informed about the innovative research being done in Alberta.

Industry Connections

The beef, cattle, cervid and sheep industries have all been affected by prion diseases. Prion diseases have significant socioeconomic impacts on these industries. The Executive Director of the Alberta Prion Research Institute regularly meets with industry members to discuss their concerns and to provide them with information about the research currently being done with the aim to help industry.

StefanieCzubandTimMcAllisterwerebothawardedwithaQueenElizabethIIDiamondJubileeMedalfortheir research contributions to the Canadian beef industry. Researchers have also been invited as guest lecturers at meetingswithindustrymembersandelectedofficials.Dr. Czub presented on bovine spongiform encephalopathy andchronicwastingdisease(CWD)atameetingbetweenrural caucus and industry members. Scott Napper gave a talk on vaccine development for CWD at The Wildlife Society20thAnnualMeetinginMilwaukee,Wisconsin.

Alberta Beef Industry ConferenceFEBRUARY19-21, 2014REDDEER,ALBERTA

Alberta Prion Research Institute management attended the annual conference to meet with industry members and to highlight prion research being done in Alberta to benefit the beef and cattle industries. This annual conference provided the opportunity to continue the ongoing partnership with industry to discuss how science and research address the issues posed by prion diseases in animals.

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TheLegacyofPrionSciencein AlbertaMAY21, 2013UNIVERSITYOFALBERTA

May20,2003wasadarkdayinAlberta’sagriculturalhistory.Theconfirmation of a domestic cow infected with bovine spongiform encephalopathy(BSEorcommonlyknownasmadcowdisease)onanAlbertafarmhaddevastatingsocioeconomicimpactsonAlberta’sbeef and cattle industries. Dozens of countries around the world closed their borders to Canadian beef. Estimated economic losses as a result of that single discovery are as high as $11 billion.

The Alberta Prion Research Institute is a lasting and positive legacy to come out of the BSE crisis. It was formed with a mandate to build a better understanding of prions and prion diseases and to build the scientific capacity in Alberta. This event noted the crisis while celebrating the scientific capacity that has been built in Alberta and the benefits to Albertans and industry from the prion research being done in the province.

The Government of Alberta has invested over $42 million to date in prion research since the Alberta Prion Research Institute was formed in April 2005. A significant portion of this research is focused on issues that concern the beef and cattle industries. Researchers have made discoveries that might add potential commercialandindustrialvaluetospecifiedriskmaterials(SRM)andtoreducetheinfectivityofSRM.Researchersarestudyingtheatypical or spontaneous forms of BSE that still occur today. The Alberta Prion Research Institute is committed to working with its partner agencies and researchers to find solutions to the serious challenges that affect the beef and cattle industries.

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Photo courtesy of Judd Aiken

Some of the best prion disease research goes on in this province, and why not? We’ve had cases of mad cow disease, and we are watching the slow but inexorable spread of chronic wasting disease. Add to that the tantalizing connections between diseases like these and Alzheimer’s and Parkinson’s, and you couldn’t make a better case for supporting this work.

J AY I N G R AM

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The Prion DiariesOCTOBER 28-30, 2013UNIVERSITYOFALBERTA,UNIVERSITYOFCALGARYANDKEYANOCOLLEGE

The Alberta Prion Research Institute once again teamed up with Jay Ingram, former host of Daily Planet and Quirks and Quarks, to host The Prion Diaries. Over 300 Albertans attended public lectures in Edmonton, Calgary and FortMcMurraytolearnmoreaboutprionsandpriondiseases.FourresearchersjoinedMr.Ingramonthetour:StefanieCzub(UniversityofCalgary and Canadian Food Inspection Agency; HermannSchätzl(UniversityofCalgary);ValerieSim(UniversityofAlberta);andHolgerWille(UniversityofAlberta).Mr.Ingramand the researchers provided entertaining and informative insight into the mystery of prions and the importance of prion research.

A LESSON ON PRIONS

Prions have dropped off the popular media radar in recent years, and yet most of us have certainly heard of at least one prion disease: bovine spongiform encephalopathy (BSE)or,morecommonly,madcowdisease.Thisdiseaseis caused by prions. These are misfolded proteins that accumulate in the brain and result, invariably, in death. Prions are responsible for neurological disorders such as Creutzfeldt-Jakob disease in humans. Evidence suggests that the protein misfolding that occurs in diseases such as Alzheimer’s,Parkinson’sandLouGehrig’smightbesimilarto prion protein misfolding.

I was so impressed by this lecture. It demonstrated a uniquewayinwhichscientistscanhighlighttherelevanceof their research to the public. This lecture seamlessly blendedIngram’sknackforcaptivatingaudiencesthroughstorytelling with expertise from the researchers who work with the disease. At numerous times during the talk, Ingram would defer to one of three experts sitting in the crowd. They would broadly discuss their research or their perspectives and experiences in treating and diagnosing the disease. In this way the lecture was both informative, but also highlighted the importance of ongoing research and understanding of prions and the diseases they cause.

