The Mastermind of the Brain Atlas

Jan Mulder, head of the brain initiative

Today we introduce a new feature on the Human Protein Atlas blog, interviews with scientists involved in the project. First out is Jan Mulder, head of the brain initiative.

– I am a biologist, specialized in neurobiology with a PhD in molecular neurobiology from Rijksuniversiteit Groningen, The Netherlands.

In 2004, at the same time that the Human Protein Atlas project was producing its first antibodies, Jan Mulder came as a post-doc to the group of Tomas Hökfeld at Karolinska Institute. In collaboration with Mathias Uhlén and the Human Protein Atlas he began to explore the possibilities to use antibodies raised against human targets on rodent brain tissue. After a three year stay in the University of Aberdeen as an Alzheimer Research Trust fellow, Jan returned to Sweden to continue the work on the rodent brain atlas at SciLifeLab Stockholm.

The first version of the Mouse Brain Atlas was launched as a part of the Human Protein Atlas database in October 2015, and aims to cover all major brain areas and subfields of the mammalian brain. It currently includes a set of genes that are well known reference genes expressed in the different cell-types that populate the brain, and genes with known or predicted specialized functions not yet studied in relation to brain and brain functions.

–Our initial aim is to provide information on the overall distribution of proteins in the central nervous system, Jan Mulder says.

The size of the mouse brain allows the protein distribution to be visualized in complete coronal cuts of the brain, thereby creating a more complete overview with preserved orientation.

–The whole idea of the Mouse Brain Atlas is to include a translational aspect to the Human Protein Atlas, Jan Mulder explains. We use the antibodies generated in the Human Protein Atlas to stain rodent brain tissues. There is actually a lot of overlap between human and rodents, especially in the protein coding DNA. The knowledge about similarities and differences in the human and mouse brain is of great importance when using animal models to study human health and disease.

By using rodent brain tissue the aim is to go from the four brain areas from human that are in the Tissue Atlas today, to 127 areas from the mouse, to allow for a better overview of the brain.

–We try to sample the mouse brain in sections with a 400 micrometer interval, Jan Mulder says. This will cover approximately 90-95 percent of all brain areas.

In addition to the Mouse Brain Atlas, there are several international brainmapping initiatives, such as the Allen brain atlas initiative in Seattle and GenSat at the Rockefeller University.

–Both these are enormous efforts mainly focusing on gene expression. With the information from our work, we can complement their data with exact localization of the proteins in the cells, Jan Mulder says.

In Jan Mulder´s group antibodies from the Human Protein Atlas against proteins expressed in the mouse nervous system are validated on mouse brain tissue using western blot and immunohistochemistry. Antibodies that pass validation are used to generate detailed protein distribution profiles.

The group of Jan Mulder is also a part of the Stockholm brain institute, a Vinnova-sponsored Berzelii-center.

–This is a collaboration between groups at KI and KTH and industry partners Atlas Antibodies and GE Healthcare. In this project we screen human brain tissue, cerebrospinal fluid and blood plasma for novel markers for neurodegenerative disorders. We are trying to find new markers in the human brain to diagnose neurodegenerative disease.

It is not impossible that also this data generated by the Jan Mulder group also will be incorporated into the Human Protein Atlas in the future.

–I think this is knowledge that will be very good to share with the public, Jan Mulder concludes.

Explore the brain specific proteome here

Explore the Mouse Brain Atlas here