August 20, 2016 at 03:50AM

Today I Learned: 1) ...that setting up a routing policy with multiple domains isn't trivial, even(?) for a University IT guy. 2) One of the big elephants in the room when it comes to synthetic biology is mutational escape from circuits. Most things humans try to program bacteria to do aren't actually good for those bacteria, so they tend to evolve out of whatever those things are. It turns out to be *incredibly difficult* to build circuits to be robust to mutation -- pretty much any circuit you can think of is one well-chosen mutation away from failure, and a population of billions of bacteria can choose mutations really well.... I've been thinking about how to get around the problem of mutational escape. One way is to reduce the mutation rate (for instance, by removing error-prone polymerases). A crazy idea I've been toying with is to grow a bacteria with multiple genomes, so that the cell can check its genomes against each other and correct errors (or die when a mutation is detected). How effective could that be? It's not perfectly effective, because even if a cell detects a mismatch between the two sets of genes, it would have no way to know which one is correct, so it would have some probability of flipping the backup copy to the mutation instead of flipping the mutated copy back to the correct sequence. Today I crunched those numbers, and figured that having a second set of chromosomal DNA to act as a correcting mechanism would reduce point mutation rate by about 50%. That's not a huge gain for the complexity that mechanism would require. 3) CRISPR was discovered in the '80s and '90s, not the '00s like I thought. That means that bacterial genome sequencing was happening well before I thought -- I assumed the bacterial sequencing craze happened in the wake of the human genome sequencing project, not before it.