SCItations

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...

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, ...

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: "...

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...

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...

As many of my readers know, I am a graduate student pursuing a PhD in molecular neuroscience. For those that think I'm crazy, maybe I am, but I hope you will feel a little crazy too after hearing a bit more about why I've chosen this path... Unless you are a student of neurophysiology or unlucky enough to have epilepsy you probably have never heard of ion channels. Ion channels are the proteins that control the “electricity” of your nervous system. Just like the components in an electrical circuit (resistors, transistors, capacitors, etc.),   ion channels are tiny elements in the circuitry of your brain. Ion channels switch on and off in precise ways to control when and where bioelectricity flows in your brain (and body).   I didn’t know ion channels existed until 2012 when I took a class in the Hendrix College Psychology department titled “Sensation and Perception.” It was here that I learned how my interaction with the world around me - my sense of taste, smell,...

I heard a great talk yesterday by Dr. Patrik Rorsman from the University of Oxford, who has a new way of thinking about type 2 diabetes. He believes some individuals who develop the disease may have a deficit in insulin exocytosis, but not by the mechanism that anyone would have predicted. It is abundantly clear that type-2 diabetes is not caused by a lack of available insulin in the pancreas. Therefore, Dr. Rorsman hypothesized that the mechanism of exocytic release of insulin may be perturbed in diabetic patients. However, when he made classical measurements to detect exocytic release in primary tissues, such as amperometry of cargo release and monitoring membrane capacitance, he saw no differences between healthy and diseased cells. It wasn’t until he engineered an elegant ATP-sensitive, feedback biosensor into his recording set-up that he detected a difference in exocytosis. What he found suggests that the equilibrium between kiss-and-run and full-fusion exoc...

As I’m reading through the abstracts for Biophysics 2018, I can’t help but get excited about all the cutting-edge research there is to discover at this meeting! Although my schedule is double and triple booked with talks and posters, I’ve bookmarked one of each type of presentation as absolute must-sees. Check it out! Sub-group Saturday talk: Progress in developing (single) inorganic voltage nanosensors Shimon Weiss (Bar Ilan University; UCLA) Nanoscale Biophysics Subgroup; Esplanade, Room 160 Saturday, 1:35 PM Why I’m excited: This is an approach to voltage-imaging that I’m not familiar with. Although great improvements have been made to genetically encoded voltage sensors, non-invasive voltage imaging is another story. I anticipate some impressive movies at this talk of membrane-embedded nanosensors detecting single action potentials! Platform talk: Dissecting function and distribution of sodium channels and gap junctional proteins using super-resolution patch-cla...

Just a quick announcement: The next couple posts are going to be cross-published on the Biophysical Society blog as part of their national meeting. I get to write about exciting, often unpublished biophysics research while I attend the conference. Exciting! You can visit the BPS blog here , or just continue reading on this site. Enjoy!

Last week I learned something wild about our brains and bodies that has to do with the way we taste food. It turns out our body knows when we are eating something nutritive or when we are just eating junk. Okay, I know you’re freaking out right now because somehow your brain is keeping track of when you eat a kale salad vs. a fried chicken thigh – like Santa making his naughty vs nice list – but that’s not quite what I mean. What I mean is that your brain knows when the food you’re eating contains calories or not. The crazy thing is that when your fed and happy, your brain doesn’t care whether you eat energy-rich foods or not and your preferences are dominated by flavor. However, if you find yourself stranded on a desert island going on a week without food, your brain is going to know whether you climbed that tree for the juicy, sweet coconut or whether you slammed that last Sweet-N-Low packet you’ve been saving in your pocket since your plane crashed. This is research I heard ab...