Student Projects
Genetics of Autism
Aim: determine gene variation associated with autism
Experimental work: analysis of DNA array data, database analysis of gene contents, quantitative PCR
Contact: Peter Burbach
Developmental Expression Of Autism Genes
Aim: determine location and timing of expression of autism candidate genes during brain development of the mouse
Experimental work: PCR, gene cloning, in situ hybridization, neuroanatomy, immunocytochemistry
Contact: Peter Burbach
Functions Of Autism Genes In Cortical Neurons
Aim: determine the effect of gain- or loss-of-function of autism candidate genes on cortical neurons in culture.
Experimental work: neuronal culturing, immunocytochemistry, confocal microscopy, cell transfection
Contact: Peter Burbach
Molecular biology of axon growth
Aim: identify the molecules that control axon growth
Experimental work: microarray & microRNA array analysis, quantitative PCR, gene cloning, cell biology, gene transfer, neuron culture, microscopy
Contact: Jeroen Pasterkamp
Development of striatal and dopaminergic pathways
Aim: understand how mesostriatal circuits are wired
Experimental work: in situ hybridization, neuroanatomy, immunocytochemistry, FACS and microarray analysis, cell and explant culture, in utero electroporation, genetic mouse models, microscopy
Contact: Jeroen Pasterkamp
Identification of receptor and intracellular signalling proteins involved in axon guidance
Aim: determine how neurons sense and respond to axon growth and guidance cues
Experimental work: proteomics, biochemistry, cell biology, in situ hybridization, neuroanatomy, immunocytochemistry, genetic mouse models, microscopy
Contact: Jeroen Pasterkamp
The molecular basis of ALS
Aim: characterize recently identified ALS susceptibility genes (in collaboration with Department of Neurology, UMC Utrecht)
Experimental work: cell biology, in situ hybridization, neuroanatomy, immunocytochemistry, genetic mouse models, microscopy.
Contact: Jeroen Pasterkamp
Development of viral vectors for RNAi in the brain
Aim: Knockdown of genes involved in energy balance in the CNS
Experimental work: viral vector technology, analysis of gene and protein expression
Contact: Roger Adan
Role of genes in energy balance and feeding behavior
Aim: determine the role of genes in the brain by studying gene expression and local knockdown of genes by RNAi
Experimental work: injection of AAV in rat brain, behavioural analysis, neuroanatomy
Contact: Roger Adan
Unravelling mechanisms of overconsumption
Aim: determine the neural substrate that underlies overconsumption
Experimental work: behavioural analysis, neuroanatomical techniques (in situ hybridisation etc)
Contact: Roger Adan
Genetics of feeding behavior
Aim: determine genotype-phenotype relationships
Experimental work: neurogenetics, bio-informatics, molecular biology
Contact: Roger Adan
Interspecies genetics of eating disorders
Aim: determine gene variations associated with eating disorder traits
Experimental work: mouse behavioral analysis, DNA genotyping, and gene expression profiling in the brain
Contact: Martien J.H. Kas
Behavioral, pharmacological and neurochemical characterisation of compulsive behavior
Aim: characterisation of a mouse model for obsessive-compulsive behavior
Experimental work: mouse behavioral analysis, micro-dialysis, pharmacological studies
Contact: Martien J.H. Kas
G-protein coupled receptors and synaptic integration in the ventral tegmental area
Aim: determine how GPCRs regulate excitatory and inhibitory input to dopamine neurons in the VTA.
Experimental work: whole-cell patch clamp recordings, pharmacology, immunohistochemistry
Contact: Geert M.J. Ramakers
The role of axon guidance molecules in acticity-dependent synaptic plasticity in the hippocampus
Aim: determine if and how axon guidance molecules regulate LTP and LTD in the CA1 field of the hippocampus.
Experimental work: field potential recordings, pharmacology
Contact: Geert M.J. Ramakers
The role of G-protein coupled receptors in cellular and synaptic plasticity in the striatum
Aim: determine how GPCRs regulate cellular excitability and excitatory and inhibitory input to medium spiny neurons in the striatum.
Experimental work: whole-cell patch clamp recordings, pharmacology, immunohistochemistry
Contact: Geert M.J. Ramakers
Measuring dopamine overflow in the striatum using fast scan cyclic voltammetry
Aim: quantify stimulus-induced dopamine overflow in the striatum and determine the effect of repeated drug exposure on stimulus-induced dopamine overflow.
Experimental work: fast scan cyclic voltammetry, pharmacology
Contact: Geert M.J. Ramakers
Striatal substrates of cocaine addiction
Aim: determine how alterations in dopamine and glutamate neurotransmission in the rat striatum underlie the progression of cocaine use to cocaine addiction.
