PrioNews | December - March 2012: Volume II, Issue 7

Launching the careers of the next generation

see page 3

Feature Storiesfrom PrioNet's science writing program see page 8

Neil Cashman receives prestigious award PrioNet is pleased to announce that Scientific Director Neil Cashman has been presented with the Genome BC Award for Scientific Excellence. This award recognizes individuals who have made outstanding contributions to the development of British Columbia’s life sciences industry across all sub-sectors, from biopharmaceuticals and medical devices to bioproducts and bioenergy—sectors which are critical to the economic future of the province and country. The award will be presented at the Life Sciences BC annual awards dinner on April 19, 2012 in Vancouver. Congratulations, Neil! ■

PrioNewsPrioNet Canada’s Triannual Newsletter

Volume II, Issue 7December 2011 - March 2012www.prionetcanada.ca

This issue of PrioNews marks the final newsletter for PrioNet as a Network of Centres of Excellence. It is with great sadness that we witness our Network come to a close in 2012, but we are confident the great research we have helped support over the last seven years will flourish for many years to come through new opportunities.

PrioNet Canada was a $35 million initiative launched in 2005 by the Government of Canada’s Networks of Centres of Excellence (NCE) program established to coordinate Canada’s research and policy response to the impact of prion diseases in Canada. Since that time, PrioNet has conducted fundamental, applied, and social research to help solve the food, health safety, and socio-economic problems associated with prion diseases such as BSE, CWD, and CJD. We recently expanded our mission to include groundbreaking research implicating prion disease mechanisms in other neurological disorders such as Alzheimer’s and Parkinson’s diseases, and amyotrophic lateral sclerosis (ALS), largely in part driven by PrioNet investigators.

PrioNet exemplified a functional, cohesive, and responsive network supporting research projects and partnerships to deliver maximum impact. PrioNet developed the foundation, partners, capacity and expertise to convert major health and economic burdens from prion and prion related disease into public policy and commercializable solutions for the benefit of Canada.

continued on next page

Message from PrioNet Canada

Research ReflectionsPrioNet’s seven year mission to build a network and develop solutions see page 4

PrionScienceBrazil & CanadaSÃO PAULO 2012 MARCH 7, 8

PrioNet’s achievements put Canada at the global forefront of prion research, made possible by its community of scientists, students, and other young professionals networking with stakeholders and partners. PrioNet’s approach of leveraging its multidisciplinary research program for maximum results, liaising synergistic activities with international partners, training highly skilled people for Canada’s workforce, and translating knowledge into practical solutions to derive socioeconomic benefits to Canadians was a uniquely Canadian solution that produced great results.

Like parts of a complex puzzle, PrioNet discoveries, assembled together, have helped to answer some of the major risk, socioeconomic, and biological questions surrounding prion and prion-like diseases. In the pages of this final newsletter, you will read a few selected examples of our success in our “Research Reflections” story.

On behalf of all Canadians who have benefited from these discoveries, PrioNet wishes to thank each and every member of the network community for their contributions over the last seven years. We know Canada will continue to benefit from the knowledge our network has created well into the future, and we look forward to seeing what remains to be discovered in this crucial field of research. ■

Dr. Neil Cashman, Scientific DirectorDr. Michelle Wong, Executive Director

Message from PrioNet Canada continued from page 1

2 PrioNews December 2011 - March 2012

Like parts of a complex puzzle, PrioNet discoveries, assembled together, have helped to answer questions surrounding prion and prion-like diseases.

A delegation of Canadian researchersrecently headed to São Paulo, Brazil, to help find solutionsto illnesses that know no borders: prion diseases and other neuro-degenerative disorders. The group of seven PrioNet scientists, from the University of British Columbia, University of Alberta, Western University, McGill University, and the National Research Council of Canada participated in the March 7-8 meetings. This exchange was organized to foster scientific and commercial collaboration between Canada and Brazil, and to create a tremendous opportunity to engage an international partner identified by the Canadian government as a key market for collaboration.

