Newly developed imaging techniques have led to surprising discoveries in the world of microbiology. A research team led by Ralph Youngmann at the Max Planck Institute (MPI) for Biochemistry and at Ludwig Maximilian University (LMU) participated, along with Eugenio F. Fornasero and Felipe Opazo, who served as working group leaders at the University Medical Center. Göttingen (UMG), and the Helmholtz Center in Munich. A high-throughput spatial imaging method called SUM-PAINT allowed them to develop a neural atlas with single-molecule resolution. They have discovered a previously unknown type of synapse. The researchers presented their findings in a study conducted by Edward Untrauer in Youngman’s laboratory. It appeared in issue no. 187/7 special magazine “Cell” (open access articlePDF available). The SUM-PAINT process described here includes a data generation and analysis workflow that can be used by researchers around the world. As noted in the study, this microscope can be used relatively easily with a standard microscope and does not require any special equipment.
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Jungmann believes that SUM-PAINT is not just a milestone in uncovering the complexity of cell biology at the molecular level. This method also has what it takes to enable breakthroughs in the discovery of new therapeutic approaches for neurodegenerative diseases. This provides an opportunity to investigate previously hidden details of neurological disorders and may thus contribute to a deeper understanding of the mechanisms underlying diseases such as Parkinson’s disease or Alzheimer’s dementia.
Synapses as complex protein structures
For the first time, SUM-PAINT makes it possible to display and map large numbers of proteins simultaneously with molecular resolution and lightning speed. As Untrauer explains, one must simultaneously examine the location, identity, and interactions of individual biomolecules to understand the complexity of living systems down to the smallest levels. There are four important challenges to overcome: In addition to the ability to combine multiple signals, this also concerns the criteria of sensitivity, throughput and spatial resolution. The team looked at the complex environment of neurons in the human brain and, for the first time, developed a neural atlas with single-molecule resolution of 30 different types of proteins. He was able to decipher the complexity of the synaptic protein composition of nearly 900 individual synapses. This generates huge amounts of data – which in turn can only be examined in detail with the help of specially developed analysis pipelines powered by machine learning. The analysis captured 1,600 features from the imaging dataset. Characteristics include protein content, distribution, and shape. The researchers discovered a previously unknown type of synapse during this analysis. It only makes up about one percent of all synapses in the human brain. It is not detectable using other imaging techniques.
This study, published on an open access basis, allows interested parties around the world to apply highly detailed imaging for their own purposes based on the methods described.
(PSZ)
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2024-04-01 17:41:54
#Precision #imaging #molecule #revealed #type #synapse
