Solving the 3D structure of coronavirus COVID-19 using Cryogenic electron microscopy (CryoEM)

Hello,

Many of you may know me on the Byte app as @wumbologyexpert
I am a chemist, lifter, and beginner pole dancer! As a chemist, I work with peptides and nucleic acids to make bionanomaterials. However, my professional hobby includes various microscopic imaging techniques, electron microscopy among others.

Recently, the coronavirus outbreak has taken a toll on global health, travel, social justice, and economic downturns. What I want to do is shed light on some of the breakthroughs that the scientific community managed to publish with very little public attention despite the virality (no pun intended) of the situation.

I made this PPT presentation in the hopes that I could turn them into short clips that I’d release as a multipart Byte series to show how cool this process is and how very relevant and “simple” cutting-edge science can be. HOWEVER in the last few days, it has been impossible for me to post these Bytes. The app keeps stalling the upload with the message: Slight delay. Retrying soon, for hours and hours.

Instead of spending more days delaying the release, I’d rather just upload the link to the PPT for all to learn.

Please comment/DM me on insta if you have questions/have genuine curiosity! Science communication is more than just a hobby for me, as I really enjoy teaching chemistry and love talking science. Feedback is always welcome!

You need to view the slides with the animations, otherwise nothing is legible!

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This seems super interesting! How long have you been a chemist ?

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Lol all my life. Jk, but I’m currently in a chemistry PhD program, so not TOO long, but I have been trained on many a microscopy techniques, including the atomic force microscopy and confocal microscopy :slight_smile:

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i remember working on DNA sequences(general biology in college for freshmen year) and wanting to to pull out my eyes trying to remember correct sequences. or trying to remember what mutation causes/produces dysfunctional proteins which in turn increase a persons likelihood of cancer. Im fairly certain the only thing i retained was what Alleles were.

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Lol I tested out of bio in college, and I’m glad that I did because I am terrible at memorizing anything, and that’s how one will pass biology classes :slight_smile:

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This is a fascinating process! Thanks for taking the time to make this powerpoint/videos!

My follow up question is how does knowing the shape help in finding a cure? As I’m typing this I realize I have literally no idea how cures are discovered/viruses are destroyed, so believe me there is no snark in the question. :slightly_smiling_face:

I don’t deserve the Bio minor I somehow graduated with

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Hello, sorry I got back to you so late! I just got back from vacay and forgot about the forum… No snark taken, and you definitely deserved the bio minor you got!!!

So these viruses are tiny, right? Molecules are tiny, tiny things, but they’re not abstract! They are physically there, as in they are tangible (which is why you can literally touch things and that they’re not imaginary… at least most things aren’t imaginary??). Like any physical thing, they have shapes and textures. Knowing the super detailed structure of the particle, we can target specific structures that are readily accessible/more exposed. We can test a bunch of molecules that will recognize and “latch” on to these sites.

If you remember what antibodies are and what they look like (a Y-shaped molecule), we can start from here. Antibodies are produced by our immune system when it detects an infection. Each antibody is specific to the antigen (the virus particle in this case) that our body is exposed to, meaning antibodies are not a one-size-fits-all. In order for our immune system to know what antibodies to make, it has to first recognize that there are foreign, and potentially toxic, particles in the system! Antibodies that latch the best to the antigen will be produced more and more. This is why the breaking news about the discovery of the virus antibodies in the last week was so huge!

So, back to vaccines, why does this matter? Vaccines are basically “dead viruses,” right? But what does that mean? A virus is made, typically, of a proteinaceous coating, which protects the DNA or RNA inside (this part is what gets injected into the host cell to be replicated). Easy enough, why not just take the virus, separate the protein from the nucleic acid, and just make random cuts along the protein and feed it into cells and see what antibodies come out? Well, not so fast. First of all, these proteins are quite large and they fold! We can’t really predict protein folding quite accurately, and if you just happen to feed cells the parts of the protein that aren’t usually on the outside or accessible when the virus is intact, then that’s kinda useless. However, if you know exactly what parts are gonna be on the outside/accessible, then you have a much greater chance of finding the right antigen to induce an immune response that will make the antibody to fight against this virus :slight_smile:

TL;DR: Things sticking on the surface of the virus can be recognized by immune system, which will trigger antibody production. We’re going to recreate the things that stick out as artificial antigens, which is basically what vaccines are.

