To investigate the dynamic life of RNA in neural cells, we employ a powerful suite of modern techniques. A key focus is on local translation—the process by which proteins are synthesized directly at the synapse in response to neuronal activity. To isolate this critical compartment, we utilize sophisticated methods such as synaptosome isolation by FACS and gradient centrifugation, allowing us to purify functional synaptic junctions and directly examine the translational events. We complement this with translatome profiling to capture a global snapshot of all the mRNAs actively being translated into proteins, giving us an unparalleled view of the functional genome. To bridge the gap between basic discovery and human disease, we utilize iPSC-derived cell types (such as neurons and astrocytes), creating human-relevant models that allow us to study disease mechanisms and screen for potential therapeutics in a patient-specific context.
Our work delves into the specific mechanisms that govern RNA function and fate. We investigate how RNA editing fine-tunes the genetic code post-transcriptionally and how RNA splicing creates a vast diversity of proteins from a limited set of genes. Furthermore, we are probing the role of RNA structure itself, understanding that its three-dimensional shape is a critical determinant of its function. Crucially, we study how these fundamental mechanisms are dynamically regulated by physiological and stress conditions. We explore how challenges such as hypoxia, fluctuations in temperature, and the cycles of sleep rewire the RNA regulatory landscape, revealing how the brain's molecular machinery adapts to the changing demands of its environment.
The ultimate goal of our research is to translate mechanistic insights into a deeper understanding of human disease. We apply our expertise in RNA biology to a range of neurological conditions where RNA dysregulation is strongly implicated. This includes epilepsy, where altered neuronal excitability may stem from faulty RNA editing or splicing; brain tumours, which often impaired RNA regulatory pathways for uncontrolled growth; and neurodegenerative diseases, characterized by the accumulation of misfolded proteins that can be directly linked to errors in RNA processing and translation.By integrating our expertise in techniques, mechanisms, and disease models, we strive to paint a comprehensive picture of RNA biology in health and disease, with the hope of identifying novel diagnostic markers and therapeutic targets for the patients of tomorrow.