Matthijs Verhage: Learning from mice
‘Mice and humans are genetically very similar, but in our department we take care not to look at mice as if they were small humans.’
Matthijs Verhage is the head of the Department of Functional Genomics at the Center for Neurogenomics and Cognitive Research. The core business of this group is gene-function research: finding out how genes and synapses work, how they save information. To generate all this knowledge, Verhage and his colleagues use mice: they change genes of these mice and study what happens.
First they formulate a hypothesis about the function of a certain gene. Then they perturbe the system, for instance by knocking out or overexpressing the targeted gene. Next, they analyse what happens, on various levels. ‘We have many tools. We use functional assays, electromicroscopy, immunocytochemistry, network analyses , we study behaviour and more.’
After Verhage’s group finds out what the result of a perturbation is, they proceed with more and more subtle perturbations, to gain more detailed knowledge about the gene function. A way to achieve this is to disable phosphorylation and thereby prevent activation. By making very small changes, sometimes changing only one amino acid in a gene, Verhage and his colleagues reveal very detailed information about gene functions. ‘Eventually, our goal is to find out how genes cooperate in networks to account for certain biological functions. For this we have to modify and study multiple genes.’
The knowledge generated by Verhage’s work has applications in the understanding and possible treatment of all kinds of brain disorders: cognitive disorders, autism, depression and epilepsy. In cooperation with other research groups, Verhage’s group is working on a new, recently discovered gene involved in human depression called piccolo.
Biology of piccolo
Currently, Verhage and his colleagues are creating two new knockout mice, one with a knocked-out piccolo gene and one with the human variation gene, which is associated with depression. ‘By studying these mice, we can learn a lot about the biology of piccolo and how the variant found in humans may influence this. This will help us to understand the genetic basis of the human disease and the environmental influences in the development of the disease.’
Since Verhage has been working at the CNCR for a number of years, he already has a lot experience in cooperating with other research groups. He has close ties to several related groups, although he thinks the Neuroscience Campus will make these even stronger. ‘Because there is money available now, we can facilitate several project more easily. The Neuroscience Campus also gives us opportunities to cross borders. We are very interested in mathematical modelling, and in laser technology to study cell processes. It is great that we will be able to use these advanced technologies.’
