Australian investigators are encouraged to register and indicate their gene/pathway/cellular system areas of interest and expertise. Registration indicates an interest in collaborating with clinical teams presenting patients with rare diseases. Registrants should nominate gene or gene families/pathways that are the direct and current interest of the team and identify the experimental models they use and indicate the tissue type/organ systems of expertise.
The registry database allows the Scientific Review Panel to elect the best-matched model system team(s) to undertake the research on the candidate disease gene/variant of interest. The intention is to identify a model system team(s) that have a track record of research in the functional studies of the specific disease gene (or orthologue) and, ideally, is poised to launch functional analyses in an immediate timeframe. The registrant(s) will be invited to form a connection with the clinical team and, when appropriate, apply for funding support of the collaborative research by the Network Catalyst Grant or other leveraged resources.
If you are a researcher and wish to register please visit the Australian Functional Genomics Registry website at: Go to Registry
The Network and Objectives
The Network will mobilise the entire Australian biomedical community of clinicians and scientists to communicate, integrate their resources, and work collaboratively to gain insights into the clinical and functional attributes of rare disease genes and cancer genes. Through the database capturing the resources and expertise existing in the Australian research community, connections will be fostered between teams with matching research interest to deliver a better understanding of the genetic and cellular disease mechanisms, develop prevention guidelines and diagnostic tests, and investigate potential therapies. The goal of the Australian Functional Genomics Network is to improve the lives of patients and their families through the coordination of functional genomics research in Australia.
The specific objectives of the Network are to:
- provide functional validation of human genetic variants that cause disease;
- develop insights into an evidence-based rationale for treatment (e.g. identification of candidate drug targets) via knowledge of disease gene function and molecular pathway;
- complement clinical disease gene discoveries by functional genomics investigation that lead to significant and impact research output, such as publications, health policy and practice of clinical management; and
- establish sustainable collaborations between clinical teams and model system research teams to conduct outstanding research that will attract further competitive funding support.
The clinical team that discovers a novel gene or potentially clinically significant variant that requires functional evaluation will submit a Connection application with all the required information. Applications assessed and approved by a Clinical Review Panel will trigger a search of the Network Registry to identify the best-matched model systems research team. While funding for connection projects is not currently available, the Scientific Review Panel will invite the connected teams to submit an ‘Acceptance’ application expressing their interest to undertake functional work using their own resources. On a positive response from the teams, the Panel will recommend the establishment of the connection with an agreement on the condition of the collaboration, which will be considered for acceptance by the combined teams. When Network Catalyst funding is available, the combined teams will be established, and agreement sought around the funding contract, the scope of work and the conditions of the award.
Genes and Variants
The Network welcomes the submission of functional genomics studies in the following categories associated with either a rare disease or inherited cancer.
- Novel gene: A gene not previously associated with disease, but supported by genetic evidence (variants in the same gene in unrelated patients with a similar phenotype) and functional data is being rapidly sought prior to publication.
- Candidate gene: A gene that has not previously been associated with disease in a single patient/family/isolated population such that additional functional data is necessary to support disease-causation.
- Novel variant in a known disease gene: A novel variant causing a phenotype that appears to be different to previously reported genotype-phenotype reports.
- Known disease genes that are of therapeutic interest. Therapeutic opportunities will include projects that propose to develop a model asset for drug screening or develop a model to evaluate the efficacy of a treatment.
The Network has no formal requirement for prior partnership. Applications are welcomed from pre-existing or newly formed teams of clinicians and model system investigators who share an interest in pursuing disease gene discovery or validating variants of unknown significance. The Network also welcomes proposals from other organizations such as rare disease foundations who are interested in funding Catalyst Grants in targeted areas. [contact us at: firstname.lastname@example.org]
Frequently Asked Questions
Who should register?
We encourage the chief investigator(s) of model system research teams that are eligible for ARC/NHMRC funds and who are interested in the Network Catalyst Grant Scheme (when funding is available) to register. The chief investigator(s) and the host institution(s) must be in Australia.
What happens to my information?
The Clinical and Scientific Review Panels and Program Officer will use the registry to identify candidates. The registry is password-protected and the information you enter will be kept secure. The visibility of your information depends on your Data Privacy and Partner registry sharing setting on the Profile Page.
