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 multi-omic 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 functional outputs of interconnected biological systems as a function of their environment. This enables an informed design of organisms and communities with highly improved environmental and industrial properties for biosecurity and health 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, multi-omics 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 micron-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 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) mass-spectrometry imaging (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

Understanding plant metabolic pathways

Plants adapt to stressors and defend themselves through a variety of metabolic processes. One of these processes is the mevalonate (MVA) pathway. Scientists at the University of Missouri and EMSL used forward genetic screening to reveal the importance of mevalonate kinase, a critical enzyme in the MVA pathway, in plant metabolic signaling. Under stress conditions, plants release adenosine triphosphate (ATP) into their extracellular matrix. The researchers showed that MVA kinase directly interacts with an ATP receptor and becomes activated when extracellular ATP is present. This study highlights the importance of the MVA pathway in stress conditions.

Investigating gene regulation in brown rot fungi

Brown rot fungi are common wood decomposers that break down cellulose and produce carbohydrates. The genes that regulate these processes are poorly understood. Scientists from the University of Minnesota and EMSL found that expression of those genes differed depending on whether the brown rot fungi was decomposing wood or another carbon source. The team characterized RNA transcripts and analyzed enzymes to investigate carbon catabolites and how they affect gene expression. Their work indicates that fungi have specialized machinery to control gene expression during wood rot.