Axon Initial Segment Biology

The axon initial segment is a key compartment in neurons, it is the site of action potential generation. The axon initial segment structure is actively reorganized to accommodate changes in network activity, making this structure an active checkpoint for signal integration. The aim of our research is to unveil the molecular mechanisms controlling axon initial segment plasticity. We want to understand how neurons can adapt to their environment and how this process is altered in neurological disorders.

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Principal Investigators

Amélie Freal
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Dementia Discovery Group

The research in our group focusses on understanding the early cell biological processes that drive Alzheimer’s Disease and other related dementias. We use human stem cell-derived neurons, astrocytes and microglia combined with CRISPR-Cas9 gene-editing to understand how genetic factors drive the earliest stages of disease pathogenesis. We use this knowledge to develop novel drugs for these disorders, with a strong focus on lipid metabolism. - more info coming soon.

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Principal Investigators

Rik van der Kant
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Molecular Neurodegeneration

Alzheimer’s disease (AD) is the most common cause of dementia, however, effective treatment or prevention of the disease is not available to date. The aim of our work is to identify early factors that drive the pathogenesis in sporadic AD. We employ different disease models and post-mortem brain material to investigate molecular pathways leading to AD pathology.

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Principal Investigators

Wiep Scheper
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Synaptic Computation

Synapses are the basic units of computation in the brain. In my team we study the computational properties of synapses in health and disease. We use physiological- and genetic perturbation experiments and computational modelling in an iterative cycle to study synaptic principles.

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Principal Investigators

Niels Cornelisse
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Neuronal mRNA trafficking and local translation

Neurons are highly polarized and interactive cells that require precise spatiotemporal regulation of their proteins for proper functioning. To achieve this, neurons have the ability to localize mRNAs and locally synthesize proteins. These processes play key roles in the development, plasticity and maintenance of neurons and dysregulation of these processes are increasingly implicated in neurodegenerative diseases. The main focus of my research group is to understand the molecular mechanisms and functional relevance of mRNA trafficking and local translation in neuronal subcellular compartments in health and disease. In particular, we are interested in the role of the endoplasmic reticulum in regulating mRNA localization and local translation and its role in presynaptic function.

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Principal Investigators

Max Koppers
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Secretory vesicle trafficking and recycling

My research group aims to uncover the molecular mechanisms involved in membrane trafficking and recycling in synapses at nanometer resolution. We study of the transport, docking and fusion of secretory vesicles and the sorting of critical synaptic proteins through endosomes. Endosome recycling is important for the maintenance of basic neurotransmission, but it is also highly dysregulated in neurogenerative diseases such as Alzheimer’s disease. We aim to understand the causal relation between disease progression and the disruption of the endolysosomal pathway.

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Principal Investigators

Jan van Weering
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Vesicle Dynamics and Synaptic Plasticity

To process information the brain is constantly changing the strength of individual contacts (synapses) between nerve cells. Strict control of synaptic plasticity is important, as dysregulation of this process is often associated with neurological and psychiatric disorders. The main goal of the lab is to advance our understanding of the mechanisms that support synaptic plasticity and their dysfunction in disorders such as Alzheimer’s, epilepsy, schizophrenia and autism to provide novel treatment options and therapeutic targets.

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Principal Investigators

Ruud Toonen
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Synapse Gene Mapping

Together with the SynGO consortium, we are helping to create an expert-curated knowledge database with information about genes expressed in the synapse, their involvement in biological processes and interaction partners. We aim to add information to the database from our own high-throughput molecular experiments. The low amount of false positives will enable us to perform meaningful and reliable pathway analyses that can aid research into synaptopathies such as autism spectrum disorder and schizophrenia. In addition, my team also focuses on innovative ways to maintain the quality of education with a growing student population.

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Other leadership

Loek van der Kallen
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Neuro-target discovery group

My group uses screening technology to identify novel, targetable disease mechanisms and biomarkers for neurological disorders. We have set-up genome-wide CRISPR-based screening approaches and use these in combination with cellular model systems to: 1) understand the function of unstudied proteins highly abundant in neurodegenerative disorders, 2) uncover novel disease mechanisms, and 3) identify how disease-related processes in brain cells can be reverted.

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Other leadership

Ruud Wijdeven
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Molecular & functional specificity of synapses

Synaptic function is tailored for processing distinct types of information in different circuits. The aim of our research is to understand the molecular processes that establish synapse-type-specific functional diversity and plasticity in neuronal networks. Our lab uses a combination of molecular and genetic tools, together with electrophysiology and high-resolution imaging approaches, to study how specializations in synaptic composition influence synaptic transmission properties to drive network function. We are interested in the dynamic molecular interactions that fine-tune synapse organization in different subcellular regions and brain regions, across neurodevelopment and plasticity, and in brain disorders associated with synapse dysfunction.

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Principal Investigators

Angela Getz
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