A Decade of High-Impact Science

CCP’s CONTRIBUTION TO THE WORLD’s LEADING JOURNALS

Over the last ten years, the Czech Centre for Phenogenomics (CCP) has evolved from a nascent infrastructure into a powerhouse of biomedical research. While CCP is renowned for its service to the user community, its scientific footprint is perhaps best measured by the calibre of publications its team has co-authored. From unravelling the fundamental “dark matter” of the genome to responding to global pandemics, CCP researchers have consistently published in the world’s most prestigious journals, including Nature, Cell, and Nature Genetics.

Decoding the Mammalian Genome: The IMPC Flagship Papers

A significant portion of CCP’s high-impact output stems from its leadership role within the International Mouse Phenotyping Consortium (IMPC). CCP researchers were instrumental in a series of landmark studies that have fundamentally changed our understanding of mammalian biology. In 2016, CCP contributed to a pivotal study published in Nature titled “High-throughput discovery of novel developmental phenotypes“. This study was crucial in identifying genes essential for life, revealing that nearly one-third of all gene knockouts result in embryonic lethality. This was followed by a 2017 breakthrough in Nature Communications regarding sexual dimorphism. The study, “Prevalence of sexual dimorphism in mammalian phenotypic traits“, utilized the massive datasets generated by centres like CCP to prove that sex influences the phenotype of gene mutations far more than previously thought, a finding that has since reshaped how preclinical trials are designed globally. Further cementing its role in metabolic research, the team contributed to a Nature Genetics study in 2018 (“Identification of genes required for eye development…”) and metabolic phenotyping papers that have become reference texts for the field.

A 2021 Nature Genetics article reported the creation of a resource of targeted mutant mouse lines for 5,061 genes, an enormous community asset in which CCP played a central part via the International Mouse Phenotyping Consortium and INFRAFRONTIER, leveraging its large-scale gene-targeting, mouse production, and phenotyping infrastructure. Follow-up Nature Communications and Scientific Reports papers in 2022 and 2024, co-authored by CCP scientists, analysed genome-wide knockout mouse databases to identify candidate ciliopathy genes and quantified how essential genes influence the success of genome-editing projects that generated thousands of new engineered mouse lines, further consolidating CCP’s position as a core node in the global “encyclopaedia of gene function”. These efforts feed directly into CCP’s rare disease and RD-Factory activities, as the same platforms enable systematic modelling of human gene variants and phenotypes.

Unravelling the Mechanisms of Rare Diseases

Beyond broad genomic screens, CCP has excelled in deep, mechanistic studies of rare diseases. A prime example is the 2023 study published in Nature, which investigated the complex autoimmune condition APS-1. The paper, “Autoimmune amelogenesis imperfecta in patients with APS-1 and coeliac disease“, relied on CCP’s advanced phenotyping to uncover why the immune system attacks tooth enamel in these patients. By creating and analysing specific mouse models, the team provided the mechanistic link between a genetic defect and a specific clinical symptom, offering new hope for diagnostics and treatment.

Responding to Global Crises: The COVID-19 Breakthrough

The agility of the CCP was put to the ultimate test during the COVID-19 pandemic, and the results were world-class. Utilizing its state-of-the-art BSL-3 facility and advanced mouse modelling capabilities, the CCP team played a key role in a 2021 study published in Nature. The paper, “Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice“, was a tour de force of translational medicine. CCP researchers generated the precise humanized mouse models needed to prove that a novel bispecific antibody could effectively neutralize the virus and prevent it from mutating to escape treatment. This publication not only showcased the centre’s infrastructure but its ability to pivot instantly to address urgent societal needs.

Setting the Standards for the Future

Most recently, CCP has continued to lead by setting the standards for the next generation of genetic engineering. In 2024, the team contributed to the “LAG-R guidelines“, published in Nature Communications. This work establishes the global gold standard for reporting animal genetic engineering, ensuring that the explosive growth of CRISPR/Cas9 technology yields reproducible and reliable science.

These publications represent just the tip of the iceberg. Over the last decade, CCP has demonstrated that it is not merely a facility for housing animals, but an intellectual hub where the function of genes is deciphered. By consistently publishing in top-tier journals such as Nature, Nature Communications, Nature Genetics, Cell, Cell Reports, EMBO Molecular Medicine and Molecular Cell, underscoring its role as a key European hub for mouse genetics, phenotyping, and translational biomedicine.