New review captures the exciting frontier of spatial biology
In a new review in Current Opinion in Chemical Biology, DANDRITE postdoc Vivek Sanjay Belapurkar, DANDRITE Group Leader Chao Sun, DANDRITE-affiliated researcher and Professor Jørgen Kjems, and assistant professor at MBG Mette Galsgaard Malle explore the latest approaches to multiplexed molecular imaging, looking at how different techniques balance multiplexing capacity with spatial resolution.
What if we could look inside a cell and see not just one or two molecules, but thousands of them, and, crucially, see where each of them is located?
That is the promise of spatial biology: to understand not only which molecules are present in a cell or tissue, but where they are located and how they are organised in relation to one another.
In the new review "Multiplexed Molecular Imaging for Spatial Transcriptomics and Proteomics”, published in Current Opinion in Chemical Biology, DANDRITE postdoc Vivek Sanjay Belapurkar (first author) and DANDRITE Group Leader Chao Sun combine their expertise in protein labelling with the expertise of DANDRITE-affiliated researcher and Professor Jørgen Kjems, and assistant professor at MBG Mette Galsgaard Malle in RNA transcript imaging to explore the latest approaches for simultaneously visualizing multiple RNA transcripts and proteins in biological samples.
The article is open access and includes graphical figures illustrating the different techniques.
Seeing more at once
Traditional molecular imaging techniques can detect only a limited number of molecules at a time. New multiplexed approaches make it possible to detect many more in the same sample, creating increasingly detailed molecular maps of cells.
But seeing more does not necessarily mean seeing more precisely. Different technologies offer different balances between multiplexing capacity and spatial resolution — and finding the right balance remains a key challenge.
“Spatial biology is on the brink of an explosion, where multiplexing capabilities have already skyrocketed. However, these multiplexing techniques rely on unconventional methods to achieve spatial resolution for pinpointing molecules in biological samples,” says Vivek Sanjay Belapurkar
“A trade-off needs to be accepted now so that the right balance of multiplexing and spatial resolution can be achieved to extract and analyse the most information from a biological sample,” he explains.
Navigating a rapidly expanding toolbox
For the authors, the aim of the review is not simply to catalogue the latest technologies, but to help researchers navigate the growing number of possibilities and choose approaches that fit their particular research questions.
"Life is four-dimensional: three dimensions of space, unfolding through time. New spatial omics technologies now allow us to monitor RNAs and proteins and read the molecular programs of individual cells as they play out across an entire organism," says Jørgen Kjems.
The review compares the multiplexing capabilities and spatial resolution of different approaches and provides an overview of where the field stands — and where it may be heading.
“Knowing which molecules are present is only part of the story. With techniques such as DNA-PAINT, we can resolve where individual proteins and RNA molecules are positioned at the nanoscale and how they are organised relative to each other. This spatial information can reveal molecular interactions and cellular structures that would otherwise be hidden,” says Mette Galsgaard Malle.
“The technologies reviewed here will be important in the future for screening for new biomarkers and relevant molecules for neurodevelopmental and neurological disorders,” says Vivek Sanjay Belapurkar.
Read the full review