In response to a Connection Application, the Scientific Review Panel will search the registry for potential matches, based on the information provided by registrants. If your team fits a match, you will be notified and your interest sought to proceed with the connection. You are welcome to re-visit the registry at any time to update the information.
What model systems are listed within the registry?
The model systems that are supported within the registry (by maintaining their most current gene annotation) are: human (including primary cells and stem cells), mouse, rat, zebrafish, roundworm (Caenorhabditis elegans), fruit fly (Drosophila melanogaster), yeast and E. coli.
What if I study more than one model system?
In the registry, you can enter information for each model system separately.
Which genes should I enter in the registry?
Key to the success of the Network is our ability to match human disease genes to researchers who can study those genes. We recognise that for any given human gene, there is a limited chance that a researcher in Australia 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 the range of genes that each team/lab can work on and the assumption 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. 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 50 non-Primary genes entered.
- Tier 3 genes are not specifically selected by the registrant but are identified by Gene Ontology (GO) terms. By registering the GO terms most relevant to your research interest, genes matching the annotations are regarded as Tier 3 genes. There may be several hundred such genes.
See also the question about “I study the entire genome”.
Entering genes into the registry is only the first step in the connection 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 establish a collaboration, you will have to indicate your readiness to undertake the research. Keep that in mind as you register your genes of interest and expertise.
Should I fill in the human orthologs of genes I study?
No. Only register genes for the model system you currently work on. Only register human genes if you are working directly with them. See also ‘Which genes should I enter into the registry?’ and ‘Are humans a “model”’.
What if I cannot find my gene in the registry?
Some genes are yet to make it to the model organism’s reference gene annotation. In that case, chose a human ortholog of the gene if known. If you think that your nominated gene(s) should be in the registry please contact us to let us know. Do not register human genes merely because they are orthologs of the genes you study in a model organism.
What if the organism I study is not listed?
The registry was constructed assuming that the majority of registrants work on one or more of the most popular model systems, but we recognize this does not cover all researchers. If your organism 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 and enter the orthologs of your genes of interest, and indicate clearly in your "Research Focus" under Model Organism tab that this is a case of exception. The match will always be based on the human gene, so if we can identify you through a search of the registry via an orthologue, you will be considered as a potential match.
I study the entire genome or am capable 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 a track record of research in orthologues of human genes associated with rare disease and cancers. You should register the set of genes that you are ready to conduct the investigation promptly. See ‘Which genes should I enter into the registry?’.
Are humans a "model" for the purposes of the registry?
Yes, if you have an appropriate system to study the candidate genes/variants. This might include biochemical assays or assays based on human cell lines or stem cells. New research on human subjects is not considered to be within the scope of supported projects by the Network.
Will only one team be chosen per disease gene/variant application?
If the Scientific Review Panel identifies more than one model system team as a potential match, all will be notified and invited to form a connection. If multiple teams working with different model systems are willing to investigate the gene or variant, the Network will encourage the multidisciplinary approach to achieve a more comprehensive analysis.
What Data Privacy Settings should I choose?
Data Privacy Settings section on your Profile page lets you choose your local data sharing preferences. The default setting for the registry is pre-selected but can be changed. The options are:
- private - your information will only be accessible by Network administrators for matching you to a submitted gene and considering you for connection opportunities.
- shared - your information will be accessible by other researchers who are registered. Registered users will be able to access your information through the provided search interface.
- public - your information will be visible publicly. Your information will be shared (see above) with registered users and will be accessible to non-registered users through the registry's public search webpage (https://www.functionalgenomics.org.au/)
What does it mean to share data with partner registries?
The Australian Functional Genomics Network has recently established linkages with similar rare disease networks around the world, with the intention to enable matches across borders when there is no expertise within the country where the disease variant is discovered. The registry software has been updated so that we can exchange data with international partners in a secure way.
Partner registry sharing section on your Profile page gives you the option to set your preference for sharing your data with the Australian Functional Genomics Network's partner registries for the purposes of establishing connections between clinician sciences who are submitting genes to partner registries and Australian model system researchers. The shared data will only be visible to the administrators of the partner registries. If your data privacy level is set "public", partner registries will gain access automatically.