5/16/2024: Decoding Plant Language

Hey there,

The biochem world is still reeling from the AlphaFold3 Launch. There’s so much great development happening behind the scenes right now. But, we’re still catching up with research from earlier in the year in this edition of the Clockwork newsletter. A big hello to all the new folks here after we announced that season 2 is just a month away.

There’s still a lot of great research to cover. Researchers at Perdue have finally isolated a receptor on petunias that can give us the framework we need to decode the molecular language plants use to communicate.

Meanwhile, a groundbreaking study may have just given us a target to help block Alzheimer’s Disease. One small malfunctioning fiber can completely crush one of the deadliest inherited risk factors for the disease.

And finally, we’re dipping back into 2023 because not nearly enough people are talking about the Harvard study that finally identified a biochemical trigger for itching. One of the body’s strangest and least understood sensations is only now coming into focus.

A lot going on this week, so let’s dive right in:

petunia rumors

The Key to Decoding Plant Language

Using a range of techniques, researchers have identified a critical receptor that will help them further decode and study how plants ‘talk’

📢 Plants are far louder than you think.

Communication between plants is a really exciting new frontier in Botany that’s been expanding for the past few years. Turns out, plants aren’t nearly as static as they seem. There’s been a lot of great discoveries illuminating a wide spectrum of airborne chemical signals put out by plants.

Now, a new paper out of Purdue has discovered another ‘word’ petunias use to communicate.

Let’s explore (-) Germacrene D and sus out exactly what ‘communication’ is in plants.

THE FLOWERS ARE TALKING?

Turns out, plants can detect all sorts of signals in the air and via their root systems in the soil. While it may seem like plants are just hanging out and photosynthesizing or whatever—they can biochemically adapt to all sorts of stimuli at the cell level.

In particular, flowers are the ‘loudest’ part of a plant. Flowers have been observed pushing out chemicals that can attract pollinators, repel pesky herbivores, or even warn other plants about infectious bacteria.

Now, researchers at Purdue have identified a new signal petunias are listening for—a smoke-like volatile called (-) Germacrene D. More importantly, the team also isolated the receptor that reacts to germacrene. This protein—PhKAI2ia—could be the critical link that allows researchers to fully unravel the complex language plants use.

THE FLOWERS ARE LISTENING??

This same team published a great paper back in 2019 describing how Petunias emit volatile organic chemicals (like germacrene) to communicate between different parts of the same flower.

All of this research has been really exciting in the Botany community—but learning that flowers communicate can’t give us a lot of insight into precisely HOW they communicate. We need to know the mechanism that allows plants to ‘hear’ as well.

That’s what makes this latest paper so exciting. The team at Purdue has effectively isolated a hyper-specific receptor—PhKAI2ia—that binds to a very specific signaling molecule. In short, they demonstrated that PhKAI2ia binds to (-) Germacrene D and activates a signaling pathway inside petunia cells. This is massive.

A KEY THAT UNLOCKS PETUNIA LANGUAGE

The Purdue team isolated PhKAI2ia based off of genes expressed in petunia cells in the presence of (-) germacrene D. They then built the structure of the receptor with germacrene in AlphaFold 2 and determined how the signal could bind to this receptor.

These steps are critical for future research, as now scientists have a way to measure if a signal has been ‘heard’ by a plant—as well as a repeatable framework for finding more receptors that ‘listen’ for these chemical signals. With these frameworks in place, we’re a giant step closer to fully decoding the intricate and delicate way plants communicate.

  | Check out the paper  | Here’s a solid write-up from UChicago Mag |

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blocking the amyloid door

Faulty Fiber Blocks Alzheimer’s

In an exciting new development, clinicians have discovered a new angle to protect folks from developing Alzheimer’s Disease

🎯 New Alzheimer’s target just dropped.

In a potentially groundbreaking paper, scientists at Columbia University may have just discovered a new angle to attack Alzheimer’s Disease.

Basically, folks who have a rare mutation in a kind of cellular fiber—fibronectin FN1—appear to completely block the onset of Alzheimer’s disease if they are susceptible to it.

This mutation only protects from the effects of another gene—APOEε4—but this discovery may help offer new insights into new ways to stop Alzheimer’s from forming in the first place.