Nearly 75 attendees, including representatives from the Canadian Consulate, the Brazilian Ministry of Science, Technology and Innovation, International Science and Technology Partnerships Canada, the Foundation for Research Support of the State of São Paulo (FAPESP), private-sector companies, and scientists from Canada and Brazil, participated in a showcase of research developments in prion and neurodegenerative research. These developments ranged from the role of cell signaling in neurodegeneration to new molecular targets which when manipulated can help stop the progression of amyotrophic lateral sclerosis (ALS).

“It was a fantastic couple of days with great science being presented on both sides,” says PrioNet member Dr. Marco Prado, who was an instrumental part of this inaugural meeting. Dr. Prado is a scientist and professor at the Robarts Research Institute at Western University who was recruited to Canada from Brazil in 2008. “We hope this event will help build research collaborations required to secure global partnerships and attract talent to Canada to grow our knowledge economy.” ■

PrioNet partners with Brazil

On November 18th, 2011 in Edmonton and March 2nd, 2012 in Ottawa, PrioNet presented the SYPA Career Workshop and Fair events, opportunities for the network's graduate students, post-doctoral fellows, and young professionals to develop career skills, make connections with potential employers, and learn about the career experiences of other researchers.

The events welcomed a total of over 60 attendees, and included invited speakers from industry, academia, government, science communication, patent law, and non-governmental organizations. Attendees reported leaving the event feeling better informed about their career options, and better connected with potential employers, having taken advantage of the chance to interact with speakers at breaks and during the interactive fair component of the day.

PrioNet SYPA Council members.

December 2011 - March 2012 PrioNews 3

"The event opened my mind to other career opportunities outside academia."Launching the careers

of the next generation

"[It was] Comforting to talk to people who know what it's like to be a student and the uncertainties we face."

PrioNet thanks its dedicated SYPA Council for their hard work in helping to put these events together, enhancing the support that PrioNet provides the next generation of prion researchers. ■

"The speakers were all excellent and represented some of the best agencies and companies that could be potential employers."


RESEARCH REFLECTIONSPrioNet’s seven year mission to build a network and develop solutionsby Alison Palmer

A robust prion research network in Canada that is established as a world leader in prion science. The kind of research capacity that is worth far more than the sum of its parts. A community of trainees poised to transform this important area of research. This is the legacy that PrioNet Canada leaves behind.

In just seven years, this network has created the kind of knowledge that will continue to benefit Canadians well into the future. A selection of these successes are presented here as a reflection on the network’s discoveries, growth, and interconnectedness.

This network influenced Canadian policymakers to adopt a framework on the management of BSE

Dr. Daniel Krewski, University of Ottawa

Risk communication and knowledge transfer

have been two cornerstones of PrioNet’s research

program. Led by Dr. Daniel Krewski, Director of

the R. Samuel McLaughlin Centre for Population

Health Risk Assessment at the University of Ottawa

and Associate Scientific Director of PrioNet, the

BSE Integrated Risk Management Framework

(IRMF) was developed to help inform Canadian and

international policy makers on the risk assessment

and management of BSE. This framework gives

policymakers the capacity to quantitatively estimate

the potential of disease spread in cattle and the

extent of human exposure. The IRMF provides

clear guidance on how to maintain Canada’s BSE

risk status, which promises to improve Canada’s

reputation in the international beef trade.

“A few years ago, before PrioNet, Canada was completely peripheral in prion research. There were a couple of excellent teams or groups…. Other than that, nobody had heard about Canadian prion research. This has changed completely. Now, clearly, Canada has become central in prion research. There are lots of good groups and lots of coordinated efforts. You can tell immediately.”