Hope this helps. Sorry it’s a large chunk.

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Do you teach/plan to teach in the future? You’re really good at explaining complex things in direct and accessible ways. That all helped a ton! I felt my IQ increase as I read!

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aw stahp

The end goal is to teach and hold my own research group, so a professor at a university somewhere. I really enjoy teaching, not because I feel like I have so much to talk about (which is kinda true, haha) but because I love seeing people reaching a solution on their own by applying what I just taught them. It’s a really good feeling that I just can’t describe :slight_smile:

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I think you’ll make a great professor. For real. :slightly_smiling_face:

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You flatter me <3

With my work being remote now, I plan on making more educational Bytes. I just hope this time the app will actually let me upload them haha!

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Legit you just summed up what my molec cell teacher tried an hour to on a really shitty livestream. That was amazing 100/10

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Haha, I can’t with all yalls compliments!

I’ve been thinking about recreating my class curriculum and animating them since I work from home now… Let me know if there is a particular topic you’re interested in or having trouble with, maybe I can come up with something in 6.5 sec :slight_smile:

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Which company has the best scientists with the best solutions in your view? It is SO inspiring to see someone such as yourself on Byte. WOW!

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Great question! However, in science, we simply cannot come up with the best solution alone. All labs, even privately-owned ones, collaborate together to develop new methods, from testing for this virus, tracking its evolution, to creating antiviral drugs and vaccines. While there isn’t a good answer to your question, I think this pandemic has shown the world that the urgent need for open information is greater than ever.

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“the urgent need for open information is greater than ever.”

Getting VC’s, startups, patent holders and others to be on board is the hard part. Getting the educational people on board? Very easy. Education usually = guaranteed paychecks or at least a much lower income risk that the ones I listed. What is the best way to get those groups to buy into that idea?

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Before we could even pitch an idea investors/to patent/etc, we have to have an idea. The ultimate showcase of one’s ability and fluency in a specific subject is by creating something new, in this case an idea or a proposal for something. (Think Bloom’s taxonomy.) The problem is, how can we develop a new research proposal, if we don’t even know what we don’t know?

The last sentence sounds like a lot of BS, but I think one of the biggest challenges of being at the forefront of research is finding the gap in knowledge, especially for young scientists. Most of us think: We’re still wet behind the ears, how can we possibly contribute to something so prestigious? And the only way to combat this problem is by making the latest research advancement more available.

For example, journal articles literally cost an arm and a leg. Go on Royal Chemistry Society, and click on any journal. 9/10, they’re not free, and you probably have to pay by the article, which are about $40 each. This is no problem for most large universities (Anyone in top 50 US schools, for example), but what about smaller colleges? So no access to new knowledge = greater challenge to develop new ideas.

If you did overcome this big hurdle, what are the chances that you can get the money to actually run the experiments you proposed? I don’t have the concrete numbers, but lesser known universities are known to receive much less grant money. Why? Because they’re less likely to have the resources they need, so agencies like NSF, NASA, NIH, DOE are not gonna be confident in their abilities to complete their stated proposal goals.

TL;DR: Access to the newest information on research and technological advancements are in the scientific communities are akin to what oxygen is to most organisms. Before we can even pitch an idea, we have to develop the idea.

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I absolutely love this response:

You are very, very, very smart. You approached in a way I did not expect AT ALL.

“For example, journal articles literally cost an arm and a leg. Go on Royal Chemistry Society, and click on any journal. 9/10, they’re not free, and you probably have to pay by the article, which are about $40 each. This is no problem for most large universities (Anyone in top 50 US schools, for example), but what about smaller colleges? So no access to new knowledge = greater challenge to develop new ideas.”

I think one way is leveraging Linkedin etc. for connections and targeting small biotechs. Small Biotechs have a hard time recruiting top-level talent. If they knew they were paying those type of costs to get great scientists? I think they would help. The other thing a person brings to the table is creativity. You using Byte shows “hyper” creativity given what your background is. You can add me on Linkedin Steven Musielski.

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Thank you for your kind words :slight_smile: I will check it out when I finally log back onto LinkedIn!

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