Molecular mapping of the nervous system in health and disease – Jan Mulder group

The Human Protein Atlas (HPA) is an international core data resource for biological data identified by Elixir (EU) and the Global Biodata Coalition. The mission of HPA is to profile the expression and distribution of all proteins in all major organs and tissues, and our research group has been involved in brain profiling efforts since 2004.

Traditionally our research group has utilized HPA antibodies to map protein distribution in the human and rodent brain. During the recent years the focus has shifted toward transcriptomics analysis of the human brain and we have released a ‘bulk’ transcriptomics dataset covering nearly 200 regions of the human brain.

Currently the group is performing high resolution spatial transcriptomics analysis to get a detailed overview of the location of transcripts in tissue and cells, and is a founding member of the SpatioTemporal Omics Consortium (STOC) that aims to organize and advance global scientific efforts to create spatiotemporally-resolved cellular atlases of all living things.

Ongoing projects

Human Protein Atlas (HPA)

Integration of in house and publicly available omics data on protein expression, distribution and function in the nervous system. The aim is to provide detailed overview of proteins important for brain functions at the level of regions and main cell types (neurons, astrocytes, oligodendrocytes, microglia, vasculature). The HPA project is funded by the Knut and Alice Wallenberg foundation and is a collaboration between the Royal Institute of Technology, Uppsala University and Karolinska Institute.

Mammalian RNA atlas

The Mammalian RNA atlas is a project that aims to map protein expression in all major organs and tissues of non-human mammalian species. The data on the mini pig is currently available, and additional data on macaque, rat, mouse and dog will be released soon. This atlas is built on ‘bulk’ transcriptomics data of about 100 tissue types for each species, supplemented with publicly available single cell and single nucleus RNA-sequencing data. This project is a collaboration between BGI, University of Aarhus, University of Turin and the Human Protein Atlas.

High resolution spatial transcriptomics

Our lab has been involved in studies applying spatial transcriptomics technologies for brain mapping. One of the most recent technologies is stereo-seq, a method that enables an mRNA capture resolution of 500nm. In collaboration with BGI and the Chinese Academy of Sciences in Shanghai, we are mapping RNA expression in developing and adult brain of various species. Utilizing the excellent tissue quality of European brain banks, our focus is on mapping the molecular and cellular organization of the human brain.

Neurodegenerative disorders

To prevent and early intervene within neurodegenerative disorders, it is important to understand molecular and cellular responses that drive neurodegenerative processes. Our lab uses antibody based and transcriptomics approaches to map changes in protein expression and distribution in disease-affected human brain material. Our focus is to find common and disease-specific cellular responses, associated with Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, multiple sclerosis, frontotemporal dementia, amyotrophic lateral sclerosis, and stroke. These projects are supported by the Hjärnfonden, Alzheimerfonden, Alzheimer Nederland, Parkinsonfonden, Dutch Research Council.

Astrocytes in health and disease

Neurons are the signaling units of the brain and therefore get most attention. The properties and many roles of astrocytes are less studied even though they are essential for many physiological processes in the brain. Our lab investigates the molecular properties of astrocytes and their intrinsic and environment-dictated gene expression signatures associated with function and disease. Understanding their adaptive and maladaptive responses in a variety of neurodegenerative conditions provides necessary tools to read the status of the brain.

Publications

All publications from group members

Funding

  • Knut and Alice Wallenberg foundation (HPA)
  • Vetenskapsrådet / Swedish Research Council
  • Hjärnfonden
  • Parkinsonfonden
  • Alzheimerfonden
  • Alzheimer Nederland (Emma Gerrits)
  • Dutch Research Council (Emma Gerrits)

Staff and contact

Group leader

All members of the group

Collaborations

  • Dr. Bart Eggen (Rijksuniversiteit Groningen – single cell transcriptomics)
  • Dr. Cecilia Lindskog (Uppsala University – HPA)
  • Dr. Chengyu Li (Shanghai Center for Brain Science – macaque brain)
  • Dr. Eleonora Aronica (Vrije Universiteit Amsterdam – amyotrophic lateral sclerosis)
  • Dr. Harro Seelaar (Erasmus university hospital Rotterdam – frontotemporal dementia)
  • Dr. Inge Huitinga (Netherlands institute for Neuroscience – multiple sclerosis)
  • Dr. John van Swieten (Erasmus university hospital Rotterdam – frontotemporal dementia)
  • Dr. Longqi Lui (BGI – Spatial transcriptomics)
  • Dr. Marcela Pekna (University of Gothenburg - glia)
  • Dr. Milos Pekny (University of Gothenburg - astrocytes)
  • Dr. Muming Poo (Shanghai Center for Brain Science – macaque brain)
  • Dr. Harro Seelaar (Erasmus university hospital Rotterdam – frontotemporal dementia)
  • Dr. Xun XU (BGI - Spatial transcriptomics)
  • Dr. Yinqi Bai (BGI – Bioinformatics)
  • Dr. Yonglun Luo (Aarhus University – mammalian atlas)
  • Dr. Zhouchun Shang (BGI – spatial transcriptomics)