The format created a sense of urgency for more research. It clearly demonstrated what science knows and what science doesn’tknowaboutthedisease.Thistalkillustratedhowresearchers and communicators can work together to make science engaging and accessible to a broad audience.

By Sydney Rudko, December 2013 graduate with honours from the University of Alberta Bachelor of Science Immunology and Infection program

Megan Tsang @TsangLikeABirdLearnedsomuchfromthe#PrionDiariestalkby @jayingram @PrionInstitute! Thank you for coming to speak!

Chelsea Matisz @ChelseaMatisz@jayingram Thanks for a great telling of the evolvingprionstory,forthewritingtips,&forbeing overall awesome and approachable.

Sydney Patricia @SPResistantAmazing talk by @jayingram and the researchers of the @PrionInstitute! Perfect blend of science communication and current research.

McMurray Musings @McMurrayMusings The presentation from the neurologist re prion disease is spellbinding – fascinating story but an even better storyteller! @PrionInstitute

O N T W I T T E R

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PRION 2013MAY25-29, 2013BANFF, ALBERTA

The Alberta Prion Research Institute hosted PRION2013,theworld’slargestannualscientific meeting on prion and prion-like protein misfolding diseases. Researchers, students, postdoctoral fellows, clinicians and policy makers from the neurological and prion fields gathered to focus on what can be done collaboratively to work towards discoveries, diagnostics and treatments for debilitating and fatal neurological diseases in humans and animals. Approximately 400 people attended.

PRION 2013 focused on four themes: socioeconomic impact; protein structure and biology; prion diseases in animals; and prion diseases and prion-like diseases in humans. The scientific program included four-and-a-half days of workshops and scientific lectures. This open scientific congress welcomed researchers across a wide spectrum of disciplines from sociology to biology, creating a broad approach to solving problems in the prion research field.

ShirleyMcClellan,formerDeputyPremierandMinisterofAgriculture,FoodandRuralDevelopment, made a special presentation at the meeting.Dr.McClellanishighly-respectedbyAlbertans and Canadians for her role in leading Alberta through the 2003 bovine spongiform encephalopathy(BSE)crisis.Sheandhercolleagues in government were adamant about the need to build the scientific capacity in Alberta to study BSE and other prion diseases. This commitment resulted in the formation of the Alberta Prion Research Institute.

Virginia M.-Y. Lee meeting with graduate students and postdoctoral fellows to discuss their research

Nobel laureate Stanley Prusiner delivering a keynote address

Shirley McClellan making a special presentation on her role in leading Alberta through the 2003 BSE crisis

Mathias Jucker speaking about his Alzheimer’s pathology research

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PRION 2013 also included an industry breakfast, which brought together industry members and researchers to discuss how they can work together to address the issues that prion diseases have on the livestock industries. The breakfast engaged industry members in a discussion about the research currently being funded by the Alberta Prion ResearchInstituteandtheAlbertaLivestockandMeatAgency.

The development of young scientists was a focus of the meeting. Graduate students and postdoctoral fellows attended a science communications workshop with notable science communicator, Jay Ingram. New to the program was the opportunity for trainees to meet with senior researchers in small roundtable sessions. Dozens of trainees took advantage of the opportunity to discuss their research with and receive career advice from internationally-respected prion and protein misfolding scientists.

Almost 200 researchers, graduate students and postdoctoral fellows from around the world presented posters

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Alberta Prion Research Institute ScientificMeetingNOVEMBER18-19, 2013EDMONTON,ALBERTA

The Alberta Prion Research Institutehosted a scientific meeting for researchers and trainees to provide updates on research projects. The focus of projects varied from an integrated risk management framework for chronic wasting disease to a blood test for Alzheimer’sdiseasetomolecularoriginsofprotein misfolding diseases. The wide range of topics is a clear indication of just how far reaching and mysterious the prion protein is and what more we need to know to deal with these diseases.

DanielleGushue,aUniversityofAlbertaMastersofSciencestudentworkingwithJuddAikenandDebbieMcKenzie,presentedher first scientific talk at the meeting. She isworkingwithDrs.AikenandMcKenzieon a project looking for biomarkers for earlier clinical diagnosis of prion diseases. Currently, prion diseases are diagnosed in humans and animals months or weeks before death, sometimes even after death. Earlier detection of prion diseases might one day lead to more effective treatments. Danielle is one of many bright and highly-skilled trainees working on research funded by the Alberta Prion Research Institute.

