Huh, cool, does each polymerase only replicate its own linear plasmid? Is there a part of the polymerase protein that’s rapidly evolving that could be defining the specificity?

The 90s was more my radio era than albums, but I’d say each of these are perfect in their own way: RATM, Midnite Vultures, Rangeela, Blackout! (Would have also said 2001, but the skits are terrible.)

What did you think of Gyokeres? Didn’t seem very threatening. Could just need more time to bed in.

I’m really rooting for this approach to catch on! Of the papers I’ve been involved in, this is probably the one I most feel is contributing a different way of thinking. Big shoutout to the co-first authors, Molly Monge (now an MD/PhD student at Cornell) and Simone Giovanetti.

“High throughput” doesn’t have to mean hard/expensive! At its heart, the difference is that instead of picking a few clones of your transformation, you take all the colonies. And with low sequencing costs and the possibility of pooling sequencing, it will generally be affordable.

Second, background mutations. Often in low-throughput approaches, each strain is generated once and split into replicate cultures for experiments. It makes the experiment a lot easier, but any background mutations are shared between replicates! Again, bulk methods can help!

First, replicates. It’s hard to do low-throughput experiments on even a modest number of samples with more than a small number of replicates per sample. Not a problem if you make your replicates in bulk using barcodes and test your hypothesis in high throughput!