Funded projects

The Solve-RD brokerage service aims to fund 50 projects (so called Seeding Grants) to functionally validate newly discovered disease genes. Below you'll find a list of all funded projects.

Jamile Hazan | Giovanni Stevanin (ERN-RND)

By exome analysis Giovanni Stevanin and his colleagues at INSERM-ICM in Paris identified rare homozygous missense variants in a new candidate gene in three patients of a consanguineous family with symptoms of a specific type of hereditary spastic paraplegia (HSP) and mild mental retardation and learning problems.

The Solve-RD RDMM-Europe Seeding Grant will allow the generation of a Zebrafish model by Jamile Hazan and her group at Sorbonne University (Paris). The successful applicant has extensive experience with the examination of the physiopathology of HSP in vertebrate models and has already done preliminary work to clarify the function of the new candidate gene.

Start date: February 2021

Bart Dermaut & Elke Bogaert | Antonio Vitobello (ERN-ITHACA)

The group of Antonio Vitobello at the University Hospital Dijon-Bourgogne identified novel gene variants in several patients with symptoms like developmental delay, skeletal abnormalities, heart defects and motoric and intellectual impairments. The symptoms are different in severity, but featured in similar patient phenotypes. Most variants emerged by de novo mutations of a gene which is involved in the regulation of posttranscriptional mechanisms.

The Solve-RD RDMM-Europe Seeding Grant will allow to study the impact of the variants in a Drosophila model by the team of Bart Dermaut and Elke Bogaert at Ghent University in Belgium. The group has vast experience in studying flies for Alzheimer's and several other neurological disorders. In addition Drosophila is the best suited model organism for the approach as the respective gene is highly conserved between fly and human.

Start date: January 2021

Pertti Panula | Bjarne Udd (ERN-EURO NMD)

The group of Bjarne Udd at the Folkhälsan Research Center (University of Helsinki) / Tampere Neuromuscular Center, Finland identified a novel disease gene in patients with adult onset distal myopathy. Solve-RD RDMM-Europe Seeding Grant funding will now allow the generation of a Zebrafish model by the group of Pertti Panula at the University of Helsinki. Zebrafish (Danio rerio) is preferred as model organism as it has an ortholog of the gene of interest. The lab of Pertti Panula has extensive experience with genetically modified zebrafish models and quantitative analysis to identify motor, sensory and social anomalies.

Start date: November 2020

Gaurav K. Varshney | Siddharth Banka (ERN-ITHACA)

The group of Siddharth Banka at the Manchester Centre for Genomic Medicine identified novel missense gene variants in several unrelated patients with neurodevelopmental disorders. The patients presented moderate to severe intellectual disability, developmental delay, behavioural problems and in addition occasional congenital malformations. Exome sequencing revealed that all patients carry rare missense variants in a novel candidate gene.

The Solve-RD RDMM-Europe Seeding grant will allow the generation of a Zebrafish model by Gaurav K. Varshney and his group at the Oklahoma Medical Research Foundation. The applicant has extensive experience with clinical collaborations, and his primary focus is the use of zebrafish and gene editing technologies to study human disease models.

Start date: October 2020

Howard Lipshitz | Antonio Vitobello (ERN-ITHACA)

The group of Antonio Vitobello from CHU Dijon identified a novel gene variant in two unrelated patients with polymalformative syndrome. The patients both present with developmental delay and multiple malformations and exome sequencing revealed that both patients carry the same rare missense variant in a gene that has not been associated with human disease so far.

To answer it´s causative implication in the disease the Solve-RD RDMM-Europe Seeding Grant will allow the generation of a Drosophila melanogaster model by Howard Lipshitz and his group at the Department of Molecular Genetics, University of Toronto, Canada. The applicant has extensive experience and a proven track record in the functional validation of human genes in Drosophila. This is the first Solve-RD Seeding Grant awarded to a scientist identified via our partner network RDMM in Canada.

Start date: September 2020

Michela Ori | Antonio Vitobello (ERN-ITHACA)

The group of Antonio Vitobello from CHU Dijon identified novel gene variants in patients with facial dysmorphism. Loss-of-function mutations of the respective candidate gene have previously been described as causative in a rare genetic disorder characterized by developmental delay and intellectual disability.

The Seeding Grant will allow the generation of Zebrafish and Xenopus mutants by Michela Ori and her group at the Department of Biology, University of Pisa, Italy to model the dysmorphic phenotype. Michela has extensive experience in molecular embrology and has previously used Xenopus and Zebrafish animal models to study craniofacial development.

Start date: August 2020

Ype Elgersma | Laurence Faivre (ERN-ITHACA)

Solve-RD partner Laurence Faivre from CHU Dijon and colleagues discovered a novel de novo missense variant in a gene in four individuals affected with a severe neurodevelopmental disorder of unknown cause.
The RDMM-Europe Seeding Grant awarded to Ype Elgersma at Erasmus University Medical Center in Rotterdam will allow to assess the pathogenicity of this rare genetic variant. The project involves expression of the mutant form in developing mouse embryos and in primary neuronal cultures and analysis of the resulting phenotypes. Ype has great expertise in functional genomic screenings to assess the pathogenicity of genetic variants identified in individuals with neurological development disorder.
Start date: August 2020

Conrad Weihl | Ana Töpf (ERN-EURO NMD)

The group of Ana Töpf and Volker Straub at the John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University identified new vary rare variants of a gene in patients with severe respiratory failure, dyspnoea and spine rigidity. The RDMM-Europe Seeding Grant of 20,000 EUR awarded to Conrad Weihl and his group at the Washington University School of Medicine will enable the functional validation of the disease causing gene in a knockout mouse model. The group has vast experience in working with mouse models of neuromuscular disorders. In addition, biochemical studies will be carried out in knockout myoblasts to unravel putative mechanism of pathogenicity.
Start date: July 2020

Sara Wells | Stephanie Efthymiou (ERN-RND)

The group of Stephanie Efthymiou and her colleagues at the UCL Institute of Neurology identified novel variants of a gene associated with severe neurodevelopmental disorders. Homozygous carriers of the alleles come up with severely delayed psychomotor development. Neurophysiological investigations indicated severe demyelination, axonal neuropathy and loss of cerebral white matter.

The RDMM-Europe seeding grant will facilitate the generation of a mouse model by Sara Wells at the Mary Lyon Centre, MRC Harwell Institute by using CRISPR/Cas9 technology to alter this novel gene. The model will play an important role in understanding the pathological consequences of the novel gene variants. In particular, the mutants will be studied for phenotypic features observed in the patient, such as neurological development, locomotor activity and behaviour. Modelling this human disease will not only help to provide further evidence on this new rare genetic disease and hence to improve diagnostic and management strategies, but will also facilitate assessment of potential treatment possibilities for patients.

Start date: July 2020

Binnaz Yalcin | Lisenka Vissers (ERN-ITHACA)

The group of Lisenka Vissers and her colleagues at Radboud University Medical Centre identified novel variants of a gene associated with complex cortical dysplasia and other brain malformations. Affected patients are clinically characterized by neurodevelopmental delay, intellectual disability and refractory epilepsy.
The RDMM Europe Seeding Grant will facilitate the characterisation of a knock-in mouse model by Binnaz Yalcin and her group at University of Burgundy, Dijon, France as part of Inserm U1231. For the validation of the novel gene variants the mouse model will be characterized by histological and neuroanatomical methods as well as in behavioural tests. By modelling this novel rare human disease we expect to improve diagnosis and future treatment possibilities for affected patients.
Start date: March 2020