Danielle Gushue Photo courtesy of Judd Aiken

The Alberta Prion Research Institute partnered with the Rio de Janeiro Research Federation(FAPERJ)andtheSãoPauloResearchFederation(FAPESP),twoofthelargest state research federations in Brazil, to host the Brazil-Canada Workshop on Advances in the Science of Prion and Prion-likeMisfoldingDiseases.Thisworkshopwas the start of a prion research partnership between Alberta and Brazil. Thirteen researchers from Brazil and 12 researchers from Canada presented their latest findings on prion and protein misfolding diseases. Eighteen young researchers from Alberta and British Columbia presented scientific posters.

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Jerson Silva, Scientific Director, FAPERJ, presenting on prion-like aggregation of an important regulatory protein in cancer

Muchofthediscussionsfocusedonfuturecollaborations between researchers and exchange opportunities for students and postdoctoral fellows from prion research labs in Alberta and Brazil to broaden their international work experiences. Brazil is an emerging leader in prion and protein misfolding science. The Alberta Prion Research Institute, FAPERJ and FAPESP are committed to pursuing research collaborations to share scientific knowledge and leverage the impact of the prion research being done in Alberta and Brazil. A second research workshop will be held in Brazil in the autumn of 2014.

Brazil-Canada Workshop on Prion and Prion-like DiseasesMARCH18-19, 2014, BANFF, ALBERTA

Stan Blade, CEO, Alberta Innovates Bio Solutions, (left) speaking with Vilma Martins, Research Director, A.C. Camargo Cancer Center

More than 50 researchers and trainees from Brazil and Canada attended the workshop

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The Alberta Prion Research Institute provided a $25,000 prize for the best peer-reviewed paper published by a young researcher in the past five years. An international panel awarded the prize to Fei Wang, Research Associate at The Ohio State University,forhispaper‘Generatingaprionwith bacterially expressed recombinant prionprotein’,publishedinScience. This paper was deemed to be most likely to have a profound impact on prion research.

Dr. Wang and his collaborators essentially created an infectious prion protein from scratch. By creating a prion without using animal cells as a base, Dr. Wang and his research team were able to show that the infectivity in animal prion disease results from an altered structure of the prion protein. This work supports the prion hypothesis Nobel laureate Stanley Prusiner firstproposedin1982.

Dr. Wang presented lectures on his winningpaperattheUniversityofCalgaryandtheUniversityofAlberta.Healsomet one-on-one with researchers at both universities to discuss his work and how this might have an impact on the research being done in Alberta. Dr. Wang toured the Centre for Prions and Protein Folding DiseasesattheUniversityofAlbertaand was very impressed by the facility. Dedicated prion research labs of this size andwithsomuchspecializedequipmentare not common around the world.

Nine young researchers from around the world were nominated for the prize. This was the second time the Alberta Prion Research Institute presented the International Young Researcher Prize. Nathan Deleaut from Dartmouth College received the first prize in 2010.

Alberta Prion Research Institute International Young Researcher PrizeNOVEMBER 6-7, 2013UNIVERSITYOFCALGARYANDUNIVERSITYOFALBERTA

I N T E RN AT I ONA L YOUNG R E S E A RCH E R P R I Z E PAN E L

Adriano Aguzzi,UniversityHospitalZurichHerbert Budka,MedicalUniversityofViennaJean-Philippe Deslys, Atomic Energy CommissionLinda Detwiler,MississippiStateUniversityCorrine Lasmézas, The Scripps Research Institute

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Pictured to the left: Fei Wang

In February 2014, Alberta Prion Research Institute staff and funded researchers participated in the filming of a documentary about CJD and its impact on patients, caregivers and loved ones. The focus of the Alberta segment was on the basic structure of prions and research being done in Alberta. Currently, there are no cures or effective long-term treatments for prion diseases. The Alberta Prion Research Institute funds research with the goal of better understanding human prion diseases andimprovingthequalityoflifeforthose suffering from them.

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Creutzfeldt-Jakobdisease(CJD)is the most common of human prion diseases, affecting one inone million.

The Alberta Prion Research Institute has a strong relationship with the CJD Foundation, a support and advocacy organization for patients and families affected by prion diseases. The CJD Foundation, based in New York City, also funds basic research on prion diseases. Closer to home, the CJD Foundation provides much-appreciated and necessary support to Canadians affected by prion diseases, as Canada does not have its own support group.

Alberta Prion Research Institute staff attended the CJD Foundation Family Conference in July 2013 to provide an update on research being done in Alberta. The CJD Foundation is part of the CJD International Support Alliance, which includes similar organizations around the globe. Florence Kranitz, President of the CJD Foundation, and Suzanne Solvyns, Director of the CJD Support Network in Australia, gave a special presentation at PRION 2013 in Banff, Alberta about the work of the CJD International Support Alliance and the patients and families they represent.