– International researcher at PRION 2011 in Montreal

PrioNet by the numbers Over its seven year mandate, PrioNet Canada has:

• Built a prion research community in Canada:

> QuadrupledthenumberofCanadianprion

researchers,from29in2005to120in2012

> Engaged120scientists,41national

andinternationalcollaborators,61differentpartners,

and16Canadianuniversitiesandinstitutionsin2012

• Advanced our understanding of prion diseases:

> Sawaseven-foldincreaseinprionresearchprojects,

from7in2005to54in2012

> Producedover680publications

• Trained the next generation of research leaders:

> Engagedover300graduatestudents,post-doctoral

fellowsandyoungprofessionals

> Grantedover225trainingawards

• Facilitated the exchange of knowledge:

> Heldatotalof65events,31national

and34international,10ofwhichwerepart

oftheNCE’sInternational Partnerships Initiative

> Garneredover370mediamentionsacrossonline

andprintnews,radioandtelevision


“PrioNet has done a fantastic job of bringing together researchers in different fields and creating a true network. I personally have several new and fruitful collaborations that stem directly from involvement in PrioNet.”

– PrioNet scientific member

Dr. David Bressler,University of Alberta

Dr. Trent Bollinger,University of Saskatchewan

Dr. Norman Neumann, University of Alberta

“PrioNet is a model I am envious of and wish we had in the States.”

– Prion researcher from the United States

This network developed strategies to mitigate the environmental impacts of BSE and CWD

PrioNet member Dr. David Bressler and his team

from the University of Alberta, in partnership with

Sanimax, have converted specified risk materials

(by-products from the beef industry) into useful

materials such as non-food packaging, shipping

materials and large-volume insulation. The added-

value of Dr. Bressler’s conversion technology will

benefit Canada’s beef and related industries, while

at the same time helping to decontaminate these

potentially infectious materials.

Dr. Trent Bollinger and his team at the University

of Saskatchewan, together with partners in

the Government of Alberta and Saskatchewan

Environment, integrated their social structure,

environmental exposure, and spatial movement

findings with results of ongoing CWD surveillance

programs for wild deer in Saskatchewan and

Alberta. This work helps to develop predictive

models that will inform strategies to better manage

the disease, such as vaccination programs.

Dr. Norman Neumann from the University of

Alberta collaborated with researchers from the

United States and Agriculture and Agri-Food

Canada to better understand patterns of

transmission and deposition of infectious prion

materials in the environment. Using a technology

called protein misfolding cyclic amplification

(PMCA), Dr. Neumann and his team were able

to help inform decontamination strategies for

controlling the spread of CWD and minimize the

impact of the disease on humans and animals.


RESEARCH REFLECTIONS This network has significantly

improved our understanding of the molecular mechanism of protein misfolding to cause disease

Proteins are generally thought to be stable

structures that fold in a specific way to perform

their function; however, the cellular form of the

prion protein has major regions that have no

stable structure. Dr. Avi Chakrabartty from the

University of Toronto and collaborators such

as Dr. Julie Forman-Kay at the Hospital for

Sick Children found that more regions of

disordered structure could hold the key to better

understanding the implications of proteins in

cell death or the elusive mechanisms of

aggregation and subsequent conversion of the

normal prion protein to the disease-causing form.

Dr. Avi Chakrabartty, University of Toronto

This network aligned major stakeholders, including Aboriginal communities, towards a solution for CWD

Dr. Stéphane McLachlan, University of Manitoba

The Canadian Cooperative Wildlife Health Research

Centre and its provincial and federal stakeholders

called on PrioNet to lead an initiative to update

and refine a strategy document for managing

CWD in Canada. PrioNet, APRI and agencies

directly engaged in managing CWD in wildlife and

livestock and in protecting public health convened

and after iterative consultations and meetings

developed “A Proposal for Canada’s National

Chronic Wasting Disease Strategy” for Canadian

policy makers.

Dr. Ellen Goddard,University of Alberta

PrioNet researcher Dr. Ellen Goddard at the University of Alberta

is collaborating with the Canadian Food Inspection Agency,

Health Canada, and the Public Health Agency of Canada to

develop a set of effective risk management policies and strategies

to control the spread of CWD in Canada, building on the success

of the “BSE Integrated Risk Management Framework”.

