🔇 The Gene Silencer

Hey there,

With the academic year kicking off—Whole mountains of new research are hitting publication. It genuinely feels like the science world snaps awake every September. We’ll have a new video next week, but for now let’s take a quick look at all the research that’s hitting the industry.

We’ve got everything from a new DNA Methylation sensor to a wild process for isolating a novel virus via Cryo-EM alone.

Let’s check out the latest molecular findings in this week’s Clockwork:

antiviral microscopy

Solving an Agricultural Pandemic with Cryo-EM

When there’s nothing left to sequence—sometimes you can just find that needle in a haystack

 🐛 There’s been a mystery illness threatening America’s bug supply

Zophobas Morio is a critical link in the U.S. agricultural supply chain. This little larvae is similar to mealworms—they are a protein-rich grub that are farmed as food for feed animals like chickens. They even have potential as an alternative protein source for human consumption as well

For the past few years, several farms producing these bugs have been hit with a mysterious pandemic that’s wiped out entire populations of these critters. It’s been hard to pin down what causes this mysterious disease until a team at Rutgers University used—get this—cryo em microscopy—to identify a novel virus that’s causing this disease. In a world where sequencing is advanced enough to allow you to identify dang-near anything, why would a team resort to Cryo-Em identification here?

Let’s get into it:

SEQUENCING IS NOT ENOUGH

When trying to figure out the cause of an illness—the go-to technology right now is sequencing. Sequencing tech has blown up in the past decade—allowing research teams to extract incredible amounts of data from small samples.

However, in virology, sometimes sequencing isn’t that big of a help. If what you’re looking for is potentially a new virus that’s not in any current databases—it can be hard to sift through sequencing data if your target isn’t already a part of a wider database.

But advances in Cryo Electron Microscopy have made it cheap enough and high resolution enough for researchers to infer protein sequences from density maps alone. So the team at Rutgers decided to effectively go looking for the novel virus that was causing this potentially devastating mealworm outbreak.

CONNECTING THE DOTS

The team at Rutgers managed to isolate two regions of potential viral protein from an infected tissue sample. A more buoyant layer turned out to be hollow viral capsids, while the lower region was whole virions with genetic code still inside.

Using newer Cryo-Em techniques—the researchers managed to solidly determine the shape of the viral capsid. While that’s not enough to determine precisely what this virus was, it was enough to allow the team to connect the dots a little.

By identifying the rough sequence of the viral capsid—scientists were able to figure out that this mystery pathogen was probably a parvovirus. This is huge because the team was then able to look for DNA fragments similar to parvoviruses in their sequencing data.

Combining those two data points allowed the team to quickly identify and isolate this novel virus. The capsid is pictured above.

NEED FOR SPEED

One of the wildest things about this paper is that the team at Rutgers was able to identify a potential mitigation strategy for the genus of this virus within 10 days of receiving their first sample. They then locked in a full identification within 48 days—which is warp speed when you’re dealing with a pandemic that could start spreading exponentially at any moment. This is a great primer for how far Cryo-EM processing techniques have come. We’re eating good over here in Molecular Biology.

| Read the paper here |

Tag, you’re muted

New Epigenetic Sensor Uncovered

A newly isolated mechanism helps cells detect methylated DNA

 🧬 Meet your gene editor.

If every single one of your cells has a full copy of your entire genome—then how do your skin cells…know…they’re supposed to be expressing skin genes and not anything else?

The answer to that question is pretty complicated—but one mechanism that allows your cells to switch genes on and off depending on what they need to do is called methylation. Basically, proteins ‘tag’ a cytosine base in a gene with a methyl group—and that tag allows maintenance proteins to latch onto that DNA during the cell cycle. By tightly editing the genome itself via these tags—your cells ensure that skin cells stay skin cells.

However, these methylation tags can go haywire over time and cause all sorts of diseases. Not only that—but these epigenetic markers are also inheritable—meaning that any changes that happen during someone’s life can be passed on to their children. This makes epigenetics are really critical area of study right now as we understand precisely how our cells fine-tune gene expression.

This field got a huge boost this month when researchers associated with Rockefeller University, the University of Tokyo and Yokohama City University identified a protein called CDCA7 as a sensor that detects methylated DNA.

In short: This is huge because science was only aware of one other methylation sensor before. Our understanding of gene maintenance just experienced a huge leap

DNA TAGS

So, CDCA7 has a region that binds to methylated DNA in the outer major groove of a DNA molecule. The other protein associated with DNA tagging—UHRF1—can’t bind to regions like this. This helps fill in some gaps in our understanding of how gene maintenance happens.

More importantly—it gives researchers more mechanistic insight into how gene tags are maintained. CDCA7 dysfunction has been connected to disorders caused by hypomethylation (not enough gene tags) so this discovery helps illuminate why.

  | Read the paper here  |