Suzanne Solvyns (left) and Florence Kranitz

Creutzfeldt-Jakob Disease Awareness and Support

Expanding Horizons: The Next Generation

The Alberta Prion Research Institute is committed to the development and training of young researchers. Over 360 highly-skilled research technicians, postdoctoral fellows and graduate students have been trained in funded labs since April 2005. The research being done in Alberta labs would not be possible without the hard work and dedication from graduate students and postdoctoral fellows.

Expanding Horizons is a professional development program that provides research trainees with access to coaching and mentoring. Providing young researchers with training outside of the lab setting will make them more well-rounded and knowledgeableresearchers.Itwillalsoequipthemwith valuable skills that are transferable to careers in government, industry or other sectors.

Seminars focus on both their career development in research and other careers that they might undertake such as those in industry and policy making. Trainees will also receive courses focused on research management and science communications. Seminars offered in 2013-14 focused on grants crafting and writing, career options in industry, interview skills, communications and media relations.

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Awards, Honours and Publications

Researcher Awards and Honours

• Stefanie Czub: 2013 ASTech Foundation Award for OutstandingLeadershipinAlbertaScience

• Stefanie Czub: Queen Elizabeth II Diamond Jubilee

MedalforResearchContributionstotheCanadianBeef Industry

• Sabine Gilch: Canada Research Chair in Prion

Diseases • Tim McAllister: Queen Elizabeth II Diamond

JubileeMedalforResearchContributionstotheCanadian Beef Industry

• Peter Stys: Royal Society of Canada Fellowship

Researchers, graduate students and postdoctoral fellows received several honours and published many papers in 2013-14. The Alberta Prion Research Institute is proud to work with such talented researchers and young scientists.

Trainee Awards and Honours

• Claudia Acevedo-Morantes (Holger Wille lab): 75th Anniversary Graduate Student Award, Faculty of Medicine&Dentistry,UniversityofAlberta

• Laura Ansell (Roger Thompson lab): Alzheimer

Society of Canada Research Program Doctoral Scholarship

• Derek Dee (Michael Woodside lab): Protein Science Young Investigator Travel Grant and Protein Society Finn Wold Travel Award, The Protein Society; Boston, USA

• Camilo Duque-Velasquez (Debbie McKenzie lab):

HonourableMentionPoster,AlbertaPrionResearchInstitute Prize, PRION 2013; Banff, Canada

• Kristen Marciniuk (Scott Napper lab): Honourable

MentionPoster,KineticsFoundationPrize,PRION2013; Banff, Canada

• Charles Mays (David Westaway lab): Junior Faculty

Award,Alzheimer’sandParkinson’sDiseasesCongress2013; Florence, Italy

• Charles Mays (David Westaway lab): First Place

Poster,UniversityofAlbertaDepartmentofMedicineResearch Day; Edmonton, Canada

• Robert Mercer (David Westaway lab): Third Place

Poster, Calreticulin Workshop 2013; Banff, Canada • A. Grant Norman (Valerie Sim lab): Universityof

Alberta Doctoral Recruitment Scholarship • Mridula Swayampakula (Michael James lab):

HonourableMentionPoster,AlbertaPrionResearchInstitute Prize, PRION 2013; Banff, Canada

• Mridula Swayampakula (Michael James lab):

UniversityofAlbertaPansyandGeorgeStrangeGraduate Scholarship

Stefanie Czub receiving the ASTech Foundation Award for Outstanding Leadership in Alberta Science

Photo courtesy of the ASTech Foundation

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W. T ED A L L I S ON • MichèleDuval,MatthewGilbert,D.EzekielWatson,TanjaZerulla,

Keith Tierney and W. Ted Allison;GrowthDifferentiationFactor6asa putative risk factor in neuromuscular degeneration; PLoS ONE

• ValerieFleisch,PatriciaLeighton,HaoWang,LauraPillay,R.Gary,Ritzel, Ganive Bhinder, Birbickram Roy, Keith Tierney, Declan Ali, Andrew Waskiewicz and W. Ted Allison; Targeted mutation of the gene encoding prion protein in zebrafish reveals a conserved role in neuron excitability; Neurobiology of Disease

• LauraPillay,LyndsaySelland,ValerieFleisch,PatriciaLeighton,CarolineCheng,JakubFamulski,R.GaryRitzel,LindseyMarch,Hao Wang, W. Ted Allison and Andrew Waskiewicz; Evaluating the mutagenic activity of targeted endonucleases containing a Sharkey FokI cleavage domain variant in zebrafish; Zebrafish

