Purity by design: Reducing impurities in bioproduction by stimulus-controlled global translational downregulation of non-product proteins

My work during my PhD here at ETH Zurich has revolved a lot around coffee. Not only did I drink substantial amounts of this invigorating magic brew but it also featured heavily in my research. Working in synthetic biology, the endeavor to predictably modify and design cell function, I earlier built a gene expression system & a cell-based therapy controlled by caffeine. Now, another milestone in my quest to introduce my favorite molecule into science has been published!

For this publication, coming out in the journal Metabolic Engineering, I went for the opposite approach. Instead of upregulating one gene, I decided to downregulate everything else. Controlling a global cellular protein production shutdown with caffeine accomplished the downregulation part. Then, I screened for protective elements which allowed me to still produce select proteins during this downregulation. As shown in the paper, my approach can be for instance used to produce biopharmaceuticals in a relatively pure way. As this is a market of over $100 billion, that could be a pretty big deal. In other terms, this could be an interesting approach for a minimal chassis for synthetic biology, less disturbed by all the surrounding cellular proteins.

In any case, rest assured that I’m not done yet with caffeine (or coffee for that matter)!

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