Advancing Technology Innovation through Discovery
Request for Applications (RFA)
Joint Collaborative Program between Genome Canada and the Canadian Institutes of
Health Research (CIHR)
Printable version
Background
This joint collaborative program was developed by Genome Canada and the Canadian
Institutes of Health Research (CIHR) to bring together Genome Canada-funded Science
and Technology Innovation Centres (S&T ICs) with Canadian researchers to focus on
applying the latest genomics technologies to identify the genetic causes of childhood
diseases. This funding opportunity will specifically focus on diseases where such
identification can be achieved rapidly with the potential for important novel biological,
clinical and commercial discoveries.
It has been twenty years since the official commencement of the Human Genome Project
and six years since its completion. Next generation sequencing technologies are
well established and third generation sequencing technologies are now being developed
and tested. With the introduction of massively parallel next-generation sequencing
techniques there is an emerging paradigm shift in our ability to identify disease
causing genetic mutations. The Genome Canada-funded S&T ICs need to be able to adapt
to this new reality as quickly as possible; equally the Canadian research community
should be able to take advantage of these technological advances just as quickly.
Canada is well positioned to take advantage of its many important resources to put
us on the leading edge in disease gene discovery. The S&T ICs are among the leaders
in the world in the application of technology to scientific problems. There are
patient cohorts ready for study, with samples available and consent for research
given. Also, Canadian researchers are well-organized and have a proven capacity
to work collaboratively.
Other countries, such as the United States, China and the United Kingdom, are moving
forward in this area as well. This joint CIHR-Genome Canada program will allow Canada
to benefit from its unique advantages to take an internationally leading role in
disease gene discovery.
June 2010 Planning Workshop
To define the parameters of the collaborative program a one-day workshop entitled
"Advancing Technology Innovation through Discovery" was held on June 8, 2010 bringing
together leaders from the fields of genetics of childhood diseases and genomics
technologies. The recommendations from that meeting have been incorporated into
this RFA.
Program Overview
The focus of the collaborative program is childhood diseases for which genes can
be identified in a short time frame and with a small number of subjects to ensure
the greatest impact with the funds available; these may include both (i) rare, Mendelian
diseases and (ii) some rare pediatric and adolescent cancers. This collaborative
program is not intended to study gene variants in complex diseases. However, should
a longer term program be developed, more complex diseases may be considered for
study in an expanded program.
Applications are expected to be pan-Canadian and must include multiple research
centres. It is expected that geneticists and clinicians will work in partnership
with the Genome Canada-funded S&T ICs to develop applications for this collaborative
program. Of the three Genome Canada-funded S&T ICs that offer sequencing and data
analysis, at least two must be involved in each application. (See Appendix 1 for
a list of S&T ICs). Applications can focus solely on rare pediatric and adolescent
cancers, on other rare Mendelian diseases or, if appropriate, can combine both disease
areas/streams in a single application.
The program has three stages:
Stage 1: Establishment of National Disease Consortia and Development of Applications
Stage 2: Application of Next-generation Sequencing Technologies for Gene Discovery
Stage 3: Validation of proposed mutations
Stage 1
Establishment of National Disease Consortia and Development of Applications.
It is envisaged that national disease consortia will bring together clinicians,
geneticists and the S&T ICs to allow the rapid assembly of patient resources across
Canada and the development of an application for funding. It is expected that no
more than one national consortium will be established in each stream: (i) rare pediatric
and adolescent cancers and (ii) other rare Mendelian diseases. This collaborative
program is short-term in nature and intended to capitalize on patient resources
already available for study, so the consortia will need to demonstrate that the
necessary experimental materials and appropriate consents are already in place.
Each consortium would be responsible for prioritizing the diseases and samples for
study. It is recommended that the consortium establish a selection committee to
undertake the prioritization process using appropriate criteria, such as:
- Likelihood of rapid, successful identification of disease related genes (e.g.
based on inheritance pattern, consanguinity, number of patients/families, additional
biochemical information, quality of clinical diagnosis); and
- Benefit to patient, family and/or healthcare system.
