Summary of the article
Rhianna-lily Smith, Gustav Ceder, Molly Campbell (2024) [Professor Ulf Landegren Discusses Advances in Spatial Biology and 3D Sequencing] Technology Networks, 31 May 2024. https://www.technologynetworks.com/proteomics/blog/professor-ulf-landegren-discusses-advances-in-spatial-biology-and-3d-sequencing-387305
Dr. Ulf Landegren, a professor in the Department of Immunology, Genetics, and Pathology at Uppsala University, has significantly influenced the fields of proteomics and spatial biology through his development of the antibody-based proximity extension assay (PEA) and in situ proximity ligation assay (isPLA). His work has led to the creation of several spin-out companies, such as Olink Proteomics and Navinci Diagnostics, and he currently serves as a scientific advisor at Single Technologies.
In a recent article published by Technology Networks, based on a video interview, Landegren shared his insights on the future of spatial biology and recent advancements in 3D sequencing, highlighting why these innovations are attracting global research interest.
Recent Developments in Spatial Biology
Landegren’s lab has developed a highly accurate technology to locate mutant DNA, which is crucial for identifying malignant cells. Unlike proteins, which are poor markers of malignancy due to their similarity in malignant and benign cells, mutations offer precise indicators of cancerous cells' location, infiltration patterns, surgical margins, and evolutionary history. This spatial distribution of tumor mutations provides a clonal history of the tumor, offering valuable insights for cancer research. RNA sequencing is also a significant focus because RNA reveals the identity of cells. Advanced technologies, like those from Single Technologies, enhance the speed of RNA sequencing. Additionally, DNA readout technologies are increasingly used to study the epigenome, revealing which genome parts are accessible for transcription.
3-D Sequencing
Landegren explains that sequencing began as a one-dimensional process, which eventually enabled the sequencing of the entire human genome. The advent of next-generation sequencing introduced two-dimensional sequencing, massively increasing the capacity to sequence DNA. The next logical step is 3-D sequencing, which allows for an even greater number of objects to be sequenced by packing them in three dimensions. This approach necessitates advanced imaging technologies to quickly and accurately capture this vast array of sequencing data.
In Situ Proximity Ligation Assay in 3-D
Using Single Technology’s 3-D sequencing, researchers can create detailed images of cellular protein activity in three dimensions, revealing how proteins are distributed and their interactions within cells. This capability is crucial for tracking signaling pathways, understanding the effects of drugs on cellular processes, and pinpointing the exact step where a drug interferes with cellular functions. The sheer volume of data generated from these analyses underscores the need for advanced technologies like those developed by Single Technologies.