S T E FAN I E C ZU B • LiseLamoureux,SharonSimon,MargotPlews,ViolaRuddat,Simone

Brunet, Catherine Graham, Stefanie CzubandJ.DavidKnox;Urineproteins identified by two-dimensional differential gel electrophoresis facilitate the differential diagnoses of scrapie; PLoS One

• CatherineVrentas,JustinGreenlee,ThierryBaron,MariaCaramelli,Stefanie Czub and Eric Nicholson; Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay; BMC Veterinary Research

S A B I N E G I L CH • TheodoreJohn,Hermann Schätzl and Sabine Gilch; Early detection

of chronic wasting disease in urine of pre-symptomatic deer by real-timequaking-inducedconversionassay;Prion

M I CHA E L J AM E S • MridulaSwayampakula,PravasBaral,AdrianoAguzzi,Nat Kav and

Michael James; The crystal structure of an octapeptide repeat of the prionproteinincomplexwithafabfragmentofthePOM2antibody;Protein Science

• TizianaSonati,ReginaReimann,JeppeFalsig,PravasBaral,TracyO’Connor,SimoneHornemann,SineYaganoglu,BeiLi,UliHerrmann,BarbaraWieland,MridulaSwayampakula,MuhammadHafizurRahman,Dipankar Das, Nat Kav,RolandRiek,PawelLiberski,Michael James and Adriano Aguzzi; The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein; Nature

• PravasBaral,MridulaSwayampakula,ManojKumarRout,Nat Kav,LeoSpyracopoulos, Adriano Aguzzi and Michael James; Structural basis of prion inhibition by phenothiazine compounds; Structure

T IM MCA L L I S T E R • ShanweiXu,JayRasmussen,NingDing,Norman Neumann,Mohamed

Gamal El-Din, Miodrag Belosevic and Tim McAllister; Inactivation of infectious prions in the environment: A mini-review; Journal of Environmental Engineering and Science

• ShanweiXu,TimReuter,BrandonGilroyed,LisaTymensen,YongxinHao,XiyingHao,Miodrag Belosevic,JerryLeonardandTim McAllister;Microbialcommunitiesandgreenhousegasemissionsassociated with the biodegradation of specified risk material in compost; Waste Management

• JayRasmussen,BrandonGilroyed,TimReuter,SandorDudas,Norman Neumann, Aru Balachandran, Nat Kav, Stefanie Czub and Tim McAllister; Can plants serve as a vector for prions causing chronic wasting disease?; Prion

DE B B I E M CK ENZ I E • AllenHerbst,PamelaBanser,CamiloDuqueVelasquez,CharlesMays,

Valerie Sim, David Westaway, Judd Aiken and Debbie McKenzie; Infectious prions accumulate to high levels in non-proliferative C2C12 myotubes; PLoS Pathogens

S C O T T N A P P E R • KristenMarciniuk,RyanTaschukandScott Napper; Evidence for

prion-like mechanisms in several neurodegenerative diseases: potential implications for immunotherapy; Clinical and Developmental Immunology

• PeterHedlin,RyanTaschuk,AndrewPotter,PhilipGriebelandScott Napper; Detection and control of prion diseases in food animals; ISRN Veterinary Sciences

• ClaudiaMadampage,PekkaMäättänen,KristenMarciniuk,RobertBrownlie, Olga Andrievskaia, Andrew Potter, Neil Cashman, Jeremy LeeandScott Napper;BindingofbovineT194APrPC by PrPSc-specific antibodies: potential implications for immunotherapy of familial prion diseases; Prion

Research Publications

The Alberta Prion Research Institute provided funding for research that led to many discoveries and publications in 2013-14.

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• PekkaMäättänen,RyanTaschuk,LiRoss,KristenMarciniuk,LisaBertram, Andrew Potter, Neil Cashman and Scott Napper; PrPSc-specific antibodies do not induce prion disease or misfolding of PrPC in highly susceptible Tga20 mice; Prion

• ClaudiaMadampage,KristenMarciniuk,PekkaMäättänen,NeilCashman,AndrewPotter,JeremyLeeandScott Napper; Nanopore analysis reveals differences in structural stability of ovine PrPC proteinscorrespondingtoscrapiesusceptible(VRQ)andresistance(ARR)genotypes;Prion

• KristenMarciniuk,PekkaMäättänen,RyanTaschuk,T.DeanAirey,Andrew Potter, Neil Cashman, Philip Griebel and Scott Napper; Development of a multivalent, PrPSc-specific prion vaccine through rational optimization of three disease-specific epitopes; Vaccine

HERMANN S CH ÄT Z L • YuzuruTaguchi,ArlaMistica,TetsuyukiKitamotoandHermann

Schätzl; Critical significance of the region between helix 1 and 2 for efficientdominant-negativeinhibitionbyconversion-incompetentprion protein; PLoS Pathogens

