Since MICS was first developed, meticulously optimized and successfully applied in a set of phenotypic CRISPR screens in Shana Kelley's and Jason Moffat's labs at the University of Toronto, many things have happened. More specifically, many screens have happened. MICS has been employed for sorting suites of cell types across species and across several different targets in various areas of biology, ranging from isolation of bacterially expressed protein binders to identification of stem cell differentiation regulators. These screening efforts now extend far beyond the Kelley and Moffat labs, and, if it had not already been one before, MICS would certainly now deserve the label of a truly collaborative technology bringing engineers and biologists together.
While we greatly enjoy seeing our technology being adopted and adapted, it certainly also poses some challenges, of which throughput is a major one. This time, we are less concerned about the number of cells we can sort in a single screen, but about the number of screens we can run. Therefore, the Kelley lab has started working on a next-generation MICS device essentially since the moment we knew MICS was working. These efforts towards higher parallelization are now well under way and will open a new dimension of sorting screen throughput.
For me, the biologist on the project, the focus shifted to investigation of our CD47-modifier QPCTL in more detail. Its molecular functions inside the cell and its impact on CD47 in the context of immuno-oncology are still not completely understood and many questions remain. Is there an anti-tumour immune effect if the tumour cell does not express QPCTL? Is CD47 the only relevant target in this context? What role does the paralogue QPCT, also known to possess glutaminyl cyclase activity, play? What other functions do QPCT and QPCTL have? To address some of these questions, we again did what we do best: more screens. We looked for genetic interactions, protein interactors, potential substrates and in vivo effects and are now assembling the puzzle pieces to see which picture emerges.
As for the publication itself, it was certainly a door-opener for presenting at conferences, resulting in many interesting conversations. It certainly also contributed a significant amount to my ability to move up the scientific career ladder and landing my next position.
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