Although I enjoyed all the chalk talks this past week, I was especially impressed by Adam’s project—ultrasensitivity in CRISPR systems. I definitely believe that CRISPR is going to fundamentally change the ways in which scientists, engineers, and clinicians approach gene editing, and I think it is of huge importance that we better optimize this amazing system. A recurring theme in the synthetic biology world at the moment, it seems, is developing “logic gates” in biological systems, or mechanisms for producing binary and predictable responses to stimuli from biological systems (I know that this theme is especially common within iGEM, of which Adam and I are a part). Binary responses rely on the concept of ultrasensitivity, or the idea that miniscule changes in the amount of stimulus in a system can induce significant changes in response to that stimulus.
The implications of creating a binary, ultrasensitive logic gate using CRISPR are broad. For synthetic biologists, CRISPR’s unique ability to target specific sequences within a cell’s genome will open new avenues for creating sequence-based logic gates. The concept: if a sequence is present in the cell, then induce a response (and if this sequence is not present, then do not induce the response—a system is considered “ultrasensitive” if the amount of noise between these two possible outcomes is at the absolute minimum). Adam’s approach for creating sequence-based ultrasensitivity is one that is also being tested by Duke iGEM this year—utilizing “decoy binding sites” to titrate stimulus in the system. Essentially, the idea is that one can remove stimulus molecules from the system until a very specific concentration of those molecules is achieved in the system, after which they will induce a response all at once. With luck, this will achieve a certain degree of ultrasensitivity!!
