BrainTrain program
Events
Training: students can apply for the oncoming courses and workshops >Read more
Video
News
CNCR scientist Heidi de Wit receives NWO-MEERVOUD grant
Principal Investigator of CNCR’s Secretory Vesicle Trafficking research team awarded with €340.000 and guaranteed tenure track appointment.>Read more
Webinar Aug. 2011
Students
Introduction of the students and their goals.
The BrainTrain research program is composed of 4 scientific Research Teams with 3 trainees each and 1 scientific Research Team with 5 trainees. Students will be offered a full traineeship to obtain their PhD at one of our renowned partner universities and work. They will benefit from various worldwide network training events.
The trainees of these research reams will work across the different laboratories involved, thus enabling them to create a multidisciplinary working attitude.
Trainees will greatly benefit from the complementary competence of the cooperating groups.
Research Team 1
Genetics of the healthy and diseased brain
Supervisor: Prof. Dr. Peter Heutink
Clinical Genetics, Section Medical Genomics, VU Medical Center, Amsterdam
I come from India. I did my Bachelor (Honours School) in Biophysics from Panjab University, India. In 2008, I got scholarship to do my master’s in Cellular and Molecular Neuroscience from Tuebingen, Germany where I worked on mouse models of Alzheimer’s disease and induced pluripotent stem cells (iPS cells) from Parkinson’s disease patients. As part of Brain-Train, my aim is to study the pathogenic mechanisms of genetic risk factors for neuro-degeneration, using High throughput – High content cellular screens with (differentiated) iPS/ES cells into neuronal phenotypes as model system. We will perform Cage and nano CAGE expression study of differentiated neurons. These differentiated neurons will serve as a tool to reach our scientific goals and to better understanding of the roles of genes in neuronal function and dysfunction involved in neuro-degeneration.
Supervisor: Dr. Piero Carninci
Omics Science Center, RIKEN Yokohama Institute, Tsurumi-ku, Yokohama, Japan
I am a Bachelor of Science (hons) graduate from the University of Queensland (UQ) in Australia. Prior to starting my PhD, I have worked as a bioinformatician with Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) and with UQ.
My PhD project involves analysing various nano Cap Analysis Gene Expression (nanoCAGE) datasets, including those involved with neurodegenerative diseases. Using the nanoCAGE technology we can accurately capture the transcriptional starting site (TSS), as well as the digital expression rate, of expressed transcripts in biological samples, such as neuron populations. Using various bioinformatic tools and statistics, we can mine nanoCAGE data to uncover differential promoter usage patterns, sophisticated co-expression patterns (e.g. antisense regulation) and build genetic networks in an attempt to understand the genetics of neurodegenerative diseases.
Research Team 2
The Synaptic Interactome
Supervisor: Prof Guus Smit
Department of Molecular and Cellular Neurobiology, CNCR, VU Amsterdam, The Netherlands.
I did my Masters in Biotechnology from the University of Pune in India. Having worked on different areas of Biology, from drug synthesis to cancer biology, I finally decided to pursue my PhD in Neuroscience because of the interdisciplinary nature of the subject in August 2010.
As a part of work package 3, research team 1, our goal within the Brain Train consortium is to characterize the interacting proteins of the AMPA receptor and provide a comprehensive dynamic map of AMPA receptor dynamics in learning paradigms using a proteomics approach. We shall use well established learning protocols such as Pavlovian fear conditioning, T maze, Barnes Maze etc, combined with large scale Immunoprecipitation followed by mass spectrometry of time resolved complexes, to gain new insights in the regulation of AMPARs in learning and memory.
Supervisor: Prof. Eckhardt Gundelfinger
Institute of Anatomy and Cell biology / Center for Interdisciplinary Neuroscience (IZN), Magdeburg, Germany
I obtained my diploma in biochemistry at the Universidad de Santiago de Chile. After that I started working in the center of cell regulation and pathology of the Pontifia Universidad Catolica de Chile where I did my master degree in cell biology researching protein sorting.