Dr. Stéphane McLachlan of the University of

Manitoba and his pan-Canadian team of more

than 20 researchers is partnering directly with

Aboriginal communities to study the impacts of

CWD in wild animals on their livelihoods, linking

traditional knowledge with western science.

Their work has illuminated new and better ways

to share information among affected

communities, scientists and government, and

is helping to secure Aboriginals’ traditional

knowledge and food systems.


Dr. Neil Cashman, University of British Columbia

This network has worked with industrial partners to embark on diagnostic, vaccine, and therapeutic strategies for these disorders

“The SYPA program has been very strong and perhaps most importantly helped provide science training but also professional training on time management and communicating science effectively. I do not know of any other organization that provides this level of support for HQP.”

– PrioNet Scientific Member

PrioNet’s Scientific Director Dr. Neil Cashman at the University

of British Columbia had a major finding identifying “prion

epitopes”, parts of the misfolded protein that can be exploited

as potential therapeutic or diagnostic targets in prion disease.

The commercial potential of this finding lies in the fact that

vaccine antibodies will bind selectively to the infectious misfolded

prions, but not to the normal prion protein; since the antibodies

recognize only specific parts of the disease-causing prions,

there is potential to apply them to multiple prion diseases.

In this year alone, Dr. Cashman also signed a collaborative

research agreement with Cangene Corporation to develop

his work on immune-based therapies for Alzheimer’s disease,

discovered a key link between prions and the neurodegenerative

disease ALS, and was part of an international research team

from Canada, France and the United States that discovered that

women who are injected with urine-derived fertility products

may be at a higher risk of developing prion disease due to the

presence of at least the normal prion protein in the products.

Dr. Andrew Potter, University of Saskatchewan

Dr. Scott Napper and Dr. Andrew Potter, both of the Vaccine

and Infectious Disease Organization-International Vaccine

Centre (VIDO-InterVac) and the University of Saskatchewan,

are applying Dr. Cashman’s “prion epitope” knowledge

and working in partnership with PREVENT and Amorfix Life

Sciences to develop vaccines for CWD. If successful, these

vaccines could potentially save Canada hundreds of millions

of dollars in management costs for CWD, and help to halt

the disease in North America.

Together with Dr. Steven Plotkin at the University of

British Columbia, Dr. Cashman’s group developed

a computational algorithm that identifies regions of

proteins that are thermodynamically most likely to

unfold. This algorithm will be used to design the active

components of potential vaccines against prion disease

and other neurodegenerative disorders.

The success of wildlife rabies vaccination programs guided us to adopt similar methods for developing and deploying a CWD vaccine. We have recently investigated two viral-delivery systems that induced robust immune responses in orally immunized white-tailed deer. We are also looking to integrate a new immunizing protein into our viral-delivery system that is superior to the one used in the injectable vaccine. In the near future, we hope to construct a candidate viral-delivery vaccine and perform immunization and challenge trials in target species. These trials will take place at the new Containment Level 3 International Vaccine Centre (InterVac) that will open later this year on the University of Saskatchewan campus. Collaborator and fellow PrioNet member Dr. Trent Bollinger, an expert in cervid ecology and behavior, will provide guidance on vaccine deployment to transition our vaccine from the laboratory to the environmental stage.

Years of design and testing of vaccine components are coalescing into effective CWD intervention strategies for both captive and wild cervid populations. These advancements can be attributed to the hard work of many members within Dr. Napper’s lab, and to the insight and collaborative efforts of our fellow researchers within the PrioNet community. Together, we have come to a point where a tool for CWD prevention may be on the horizon. The vaccines we are developing have the potential to help environmental agencies control and contain the spread of CWD across our continent, eliminate risks in both farming and hunting of cervids and to provide a better quality of life to deer and elk populations. ■


Ryan Taschuk is a Ph.D. student with Dr. Scott Napper at the University of Saskatchewan.

A war on two fronts Developing vaccines to combat CWD in both captive and wild cervidsby Ryan Taschuk

For decades since it was identified as a prion disease, chronic wasting disease (CWD) has spread rapidly throughout deer and elk populations in North America. This highly transmissible, highly infectious, and fatal disease continues to be a scourge upon wild and captive cervid populations, with culling of infected herds as the only—and costly—intervention strategy.