• YuzuruTaguchiandHermann Schätzl; Identifying critical sites of PrPc-PrPSc interaction in prion-infected cells by dominant-negative inhibition; Prion

• Hermann Schätzl; Cellular mechanisms of propagation and clearance; Prions and Prion Diseases (ed. Wen-Quan Zou and Pierluigi Gambetti)

VA L E R I E S I M • LeonardoCortezandValerie Sim; Implications of prion

polymorphisms; Prion • JitendraKumarandValerie Sim; D-amino acid-based peptide

inhibitors as early or preventative therapy in Alzheimer disease; Prion

• JodyCampeau,GengshuWu,JohnBell,JayRasmussenandValerie Sim; Early increase and late decrease of Purkinje cell dendritic spine density in prion-infected organotypic mouse cerebellar cultures; PLoS ONE

• LeonardoCortez,JitendraKumar,LudovicRenault,Howard Young and Valerie Sim;MouseprionproteinpolymorphismPhe-108/Val-189affectsthekineticsoffibrilformationandtheresponseto seeding: evidence for a two-step nucleation polymerization mechanism; The Journal of Biological Chemistry

• PatrickWalsh,GillianVanderlee,JasonYau,JodyCampeau,Valerie Sim, Christopher Yip and Simon Sharpe; The mechanism of membrane disruption by cytotoxic amyloid oligomers formed by PrP(106-126)isdependentonbilayercomposition;The Journal of Biological Chemistry

DAV I D W E S TAWAY • RobertMercer,LiMa,JoelWatts,RobertStrome,Serene

Wohlgemuth,JingYang,NeilCashman,MichaelCoulthart,GeroldSchmitt-Ulms,Jack Jhamandas and David Westaway; The prion protein modulates A-type K+ currents mediated by Kv4.2 complexes through dipeptidyl aminopeptidase-like protein 6;The Journal of Biological Chemistry

• CharlesMays,JanakyCoomaraswamy,JoelWatts,JingYang,KerryKo,BobStrome,RobertMercer,SereneWohlgemuth,GeroldSchmitt-UlmsandDavid Westaway; Endoproteolytic processing of the mammalian prion glycoprotein family; FEBS Journal

• CharlesMays,ChaeKim,TracyHaldiman,JacquesvanderMerwe,AgnesLau,JingYang,JenniferGrams,MicheleDiBari,RomoloNonno,GlennTelling,QingzhongKong,JanLangeveld,Debbie McKenzie, David Westaway and Jiri Safar; Prion disease tempo determined by host-dependent substrate reduction; The Journal of Clinical Investigation

HOLG E R W I L L E • CosminPocanschi,SepehrEhsani,MohadesehMehrabian,

Holger Wille, William Reginold, William Trimble, Hansen Wang, AdelindaYee,CherylArrowsmith,ZoltánBozóky,LewisKay,JulieForman-Kay,JamesRiniandGeroldSchmitt-Ulms;TheZIP5ectodomainco-localizeswithPrPandmayacquireaPrP-likefoldthat assembles into a dimer; PLoS One

DAV I D W I S H A RT • Nataraj Pagadala, Trent Bjorndahl, Nikolay Blinov, Andriy

Kovalenko and David Wishart;Moleculardockingofthiaminereveals similarity in binding properties between the prion protein and other thiamine binding proteins; Journal of Molecular Modeling

M I CHA E L WOOD S I D E • HaoYu,DerekDeeandMichael Woodside; Single-molecule

approaches to prion protein misfolding; Prion

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International Research Advisory CouncilLinda Detwiler (Chair),MississippiStateUniversity

Corinne Lasmézas, The Scripps Research Institute

Jean Manson, The Roslin Institute

Ralph Matthews,UniversityofBritishColumbia

Detlev Riesner,Heinrich-Heine-UniversitätDüsseldorf

Glenn Telling,ColoradoStateUniversity

Inga Zerr,Georg-August-UniversitätGöttingen

The Alberta Prion Research Institute also acknowledges and thanks previous members of the International Research Advisory Council for their years of service, scientific advice and dedication.

Adriano Aguzzi,UniversityHospitalZurich

Bertram Brenig,UniversityofMunich

Byron Caughey,NationalInstitutesofHealthRockyMountainLaboratories

Jean-Philippe Deslys, Atomic Energy Commission

Chris Dobson,UniversityofCambridge

Richard Johnson, The Johns Hopkins Hospital

Kiyotoshi Kaneko,TokyoMedicalUniversity

Joseph Martin,HarvardUniversity

Danny Matthews,AnimalHealthandVeterinaryLaboratoriesAgency

Michael Miller, Wildlife Research Center

J. Mark Sutton, Health Protection Agency

Charles Weissmann, The Scripps Research Institute

John Williams, Parco Tecnologico Padano

Kazuya Yamanouchi, Nippon Institute for Biological Sciences

The Alberta Prion Research Institute relies on members of its International Research Advisory Council, an independent group of international prion and protein misfolding experts, to provide its most senior level of scientific advice. The Alberta Prion Research Institute thanks the members of the International Research Advisory Council for their scientific expertise and commitment to excellence in prion research.

