The aim of BRAINSCAPES is to map in detail the biological mechanisms underlying multiple brain disorders ('brainscaping').

Recent genetic discovery studies have provided unprecedented insight into the genes involved in brain disorders. The next step is to use this knowledge for gaining mechanistic disease insight. In BRAINSCAPES we will develop novel analytic and experimental tools to study the functional consequences of risk genes on the function of specific cells, their circuits and functional output. We aim to provide insight into the molecular and cellular basis of complex brain disorders that can be used to design novel treatments.

The next step in brain related research

We won’t stop until we know it all, by using 5 complementing strategies:


May 29, 2024

A chromatin-accessibility map of the human embryonic brain

Through a tightly organized cascade of patterning, specification and differentiation events, the human brain develops into a highly complex system capable of unique cognitive abilities beyond those of other mammals. Although gene expression across the developing brain has been described at single-cell resolution, similar atlases of chromatin accessibility have been primarily focused on the regulatory landscape of the developing human forebrain in the second-trimester of pregnancy. A collaboration between Marijn Schipper and Danielle Posthuma from CNCR-CTG and Camiel Mannens and Sten Linnarsson from the Karolinska Institute Sweden has opened a new window in creating the first map of chromatin accessibility and paired gene expression in the entire embryonic human brain in the first three months of development. The study is published May 1, 2024 in Nature.
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January 25, 2024

About the strength of consortia (part 1)

On 12 December 2023 the Annual Amsterdam Neuroscience meeting took place at the RAI Amsterdam. In the afternoon a special session was dedicated to “Consortia at work”. Different “duos” involved in large consortia explained the strength and added value of these collaborative initiatives. In this first part we highlight the talk by Prof. dr. Huib Mansvelder and Prof. dr. Boudewijn Lelieveldt, two of the lead-PIs of BRAINSCAPES, who shared their experiences and involvement in the prestigious US Brain Initiative Cell Atlas Network (BICAN). This large-scale effort sees eleven different groups (and techniques) combined to develop cell atlases of the primate brain. In the past years BICAN’s predecessor has yielded its first important successes, and achieved things that no other single lab could do at this scale. Besides this, consortia help to extend networks and (importantly) are also just great fun! 
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October 6, 2023

Single-cell reference mapping to construct and extend cell-type hierarchies

Single-cell RNA-sequencing is increasingly used to map the cellular heterogeneity of complex tissues. For example, more than 300 studies profiled a total of over 44 million cells across different brain regions, ages, and species. Since different research groups usually specialize in different cell-type compartments, these datasets usually differ in terminology and annotation depth. Our understanding of cellular diversity can be greatly enhanced by integrating these datasets to obtain a comprehensive atlas. In a recent publication, Lieke Michielsen, Marcel Reinders and Ahmed Mahfouz, in collaboration with the group of Fabian Theis (Helmholtz Centrum München), present ‘treeArches’, a framework to automatically build and update such reference atlases with a corresponding cell-type hierarchy. The atlas can be used to transfer cell annotations to new unlabeled datasets, facilitating reproducible analysis.
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May 22, 2023

In the spotlight: interview with VICI recipient Dr. Ingo Willuhn

Recently, BRAINSCAPES PI Dr. Ingo Willuhn and his team were awarded an NWO VICI grant for their research into the function of serotonin and dopamine across brain regions. While there are already quite extensive insights into the individual action of these two neuromodulators, there is little understanding of the combined effects of these two systems on the brain. The VICI grant will allow Dr. Willuhn and his team to study interactive dopamine and serotonin signals in multiple brain regions. With this they aim to improve knowledge on the neurobiology of dysregulated behaviors, such as impulsivity which is a core symptom of several psychiatric disorders. Thus, ultimately, the findings may lead to the improved treatment of psychiatric disorders. Now that the good news has been received, Dr. Willuhn is organizing things to get started on the research. We have asked him a few questions on how things are going.
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March 23, 2023

Similar but not the same: generating midbrain dopaminergic neuron heterogeneity during development

In their review recently published in Nature Reviews Neuroscience, Oxana Garritsen, Eljo van Battum, Laurens Grossouw and Jeroen Pasterkamp provide a comprehensive overview of the different molecular subsets and heterogeneity of dopaminergic neurons in the ventral midbrain of mice and humans. The authors first compare the currently defined subsets and then address molecular mechanisms that generate this diversity and that regulate subset positioning and target innervation in embryonic and early postnatal development. In addition, axonal wiring mechanisms and biological functions of dopaminergic neuron subtypes are extensively discussed. To further understand and treat diseases related to dopaminergic neurons, such as Parkinson disease, this review highlights the necessity of obtaining more extensive knowledge on midbrain dopamine neuron heterogeneity.
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February 23, 2023

Short report of the BRAINSCAPES Career afternoon

On February 22nd a BRAINSCAPES Career afternoon was organized by our Career and Training Committee. The aim of the event was to offer our PhD students and post-doctoral researchers the opportunity to gain practical insights into different career paths after completing a PhD or post-doctoral research period. As such we invited two consortium members and two external speakers to tell their career story. The interactive setup and lively discussions gave interesting insights which are hopefully of value for our new talents in shaping their own future career path.
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This figure summarises all the ways genetic association results for the 12 individual psychiatric disorders were annotated and the extent to which annotations shared between psychiatric disorders were identified. First, overlap in SNPs, mapped genes, and genomic loci was examined. Subsequently, gene set and gene property analyses were conducted, examining, for each of the 12 psychiatric disorders, whether the genetic signal was enriched in 9,508 gene sets, 565 cell types and 53 tissue types. Partitioned LDSC was used to test for enrichment of 61 functional genomic categories. All pictures used in this figure are illustrations and do not reflect the actual pathways identified in the analysis.
December 12, 2022

Exploring the genetic overlap among twelve psychiatric disorders

In a study published in Nature Genetics, Cato Romero, Mats Nagel, and Sophie van der Sluis teamed up with colleagues from the Complex Trait Genetics department and the Million Veteran Program to scrutinize the genetic similarity of twelve psychiatric disorders. Besides identifying shared genes and biological substrates between pairs of disorders, they also elucidated the challenges jeopardizing the future success of cross-trait genetic research. 
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November 28, 2022

Optimizing study designs for iPSC-based disease modelling

In a study published in Molecular Psychiatry on Nov 24th, three Brainscapes teams across two work packages worked together to optimize statistical power for iPSC-based study designs. Their analyses demonstrate that published case-control iPSC studies are generally underpowered. 
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October 6, 2022

BRAINSCAPES consortium day 2022

On Friday, September 30, the BRAINSCAPES annual meeting was held in Leiden at the CORPUS congress center. Over 50 members participated in the event and well represented the 7 institutes that are involved in the project.
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July 20, 2022

Characterising social stress responsive ventral tegmental area neurons

Researchers from UMC Utrecht characterized neurons in the ventral tegmental area that respond to stress, paving the way for future research into the functional contribution of this population to stress-driven changes in reward processing.
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