LET’S BREAK DOWN APOEε4 FIRST

APOEε4 is a mutated variant of a near-ubiquitous protein in your brain and other organs. This little machine basically helps build little lipid bubbles that move proteins and fats around your cells. The ε4 variant of APOE is extremely bad news. Folks with two copies of the faulty ε4 APOE gene essentially have a near 100% chance of developing Alzheimer’s disease. They also generally experience symptoms far earlier in life and don’t live as long.

APOEε4 is so bad that some researchers call it ‘the most pathogenic mutation in history.’

Alzheimer’s is incredibly complicated and difficult to study—so we don’t fully understand the mechanism that causes APOEε4 to either kick off or worsen Alzheimer’s. It could be that as APOE goes haywire, it pushes all sorts of cellular junk through the blood-brain barrier, causing amyloid plaques to build up in critical parts of the brain.

But in this new paper out of Columbia—researchers showed that a rare mutation in another protein—Fibronectin—seems to stop folks with the APOEε4 from developing Alzheimer’s Disease. What gives?

HOW COULD FIBRONECTIN STOP APOEε4?

To be clear—this was a genetic study. Researchers found folks who had the APOEε4 mutation but no symptoms and found they had a rare mutation of Fibronectin in common. This FN1 variant of Fibronectin basically makes it non-functional.

Fibronectin is one of the many fibers on the outside of your cells that helps hold junctions together. It also helps with signaling. In the image above, Fibronectin is bonded to an integrin at the basal membrane in the blood-brain barrier—which will allow that integrin protein to open up and let stuff into the brain.

So, one mechanism here could be that fibronectin is the doorway that faulty APOE uses to bring all sorts of gunk across the BBB. If the door is broken, the bad stuff can’t accumulate and cause Alzheimer’s Disease. Slick.

SO, WHY IS THIS A BIG DEAL?

While on the surface this seems like a niche discovery that will only help a small cohort of people—there’s actually a lot going on here.

First of all, as we get more data on APOEε4—even the non-mutated version of this protein looks more and more like a potential cause of AD. If we can block the mechanism that makes APOEε4, that could potentially be a route to treating Alzheimer’s more broadly.

More importantly—this FN1 mutation of Fibronectin is small enough to use in CRISPR therapy. Finding a rare mutation that alleviates a disease is one of the ways scientists developed really successful CRISPR therapies for sickle cell anemia.

With how complicated AD is to treat and understand—every clear and coherent target for therapy is a borderline miracle. We’re years away from having any concrete data about whether this FN1 mutation could be used to treat Alzheimer’s more broadly, but this is definitely a treatment angle to watch.

| Read the paper here |

scratching the biochemical itch

Harvard Scientists Uncover Critical Clue About What Causes Itching

After years of confounding the medical profession—we have our first real biochemical source of itching

 🤏 Itching has been a serious medical mystery for years.

But scientists at Harvard Medical School recently published research that illustrates a biochemical mechanism that can at least offer relief to folks suffering from chronic itching caused by certain bacteria.

MEET THE V8 PROTEASE

The team at HMS focused on the bacteria Staphylococcus aureus—a usually benign member of the human microbiome. S. aureus colonizes about 30% of people with no issue. However, S. aureus can go hogwild in some cases and cause conditions like eczema. The itch that develops when folks get hit with an S. aureus dermatitis is particularly pervasive and uncomfortable.

Using mouse models, HMS scientists discovered a new protein put out by S. aureus—the V8 protease. This nasty little molecule might help unlock a treatment path for itching broadly.

PAR-1 FOR THE COURSE

To keep it quick—V8 protease attacks and cuts PAR-1 receptors on sensory neurons in your skin. PAR-1 is a pretty classic signaling receptor that has a lot of jobs across your cellular landscape.

Since PAR-1 does so much across the body—there’s already drugs that inhibit this receptor. The Harvard team used one of these treatments on mice who were exposed to S. aureus itching and found that the PAR-1 itching response completely stopped.

While this finding doesn’t help explain the mechanism for how the V8 protease and PAR-1 lead to an itch signal—it still unlocks a lot of different angles for studying new ways to treat chronic scratching.

 | Check out the paper here | Or a HMS summary here |

we got games

Biology Connections #3

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

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