🗑 Hijacking the bacterial trash collector

Hey there,

It’s another catch-up week here. There’s a lot of great research that came out earlier in the year that we really want to dive into.

So check out this week’s roundup of some of the best research from the first half of 2024! We’re covering new insights into the precise mechanism that triggers the opening of stomata in plants.

Meanwhile—new data on PROTAC antibiotics is adding to hopes that we have another weapon for fighting pathogens like drug-resistant Tuberculosis.

And finally—let’s check in on a fresh mechanism that helps mitigate inflammation during periods of cellular stress by cleaning up leaky mitochondrial DNA.

There’s never a dull moment here on the cutting edge of the life sciences! Let’s dive into the research:

spreading those stomata

New Insights into How Stomata Open

A clever study has resolved our understanding on how light opens plant pores down to a single subunit of a single proton pump

 🍃 Leaves need to open up.

One of the most important steps that activates photosynthesis in vascular plants is opening up the stoma. Stoma are the little pores in the plant epidermis that let CO2 in and allow water to evaporate out. For years, scientists have been refining our understanding of how this works, and we might have just unlocked the final step.

Let’s explore how a single residue—Threonine 881—kicks off the photosynthetic party.

WHAT DO STOMATA DO?

For background: stomata are little pores found on the surface of every vascular plant. Their main job is to open up and allow water to evaporate out. This creates upward pressure that helps plants bring water up through their roots—which also helps bring in nutrients and minerals from the soil.

Plants use those resources to power their photosynthetic activity during the day—so stomata are light-activated. Basically, in the presence of blue or red light, proton pumps in the membranes of guard cells surrounding the stoma will activate and shove as many protons out as possible. This creates a negative charge that brings potassium ions into the guard cell—which allows them to retain more water. The influx of water causes the guard cells to swell. Guard cells are so well-anchored to the tissue around them that they end up bowing outward—which leads to a fully opened stoma.

That’s cool—but what actually kicks this off? How do these proton pumps sense blue/ red light?

DISCOVERING THR881

There’s been a lot of great research surrounding the photoreceptors that detect light in these guard cells and kick off stomatal opening.

And our understanding has now been refined to the single residue level in Arabidopsis thaliana plants thanks to a new paper in Nature Communications.

Basically, scientists at Nagoya University in Japan did enough testing to determine that a single threonine residue—Thr881—gets phosphorylated by photoreceptors in the guard cell cytoplasm. That single phosphorylation opens up a tag on the tail-end of the PM Proton Pump, allowing a 14-3-3 protein to bind there and activate the proton pump.

That phosphorylation is passed on to the PM proton pump via photoreceptors BLUS1 and BHP. These photoreceptors get activated by blue light and ‘pass on’ that phosphorylation to the THR881 residue.

WHAT COMES NEXT?

There’s still a lot to learn here as scientists continue sussing out this mechanism. The main next step is determining exactly how Thr881 phosphorylation helps 14-3-3 bind to the PM proton pump. There are a lot of possibilities and plenty of new avenues for future experimentation.

For now, a better understanding of this mechanism can help us find treatments for certain kinds of plant disease—and can even assist in the design of new engineered signaling mechanisms that can make plants hardier or better able to manage their resources.

  | Check out the paper here  | And this write-up from Nagoya University  |

taking out the trash

Tuberculosis Gets Hijacked by New Class of Antibiotics

Every weapon that helps us beat drug-resistant TB is a huge deal.

🦠Congrats TB, you played yourself.

At least that’s what scientists are saying after looking over the results generated by a new class of anti-TB drugs called Homo Bacterial Proteolysis Targeting Chimeras. Let’s call them Homo-BacPROTACs for short.

PROTACs are nothing new in the world of antibiotics. Basically, scientists have been frantically hunting for new ways to combat drug-resistant bacteria—and PROTACs may be a great solution.

To really oversimplify how PROTACs work—these are compounds that basically hijack ‘clean-up’ machines inside bacteria that normally break down old and unused proteins. Regular PROTACs reprogram the bacterial clean-up crew to attack and destroy necessary proteins—which in turn then kill the bacterium.

In a new study printed in Nature—scientists announced their development of Homo-BacPROTACs. This twist on the PROTAC technology has some serious advantages—especially in fighting drug-resistant variants of Tuberculosis. Let’s break down the breakdown here:

KILL THE GARBAGE MAN

PROTACs can basically ‘tag’ any protein for the bacterial clean-up system—CLPC1—to blow up. So, this research team made Homo-BacPROTACs that target the clean-up system itself. So CLPC1 gets directed to destroy other copies of itself—effectively disrupting the bacterial garbage system.

REMARKABLE EFFICACY

Cells are pretty crowded as it is, so without an active degradation system, trash piles up and prevents cellular activity from continuing. In short, Homo-BacPROTACs kill TB cells by stabbing them in their little bacterial kidneys.

The best part about these PROTACs is they attack the trash system in prokaryotes only. Us Eukaryotic folks have a completely different set of machinery that degrades our old and unused proteins—so side effects could be really limited in PROTAC treatment.

More importantly, PROTACs kill a wide spectrum of TB variants—and even kill TB cells locked away inside human macrophages. This has huge implications for TB specifically—as PROTAC treatment might be able to stop TB much earlier in the infection cycle.

Ultimately—this is a really exciting new weapon we’re testing in one of the longest wars we’ve ever fought as a species. TB has been infecting us since before we were even human—and it is high time we found more ways to put the world’s deadliest pathogen in the rear-view mirror.

 | Check out the paper here  |

don’t stress

Discovering a new clean-up system for Mitochondrial DNA

New insights into TFAM help scientists understand how cells clear loose mtDNA after moments of stress

⚡ Sometimes the powerhouse gets leaky.

Stress is a wild process at the biochemical level. When your cells experience stress or strain—the mitochondria that power your cells can get overactive. This causes mitochondrial DNA (mtDNA) to leak into the surrounding cytoplasm.

This is bad—because DNA material of any kind found loose in your cytoplasm will kick off inflammatory responses that can just amplify cellular stress.

But now, scientists at Guangzhou Medical University have identified a key clean-up mechanism that helps clear mtDNA when it slips into the cytoplasm. Turns out, the classic Mitochondrial Transcription Factor A—or TFAM—can tag mtDNA to be cleared by an established cellular pathway.

Let’s explore the details:

MEET TFAM

TFAM is an important ‘shepherd’ molecule that helps manage and maintain the Mitochondrial genome. Mitochondria aren’t just static powerhouses—they have their own DNA and internal processes that are necessary to maintain ATP production (and a LOT more).

TFAM is a classic transcription factor that helps package and prepare mtDNA for replication. But apparently, now there’s more to this little protein shepherd.

TFAM’S NEW SECRET

Scientists at Guangzhou Medical University in China have uncovered a binding domain on TFAM that attracts IL3, an autophagy protein that helps ‘tag’ unwanted compounds for destruction.

This is a huge discovery—because it helps us better understand how cells work their way out of stressful situations. It also gives folks a new angle to study diseases centered around mitochondrial dysfunction. Maybe TFAM can be a new angle for developing better treatments for these kinds of diseases.

| Read the paper here | 

we got games

Biology Connections #5

Test your life sciences cred with this specific take on the NYT connections format.

This section is brazenly adapted from the good folks over at Nerdfighteria’s We’re Here Newsletter

Share your results on social media—but make sure you include a link back to our newsletter (https://clockwork.beehiiv.com/subscribe)