Experimental work: drug self-administration, stereotaxic surgery, behavioral pharmacology
Contact: Louk Vanderschuren
The neurobiology of social motivation and reward
Aim: determine which neural systems are involved in the motivational and rewarding properties of social play behavior in adolescent rats.
Experimental work: place conditioning, runway conditioning, visual analysis of behavior, behavioral pharmacology
Contact: Louk Vanderschuren
The genetic basis of alcohol abuse
Aim: determine which genes are responsible for the escalation of alcohol intake in mice.
Experimental work: drug self-administration, PCR, in situ hydridisation
Contact: Louk Vanderschuren
Open search for Lmx1a and/or Lmx1b interacting proteins
Aim: find and characterize the (protein-) complex that Lmx1a and/or Lmx1b require for their regulation
Background: Among several of the already characterized transcription factors found to be involved in mdDA neuronal development, are the LIM homeodomain proteins Lmx1a and Lmx1b. Both are required to trigger differentiation into mdDA neurons, and are expressed in overlapping fields in DA cell progenitors, early in the molecular program. It is already known from previous studies, with Lmx1b knock-out mice, that lack of Lmx1b results in improper differentiation of mdDA neurons; the mice showed absence of Pitx3 expression in TH positive neurons, a factor required for proper specification of mdDA neurons. Together with this improper specification, an early loss of neurons was also found in the knock-out mice.
To investigate how these factors are exactly involved in mdDA development and maintenance, we first have to identify the role of these transcription factors in the molecular cascade.
Contact: Marten Smidt
The role of Lmx1a in midbrain development
Aim: analyze several genes from a list of candidate genes that seem to be regulated by Lmx1a
Background: Among several of the already characterized transcription factors found to be involved in mdDA neuronal development, are the LIM homeodomain proteins Lmx1a and Lmx1b. Both are required to trigger differentiation into mdDA neurons, and are expressed in overlapping fields in DA cell progenitors, early in the molecular program.
To investigate what the role of the transcription factor Lmx1a is in the molecular cascade of mdDA development and maintenance, we want to identify (in)direct targets of Lmx1a.
One option to find these downstream targets of Lmx1a is by means of Micro array analysis. A large collection of genes that are expressed in Lmx1a overexpressing MN9D-cells was generated already. Now, of this list with candidate genes, the genes that are involved in the pathway(s) leading to mdDA neurons have to be identified.
Contact: Marten Smidt
Functional analysis of schizophrenia candidate genes in mice
Aim: characterisation of a mouse model for schizophrenia
Experimental work: mouse behavioral analysis, gene expression analysis and pharmacological studies
Contact: Martien J.H. Kas
Functional Characterization of a Bacterial Cyclic Nucleotide Regulated K+-channel
Cyclic nucleotides (cNMPs) are important secondary messenger molecules that mediate a multitude of processes by activating several different proteins in the signalling cascade. One such family of proteins relates to ion channels. Upon binding cNMPs the channels open, which results in change in membrane potential of cells. Channels regulated by cNMPs have been extensively characterized in sensory systems like rod- and cone-photoreceptors, and excitatory cells in heart and brain, but the molecular mechanism of activation remains poorly understood. The aim of the current project is to comprehend the effects of ligand binding on channel opening.
The project involves functionally characterizing a bacterial homolog (mlCNG) of cNMP regulated channel by electrophysiological methods. The mlCNG channel serves as a useful model system, as structural reference data is available on the domains of the channel separately. Furthermore, the channel protein has also been studied with respect to ligand binding, but the activation profile by electrophysiological measurements is lacking. Electrophysiological measurements will be performed on the mlCNG channel by patch-clamp techniques on giant bacterial sphaeroplasts and liposomes.
This project will be undertaken as collaborative effort between Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology (G.M.J. Ramakers) and the NMR Spectroscopy Research Group (M. Baldus), Bijvoet Center for Biomolecular Research at the University of Utrecht.
Contact: Dr. G.M.J. Ramakers (g.m.j.ramakers@umcutrecht.nl), Prof. Dr. M. Baldus (m.baldus@uu.nl; http://www.nmr.chem.uu.nl) or Dr . A. A. Cukkemane (a.a.cukkemane@uu.nl; http://www.nmr.chem.uu.nl).
The importance of stress hormone pulsatility for keeping the brain responsive to stress.
Objective: The importance of stress hormone pulsatility for keeping the brain responsive to stress.
Techniques: field potential recordings in slice preparations from rodent brain
Contact: Henk Karst
The influence of early life environment on behavioral function in adulthood
Objective: The influence of early life environment on behavioral function in adulthood.
Techniques: behavioral observations, neuropharmacology
Contact: Henk Karst
