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iPSCs, the new model organism?

Induced pluripotent stem cells. The name doesn't exactly roll off the tongue and it certainly doesn't conjure images of mice, fruit flies, monkeys, or any of the other classic model organisms used for basic biomedical research. These so called "model organisms" are just that; animals that help scientists model the way that the most promising human therapeutics in the collective pipeline will behave in humans. And now induced pluripotent stem cells, or iPSCs, are becoming an increasingly popular tool used for developing and testing novel drugs way before we expose any real human patients to them. The upside to using model organisms is pretty obvious -- we minimize exposure of humans to potentially unsafe molecules. The downsides are many, but one big one is that sometimes potential new drug molecules look really promising when they are given to a mouse with a human-like disease, but then that same molecule does nothing (or worse, is toxic!) when it goes into human clin...

AlphaFold2 Part 2: The ion channel challenge

Last month I wrote about the wonders and perils of the artificial intelligence program that predicts 3D protein structures, AlphaFold2. As an ion channel enthusiast , I naturally wanted to know how AlphaFold2 performs at predicting the structures of proteins embedded in cell membranes. When I search PubMed for articles that mention both "AlphaFold" and "ion channel" I only get 34 hits. This surprised me, given the hype and the general paranoia around AI replacing humanity. If we use these search results as a proxy for the state of the ion channel protein structure prediction field, I'd say the juice is still in the coconut. I wanted to know how well AF2 would do at predicting an ion channel protein structure, so I asked it to generate the structure of Kv2.1, a voltage-gated potassium ion channel that I studied during graduate school. Kv2.1 is a pretty important protein. It regulates neuron firing throughout the brain and body where it helps us learn new stuff, ...

My take on AlphaFold2

I haven't spent too much time thinking about AlphaFold2 (AF2) since it entered the structural biology zeitgeist, but I was watching Veritasium's recent video on the topic and thought I would learn a bit more about it. For those who haven't heard of AlphaFold2, I highly recommend watching the video linked above, which explains AF2 better than I ever could. But the tl;dr version is this: AlphaFold2 is an artificial intelligence that takes any amino acid sequence (the building blocks of all proteins) as its input, and outputs the 3D protein structure it thinks that sequence is most likely to take. For some sequences, AlphaFold2 can do quite well at this notoriously complex task. On its debut in 2021, it was able to predict the 3D position of atoms in some protein backbones to within a few hundred nanometers! There are a plethora of articles out there speculating about how AF2 is going to change biology and the world at large. But someone recently asked me my opinion: "...

Gene therapy to prevent side effects from aminoglycoside antibiotics

If you know me, you know that I am passionate about antibacterial soap. Passionate about how much a hate it, that is. I know it has it's place, like in hospitals, or in the homes of immunocompromised people, probably. But you won't find it in my house because I happen to think of antimicrobial resistance (AMR) as a real life boogey man, and as a healthy enough individual I want to do my best to not contribute to that particular monster. Development of, and access to novel antibiotics is a recognized unmet global public health need . That's one reason I found this study published last month so exciting. Ok, it was also because it overlaps with my interests in sensory neuroscience, but I won't be talking about that here. The Indiana University authors of the linked paper are searching for a therapy that, when used prior to or in combination with aminoglycoside antibiotics, will prevent drug-induced hearing loss. You see, aminoglycosides (AGs for short) are a class of ant...

Precision murder -- wait, no -- medicine

A non-zero amount of what we call ‘medicine’ could be described as just controlled cell murder.  This was my revelation after researching a new treatment for certain cardiac arrhythmias called Pulsed Electric Field Ablation, which I became interested in when my father-in-law asked me how it worked during our Christmas visit. “How can it kill the heart cells and leave the nerves and blood vessels intact?” I had no idea. I know next-to-nothing about medical treatments for cardiac patients, much less how this Pulsed Field Ablation technique could have fewer side effects than the standard-of-care ablation techniques. A quick Google search piqued my curiosity when I learned that PFA is also sometimes called “high frequency irreversible electroporation”. While less catchy, that name revealed a bit more about the mechanism of action behind PFA - electroporation - which happens to be something I actually do know something about. Electroporation refers to the formation of holes (pores) in c...