Dresden International Graduate School for Interdisciplinary Life Sciences

At our Institute for Clinical Genetics, we provide specialized care for patients with intellectual developmental disorders, brain malformations, complex syndromic conditions, metabolic diseases and genetic tumor risk syndromes (GENTURIS). The close integration of clinical care and translational research is a defining feature of our institute - particularly in the context of these complex conditions. Our research is therefore organized around the following key objectives:

• Identifying and validating disease-causing genetic variants
• Associating novel disease genes with a specific phenotype
• Investigating underlying pathomechanisms using state-of-the-art technologies to elucidate how genetic variants contribute to disease
• Developing personalized therapeutic strategies

To achieve these goals, we integrate large-scale sequencing, multi-omics approaches, bioinformatics, and big data analysis with functional studies in cellular, patient-derived, and in vivo models. This combined approach enables us to investigate how genetic variation affects biological processes and drives disease.

As part of the DKFZ/NCT/DKTK-MASTER program, we apply high-throughput multi-omics technologies to analyze patient-derived and tumor samples, identifying clinically relevant genetic variants. We evaluate genetic variants of potential clinical significance for hereditary cancer risk, and study variants of uncertain significance and novel candidate genes by assessing their functional impact and the molecular pathways they affect.

To dissect disease mechanisms, we employ a range of experimental approaches – including biochemical and molecular analyses and advanced 3D cell culture models. These models allow us to study how genetic alterations influence cellular behavior and to test targeted interventions, such as pathway-specific inhibitors. Our overarching goal is to improve diagnostics, refine risk assessment, and contribute to the development of genomically informed therapies.

With a particular focus on neurodevelopmental disorders, we investigate how neurons develop, migrate, and form functional networks during brain development – and how disruptions to these processes contribute to disease. Using advanced molecular biology techniques, we manipulate genes and identify affected biological pathways across diverse experimental systems – from cell-based models to more complex in vivo approaches. By linking genetic variation to neuronal dysfunction, these studies aim to deepen our mechanistic understanding of neurodevelopmental conditions and ultimately support the development of novel therapeutic strategies.

Through comparative and evolutionary genomics, we aim to identify genes underlying conserved traits ancestral to mammals. Incorporating evolutionary constraints as a framework to quantify gene involvement in specific adaptations provides a powerful tool for improving genetic risk assessment and advancing personalized medicine.