A L B E RTA P R I ON R E S E A RCHI N S T I T U T E S TA F F

KEVIN KEOUGHExecutive Director

RON CLARKSONDirector, Prion Programs

CINDY LIEUCommunicationsManager

PEARL DOUGLASOperations Specialist(May 2009 to December 2013)

MIKIE FONGOperations Specialist (January 2014 to present)

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Prion 101Prion diseases are fatal, transmissible diseases associated with a sponge-like degeneration of brain tissue in humans and animals. For these reasons, prion diseases are also called transmissible spongiform encephalopathies or TSEs. Prion diseases are transmissible from host to host of a single species and sometimes from one species to another.

The following are some examples of prion disease and the mammals they affect:

• Bovinespongiformencephalopathy(BSEorcommonlyknownasmadcowdisease);

• Chronicwastingdisease(deer,elkandmoose);• Creutzfeldt-Jakobdisease(humans);• FatalFamilialInsomnia(inheriteddiseaseofhumans);• Scrapie(sheepandgoats);and• VariantCreutzfeldt-Jakobdisease(vCJD;humans,

acquiredfromeatingbeefinfectedwithBSE).

Veryrecentevidencesuggeststhattherearesimilaritiesin the ways in which the proteins misfold in prion diseases and how the process happens in more common human neurodegenerative diseases and dementias. Other neurological diseases are also associated with different misfolded proteins:

• Alzheimer’sdisease;• Amyotrophiclateralsclerosis(ALSorcommonly

knownasLouGehrig’sdisease);• Frontotemporaldementias;• Huntington’sdisease;and• Parkinson’sdisease.

What are prions and prion diseases?

A prion is a class of protein found in the brains of mammals that when misfolded (becomes an abnormal shape) causes various fatal infectious diseases of the nervous system. All proteins fold and can misfold, but not all misfolded proteins cause disease.

Prions are infectious prion proteins in a misfolded form. Prion diseases are unique. There is no genetic material in proteins that can mutate and replicate to cause infections and diseases. Viruses and bacteria cause diseases, but those contain genetic material such as DNA or RNA.

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Photo courtesy of Judd Aiken

Where Are We Today?

The World Organisation for Animal Health (OIE – historically Office international des épizooties) categorizes countries based on their risk for occurrence of bovine spongiform encephalopathy (BSE). Canada is categorized as being a controlled risk for BSE. To apply for negligible risk status, a country has to have no cases for 11 years after the birth year of the youngest animal diagnosed. The Canadian Food Inspection Agency confirmed a diagnosis of BSE in a six-year-old beef cow from Alberta in February 2011, the 18th and last known case of BSE in Canada. Canada will be eligible to apply for negligible risk status in 2015.

InAlberta,205casesofchronicwastingdisease(CWD)have been confirmed in wild deer since the disease first appeared in the province in September 2002. In November 2012, the first case of CWD in a moose in Canada was confirmed. Chronic wasting disease is a growing concern as the disease continues to spread in Alberta and Saskatchewan. It is also of concern because CWD prions are shed into the soil through the saliva, urine, feces and decomposed carcasses of infected animals, which can lead to infection of more animals. Prions can live in the soil for years, perhaps even decades, making the spreadofCWDthatmuchmoredifficulttocontrol.

The incidence of human neurodegenerative diseases is increasing with the aging population. This will result in increased demands on the healthcare system and the caregivers of those with neurodegenerative diseases and dementias. Evidence suggests that prion diseases share some characteristics in common with neurodegenerative diseasessuchasAlzheimer’s,Parkinson’sandLouGehrig’s.Researchers are increasingly looking to prions as a possible model to explain how other protein folding diseases spread throughout the brain.

The Alberta Prion Research Institute continues to support research on animal prion diseases such as BSE and CWD andhumanneurodegenerativediseasessuchasAlzheimer’sandLouGehrig’s.Itinvestsinfundamentalandappliedresearch that takes an interdisciplinary approach to solving the prion mystery. It is partnering with researchers, governments, industry and other agencies to work towards discoveries, diagnostics and treatments for debilitating and fatal neurological diseases in humans and animals.

