Author: Birte Zurek

The ‘Mouse Genetics and Genomic Medicine’ virtual conference organised from 23-24 September 2021 by the International Mouse Phenotyping Consortium –IMPC (https://www.mousephenotype.org) will celebrate the occasion of the 10th anniversary of the establishment of the IMPC.

Solve-RD will present a poster on "Model Matchmaking via the Rare Diseases Models & Mechanisms Network (RDMM-Europe)".

In medical genetics, there is a critical need for model organism research, to assess new disease-gene associations, to understand pathophysiology and to test potential therapies. Within the Solve-RD project we established the European Rare Disease Models & Mechanisms Network (RDMM-Europe) to facilitate fruitful collaborations of model organism researchers and clinicians following patients with rare diseases (RD). The principle of this brokerage service is to fill the gap between RD gene discovery and functional validation. For that purpose, we connect Solve-RD clinicians that have discovered new disease-causing genes with model organism investigators (MOIs) that can study the mechanistic role of the given genes in health and disease by using an appropriate model organism or cell culture system. Solve-RD supports these validation projects with 50 Seeding Grants of 20,000 EUR each.

For the selection of candidate genes and model matchmaking, a two-committee process and a registry were set up using the structures of the successful Canadian RDMM Network as role model. The RDMM-Europe registry is a database that allows all interested MOIs to register the genes and model organisms they work with. Registrants express interest in getting linked to clinicians representing patients with RD and collaborating in projects funded by Solve-RD. The RDMM-Europe registry is also linked to international partner networks. Connection Applications on novel RD candidate genes are submitted by Solve-RD clinicians and are evaluated and approved by the Clinical Advisory Committee. Upon approval, the project management office opens a call for tender to identify best matching MOIs for the requested validation work and invites them to submit Seeding Grant Applications. They are evaluated by a Scientific Advisory Committee and approved for funding.

To date, we have awarded 23 Seeding Grants to MOIs and have linked Solve-RD scientists to model researchers in eight European countries, Canada, USA, Qatar and Australia. Linking scientists across borders via the RDMM network and supporting these joint projects will advance RD research and will benefit patients and families living with RD.

View the poster here.

Núria Dueñas, a medical oncologist and PhD candidate at the Catalan Institute of Oncology (ICO/IDIBELL) in Barcelona, spent 6 weeks at the Institute of Human Genetics of the University Hospital Bonn, Germany to conduct research with Solve-RD partner Stefan Aretz. They investigated whether different hereditary colorectal cancer risks can be in part attributable to the accumulation of low-risk SNPs in patients with Lynch syndrome. Her stay was supported by the EJP RD fellowship program.

Núria Dueñas is a medical oncologist with a special interest in cancer genetics and hereditary cancer. Since 2018, she works as a physician in the Hereditary Cancer Program of the Catalan Institute of Oncology (ICO/IDIBELL) in Barcelona and as a PhD student co-supervised by Marta Pineda and Joan Brunet. In the past years, she focussed on hereditary colorectal cancer (CRC) and Lynch syndrome (LS). Her PhD project is on risk estimation and phenotype-genotype correlation in LS.

In LS, as in other hereditary cancer predisposition syndromes characterized by incomplete penetrance, one of the main challenges is to identify which risk-modifying factors may be modulating the expression of the oncological disease. Common low-risk alleles (SNPs) for CRC can be integrated in Polygenic Risk Scores (PRS) which have been shown to model CRC risk in the general population as one type of genetic risk modifiers, but to date their effect on CRC risk in LS individuals is still largely unknown.

Núria spent 6 weeks at the Institute of Human Genetics of the University Hospital Bonn, Germany in the group of Stefan Aretz. They investigated whether different CRC risks can be in part attributable to the accumulation of low-risk SNPs in LS individuals. In particular, Núria gathered and aggregated clinical data of the LS cohort in Bonn (n=500) and supported the biostatistics team in Bonn to apply the Barcelona PRS pipeline. This collaborative project continues now that she is back in Barcelona through the application of additional models to calculate the PRS. Also, a meta-analysis combining the two populations included (Bonn and Barcelona) will be conducted. The collaborative study will hopefully lead to a first publication of the findings; follow-up projects are already planned.

The EJP-RD mobility fellowship has been a unique opportunity for Núria. She said: “Collaborating with professionals from different specialties and different countries has helped, not only to generate new knowledge in translational research and in the development of research projects but also to learn different ways of approaching scientific research”. Moreover, she has had the chance to refresh her German speaking skills – at least to order food and drinks by herself. And she was able to enjoy the rainiest summer of her life!