Basak lab

The ventral tegmental area (VTA) is part of the reward system and is characterised as having a heterogeneous cell population that are organized in neural populations that exhibit a more gradual transition, making it difficult to define VTA borders. Extensive research has been done on the VTA, however not on a single cell level. As part of the BRAINSCAPES consortium, we are using single cell RNA-sequencing/ChIC-sequencing to generate reference atlases of the diverse cell populations within the VTA.
 
Our project will provide a new resource whose quality, precision and depth exceeds current literature. This data can be reused by researchers analysing traits linked to different mental disorders, such as depression, as well as those working on neurodegenerative disorders that affect the dopaminergic system, such as Parkinson’s Disease.
 
We also aim to determine how histone methylation contributes to the cellular heterogeneity in the adult brain and determine if long term histone modifications play a role in eating and stress disorders.

The cellular diversity of the reward system is just being discovered. Its developmental origins is yet to be fully understood. Determining the origins of this diversity may help us better understand how our brain is build, as well as whether the underlying molecular program is affected in neurodevelopmental disorders.

We aim to delineate the molecular and cellular mechanisms behind epigenetic regulation of cell fate decisions of neural stem cells (NSCs) during the development of the reward system. For this, we use mouse genetics, bioengineered and pattern organoids, CRISPR-mediate gene ablation and computational tools.

The reward system is defective in several psychiatric and neurodevelopmental disorders. Neurogenetics have identified thousands of risk alleles in hundreds of genes that are altered in patients of neurodevelopmental/psychiatric disorders. A missing link is the identification of how such a large number of mutations lead to diseases with similar sympthoms. A working hypothesis is respective fields is that specific cell types are affected in patients with different mutations. Recent advances in single cell genomics and computational biology offer tools to test these questions in silico. In addition, the boom of CRISPR-mediated gene editing and induced pluripotent stem cell derived neural organoid modelling provide the experimental tools to dissect the function of these mutations.

We have a special interest in understand how this hub of reward and social interaction is altered upon mutations associated with autism spectrum disorder (ASD). We use in utero electroporation assisted CRISPR-mediated gene editing, bioengineered and pattern organoids, to test the data-driven hypothesis.