Analyzing biology cell by cell and molecule by molecule
1Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala University, Uppsala, Sweden
In basic research and clinical medicine alike, there is a current drive to understand the complexity of tissues by analyzing cells one by one, and molecular assays increasingly aim to characterize individual molecules and the company they keep.
We have developed a family of molecular tools that allow parallel analyses of large sets of proteins or nucleic acids, and that can be used to investigate the molecular composition of individual cells, or map out the distribution of proteins and their interaction partners inside cells in tissues.
The proximity ligation mechanism solves important problems of multiplexing sensitive and specific protein assays, and it can be used to rapidly measure large sets of proteins in 1 µl plasma samples from large cohorts for biomarker studies. Variants of the technique are useful to visualize the distribution of proteins, protein interactions, and protein modifications among cells, and yet other variants permit sensitivity of measurement to be further augmented as needed.
In a recent development the superRCA technique allows individual detected molecules to be magnified to easily detectable clusters of DNA strands that can be detected and enumerated in a regular flow cytometer for digital measurements of nucleic acids or proteins.
Several of the developed methods for imaging proteins in tissues or measuring them in e.g. plasma, are being made available on a national basis as some of the services from SciLifeLab, for scientists who require high-performance protein measurement, event at the level of single cells.