RNA, Protein design, and the Sunday Scaries


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.

Transcription regulation by the Mediator complex | Nature Reviews Molecular Cell Biology

This is some deep molecular biology. If you ever wanted to know just how deep this rabbit hole goes, have a little glance at this paper. Developmental biology happens because of a lot of moving parts that are not connected in a way that makes much sense to the human mind.


Something | The Beatles | Pomplamoose – YouTube

If you are not familiar with Pomplamoose, you are in for a treat. This is some old school Pomp, just Nataly Dawn and Jack Conte. If that name sounds familiar, it’s probably because Jack Conte also started Patreon. Patreon provides more money to the Arts than the National Endowment for the Arts.


Why does Idaho have to cut budget amid a booming economy? | Idaho Statesman

I work for the Idaho Government, and I would love to know.






And that’s how my whole day has been | The Bloggess

Jenny Lawson is wonderful and is coming out with a new book in 2020 or 2021, I think? She said she submitted a draft a bit ago. I am really looking forward to it. She has a wonderful sense of humor.


Helium is, in fact, running out. I wish the USA had continued to maintain supplies.


How a Tranquilizer Dart Works in Slow Motion – The Slow Mo Guys – YouTube

I did not know any of this. Slow Mo Guys are delightful as always.


Epic Rock Wallet – YouTube

This is wonderful and disturbing. It’s a great optical effect. He makes a coin purse out of a rock.


Experimentally guided computational antibody affinity maturation with de novo docking, modelling and rational design

Computational protein design is absolutely amazing these days. I want to learn.


Nate Bethea on Twitter (@inthesedeserts) tweeted something

He deleted it later. Probably because it’s true. Adapted here:

Something that you may not get if you don’t spend a lot of time on the internet: Nothing is more “Connected” than imagining something that makes you furious and then ruining your entire life over how furious this thing you’ve imagined makes you.


The RedDot Comic (@the__reddot) / Twitter


Preparation and characterization of hyaluronan/chitosan scaffold cross‐ linked by 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide – Deng – 2007 – Polymer International

I wonder if crosslinked amine/carboxylic acid saccharides could make battery separators. One will be negatively charged, one will be positively charged. Put together with EDC, they will make a pretty sturdy material. I don’t know how fast it will degrade in a battery cell, though.


The ‘Sunday Scaries’ and the Anxiety of Modern Work – The Atlantic

I definitely get the Anxiety Rush on Sunday evenings. I use the weekends for blogs, vlogs, grant proofreading, paper writing, and home maintenance. But I also need to relax ENOUGH that I’m not a complete mess when it’s time to get in front of students.

“Burnout and the anxiety that accompanies it are so much about living under our current iteration of capitalism and about class insecurity.” From roughly the end of World War II to 1970—a period that’s often called the Golden Age of American capitalism—Petersen says, “there were a ton of jobs that weren’t great, but the difference was that people were more secure in their class position … [Now] it’s this huge combination of not only ‘How am I going to do in my job?,’ but all these other things that I’m anxious about—‘If I lose my job, then I’m not going to have medical insurance.’” This goes some way toward explaining the need to make weekends both productive and relaxing—workers need to both get stuff done and also make sure that they’ve sufficiently recharged to get more stuff done during the week.


SB50 Could Make California Livable Again – The Atlantic

Here’s an example where I think conventional conservative/liberal descriptions break down. Local governments make heavy restrictions on construction. This is not just left-leaning neighborhoods. It’s anywhere locals with money don’t want more development. Ideology is pretty much irrelevant. These regulations make it impossible to address housing shortages. Building codes and safety are one thing. Limiting a region to single-family homes kills affordability.

“Then there are the NIMBYs, who argue that S.B. 50 will destroy neighborhoods’ homegrown character, hurt home values, and harm the environment: Goodbye to green, single-family neighborhoods, and hello to traffic-gnarled, high-rise apartments.”

The “green single-family neighborhoods” thing is really dishonest. Apartments are almost inherently more energy and materials efficient. And besides, NIMBY’s home values are 100% of their real concern. They bought into the biggest and most obvious asset bubble ever, and they don’t want it to pop before they cash out.

S.B. 50 failed.


The Great Affordability Crisis Breaking America – The Atlantic

“What is perhaps most frustrating is that the Great Affordability Crisis is amenable to policy solutions—ones most other rich countries adopted decades ago. In other developed economies, child care, early education, and higher education are public goods, and do not require high-interest-rate debts or endless scrambling by exhausted young parents to procure. Other wealthy countries have public-health systems that cover everybody at far lower cost, whether through socialized or private models. And numerous proposals would transform residential construction in this country, including [S.B. 50] that just failed in California’s legislature.”