The Government of Alberta and the Alberta Prion Research Institute are committed to prion and protein misfolding research for the benefit of Albertans. 32

What Comes Next? Much is still unknown about prions and prion diseases. �ere are still many questions to answer. �ere are risks that still remain. �e most recent case of classical BSE (the form that can infect humans) was discovered in Alberta in early 2011. A somewhat di�erent form of BSE has been found to occur spontaneously. Researchers have not yet found a way to stop or slow down the spread of chronic wasting disease. Reliable and inexpensive live testing of prion diseases in animals and humans does not exist. Finding treatments, cures and means of prevention for neurodegenerative diseases and dementias is of increasing urgency with an aging population.

�e Alberta Prion Research Institute is committed to the prevention, mitigation and treatment of prion and prion-like protein misfolding diseases in animals and humans. It exists to build understanding of these mysterious infectious agents known as prions and to build the scienti�c capacity in Alberta. In terms of prion research where experiments take months or even years to complete, nine years is a short period of time to have established and built Alberta’s signi�cant research capacity in prion and protein misfolding diseases since the formation of the Alberta Prion Research Institute in April 2005.

Alberta is in a position to capitalize on the world-class scientific capacity that has been built in the province since April 2005. Alberta has some of the best prion researchers and some of the best prion research facilities to help solve the prion mystery.

The advances that have been made in prion science right here in Alberta would not have been possible without the Government of Alberta’s investment and commitment to research through the formation of the Alberta Prion Research Institute.

Researchers in Alberta have made significant contributions to the prion and protein misfolding fields with funding from the Government of Alberta and the Alberta Prion Research Institute. These are just a few of them. Visit prioninstitute.ca to learn more about the global impact of the Alberta investment.

Alberta Investment, Global Impact.

May 2003 Discovery of the �rst domestic cow infected with bovine spongiform encephalopathy has devastating impacts on Alberta’s economy and the beef and cattle industries

April 2005 Government of Alberta creates the Alberta Prion Research Institute with funding of $35 million over seven years for prion and protein misfolding research

2006 Design and building of the Centre for Prions and Protein Folding Diseases at the University of Alberta begins

2006 �e �rst Alberta Prion Research Institute funding grants are awarded

2009 Funding provided to the University of Calgary to build a new prion research facility

2009 Jan Braun and her team identify three proteins that regulate the folding of essential synaptic proteins

2009

David Wishart and Michael Woodside develop techniques to use optical tweezers to pull apart single protein molecules

2010 Stefanie Czub and her colleagues discover a biomarker that could indicate the presence of BSE in cattle

2007 David Westaway and his collaborators de�ne a mammalian glycoprotein called shadoo, the �rst discovery of a prion-like protein synthesized in the brain since the prion protein was identi�ed in the 1980s

2009 Frank Jirik and his colleagues develop animal models to study the normal function of the prion protein

2010 Judd Aiken and Debbie McKenzie discover variant strains of chronic wasting disease

2011 David Bressler leads a team that develops new methods to break down and reassemble speci�ed risk materials from cattle into safe, decontaminated parts that have potential commercial value

2010 Gerald Zamponi and his research team �nd that normal prion proteins protect brain cells from fatal chemical hyperactivity

2012 Tiejun Gao and Highmark Renewable Research Inc. develop a technology to turn organic waste into combustible and renewable biogas

2012 Miodrag Belosevic and Norman Neumann discover that prions are highly susceptible to ozone inactivation

2012 Tim McAllister and his colleagues �nd a way to reduce the infectiousness of speci�ed risk materials in cattle during composting

2012 �e University of Calgary recruits Sabine Gilch and Hermann Schätzl, increasing the total to 11 world-class researchers recruited to Alberta since 2005

2012 Evelyn Merrill and her colleagues in the Governments of Alberta and Saskatchewan learn how mule deer population density could reduce the spread of chronic wasting disease

April 2012 Government of Alberta renews funding of the Alberta Prion Research Institute with $15 million through March 2015

2012 Launch of the Alberta Alzheimer Research Program in partnership with the Alzheimer Society of Alberta and Northwest Territories

2013 Valerie Sim and her research collaborators �nd conditions under which prions can assume slightly di�erent shapes in the brain

2013 David Westaway and his collaborators discover that the cellular prion protein is reduced early on in many types of prion infections, suggesting a host protective response and a new point of intervention to slow disease progress

2013 Michael James and his colleagues determine a 3-D structure of the prion to identify a site where antibodies could bind to the prion molecule

2013 Launch of the Expanding Horizons professional development program for young scientists

Funded by the Government of Alberta

Phone: +1 780-427-1956Fax: +1 780-427-3252Email: prion@albertainnovates.caTwitter: @PrionInstitute

ALBERTA PRION RESEARCH INSTITUTE

Alberta Prion Research Institute1800 Phipps-McKinnon Building10020 - 101A AvenueEdmonton, Alberta, Canada T5J 3G2

prioninstitute.ca

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