It seems that scientists are using many types of microscopy in combination with cutting edge software to answer their complex question. They seek to view tissues and cells in great detail over time to gain spatial and temporal information. There are some microscopy techniques that have been around for quite some time that can provide the desired resolution, such as cryo-electron microscopy, but the system doesn't work well with live cells.

With single-molecule resolution, researchers can now observe changes of individual molecules and their behavior over time. This involves labeling the molecule with a fluorophore, capturing spatiotemporal data and then using computation analysis for detection and tracking of the molecule. One example tracks VEGF2-2 activation and mobilization on the surface of endothelial cells. Using single-molecule imaging the scientists revealed the role that VEGF (signaling protein) has on stabilizing VEGF-2 (ligand) interactions at the receptor. Gaining this type of information will help scientists develop a deeper understanding of cell biology.

Other scientists are using techniques like (FILM) and fluorescence resonance energy transfer (FRET) to visual changes over time. These methods provide a way to discriminate between cell states and environments of a fluorophore. Researchers used this tool to determine intestinal stem cell behavior in different environments. The team from the University of Cork in Ireland, using this technique found that stem cells have the ability to increase their metabolism in low glucose environments whereas differentiated cells cannot. Again, they can leverage this knowledge and apply it to other areas of cell biology to learn more specific details.

An emerging field in cell biology is using these advanced microscopy techniques and applying them to the transcriptome, or the total profile of expressed RNA within a cell or tissue. This research aims to bridge the gap between spatial information gained from traditional RNA sequencing and molecular profiles gained for imaging techniques. Several research groups are working in this space and developing new tools. Much of the work leverages current imaging techniques such as single-molecule fluorescence in situ hybridization (smFISH) and computational analysis such as t-Distributed Stochastic Neighbor Embedding (tSNE) to visually map gene expression in a beautiful way that can link structure and function. Scientists involved in this research are confident that these techniques can be applied to a wide variety of cell states and cell types.

These are just a few examples of the great breadth of work currently being conducted by cell biologists. While we have come a great distance in our fundamental understanding of how cells function, scientists are pushing these boundaries and seeking to make new discoveries with cutting edge technology and innovative thinking.

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