I had the opportunity to join the lab of Professor Eckart Gundelfinger in 2009 at Leibniz institute for neurobiology and initiate a PhD in Neurobiology.
Our group is interested to study the mechanisms of synaptic plasticity associated to the extracellular matrix (ECM), in particular, the role of ECM-modifying and -degrading enzymes, such as the matrix metalloproteinase ADAMTS4, on synaptic modification.
Recent work in our laboratory has shown that enzymatic removal of ECM components facilitates lateral diffusion of membrane molecules, including AMPARs. Brevican is one of the most abundant chondroitin sulfate proteoglycans of ECM in adult brain. Previous reports showed that proteolytic cleavage of brevican by ADAMTS4 is associated with enhanced neuronal plasticity, although the mechanisms involved are unknown.
Our research will include a variety imaging technique such as; single molecule tracking, STED microscopy and life cell imaging that will provide insights in the role of ADAMTS4 role in synaptic plasticity.
Supervisor: Prof. Helena Danielson
Beactica AB, Uppsala, Sweden
Leaving the cross-country tracks of Europe behind in 2005, I began my studies of Biotechnology at the University of Applied Sciences in Weihenstephan. Finishing these studies in the beginning of 2010, I could start right away as a PhD student and Early Stage Researcher at Beactica in Uppsala.
In work package 3 of research team2 we are aiming to describe synaptic protein-protein interactions by using Surface Plasmon Resonance (SPR) based biosensors. Specifically, we want to provide a quantitative description of the interaction of the AMPA receptor with the recently identified AMPA-receptor interacting protein GriaIP. Having understood and described the interaction will be followed by screening for compounds that are able to interfere with GriaIP in order to enhance synaptic function. Furthermore, molecular modeling will be used to enrich the results of the SPR biosensor based studies to map potential binding sites.
Research Team 3
Functional Genomics of the Synapse
Supervisor: Dr. Heidi De Wit (coördinator)
Dept of Functional Genomics, CNCR, Secretory Vesicle Trafficking group, VU University Amsterdam, The Netherlands
As early stage researcher participating in research team 3, I will focus on characterising molecular mechanisms involved in secretory vesicle transport processes and exocytosis in neuronal synapses as well as neuroendocrine cells. In order to understand links between genetic variation and synapse-related diseases, we will study alterations on the proteomic level of the synapse due to genetic manipulations and genetic effects on the molecular and cellular secretion mechanism. Our main focus will be on the role of the actin cytoskeleton and SNARE-proteins together with regulatory proteins, like SM-proteins in early steps of the secretory pathway (i.e. tethering, docking, priming). To succeed we will combine a variety of imaging techniques, including electron microscopy (EM, IEM, CLEM) and life cell imaging as well as secretion assays.
Supervisor: Prof. Angus Silver
University College London, Department of Neuroscience, Physiology and Pharmacology London, The United Kingdom
After finishing my Masters in Hungary in Technical informatics and in Biomedical engineering I had the opportunity to join the Silver lab in June 2010.
As a first part of my PhD I am studying gap junction induced synchronization and desynchronization in the thalamic reticular nucleus (TRN). The TRN is a thin layer of GABAergic neurons, which boarders and inhibits the thalamic relay nuclei. It receives glutamatergic excitation from the deep layer of neocortex and also collaterals from the rest of the thalamus. It is known that the major way of communication between these neurons are made by Connexin36 containing gap junctions, although their subcellular location is unknown. The rhythmic behavior of these cells could highly influence the firing pattern of other thalamic and neocortical neurons. Our research will include a variety of electrophysiological techniques guided by two-photon microscopy for identifying coupling behavior as well as intrinsic cell properties so we can build anatomically and biologically correct, multicompartmental models.
Supervisor: Prof. Tomas Kuner
Institute of Anatomy and Cell biology / Center for Interdisciplinary Neuroscience (IZN), University of Heidelberg, Germany
In August 2010 I joined the group of Prof. Thomas Kuner, which is part of the BrainTrain research team 3. We are particularly interested in studying synaptic transmission in thalamic relay cells at defined giant synaptic terminals. To relate cellular function to network and behavioral function, we generate spatio-temporally controlled genetic manipulations in cortical projection neurons or thalamic relay neurons using viral gene transfer and mouse genetics. The functional and structural consequences of these perturbations can be assessed using acute brain slice physiology, imaging, 3D-immunohistochemistry and serial sectioning scanning electron microscopy. Behavioral assays will be adopted to define the contribution of these giant synaptic connections to sensory-motor integration.
