Step aside CRISPR, RNA editing is taking off
Although gene editing is flashy, there are advantages to a more temporary solution. Gene editing needs to be done perfectly the first time or it causes bad permanent consequences. RNA editing can have a dose-dependent, time-limited effect. If bad things start to happen, doses can be removed and the effects reversed. Not so much for DNA editing. The downside is that the RNA to be edited needs to be present in the first place. If a gene is underexpressed or absent, RNA editing won’t help.
Incorporating an allosteric regulatory site in an antibody through backbone design
Protein design has come a long way. Here’s a paper that takes an antibody and redesigns the antibody gene to make it into a sensor for Zinc ions. Basically, nature made this antibody to be an always-on grabber for a molecule called fluorescein. These folks made it grab fluorescein only if there is a bunch of Zinc present. Designing that kind of function with accurate software was a dream 20 years ago.
Poorly Drawn Lines:
Modeling Peptide-Protein Structure and Binding Using Monte Carlo Sampling Approaches: Rosetta FlexPepDock and FlexPepBind.
Imagine you want to cure a viral infection. To do that, you could make a new molecule that binds to a virus coat protein and keeps it out of human cells. But all you have is the virus’s DNA sequence. How do you do it? First, you need to be able to predict what the virus’s coat protein looks like (you can use Rosetta, a computer program for protein structure prediction). Then you need to design a binding molecule (use Rosetta some more, see the paper above). There are other strategies, of course, but this is an interesting one. And I think it’s one that will get better and faster with time.
I was on a road trip with my wife and she got me a gas station coffee. It was super hot and we started talking about a safety mascot for hot coffee. Here’s what we came up with. It even turned into a safety video and a post on StudentProTips.
Youtube put out a caution about burnout. Penny arcade summed it up. “Creators: you’re feeling burned out because you are light bulbs. And there are always more light bulbs. You create young, energetic light bulbs with every video you make.”
Good educational content is distinct from aspirational content. As a chemistry professor, my primary job is to produce more chemists (and educate non-chemists who need the background). The point is not to generate a great many more chemistry professors. Complexly and the Scishow folks make great educational content. Aspirational content is the opposite: it endeavors to sell the idea that you too can become an aspirational content producer. Mostly by watching more aspirational content.
I made a youtube video every weekday in 2017. That experience pulled me into the world of battery chemistry. Daily vlogging was hard but taught me something about social media, science outreach, and the topics that people are interested in. I was a little surprised to find that people were so interested in batteries. I like the opportunity to explore something that is of wide interest. Everyone has a battery in their pocket, and everyone wants them to last longer.
We’ve been selecting aptamers in the lab for the last year. Having a qPCR on the bench has really helped, and so we wrote up a methods paper in ACS Combinatorial Science. The company that made our qPCR instrument has put up a blurb about it, too.
The qPCR function is great for cycle course optimization, and we have been using the melt curve analysis function of the Open qPCR (thermofluorimetry) to do a binding assay. It works pretty well. We put a dye in with the aptamer and measure the temperature at which the dye dye-DNA complex melts. The bound aptamer has a different melt temperature, so it gives a specific signal. We plot that specific signal as a function of concentration and to determine the binding constant. It’s based on the Easley lab’s method paper from 2015 with low-cost equipment.
The instrument simplifies some of the more touchy parts of the aptamer selection. Undergrads have been turning rounds pretty efficiently this year with the help of the open qPCR instrument.
We have also been using graphene oxide to try some selections. I have only heard of graphene oxide SELEX recently, but it grabs unstructured DNA to separate them from aptamers bound to target. It’s looking good. I hope to report on that soon.