A clinician who has discovered a new gene as the cause of a rare disease submits a Connection Application to the Clinical Advisory Committee (CAC). If approved, CAC sends the human gene to the Scientific Advisory Committee (SAC) and bioinformatics core, which will attempt to match a new disease gene to as model organism/system researchers as possible, based on the genes that model organism/system researchers have self-declared in the Registry (see BIC report template). The SAC will then invite model organism/system researchers to submit a 2-page proposal to study the gene (receipt deadline within a week or two). Invitees will have one week to respond to an invitation, and then must apply for the next grant deadline. Submissions can be submitted on either the first or third Fridays of the month. Decisions will be made in one week, at the next SAC conference call (second and fourth Fridays of the month). Up to four projects will be funded from each Connection application. Recommendations for establishing a connection between model organism/system researcher will be reviewed with the clinician and accepted or not. Following a successful connection, the basic scientist lab will be connected to the clinician scientist and receive $30,000 to seed immediate collaborative experiments. See process and workflow for more details.

A maximum of $30,000 will be awarded for each Catalyst grant. Model organism/system researchers are expected to provide evidence that they/their lab is set up to do the work proposed in a timely fashion. Where the budget for the proposed work exceeds the Catalyst grant of $30,000, applicants are required to describe what work the Catalyst grant funds will cover and how additional funds will be garnered.

To apply for a Catalyst Grant, you must:
• Be affiliated with an eligible Canadian institution or organization by the time the funding begins;
• Not be employed by Canadian federal government departments or agencies or for-profit organizations unless affiliated with a university;
• Not have a financial interest holding of more than 5% in a company proposed as an industry partner for research funding;
• Consent to the public disclosure of personal information in the case of a serious breach of Agency policy For more information, please see the Canadian Institutes of Health Research (CIHR) Application Administration Guide .

The Network has no formal requirement for partnering. Applications are welcomed from pre-existing or newly formed teams of clinicians and model organism/system researchers who share an interest in pursuing a disease gene discovery. The Network also welcomes proposals from other organizations such as rare disease foundations who are interested in supporting Catalyst Grants in targeted areas. [contact us]

The specific objectives of this funding opportunity are to:
• provide functional validation of human genetic variants that cause disease;
• supplement clinical disease gene discoveries by generating functional data so as to get higher impact publications;
• develop insights into potential rationale for treatment (e.g., identification of candidate drug targets) via knowledge of a disease gene pathway; and
• establish longer term collaborations between basic scientists and clinicians that will lead to subsequent grant funding in support of outstanding basic and/or applied research.

Investigators who have submitted successful Connection applications and model organism/system researchers who are awarded a Catalyst grant will be expected to sign an Agreement which sets out the ground rules and operative principles of the Network for investigators who wish to collaborate and receive funding. Successful applicants will be sent an MOA with notification of a successful Connection application, and with notification of a successful Catalyst Grant application. Review the MOA Form

A one page report summarizing findings to date will be due six months after a $30K catalyst award has been made and at completion of the seed-funded project.

What is the RDMMN registry?

• The RDMMN registry is an online registration tool and a database of Canadian model organism/system researchers and the specific genes they study. The Scientific Advisory Committee uses the RDMMN registry to determine which scientists are doing work relevant to a newly identified human disease gene. Registrants who meet the criteria for a given gene will be invited to apply for a Catalyst Grant.

What is the purpose of the RDMMN registry?

• The purpose of the RDMMN registry is to collect information about model organism/system researchers, focusing on genes they are studying. The registry is used by the Scientific Advisory Committee and the Bioinformatics Core to look for orthologs of a newly identified human disease gene. Model organism/system researchers studying the identified genes may be invited to apply for a Catalyst Grant.

Who should register?

• All model organism/system researchers eligible for CIHR funds should register if they want to be considered for a Network Catalyst Grant.

Who will see the information I submit?

• The Scientific Advisory Committee and the Bioinformatics Core will use the registry to identify candidates that will be invited to submit a Catalyst Grant application. Your information will not be viewable by other Registrants. The registry is password-protected and the information you enter will be kept secure and strictly confidential. You can think of it as how any information provided to a funding agency for grant application purposes would be used.

What happens after I fill in my information?

• In response to a Connection Application, the Scientific Advisory Committee will search the registry for potential matches, based on the information provided by registrants. If you emerge as a match and meet the other criteria, you will be invited to apply for a Catalyst Grant. There is no need to further contact the Network, though you are welcome to revisit the registry at any time to update your information.

What is the process for making a catalyst grant award?

• Briefly, the Scientific Advisory Committee (SAC) will attempt to match a new disease gene to as many model organism/system researchers as possible, based on the genes that model organism/system researchers have self-declared. The SAC will then invite the model organism/system researcher to submit a 2-page application (receipt deadline within a week or two). The SAC will review the applications (within a week), and for those accepted, will invite the clinician scientist to establish a connection with the corresponding model organism/system researcher. Following a successful connection, the basic scientist lab will be connected to the clinician scientist and receive $25,000 to seed immediate collaborative experiments.

What model organisms are directly supported within the registry?

