Seminar: Building cooperative biological functions

Written by: Karmella Haynes. Our first invited speaker is Mo Khalil from Boston University. Eukaryotic systems operate using combinations of modules (proteins and DNA), and not necessarily bimodal switches. Mo discussed his interest in harvesting the combinatorial functionality of the gene-regulation machinery. He has done beautiful work to dig deeply into the function of these proteins by engineering variants that show intermediate levels of activity. By modifying specific amino acids within the regulator proteins, he demonstrated the tunability of protein-DNA and protein-protein interactions in yeast.

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Chromatin is a relatively new frontier for rational design of biological systems. A major outstanding question is how do the components of chromatin cooperate to regulate gene expression? Mo argues (and I agree) that we can only fully understand it by attempting to build it. To this end, his group systematically targeted a bevy of synthetic fusion chromatin proteins to a reporter gene. The synthetic chromatin proteins can be turned on and off through a regulatable promoter. This system has made it possible to generate a novel set of classifications that describes how chromatin proteins work together, synergistic activators, dominant repressors, etc. rather than as single actors (i.e., activator or repressor). Mo’s system opens up a world of possibilities for expanding our understanding of chromatin mechanisms, and represents some of the pioneering work to push the boundaries of chromatin research and bioengineering.

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