Univ.-Prof. Dr. Gaia Novarino
The Novarino group investigates the genetic basis of neurodevelopmental disorders, including epilepsy, intellectual disability, and autism. These conditions affect millions worldwide and are often resistant to treatment. Neurodevelopmental disorders result from mutations in numerous genes, many of which have poorly understood roles in brain development and function. By integrating molecular biology, cellular studies, and behavioral analyses, the group aims to uncover the mechanisms driving these disorders. In addition, our research seeks to uncover convergent mechanisms across similar disorders caused by mutations in different genes. In addition to advancing treatment strategies, this research enhances the overall understanding of brain function, offering valuable insights into the complexity of the human brain and its development.
Focal points of interest
Excitation-Inhibition Ratio in Neural Circuits: We are exploring how disruptions in GABAergic signaling impact the balance of excitation and inhibition, a key factor in neurodevelopmental and neuropsychiatric disorders.
GABAergic Cells and Seizure Disorders: Understanding how deficits in GABAergic signaling contribute to hyperexcitability and the development of epilepsy.z as
Multi-omics of mouse models for neurodevelopmental disorders: We are exploring how mutations in various genes impact different cell types of the brain (with Christoph Bock & Igor Adameyko).
Synaptic development: Studying how mutations in autism-related genes change synaptic development and composition.
Technical proficiency and instrumentation
The Novarino group employs a diverse range of cutting-edge techniques and instrumentation to investigate the genetic, molecular, and cellular mechanisms underlying neurodevelopmental disorders. Our technical expertise spans molecular biology, biochemistry, imaging, and behavioral neuroscience, enabling a multidisciplinary approach to complex questions in brain development and function.
Key methodologies include the generation of mouse and human stem cell models for neurodevelopmental disorders; molecular and cellular techniques; electrophysiology; behavioral analyses; transcriptomics, proteomics, and metabolomics of brain cells and tissues. We are particularly specialized in the integration of these techniques, allowing our group to bridge molecular insights with system-level understanding, paving the way for identifying novel therapeutic targets and biomarkers for neurodevelopmental disorders.
Aspirations for the next 5 years
The Novarino group aims to advance the understanding of neurodevelopmental disorders by uncovering shared and unique molecular pathways. Within this consortium, we aspire to deepen insights into GABAergic neuron function, metabolic contributions, and synaptic proteome changes while fostering translational research to bridge preclinical findings to therapeutic applications.
References
- Knaus SL, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz AL, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G (2023) Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell 186, 1950–1967.e25.
- Deliu E, Arecco N, Morandell J, Dotter CP, Contreras X, Girardot C, Kaesper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G (2018) Haploinsufficiency of intellectual disability-gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience 21, 1717–1727.
- Tarlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch C, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan AO, Gunel M, Gleeson JG, Novarino G (2016) Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorders. Cell 67, 1481–1494.
