A fluorescent protein called GFP (Green Fluorescent Protein) has been used in fluorescence microscopy to allow visualizations and locations of structures it attached to. This protein was able to be used in electron microscopy however, but now an equivalent has been created that can be used electron microscopy allowing for much higher resolutions which could lead to new knowledge of proteins functions.
This new protein is much more versatile and easier to use than other methods and was created by starting with a protein similar to HRP (Horseradish Peroxidase, a common tag but only useful in some cell compartments). This new, yet similar, protein was called Ascorbate Peroxidase (APX) and can function in more areas in the cell such as the cytosol. They also made it able to bind to molecules that HRP can bind to as well, a molecule called DAB, this engineered APX protein is called APEX.
In order to visualize this in electron microscopy, they send a small ring of DNA into the cell where the sequence for the protein they want to visualize is also combined with the sequence to make the APEX protein. When the cell synthesizes the target protein, the APEX protein is bound to it. They then need to inject the DAB molecule into the cell (this needs to be done before imaging with the electron microscope anyway), which interacts with the APEX to clump together and form polymers which can then be detected by the microscope.
With this new technique they were able to visualize structures within mitochondria cells, before with fluorescent imaging the mitochondria would show up as a few pixels. This new protein can even image structures within other areas of the cell besides the cytosol such as the nucleus and endoplasmic reticulum. At the moment researchers are using this technique to image structures within entire cells like neurons in order to understand interactions they make with other cells. They are also working on engineering the molecule to bind to heme, which is found in blood.
The photo here is showing a mitochondria stained with the APEX, the white streaks being the intermembrane space while the darker regions contain the APEX stain.