My aim is to unravel the neurobiological mechanisms underlying drug addiction with a particular focus on relapse mechanisms related to alcohol and nicotine. These studies have a strong multidisciplinary character and include behavioural analysis, proteomics, neurophysiology and opto- and chemogenetic approaches.
The focus of my team is on cognition and how it is affected by neuropsychiatric ailments, such as depression. We study maladaptation of synapses and circuitry brought about by unique molecular signatures in hippocampus and prefrontal cortex.
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.
My research focuses on studying the topological organization of the human brain network, in health and disease. We map and study the human connectome, the ‘road map of the human brain’ and how complex brain function and disfunction may arise from the topological network properties of the human brain network. With my background I bridge psychology, neuroimaging, mathematics, informatics and medicine.
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.
Our goal is to understand the specific molecular, cellular and network adaptations that occur in the brain in the earliest stages of Alzheimer’s diseasse, and to test how these adaptations can be used for early disease diagnosis and intervention.
We want to understand how events at the synaptic and cellular levels are involved in behaviour. To reach this goal, we take a multidisciplinary approach in which we combine electrophysiological recordings and imaging from single neurons and networks of neurons with behaviour. By using molecular interventions, optogenetics and assessing the consequences at different levels of organization, we try to get an understanding of the causal relationships between activity of synapses, neurons, neuronal networks, and cognitive behavior. In collaboration with the Neurosurgery department at the VU medical centre, we study the function of human neuronal circuits to test whether basic principles discovered in rodents hold in human cortical microcircuits.
Our research aims to discover new glial-based mechanisms of information processing in the brain in health and disease, with a focus on the role of astrocytes in the regulation of myelin and synaptic plasticity.
We study the interactions between neurons and glial cells, both in the healthy brain and in the context of neurological diseases. In particular we focus on the white matter disease MLC, a disease characterized by dysfunctional astrocyte water and ion homeostasis leading to chronic white matter oedema. Our team is embedded in both the VU University medical center (Department of Childhood Neurology headed by Prof. Marjo van der Knaap) and the CNCR (Department of Integrative Neurophysiology headed by Prof. Huibert Mansvelder).
My research aims to unravel cellular and circuit mechanisms by which the cerebral cortex transforms sensory signals into perception, and ultimately into behavior.
We study how individual cortical neurons encode sensory stimuli and how sensory representation is affected by behavior. The rodent barrel cortex is an excellent system to study these questions since the individual sensory organs (facial whiskers) are represented by easily identifiable cortical columns. Additionally, our group is part of an international effort to understand human brain function at (sub)cellular resolution.
Our goal is to gain mechanistic insight into the neural circuitry, cells and molecules that support persistent memories of negative and positive experiences.
The main goal of my research team is to identify the bio-molecular framework on which aversive associative memories are built and maintained throughout their lifetime.
I aim to mechanistically understand how assemblies of synaptic proteins contribute to synaptic plasticity in health and disease
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.
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.
Complex behaviors that arise in response to stimulus-rich and demanding environments require the coordinated function of different brain circuits at distinct time-scales, to maintain higher-order cognitive functions, such as attention, learning, memory and decision-making. Our main goal is to identify the neuromodulatory forces that mediate these processes, highlighting maladaptations that lead to aberrant cognition.
We aim to understand the role of neuronal oscillations for cognition in health and disease.
The main focus of my research is unravelling the cellular basis of human cognition. Traditionally the research on neurobiology of human intelligence focuses on either studying genetic variants associated with intelligence GWAS or imaging of brain areas of intelligence. My ambition is to link these two approaches by studying the function and gene expression in human neurons from neurosurgery in relation to cognition.
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.
At Neurospector we aim to accelerate drug development for brain disorders by using predictive human neuron cell models and scalable live microscopy read-outs of neuronal activity.
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.
While twin- and family studies have shown that many traits are considerably heritable, the role of specific genes in heritable traits remains poorly understood and genes that are identified, only explain a small portion of the trait variance. The focus of this group is on modeling complex and dynamic traits in such a way that the probability to uncover the genetic basis is maximized.
Research in this group aims at elucidating underlying biological pathways of brain-related traits and translating these to modifiable targets that can aid in treating brain disorders. We integrate knowledge from different fields, including psychiatry, genetics, neuroscience, machine learning, bioinformatics and mathematics.
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.
Although a glial component in neurological disorders is increasingly appreciated, we still lack proper understanding of neuron-glia communications. Our goal is to identify and describe glial defects in neurodevelopmental disorders, and to perform proof-of-concept studies for glial-targeted therapy strategies using advanced stem cell technologies.
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.
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.
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.
My Neuroproteomics team aims to (1) describe the protein complex nano-machinery that underlies synapse function and plasticity, and (2) reveal the alteration of synapse/tissue proteomes in cases of neuro-degenerative and neuropsychiatric disorders. Mass spectrometry based quantitative proteomics analysis is the leading technology behind these studies.
The Vision and Cognition group is led by Pieter Roelfsema, also director of the Netherlands Institute for Neuroscience. Research of this group is directed at understanding cortical mechanisms of visual perception, memory and plasticity. One of our goals is to create a visual cortical prosthesis to restore vision in blind people.
The overall objective of the Laboratory for Neuroregeneration is to unravel the biological mechanisms that govern successful regeneration in the PNS and that underlie degeneration and regenerative failure in the CNS. The primary long-term research objective is to make significant contributions to the field of restorative neuroscience and neurology.
The Sleep & Cognition group of Eus van Someren and Ysbrand van der Werf works at several locations, including their home base of Netherlands Institute for Neuroscience (KNAW), the VU University (FALW-Integrative Neurophysiology), the VUmc (Dept. Anatomy and Neurosciences) and the Leiden University Medical Center (Sleep Center Leiden). Against the background of their 24-hour rhythm, driven by the circadian clock of the brain, sleep and wakefulness show a mutual dependency.
