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A selection of articles by Georgios Hatzopoulos (June 2019)

Opto-magnetic capture of individual cells based on visual phenotypes
From e-Life (2019)

Paraphrasing the Anna Karenina’s principle, all happy cells are alike, every unhappy cell is unhappy in its own way. How can we identify those rare, unhappy cells within a mixed population? Despite the advances in sorting techniques, there are still technical limitations making the isolation of rare cells challenging. To address this problem, Binan et al., created a new approach that allows the isolation of live cells based on specific traits. They call their new method Single Cell Magneto-Optical Capture (scMOCa). The approach is based on their earlier technique termed Cell Labelling via Photobleaching (CLaP) that allows tagging of individual cells. Even though they are not too good in naming techniques, the outcome is quite neat. How does it work? Add biotin-4-fluorescein (B4F) to the cells, find the interesting ones with a confocal microscope and illuminate them with 473 nm excitation laser to crosslink biotin to plasma membrane. Next, add streptavidin-coated ferromagnetic beads and then use a strong magnet to pull out the cells of interest. That’s it! Simple, cheap and it can be used in many cell types. Using this method would allow to select those cells with weird phenotypes that have been disregarded, allowing to study them in detail.

Binan L. et al, “Opto-magnetic capture of individual cells based on visual phenotypes“, eLife, 2019.

Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes
From Science (2019)

What would make a protein ideal for experiments in cells? Any cell biologist would love to be able to add a chemical group or a bright dye at a specific position on the protein of interest. One powerful way to accomplish this is by introducing a non-canonical amino acid (ncAA) at a specific position. The ncAA are synthetic amino acids designed to hold certain chemical functionalities such as coupling to fluorophores. The method to introduce ncAA into proteins is called genetic code expansion. Through a painstaking process, it is possible to re-programme a specific codon (usually a stop codon) to incorporate a ncAA instead. However, the major drawback is that every stop codon in the host cell is a potential target for the incorporation of ncAA leading to non-specific modifications.

In this novel paper by the Lemke group, they hop onto the phase separation trend and in an intuitive way combined it with the genetic code expansion. The novelty they introduce is that they bring all the necessary components for the translation of the desired mRNA into close proximity; limiting the non-specific modifications. The most efficient way they achieve this is by using proteins FUS and EWSR1 that are known to undergo phase separation in cells. The outcome is astounding. Membraneless organelles can build designed proteins from natural and ncAA, carrying new functionalities. They finish the paper with the conclusion that this novel concept could be the basis for development of new types of organelles that extend the functional repertoire of natural complex living systems.

Reinkemeier C. et al, “Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes“, Science 29, March 2019.

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