• The model organisms/systems that are supported within the registry (by maintaining their most current gene annotation) are human, mouse, rat, zebrafish, roundworm, fruit fly, yeast, E. coli, and human cell models.

Which genes should I enter into the registry?

• Key to the success of the Network is our ability to match human disease genes to model organism/system researchers who can study those genes. We recognize that for any given human gene, there is a limited chance that a model organism/system researcher in Canada is actively studying that specific gene. Therefore we need to be able to cast a wider net. On the other hand, we must strike a balance between restricting the genes registered and assuming that every lab can study any gene.

To reach this balance, genes are divided into Tiers:
• Tier 1 or “Primary” genes are those you currently work on in a model organism/system. You must be able to immediately, specifically and rapidly study them in your laboratory. Genes you have recently published on are especially good Primary genes. We expect this to typically be between one and ten genes.
• Tier 2 genes are those you do not mark as “Primary”. Carefully choose genes which you are not necessarily actively investigating but would be able to work on rapidly and specifically with minimal set-up time. These might be paralogs of Tier 1 genes, or members of the same complexes or pathway. For most registrants we expect there might be between one and 100 non-Primary genes entered.
• Tier 3 genes are not specifically selected by the registrant. Instead, we use Gene Ontology (GO) terms selected to infer them. The registry suggests GO terms based on GO term associations of Tier 1 and 2 genes that are already in the registrant’s profile. By indicating the GO terms most related to your work, genes having those annotations will be considered as Tier 3 genes. The registrant should be selecting only the most relevant and most specific GO terms to add to their profile. There may be several hundred such genes.

See also the question about “I study the entire genome”.

• Remember that entering genes into the registry is only the first step in the Catalyst Granting process. For a given human gene needing a match, we will first look for registrants who list an ortholog as a Primary (Tier 1) gene. If no match is found, the other Tiers will be searched. If a gene you entered comes up and you are invited to apply for a Catalyst Grant, you will have to provide evidence of your readiness to study that gene. Keep that in mind as you select your genes.

What if I study more than one model organism/system?

• In the Registry you can enter information for each model organism/system separately.

Are humans a “model” for the purposes of the Network’s Registry?

• Yes, if you have an appropriate system to study candidate genes as would be required to contribute to the understanding of the identified human disease genes. This might include biochemical assays or assays based on cell lines. New research on human subjects is not considered to be within the of RDMMN Catalyst Grant projects. Do not register human genes merely because they are orthologs of the genes you study in a model organism.

What if the organism/system I study is not listed?

• The Registry was constructed assuming that the vast majority of registrants work on one or more of the most popular model organisms/systems, but we recognize this does not cover all researchers. If your organism/system is not listed, you have two options. One is to let us know and we can consider adding it, if technically feasible. Alternatively, you can select the most closely related organism/system and enter the orthologues of your genes of interest, and indicate clearly in your “Research Focus” under Model Organism/System tab that this was done. Remember that the match will always be to a human gene, so as long as we can identify you though a search of the registry via an orthologue, you will be considered as a potential Catalyst Grant applicant.

What if I cannot find my gene in the registry?

• Some genes still haven’t made it to the official organism/system’s reference gene annotation. In that case, choose a human ortholog of the gene if known. If you think that your gene should be in the registry, please contact us to let us know.

Should I fill in the human orthologs of genes I study?

• No. Only register genes from the model organisms/systems you currently work on. Only register human genes if you are working on them. The only exception is when your model organism/system gene cannot be found in the registry (see What if I cannot find my gene in the registry?). See also Which genes should I enter into the registry? and Are humans a “model”.

I study the entire genome, or have the ability to assay the function of any gene. How do I select which genes I should list?

• We recognize that many labs can study any gene. The intention of this program is to identify researchers who have an existing history of research in orthologs of genes identified in human rare disease studies (ideally, who are poised to immediately conduct functional analyses that inform a human disease gene that has been discovered). You should register the genes that you can specifically and rapidly study in your laboratory. See “What is the purpose of the RDMMN registry” and “Which genes should I enter into the registry?”.

RDMM will consider awarding an additional one year of funding for a subset of those projects that have achieved significant, promising results obtained from experiments proposed in the original application and that propose new and important deliverables that will advance the overarching objectives of the RDMM.

Examples would include, but not be restricted to, proposals that:

• incorporate functional validation, beyond model creation and phenotyping, to better understand the underlying pathophysiology of the disease
• describe a route to the development of future therapies
• analyze additional patients with newly identified mutations in the same gene, using the model that was established, to build a convincing group of cases that allow genotype-phenotype correlations
• describe a critical pathway to a larger grant application

Eligibility:

Applications may be submitted by any investigator who has already been awarded a catalyst grant from RDMM. Generally, applications should be submitted after completion of the 12-month term of the initial catalyst grant, but will be accepted as early as 9 months after the start of the initial catalyst award if justified.
*NOTE: Investigators who have secured funds from another source, other than a match, for this project (ie. CIHR) are not eligible to apply.

Application Procedure:

Complete the Application for Renewal of RDMM Catalyst Grants form.

Submit applications to the RDMM Network at info@rare-diseases-catalyst-network.ca. Decisions will generally be available within two weeks.