My work looks to change that. Our team at the University of Saskatchewan, under the supervision of Dr. Scott Napper, is working to create an injectable vaccine to protect captive cervids from being infected with prions and developing CWD. Promising results from these vaccine studies have led to a partnership with the Pan-Provincial Vaccine Enterprise (PREVENT) to develop and commercialize this technology.

While this vaccine will be beneficial for farmed animals, the geographical spread and environmental accumulation of prions would continue to increase across North America in wild cervid populations. Using the injectable vaccine for wild cervids is an unrealistic option, as it would require a camouflaged army—likely composed of graduate students—to scour the brush of North America to track, capture, and vaccinate millions of potential hooved targets. Instead, we decided to transition our injectable vaccine technology into an oral delivery system for wild deer and elk. Although many factors need to be considered when developing a vaccine of this scope, our primary research goals were to efficiently deliver a vaccine to free-ranging cervid population that confers a prolonged duration of protection against CWD.

To guide us in our vaccine development strategy, we looked at current wildlife vaccination campaigns for combating rabies in Western Europe and North America. These programs use viral vaccine delivery technology, where manipulated viruses deliver the immunizing protein from the rabies virus to wild carnivores when consumed. The efficacy of these viral-delivery programs is high—epidemiological studies show dramatic decreases in the incidence of rabies in baited areas, with some countries able to claim eradication of the virus within their borders.

is PrioNet’s scientific communications program for students and other young professionals.


Going to the heart of prion research in Canada An opportunity to connect with leading prion researchersby Jason Yau

With the support of PrioNet’s student exchange program, I recently traveled to Canada’s leading-edge effort to study, treat, and prevent prion diseases —the Centre for Prion and Protein Folding Diseases (CPPFD) at the University of Alberta.

Opened in 2006, the CPPFD houses scientists at the forefront of research into prion diseases and other neurodegenerative disorders. They include Alzheimer’s disease researcher Dr. Satyabrata Kar, and prion researchers Dr. Judd Aiken and Director Dr. David Westaway. In addition to the focus on prion pathology, the Centre also has many affiliations with other faculties of the University of Alberta such as medicine, science, and agriculture and environmental sciences. The Centre has launched many collaboration projects that look into ending the spread of BSE and other prion-related diseases in humans, livestock, and wildlife.

As a Ph.D. student in structural biology and biophysics at the University of Toronto, I traveled to Edmonton with the intention of learning various tissue culture techniques in Dr. Valerie Sim’s Laboratory. We hoped to study the harmful effects of protein aggregates in cell and brain slice cultures as a model system to look at toxicity in disorders such as Alzheimer’s and Parkinson’s disease. One leading hypothesis for toxicity suggests that intermediates can interact and disrupt the integrity of the cell membrane, leading to increased cell death. Combined with our structural and membrane interaction studies of these protein aggregates, our ultimate goal is to address whether there is a correlation between aggregate structure, membrane disruption, and toxicity in neuronal cultures.

During the visit, I was impressed that the Centre fosters an incredibly tight-knit research community. Their goal is simple but focused—to advance the knowledge of prion disorders and create a training center for future prion scientists. For example, every week trainees present their latest experimental data at communal meetings. Supervisors and members of different labs are invited and encouraged to give immediate feedback. This experience not only helps students immensely in preparing for conferences and meetings, but also facilitates the exchange of ideas between people from different areas of expertise. In addition, the Centre invites lecturers such as Dr. Paul Fraser and Dr. Sheena Radford, both well-known for their contributions in the amyloid research field, to give students the chance to hear about the latest advancements in prion research from around the world. This remarkable learning environment at the CPPFD pushes the limits of science and prion research as a unified group.

