Our brain is made up of billions of neurons that are precisely connected into neural circuits, forming an immensely complex network that encodes our thoughts, memories and personalities. Cognitive disorders such as autism and schizophrenia are thought to somehow result from changes in the connectivity of this network. Our lab aims to unravel the molecular mechanisms that control neuronal connectivity in developing circuits, and determine how perturbations in this process affect cognitive function.
During brain development, neurons connect with specific target neurons through highly specialized cell-cell contacts called synapses. Synapses are central to the functioning of the brain, and a loss of synaptic connectivity is thought to underlie many cognitive disorders. Understanding the molecular mechanisms that control the formation and maintenance of synaptic connections is therefore essential in order to gain insight into these disorders. However, many fundamental questions about circuit formation are still unanswered. How do neurons recognize their appropriate partners? How are nascent cell-cell contacts differentiated into functional synapses? And how is it that synapses between different types of neurons are structurally and functionally distinct?
To address these questions, we use a combination of proteomics, neuronal cell culture, conditional mouse genetics, viral vectors, electrophysiology and anatomical technques. With this approach, we aim to obtain new insights into the molecular mechanisms that establish precise synaptic connectivity under normal and pathological conditions. Ultimately, these insights will guide the development of new strategies for improved diagnostics and treatment.
Unbiased Discovery of Glypican as a Receptor for LRRTM4 in Regulating Excitatory Synapse Developmentde Wit J, O'sullivan m, Savas J, Condomitti G, Caccese M, Vennekens K, Yates J, Ghosh ANEURON, 79, 696-711, 2013 LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formationDe Wit J, Sylwestrak E, O'sullivan m, Otto S, Tiglio K, Savas J, Yates J, Comoletti D, Taylor P, Ghosh ANEURON, 64, 799-806, 2009
20/08/2015 - Genetic analysis of human patients has shown that mutations in genes involved in synaptic communication can drive neuropsychiatric and neurological diseases such as autism spectrum disorder and Alzheimer’s disease.
15/06/2013 - “When I was fourteen, I already knew I wanted to be a scientist. I was fascinated with biology and how things work. The brain is the last great frontier,” says Joris de Wit.
Joris de Wit
PhD: Netherlands Institute for Brain Research, Amsterdam, '04
Postdoc: Center for Neurogenomics and Cognitive Research (CNCR), The Netherlands, '04-'06
Postdoc: University of California San Diego (UCSD), US, '06-'10
Assistant Project Scientist, University of California San Diego (UCSD), US, '10-'12
VIB Group Leader since January 2013