Patient consent and Research Ethics Board (REB) approvals will have to either exist
or be likely to be obtained in a timely manner. In this context and, given the involvement
of vulnerable populations (children) and the central role of consent, confidentiality
and other important issues, all applicants must consider the ethical, environmental,
economic, legal and social (GE3LS) implications of their proposals and integrate
plans to effectively address them beginning in stage 1.
The CIHR Institute of Genetics is in the process of catalyzing the creation of a
Canadian Rare Diseases Consortium. In addition, the CIHR Institute of Cancer Research
is engaging their community to develop a Pediatric and Adolescent Cancer Consortium.
Those interested in learning more about these efforts, should contact Stephanie
Robertson (Institute of Genetics) for the Canadian Rare Diseases Consortium, or
David Hartell (Institute of Cancer Research) for the Pediatric and Adolescent Cancer
Consortium. Contact information is below.
Stage 2
Application of next-generation sequencing technologies for gene discovery by targeted
enrichment, including whole-exome, or whole-genome sequencing.
The sequencing and preliminary bioinformatics analysis (calling bases and variants)
will be undertaken by Genome Canada-funded S&T ICs. During this stage of the program
early results identifying genetic mutations for rare childhood diseases should be
expected with minimal follow-on validation efforts.
Stage 3
Validation of proposed disease mutations.
It is expected that many of the results from sequencing small cohorts will require
follow-on validation to identify the mutations causing disease. We anticipate that
validation will take up to 12 months to achieve. Precise methods of validation will
depend upon the nature of the specific genes identified but could involve sequencing
the specific gene from a larger cohort of patients and their relatives, functional
studies in animal models, gene expression analysis, and other approaches. Validation
will therefore require multiple disciplines and expertise, including bioinformatics,
molecular biology, genetics, cell biology, GE3LS experts, etc. and will require
active collaboration between the S&T ICs and the geneticists and clinicians.
Application and Peer Review Process for Stage 2 & 3
Genome Canada will manage the review process. Consortium leaders must submit completed
applications for funding by October 15, 2010 to:
Name: Kim Corbett
Title: Program Manager, Genome Canada
Phone: 613-751-4460 ext 120
E-mail: kcorbett@genomecanada.ca
Funding applications must:
- summarize the demonstration work related to the formation of the consortium;
- address the review criteria;
- describe the key activities to be undertaken in stages 2 and 3, as well as potential
follow-on activities funded through other mechanisms; and
- provide a detailed budget.
The application form, including a budget template, will be made available through
Genome Canada.
The applications will be reviewed by a small expert panel to identify the proposals
that best respond to the RFA. In addition to the overall quality of the research,
the evaluation criteria will include (note that these descriptors are not all inclusive):
- Are the diseases well selected with respect to the potential for rapid identification
of the causative genes based on information from a relatively small number of subjects,
and is there an efficient downstream validation process proposed?
- Will identification of the causative genes for these diseases make a significant
impact on the field?
- Are the priorities assigned to diseases/resources well justified?
- Is the most appropriate technology for the proposed work being put forward?
- Is the community of researchers comprising the team appropriate (e.g., both geographic
and disciplinary representation)?
- Have the applicants made a convincing case for the timely availability of patient
material, including receiving the appropriate consent?
- Have applicants considered GE3LS implications of their proposals and integrated
plans to effectively address them?
- Is the proposed budget reasonable relative to the proposed project activities?
Results will be made available by November 30, 2010.
Potential Follow-on Stage
Given that one of the key outcomes of any investment should be translation into
benefits and impact, it is expected that the findings arising from this program
will be taken forward for further study using funding programs of other organizations,
such as CIHR Operating Grants competitions or Institute-led strategic initiatives,
other Genome Canada or regional Genome Centre funding opportunities, competitions
launched by other non-profit organizations or opportunities to access institutional
funds. In particular, the following two CIHR Strategic Initiatives represent opportunities
for continued support:
- Rare Diseases Emerging Teams: Translating Basic Biology to Enhanced Patient Care
(October 2010 program launch) co-led by the CIHR Institute of Genetics and the CIHR
Institute of Nutrition, Metabolism and Diabetes
- Pediatric and Adolescent Cancer – Prevention or Mitigation of the Adverse Consequences
of Treatment (launched June 2010)
http://www.researchnet-recherchenet.ca:80/rnr16/vwOpprtntyDtls.do?prog=1024&tag=1
led by the CIHR Institute of Cancer Research
These two RFAs, that represent a combined total funding commitment of close to $20 million,
could provide up to five years of follow-on funding to build on the successes
of the CIHR/Genome Canada program.
