MIT Engineers Pioneer Cost-Effective Protein Purification For Cheaper Drugs

There are a wide variety of protein-based drugs that are used to treat various serious conditions. Insulin is perhaps the most well-known example, which is used for life-saving treatments for diabetes. New antibody treatments also fall into this category, as do various vaccines.

A significant cost element in the production of these treatments is the purification step, wherein the desired protein is separated from the contents of the bioreactor it was produced in. A new nanotech discovery from MIT could revolutionize this area, making these drugs cheaper and easier to produce.

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Broken Genes And Scrambled Proteins: How Radiation Causes Biological Damage

If decades of cheesy sci-fi and pop culture have taught us anything, it’s that radiation is a universally bad thing that invariably causes the genetic mutations that gifted us with everything from Godzilla to Blinky the Three-Eyed Fish. There’s a kernel of truth there, of course. One only needs to look at pictures of what happened to Hiroshima survivors or the first responders at Chernobyl to see extreme examples of what radiation can do to living tissues.

But as is usually the case, a closer look at examples a little further away from the extremes can be instructive, and tell us a little more about how radiation, both ionizing and non-ionizing, can cause damage to biochemical structures and processes. Doing so reveals that, while DNA is certainly in the crosshairs for damage by radiation, it’s not the only target — proteins, carbohydrates, and even the lipids that form the membranes within cells are subject to radiation damage, both directly and indirectly. And the mechanisms underlying all of this end up revealing a lot about how life evolved, as well as being interesting in their own right.

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Illuminating The Inner Workings Of A Venus Flytrap

As a carnivorous plant, Venus flytraps have always been a fascinating subject of study. One of their many mysteries is how they differentiate an insect visit from less nutritious stimulants such as a windblown pebble. Now scientists are one step closer to deciphering the underlying mechanism, assisted by a new ability to visualize calcium changes in real time.

Calcium has long been suspected to play an important part in a Venus flytrap’s close/no-close decision process, but scientists couldn’t verify their hypothesis before. Standard chemical tests for calcium would require cutting the plant apart, which would only result in a static snapshot. The software analogy would be killing the process for a memory dump but unable to debug the process at runtime. There were tantalizing hints of a biological calcium-based analog computer at work, but mother nature had no reason to evolve JTAG test points on it.

Lacking in-circuit debug headers, scientists turned to the next best thing: add diagnostic indicator lights. But instead of blinking LEDs, genes were added to produce a protein that glows in the presence of calcium. Once successful, they could work with the engineered plants and get visual feedback. Immediately see calcium levels change and propagate in response to various stimuli over different time periods. Confirming that the trap snaps shut only in response to patterns of stimuli that push calcium levels beyond a threshold.

With these glowing proteins in place, researchers found that calcium explained some of the behavior but was not the whole picture. There’s something else, suspected to be a fast electrical network, that senses prey movement and trigger calcium release. That’ll be something to dig into, but at least we have more experience working with electrical impulses and not just for plants, either.

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New Microscope Directly Images Protein Atoms

There’s an old joke that you can’t trust atoms — they make up everything. But until fairly recently, there was no real way to see individual atoms. You could infer things about them using X-ray crystallography or measure their pull on tiny probes using atomic force microscopes, but not take a direct image. Until now. Two laboratories recently used cryo-electron microscopy to directly image atoms in a protein molecule with a resolution of about 1.2 x 10-7 millimeters or 1.2 ångströms. The previous record was 1.54 ångströms.

Recent improvements in electron beam technology helped, as did a device that ensures electrons that strike the sample travel at nearly the same speeds. The latter technique resulted in images so clear, researchers could identify individual hydrogen atoms in the apoferritin molecule and the water surrounding it.

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Behind The Scenes Of Folding@Home: How Do You Fight A Virus With Distributed Computing?

A great big Thank You to everyone who answered the call to participate in Folding@Home, helping to understand proteins interactions of SARS-CoV-2 virus that causes COVID-19. Some members of the FAH research team hosted an AMA (Ask Me Anything) session on Reddit to provide us with behind-the-scenes details. Unsurprisingly, the top two topics are “Why isn’t my computer doing anything?” and “What does this actually accomplish?”

The first is easier to answer. Thanks to people spreading the word — like the amazing growth of Team Hackaday — there has been a huge infusion of new participants. We could see this happening on the leader boards, but in this AMA we have numbers direct from the source. Before this month there were roughly thirty thousand regular contributors. Since then, several hundred thousands more started pitching in. This has overwhelmed their server infrastructure and resulted in what’s been termed a friendly-fire DDoS attack.

The most succinct information was posted by a folding support forum moderator.

Here’s a summary of current Folding@Home situation :
* We know about the work unit shortage
* It’s happening because of an approximately 20x increase in demand
* We are working on it and hope to have a solution very soon.
* Keep your machines running, they will eventually fold on their own.
* Every time we double our server resources, the number of Donors trying to help goes up by a factor of 4, outstripping whatever we do.

Why don’t they just buy more servers?

The answer can be found on Folding@Home donation FAQ. Most of their research grants have restrictions on how that funding is spent. These restrictions typically exclude capital equipment and infrastructure spending, meaning researchers can’t “just” buy more servers. Fortunately they are optimistic this recent fame has also attracted attention from enough donors with the right resources to help. As of this writing, their backend infrastructure has grown though not yet caught up to the flood. They’re still working on it, hang tight!

Computing hardware aside, there are human limitations on both input and output sides of this distributed supercomputer. Folding@Home need field experts to put together work units to be sent out to our computers, and such expertise is also required to review and interpret our submitted results. The good news is that our contribution has sped up their iteration cycle tremendously. Results that used to take weeks or months now return in days, informing where the next set of work units should investigate.

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Coronavirus And Folding@Home; More On How Your Computer Helps Medical Research

On Wednesday morning we asked the Hackaday community to donate their extra computer cycles for Coronavirus research. On Thursday morning the number of people contributing to Team Hackaday had doubled, and on Friday it had doubled again. Thank you for putting those computers to work in pursuit of drug therapies for COVID-19.

I’m writing today for two reasons, we want to keep up this trend, and also answer some of the most common questions out there. Folding@Home (FAH) is an initiative that simulates proteins associated with several diseases, searching for indicators that will help medical researchers identify treatments. These are complex problems and your efforts right now are incredibly important to finding treatments faster. FAH loads the research pipeline, generating a data set that researchers can then follow in every step of the process, from identifying which chemical compounds may be effective and how to deliver them, to testing they hypothesis and moving toward human trials.

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Join Team Hackaday To Crunch COVID-19 Through Folding@Home

Donate your extra computer cycles to combat COVID-19. The Folding@Home project uses computers from all over the world connected through the Internet to simulate protein folding. The point is to generate the data necessary to discover treatments that can have an impact on how this virus affects humanity. The software models protein folding in a search for pharmaceutical treatments that will weaken the virus’ ability to attack the human immune system. Think of this like mining for bitcoin but instead we’re mining for a treatment to Coronavirus.

Initially developed at Standford University and released in the year 2000, this isn’t the first time Hackaday has advocated for Folding@Home. The “Team Hackaday” folding group was started by readers back in 2005 and that team number is still active, so let’s pile on and work our way up the rankings. At the time of writing, we’re ranked 267 in the world, can we get back up to number 30 like we were in 2008? To use the comparison to bitcoin once again, this is like a mining pool except what we end up with is a show of goodwill, something I think we can all use right about now.

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