Research Team 4
Synaptic plasticity in neural networks
Supervisor: Dr. Rhiannon Meredith
Dept of Integrative Neurophysiology, CNCR, VU University Amsterdam, The Netherlands
A steadfast scientific goal of mine is to understand the changes that lead up to and bring about cognitive and behavioural deficits in an affected population. I hold a BSc in Biochemistry & Genetics from Rutgers University in New Brunswick, NJ USA, and an MSc in Neurobiology from Basel University in Basel, CH. Having previously addressed part of my scientific pursuits through the lens of molecular biology, I now seek to incorporate electrophysiology and large network imaging to probe connectivity and function of brain regions affected in neurodevelopmental disorders.
The overall aim of my PhD is to elucidate the contribution of GABAergic signalling in the manifestation of cognitive and behavioural deficits observed in neurodevelopmental disorders, and specifically in Fragile-X Syndrome. I will be using multi- patch electrophysiology techniques in order to probe connectivity and synaptic signalling in brain areas of interest, along with multi-photon network imaging to probe the function of large networks of interconnected neurons. Additionally, behavioural paradigms known to be driven by specific brain regions will be incorporated into my research, in order link brain-circuitry (dys)function to behaviour. Finally, having identified dysfunctional circuits correlated with abnormal behaviour, pharmacological interventions will be tested in an effort to re-establish canonical circuit function and behaviour.
Supervisor: Dr. Rhiannon Meredith
Dept of Integrative Neurophysiology, CNCR, VU University Amsterdam, The Netherlands
In October 2009 I joined the group of Rhiannon Meredith participating in research team 4. Being an early stage research affiliate, my part of the project focuses on the development of neuronal networks in a model for mental retardation and autism – the fragile X syndrome. Fragile X syndrome is known to be the most common genetic cause of mental retardation in humans and is closely related to autism spectrum disorders. Correct network wiring in the brain is crucial for memory function but also social behaviors. Fragile X patients experience learning difficulties and impairments in a range of social behaviors. Our research is testing the hypothesis that alterations in brain networks in Fragile X syndrome during early developmental periods underlie impaired function later in life in this syndrome.
Spontaneous synchronized network activity during early brain development underlies correct network wiring. We are interested in how this spontaneous activity is affected in fragile X and its underlying mechanisms. We investigate this using a combination of 2-photon calcium imaging and electrophysiological techniques using a mouse model for fragile X syndrome, the Fmr1-KO mouse.
Supervisor: Prof. Claudia Bagni
Department of Human Genetics –Laboratory of Molecular Neurobiology KULeuven-VIB, Leuven Belgium
I am an Indian PhD student with a master degree in Regenerative Medicine. Since November 2010 I am pursuing my PhD directed by Prof. Claudia Bagni in the Laboratory of Molecular Neurobiology at the Katholiek University of Leuven (Belgium) and I am associated to the research group 4 of the Brain Train Program. My research is mainly focused on the identification and characterization of the molecules involved in the regulation of the mRNA encoding for the Post-Synaptic Density-95 (PSD-95) protein. PSD-95 is a centerpiece of an extensive postsynaptic complex that organizes receptors and signal transduction molecules at the postsynaptic area. PSD-95 expression levels are crucial for a correct synaptic transmission. Among the molecules that regulate PSD-95 mRNA is the Fragile X mental retardation protein (FMRP), an RNA binding protein involved in RNA translation, transport and stability. Specifically, FMRP regulates PSD-95 mRNA stability in hippocampus, whilst in cortex seems to regulate its translation. During my PhD, I will explore the different mechanisms that regulate PSD-95 mRNA in both brain regions and specifically the protein complexes involved in such a brain specific regulation. These studies should provide more insights in deciphering the molecular basis of mental retardation. To achieve my objectives I will use several molecular and cellular biology techniques together with mice models of mental retardation.
