I was thinking about why I am doing this vlog and blog. I am worried about national politics. I am worried about science in this new age. I am worried about changes in the economy and how those are going to affect my life and the lives of people I love. I want national policy to reflect my priorities. I know that if I tune into the news, I am going to see mostly reports about national policy. I know that national policy is not going to reflect my perspective for the foreseeable future.  So I know the news is going to be full of terrible, depressing, frustrating stuff all the time.

But I also know that national policy is not the only thing that matters. Every teacher that keeps teaching matters. Every scientist who keeps doing experiments matters. Every caregiver and every nurse who gets through another very hard day doing God’s work matters.

I’m not going to see lots of news that reflects individuals doing good, creative, interesting things. I’m not going to see a lot of news that reflects the lives of individuals doing hard mundane things.

I can tune into YouTube and watch positive people strive to produce something decent and good every single day. I can watch people try to communicate the importance of their work every day. There are people who put up tutorials on how to change the serpentine belt on their Hyundai. There are people who put up videos on how their 3-D printers are working. There are people who put up make-up tutorials. It makes them happy.

I want to help give voice to the positive, decent, day-to-day fun or challenging aspects of our modern life. Because these are good and they deserve to be shared. The keys to a good life are things like knowing how to cook a good meal or knowing how to make friends or knowing how to play a really good game or solve a really interesting puzzle or how to cure someone of their disease or caring for someone who is healing or even caring for someone who is dying.

These things are unlimited. We can share them without diminishing them. By sharing them we help make them abundant.

I’m traveling Monday, so I’ll be updating early. Here’s a quick description of a DIY spectrophotometer I’m going to use to illustrate some ideas for my instrumental analysis students.

I’m traveling Monday, so I’ll be updating early. Here’s a quick description of a DIY spectrophotometer I’m going to use to illustrate some ideas for my instrumental analysis students.

This morning I saw an animal scurry across the street on my way into work. I’m not sure if it was a very small cat or a very large rat (it was 4AM and still dark). It got me thinking about rats.

I remember reading in Rats that some pest control technicians thought that the older, experienced rats could read. I laughed about it at the time. But there was an article recently about pigeons that can read, so maybe it’s not too far-fetched. I mean, they are recognizing words, not interpreting language, but that could still be an important survival advantage. Being able to recognize “POISON,” for instance, could definitely be an advantage for a rat.

That makes me think of Mrs. Frisby and the Rats of NIMH and how different the book was from the animated movie. The book was more “realistic” and didn’t have the deus ex machina ending. Still, both had a bit of an anti-research subtext. People feel bad for the rats, but lab animals are still necessary.

Maybe not forever, though. There’s  Organ on a Chip technology coming that may make it possible to perform tests on human tissue instead of animals. That would have a lot of advantages. Animal experiments are not always relevant to people. A human organ-on-a-chip would have the biochemistry perfectly matched to human. It would also be easier to get huge amounts of rich, biochemical data from the system. It’s hard to continuously monitor a live animal.

Finally, I see huge potential for personalized medicine in the organ-on-a-chip. This is already happening in cancer treatment.

I’ve been reading the literature on conformation switching Aptamers. The idea is to perform rounds of selection to find DNA molecules that change their shape or conformation when they bind a target. The main strategy seems to be to select by releasing DNA from a capture particle.

Morse, D. P. Direct Selection of RNA Beacon Aptamers. Biochem. Biophys. Res. Commun. 2007, 359 (1), 94–101 DOI: 10.1016/j.bbrc.2007.05.072.

Nutiu, R.; Li, Y. Structure-Switching Signaling Aptamers. J. Am. Chem. Soc. 2003, 125 (16), 4771–4778 DOI: 10.1021/ja028962o.

The fact that this works suggests something about the mechanism by which DNA Aptamers operate. One of the big questions that comes up in the lab is whether Aptamers are being folded around their target (an induced fit model) or whether they are switching back and forth between a folded and unfolded state even without the target (an equilibrium binding model). The fact that target can force Aptamers off of a capture particle suggests that the induced fit model may be appropriate in some cases.

On the other hand, a capture based selection strategy (Spiga et. al.) seems to fit either model. As long as the confirmation switches back and forth fast enough, an equilibrium model could account for partitioning between a capture particle and solution.

The downside to this strategy is that the particles need to have enough capacity to absorb all of the nonbinding DNA (which may be quite a lot of DNA at the beginning of the selection).

Spiga, F. M.; Maietta, P.; Guiducci, C. More DNA–Aptamers for Small Drugs: A Capture–SELEX Coupled with Surface Plasmon Resonance and High-Throughput Sequencing. ACS Comb. Sci. 2015, 17 (5), 326–333 DOI: 10.1021/acscombsci.5b00023.

Anyway, if you have a favorite conformation switching aptamer selection paper (and who doesn’t?!), maybe leave it in the comments or shoot me an email.

Open source projects I use all the time:

• krita.org
• www.gimp.org
• inkscape.org
• www.audacityteam.org
• www.openoffice.org
• notepad-plus-plus.org

Whether for tutorials, editing images or manuscripts, there are open source projects that can help a scientist get a lot done for free. Not everything – I bought the Corel Videostudio software I use to edit the Vlog. I use Microsoft Office for various reasons. But when I can, I prefer to use an open alternative. Both because I am cheap and because I feel like it’s making the software ecosystem more open and accountable.

Matt Might writes some great material on his blog about what it means to earn a PhD and his experiences in academic science. I’ve learned a lot reading his posts and I recommend it highly. One of my favorite articles is “The illustrated guide to a Ph.D.” He talks about the Ph.D process and how that moves a student to the edge of human knowledge.

I was thinking about this in terms of paradigms. The typical student paradigm will get a person through a bachelors. I think it’s natural for students to approach their education as absorbing all the amazing knowledge that has been accumulated by humans.It’s like learning recipes that have been handed down for generations. These recipes work well, and learning them is very satisfying. They always produce good results.

The paradigm that gets a person to the edge of human knowledge is very different. As a student approaches the edge, everything gets less certain. The recipes stop working well. Sometimes they don’t work at all. It requires a lot of critical thinking to understand what recipes are applicable to your particular situation. It takes a lot of patience and failure to invent the right recipes.

But the paradigm of “learn the recipe, produce the result” will be deeply disheartening. That paradigm worked really well in the early years. At the edges of human knowledge, that paradigm will make the world feel hostile and cruel. It will feel like every paper is a trap with the key bits left out just to screw with the unwary student who tries to replicate the result.

The new paradigm is that everything is uncertain. Every uncertainty is an opportunity to bring experiment, observation, and ingenuity to bear. That is a hard and overwhelming perspective at first. Everything is uncertain? Yes. I think that’s a useful world-view for people to adopt.