Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder for which an effective treatment is still lacking. We recently made a breakthrough by elucidating the molecular mechanism underlying a subtype of CMT (CMT2D) and demonstrating the therapeutic potential of an innovative treatment modality - tRNA. With this project we aim to show the feasibility of using a viral vector to deliver the tRNA molecule to peripheral nerves and to advance the development of a novel gene therapy for CMT.

Matchmaking event (Amsterdam-Schiphol 8 November 2018) to bring (potential and existing) scientific and non-scientific partners together to get the best NWA LEAD application possible and get to know each other. We aim to inspire and find new partners and stakeholders that want to be involved in this and related projects to shape a first-class application and consortium.

Traumatic events can haunt one for life. Intrusive and recurrent recollections of the trauma are the main feature of posttraumatic stress disorder (PTSD), a disorder one can develop following trauma. This suggests a role for a maladaptive trauma memory trace in PTSD. Studies in transgenic mice have demonstrated alterations in the distribution of cells that store the trauma memory, but the molecular mechanisms are unknown. In this project I will make use of a state-of-the-art technology, spatial transcriptomics, to close this knowledge gap by revealing the full gene expression of trauma memory cells and thereby molecular pathways involved in PTSD.

The left hemisphere (LH) of the brain is dominant for language function in the majority of the population. Yearly, over one million people worldwide suffer LH-damage due to stroke and remain permanently impaired in language functioning. Patients with LH-damage may show global right-hemisphere (RH) activity for language, but little is known about RH-recruitment during language use. My project aims at a fundamental understanding of dynamic RH-recruitment in LH-stroke, i.e., during language use at the actual millisecond timescale of language processes. Understanding the mechanisms of RH-recruitment is important for neurolinguistic and neuroscience theory as well as for clinical applications. I will recruit (premorbidly right-handed) patients with stroke-induced damage to the LH and matched controls. I will employ two well-established experimental paradigms that measure word-production processes and advanced neuroimaging techniques to examine structural and functional aspects of RH-recruitment during language use. This approach is unprecedented in the study of language neuroplasticity. For function, I will employ magnetoencephalography to measure the brain’s electrophysiological signal, a direct measure of neuronal activity with millisecond temporal-resolution. Neuronal operations leave behind particular fingerprints in the electrophysiological signal, allowing one to track language processes in different brain areas. Using these neuronal fingerprints, I will examine whether the new RH-language system in patients is capable of performing the same neuronal operations as the language-dominant LH of matched controls. For structure, I will employ tractography on diffusion-weighted imaging data to estimate the integrity of the corpus-callosum fibres, connecting different areas in the two hemispheres. I will assess whether poor integrity of different parts of the corpus callosum imposes structural constraints on RH-recruitment. My results will elucidate structure-function relationships that shape brain organisation and will help refine existing anatomical models of language function. Additionally, they will contribute to developing personalised language-treatment strategies that make maximal use of a patient’s neuroplastic potential.