The collaborative effort between research groups makes it possible to uncover all aspects of a global issue as puzzling as prion diseases, which individually would be hard to achieve. The CPPFD sets a great example for how a multidisciplinary research community benefits all research groups and encourages high-quality collaboration projects. Combining our knowledge, and overlapping different research expertise, is the key for Canada to solve the mystery and develop solutions to prion and prion-like diseases. ■

This remarkable learning environment at the CPPFD pushes the limits of science and prion research as a unified group.

Jason Yau is a Ph.D. student with Dr. Simon Sharpe at the University of Toronto.

Oligomers being studied under the microscope.

PrioNews is published by PrioNet Canada Suite 200, 2386 East Mall, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3 tel: 604-222-3600 fax: 604-222-3606 web: www.prionetcanada.ca To subscribe, e-mail: [email protected]

PrioNet Canada is made possible by the federal government’s Networks of Centres of Excellence program.

Calendar of Events

8th International Congress on Mental Dysfunction & Other Non-Motor Features in Parkinson's Disease and Related DisordersMay 3-6, 2012 Berlin, Germany www2.kenes.com/MDPD2012

PRION 2012May 9-12, 2012Amsterdam, the Netherlandswww.prion2012.com

PrPCANADA and Protein Folding Conference 2012June 25-27, 2012Toronto, Ontariowww.prionmeeting.ca

CJD 2012 and the 10th Annual CJD Foundation Family ConferenceJuly 13-15, 2012Washington, D.C.www.cjdfoundation.org

Alzheimer’s Association International Conference (AAIC)July 14-19, 2012Vancouver, British Columbiawww.alz.org/aaic

26th Annual Symposium of the Protein SocietyAugust 5-8, 2012San Diego, Californiawww.proteinsociety.org

► PrioNet participated in the American Association for the Advancement of Science (AAAS) meeting in Vancouver February 16-20, 2012. The event welcomed over 4,400 attendees and 700 media, plus 6,400 participants in Family Science Days. PrioNet scientific member Marco Prado participated in a symposium entitled "Establishing research collaborations with emerging economies: Canada’s experience in India and Brazil", and Ralph Matthews participated in another entitled "Everyone's an Expert but Who Is Listening?" Various presentations are now available for online viewing on the AAAS website, at www.aaas.org.

► PrioNet held a second Career Workshop and Fair event in Ottawa in early March, which included 14 presenters from government, industry, academia, patent law, science journalism and not-for-profit sectors, and over 25 graduate and student post-doctoral fellows from across the country. Podcasts are available for both the Ottawa and Edmonton presentations at www.prionetcanada.ca/podcasts. (See page 3 for more information about the event.)

► PrPCANADA and Protein Folding Conference 2012 is scheduled to take place June 25-27, 2012 in Toronto. This meeting is a unique opportunity for network members to share their latest results and make connections with other protein folding researchers. Register today at www.prionmeeting.ca.

► Conference Support was awarded to: Eddie Pokrishevsky of the University of British Columbia to attend the RNA-Binding Proteins in Neurological Disease meeting in Washington, D.C.; Aram Elagoz from McGill University to attend the Society for Laboratory Automation and Screening (SLAS) 2012 in San Diego, California; Nathalie Daude from the University of Alberta to attend the Biology and Translational Aspects of Neurodegeneration meeting in Venice, Italy.

► PrioNet granted Training and Travel Exchange Awards to: Jason Yau from the University of Toronto, Megan O’Neill from the University of British Columbia, and Thomas Rosendal from the University of Guelph to travel to the Centre for Prions and Protein Folding Diseases at the University of Alberta; Maxime Beland to travel from his home at the University of Sherbrooke to the University of Western Ontario; Pawel Stocki to travel from his home at the University of Toronto to the University of British Columbia; Jake Pushie to travel from his home at the University of Saskatchewan in Saskatoon to travel to the University of California – Santa Cruz; John Gray to travel from his home at the Canadian Inspection Agency in Lethbridge to the NIH – Rocky Mountain Laboratories in Hamilton, Montana.

Visit prionetcanada.ca for more details


Network Notes

Documents

PrioNews | December - March 2012: Volume II, Issue 7