Supervisor: Prof. Claudia Bagni
Department of Human Genetics –Laboratory of Molecular Neurobiology KULeuven-VIB, Leuven Belgium
Fragile X Tremor Ataxia Syndrome (FXTAS), is a late adult-onset neurodegenerative disease characterized principally by movement and cognitive disorders. This syndrome affects carriers of the permutation condition (55-200 CGG repeats) presents in the FMR1 gene.
The pathogenic basis of the FXTAS is the over-expression of the FMR1 mRNA that, according to the RNA toxic gain of function model, leads to the formation of intranuclear inclusions possibly responsible of the neurodegeneration observed in both patients and mouse model for the syndrome.
During my PhD project, I will characterize the mostly expressed FMR1 mRNA isoforms produced by alternative splicing events of the FMR1 gene in a mouse model for FXTAS. The analysis will be performed in different regions of the brain and at different developmental stages. Finally I will try to unravel which of the isoforms is mainly responsible for the FXTAS.
Supervisor: Dr. Uwe Maskos
Dept. of Neuroscience, Neurobiologie intégrative des systèmes cholinergiques, Pasteur Institute, France
I am a PhD student working in the laboratory of integrative biology of cholinergic system at the Pasteur Institute in Paris.
My project will focus on the involvement of nicotinic acetylcholine receptors in the early stage of Alzheimer’s disease (AD). We are mainly interested in the subunits alpha7 and beta2 that were shown to interact with the pathogenic peptide Abeta. In order to dissect the role of these two subunits we will make use of knock out mice. In the first year of my thesis I will apply several technique such as molecular biology, for the production of lentiviral vectors. I will also perform stereotaxic injections in mouse brain for the delivering of lentiviruses in specific brain’s areas and the local expression of exogenous proteins, and imaging techniques such as fluorescence and confocal microscopy.
Research Team 5
Synaptic transmission and behavioral function
Supervisor: Dr. Oliver Stiedl
Behavioral Neuroscience Research Group, Dept. of Functional Genomics, CNCR, VU University Amsterdam, The Netherlands
As ESR 1 of WP 5 I will use brain-area-specific interventions targeting hippocampus, amygdala and prefrontal cortex. I will investigate the autonomic consequences of these interventions on heart rate dynamics and neural responses (EEG & multi-unit activity). Behavior tests will include hippocampus-dependent fear learning tests on working and reference memory function and fear extinction. Additionally, I will use non-linear methods to assess heart rate dynamics as translational tool with diagnostic features. To minimize human interference, we establish new approaches to monitor fear memory with ECG and neural activity at longer time scales.
Supervisor: Dr. Per Svenningsson
Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
As PhD student in research team 5, I will perform molecular and biochemical studies on serotonin receptors, adaptor proteins and signal transduction pathways. One such adaptor protein, p11, interacts with 5-HT1B receptor and recruits these receptors to the membrane. P11 expression is increased in the rodent brain after antidepressant therapies and decreased in a mouse model of depression and in brain tissue from depressed patients.
We will characterise the cognitive and autonomic phenotype of p11-deficient mice by combining multiple scientific approaches: Protein phosphorylation assays, Glutamate release measurements, Stereotaxic injections/ viral gene transfer, Electrophoresis: 1, 2D-PAGE, Immunoprecipitation/Western blot and Postsynaptic membrane fractionation.
Supervisor: Dr. Christian Gutzen
Biobserve, Bonn, Germany
As early stage researcher in research team 5, I will develop advanced and innovative soft- and hardware for a wide range of behavioral experiments.Besides the refinement of currently available methodology by an inclusion of posture analysis, I will combine behavioral, autonomic and electrophysiological methods in long-term experiments by the synchronization of multiple independent measures and the interface of various hardware components with adequate software. Nonlinear algorithms may further increase the sensitivity of behavioral measures and their qualitative judgment of changes with regard to physiology and pathology.