Funding Available
CIHR and Genome Canada will contribute equal amounts, up to $2 million each, to
this collaborative program. It is expected that additional funders will be sought
by all participants (both funders and applicants) to help augment the scale of the
program and speed development of results. There is no requirement for co-funding.
Timeline
July 28, 2010
RFA Released
October 15, 2010
Applications submitted
November 30, 2010
Announcement of results of review
December 2010
Initiate sequencing and primary data analysis
January 2011 – December 2011
Validation of variant list
Contacts
CIHR Contacts
Institute of Genetics
Name: Stephanie Robertson
Title: Assistant Director
Phone: 613-954-0533
E-mail: Stephanie.robertson@cihr-irsc.gc.ca
Institute of Cancer Research
Name: David Hartell
Title: Associate, Institute Strategic Initiatives
Phone: 613-941-4329
E-mail: David.hartell@cihr-irsc.gc.ca
Genome Canada Contact
Name: Kim Corbett
Title: Program Manager
Phone: 613-751-4460 ext 120
E-mail: kcorbett@genomecanada.ca
About the Funders
The Canadian Institutes of Health Research (CIHR) is the Government of Canada's
agency for health research. CIHR's mission is to create new scientific knowledge
and to catalyze its translation into improved health, more effective health services
and products, and a strengthened Canadian health-care system. Composed of 13 Institutes,
CIHR provides leadership and support to more than 13,000 health researchers and
trainees across Canada.
CIHR Institute of Genetics supports research on the human and model genomes and
on all aspects of genetics, basic biochemistry and cell biology related to health
and disease, including the translation of knowledge into health policy and practice,
and the societal implications of genetic discoveries.
CIHR Institute of Cancer Research fosters research based on internationally accepted
standards of excellence, which bear on preventing and treating cancer, and improving
the health and quality of life of cancer patients.
Genome Canada is a not-for-profit Corporation that acts as the primary funding and
information resource relating to genomics research in Canada. Its main objective
is to position Canada as a world leader in genomics research. Dedicated to developing
and implementing a national strategy in genomics research for the benefit of all
Canadians, it has received $915 million in funding from the Government of Canada
since 2000 to which has been added close to $1.0 billion in partnered co-funding
and interest earnings. Genome Canada will work closely with its regional Genome
Centres (Genome British Columbia, Genome Alberta, Genome Prairie, Ontario Genomics
Institute, Genome Quebec, and Genome Atlantic) to facilitate the interaction between
the genetics community and its technology providers as well as ensuring effective
collaborations between S&T ICs.
Appendix 1
Genome Canada-funded Science and Technology Innovation Centres that offer sequencing
and data analysis
Genome Sciences Centre
675 West 10th Avenue
Vancouver, British Columbia
http://www.bcgsc.ca/platform
Contact: Robyn Roscoe
Head, Strategic Planning & Project Management
rrscoe@bsgsc.ca
McGill University and Genome Quebec Innovation Centre
740, Dr. Penfield Avenue, Room 7104
Montreal, Quebec
http://www.gqinnovationcenter.com/index.aspx
Contact: Alexandre Montpetit
Assistant Scientific Director
Alexandre.montpetit@mail.mcgill.ca
The Centre for Applied Genomics
The Hospital for Sick Children
MaRS Centre – East Tower
101 College Street, Room 14-706
Toronto, Ontario
http://www.tcag.ca/
Contact: Jo-Anne Herbrick
Facilities Manager
jherbrick@sickkids.ca
