Cell Signaling and Communication

Billions of cells, each with a one-of-a-kind role and behavior, make up living systems. Our expertise in systems biology, functional genomics, and biochemistry, enhanced by state-of-the-art capabilities in high-resolution imaging and single-cell multiomics measurements, helps untangle the mechanisms by which cells communicate and exchange chemical signals. Quantitative studies of how individual cells grow and interact with their neighbors or hosts provide a critical understanding of molecular-level events underpinning the behaviors of complex biological systems and their responses to the changing environment. 

The science 

Expertise in the Cell Signaling and Communication Integrated Research Platform (IRP) allows us to localize and isolate individual cells from complex biological samples for further structural and functional analyses. Then, researchers can observe the live, intact cells and measure their unique responses over time to capture minute differences in cellular functions and outputs. Our technical capabilities enable labeling and characterization of subcellular structures and molecules in real time to quantify how, when, and where organisms exchange molecular signals and nutrients to foster interactions. As we begin to better understand and differentiate single-cell behavior, we are poised to predict the functional outputs of interconnected biological systems as a function of their environment. This enables an informed design of individual organisms and multicellular/multispecies systems with highly improved environmental and industrial properties for biomanufacturing and biosecurity applications. 

How we do the science 

The amalgamation of high-throughput omics measurements with high-resolution visualization technologies serves as a stepping stone towards understanding the molecular interactions regulating a microbiome’s response in a quantitative and predictive fashion. The Cell Signaling and Communication IRP enables user science through its current capabilities and strengths in cell isolation, multiomics measurements, and live and fixed single-cell fluorescent imaging, including the following: 

• Advanced sample preparation and cell separation technologies to isolate individual cells or unique populations based on their size or optical properties for propagation and downstream phenotyping and omics analyses. These approaches are crucial to obtaining samples from distinct microenvironments that allow us to assess functional heterogeneity within spatially structured communities. 
  • Fluorescence-activated cell sorting (FACS) 
  • Laser capture microdissection (LCM) 
  • High-precision single-cell isolation and dispensing (cellenONE) 
• Next-generation sequencing and mass spectrometry to capture micrometer-scale heterogeneities in gene and protein expression within distinct subpopulations or individual cells, which are otherwise lost using traditional bulk analysis. 
  • Nanodroplet processing in one pot for trace samples (NanoPOTS) 
  • Bulk single-species and meta-transcriptomic analyses 
  • Single-cell/subpopulation transcriptomics 
  • Split-pool barcoding transcriptomics 
• New chemical biology and mass-spectrometry imaging (MSI) to capture the interactions of small molecules and provide information on the movement, localization, and functional state of proteins/enzymes: 
  • Matrix-assisted laser desorption/ionization (MALDI) MSI 
  • Activity-based probe imaging 
  • Activity-based proteomics 
• Single-molecule and super-resolution fluorescence microscopy helps us visualize morphological features and molecular complexes in live cells with nanometer spatial resolution, shedding light on the dynamics and localization of discrete functions within complex microbial systems. These capabilities are complemented with live microscopy measurements, which allow time-resolved observations with minimal damage to understand dynamic processes in live or intact cells:  
  • Structured illumination microscopy (SIM) with confocal Airyscan imaging 
  • Fluorescent in situ hybridization (FISH) 
  • NanoLive holographic microscopy 
  • Lattice light-sheet (LLS) live microscopy 

Research in action

Community phenotyping 

Community phenotyping identifies the characteristics and collective traits of groups of organisms. Researchers examine how regulatory adjustments within organisms can impact neighboring cells. This information is critical to understanding how molecular-level events influence the genetic expression of traits, which then drive biological system behaviors. 

Live cell interactions

Researchers develop and deploy high-resolution dynamic imaging to capture real-time molecular activities within cells. These measurements shed light on the breadth and complexity of biological interactions across space and time and are key to revealing the structure–function relationships of multicellular systems. 

Metabolic mapping

An understanding of organism interactions, signaling, and resource sharing is vital in predicting how individual cells and communities will adapt and acclimate to changing environments. Capturing the breadth and complexity of biological interactions across space and time is key in revealing organismal relationships. These relationships influence microbiome function, stability, and plasticity.