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1+1=3 observing the same sample with multiple technologies to gain deeper insights in biology function

Understanding biology is increasingly more complex and requires to combine a growing number of techniques to highlight subtle differences that drive a cell from a physiological state to a highly aggressive tumorous cell. In the strive to decipher biological mechanisms underlying tumorigenesis, imaging takes an ever growing importance.

Rendering of 'C Merge' view
Rendering of ‘C Merge’ view

Initiated 20 years ago, Institut Curie has taken a leadership in developing imaging technologies from the molecular to the whole organism level. From electron microscopy, chemical mapping and nanoSIMS to light microscopies, the imaging plateform has grown into a multipolar and integrative core facility of Institut Curie.

To further integrate imaging technologies into a continuum scale, two scientist from Institut Curie (Xavier Heiligenstein and Perrine Paul-Gilloteaux) have developed an intuitive and multi-modal software to combine informations obtained with different microscope from the exact same object. More specifically, this approach, named correlative microscopy aims at merging the functional informations from the live cell fluorescence imaging together with the ultrastructure information from the high resolution and contextual electron microscopy for example.

Although initially created to correlate images from light and electron microscopy images, eC-CLEM (for easy Cell Correlative Light and Electron Microscopy) is conceived to be compatible between every type of imaging modalities, from cell to whole organism level.

Based on tumor location paradigm from the medical field, the statistical approach used by eC-CLEM allows registration of object with a precision of a few percentile of the lowest resolved image, allowing to locate and decipher structures with high efficiency and precision.

The combination of two technologies bring a higher insight hence 1+1=3 (A reference often used by Pr Paul Verkade).

The mathematical approach is described in a paper published in Nature Methods 1 in February 2017 but has already been used for several high quality and impact journals 2–4.

eC-CLEM opens a bottleneck in image processing in correlative microscopies, widening the application range to more multiplexed, multi-modal imaging approaches, especially correlative light and electron microscopy.

  1. Heiligenstein X, Paul-Gilloteaux P, Belle M, et al. eC-CLEM: easy Cell Correlative Light to Electron Microscopy. Nat Methods. 2017.
  2. Delevoye C, Heiligenstein X, Ripoll L, et al. BLOC-1 Brings Together the Actin and Microtubule Cytoskeletons to Generate Recycling Endosomes. Curr Biol. 2016;26(1):1-13. doi:10.1016/j.cub.2015.11.020.
  3. Karreman MA, Hyenne V, Schwab Y, Goetz JG. Intravital Correlative Microscopy: Imaging Life at the Nanoscale. Trends Cell Biol. 2016;26(11):848-863. doi:10.1016/j.tcb.2016.07.003.
  4. Hampoelz B, Mackmull M, Machado P, et al. Pre-assembled Nuclear Pores Insert into the Nuclear Envelope during Early Development. Cell. 2016:1-15. doi:10.1016/j.cell.2016.06.015.

Image © Xavier Heiligenstein / Institut Curie