New Technique Enhances Understanding of Cellular Communication

Cells communicate and interact with their environment through the secretion of proteins, which serve as messengers or signals for communication between cells. Studying these secreted proteins, particularly those from immune cells, and correlating them with their source cells can provide valuable insights into immune responses in patients with chronic diseases like cancer, autoimmune disorders, and infectious diseases. This knowledge can also accelerate the development of immunotherapies. However, understanding how cells interact and coordinate with each other in response to stimuli or pathogens remains a challenge for scientists.

To address this gap, a team of researchers from the National University of Singapore (NUS) has developed a novel technique called time-resolved assessment of single-cell protein secretion with sequencing (TRAPS-seq). Led by Assistant Professor Cheow Lih Feng, the team aims to study immune cell responses at a single-cell level. By capturing secreted proteins using surface proteins on cells, TRAPS-seq allows for the analysis of these proteins using existing techniques. The key advantage of TRAPS-seq is its ability to track the source cell and measure changes in protein secretion over time in response to stimuli.

The researchers reported  this breakthrough in Nature Methods. TRAPS-seq offers a powerful tool for gathering data on cell functionality. By modifying surface proteins on cells, the technique anchors secreted proteins, enabling correlation with the cell's functionality, transcription, and surface phenotypic profiles. The NUS team tested TRAPS-seq by monitoring the secretion of three types of cytokine proteins from T cells. They observed dynamic changes in protein secretion over time and identified sub-populations of T cells with different secretion profiles, demonstrating the method's potential for uncovering new cellular mechanisms.

The researchers are currently able to profile three secreted proteins simultaneously and aim to increase this number to 10. While immediate applications are likely in immunology profiling, TRAPS-seq has the potential to study any secreted protein. The researchers envision adapting extensive catalogues of antibody pairs for ELISA to TRAPS-seq for detecting a broad range of secreted proteins in various applications. This innovative technique holds promise for scientists in their pursuit of therapeutic targets related to dysregulated protein secretion.