Weird Science: A drug for exercise?

Scientists have found a protein that's able to detect a change in blood flow during exercise - and could point the way to a new Star Wars-inspired drug that offers a workout's benefits.

During physical activity, as the heart pumps more blood around the body, the Piezo1 protein in the endothelium - or the lining of the arteries taking blood from the heart to the stomach and intestines - senses the increased pressure on the wall of the blood vessels.

In response, it slightly alters the electrical balance in the endothelium and this results in the blood vessels constricting.

In a clever act of plumbing, that narrowing of the blood vessels reduces blood flow to the stomach and intestines, allowing more blood to reach the brain and muscles actively engaged in exercise.

The research team behind the findings, based on mice studies, say this is a big deal because it identifies for the first time a key biomolecular mechanism by which exercise is sensed.

They believe the health benefit of exercise may be linked with the fact that blood flow is being controlled to the intestinal area.

"If we can understand how these systems work, then we may be able to develop techniques that can help tackle some of the biggest diseases afflicting modern societies," said the study's lead author Professor David Beech, of UK's University of Leeds.

"We know that exercise can protect against heart disease, stroke and many other conditions.

"This study has identified a physiological system that senses when the mammalian body is exercising."

The researchers also investigated the effect of an experimental compound called Yoda1 - named after the character from Star Wars - on the action of the Piezo1 protein.

They found that it mimicked the action of increasing blood flow on the walls of the endothelium which is experienced during physical activity, raising the possibility that a drug could be developed which enhances the health benefits of exercise.

"One of our ideas is that Piezo1 has a special role in controlling blood flow to the intestines and this is really an important part of the body when we start to think about something called the metabolic syndrome which is associated with cardiovascular disease and type 2 diabetes," Beech said.

"By modifying this protein in the intestines then perhaps we could overcome some of the problems of diabetes and perhaps this Yoda1 compound could target the Piezo1 in the intestinal area to have a functional effect.

"It may be that by understanding the working of the Yoda1 experimental molecule on the Piezo1 protein, we can move a step closer to having a drug that can help control some major chronic conditions."

The mystery within us

Ninety-nine per cent of our gut microbes are completely unknown to science.

That's according to a new survey of DNA fragments circulating in human blood, which suggests our bodies contain vastly more diverse microbes than anyone previously understood.

The overwhelming majority of them have never been seen before, let alone classified and named.

The survey was inspired by a curious observation in the Stanford University lab of Professor Stephen Quake, made while searching for non-invasive ways to predict whether an organ transplant patient's immune system would recognise the new organ as foreign and attack it - an event known as "rejection".

Ordinarily, it takes a tissue biopsy - meaning a large needle jabbed into one's side and at least an afternoon in a hospital bed for observation - to detect rejection.
The lab members figured there was a better way.

In theory, they might be able to detect rejection by taking blood samples and looking at the cell-free DNA - bits and pieces of DNA circulating freely in blood plasma - contained therein.

Apart from fragments of a patient's DNA, those samples would contain fragments of the organ donor's DNA as well as a comprehensive view of the collection of bacteria, viruses and other microbes that make up a person's microbiome.

Results of a series of studies suggested there were identifiable changes to the microbiomes of people with compromised immune systems, and that positive tests for the organ donor's DNA were a good sign of rejection.

But there was something else, too - something weirder.

Of all the non-human DNA fragments the team gathered, 99 percent of them failed to match anything in existing genetic databases the researchers examined.

Quake and his colleagues now hope to study the microbiomes of other organisms to see what's there.

"There's all kinds of viruses that jump from other species into humans, a sort of spillover effect, and one of the dreams here is to discover new viruses that might ultimately become human pandemics."

Understanding what those viruses are could help doctors manage and track outbreaks, he said.

"What this does is it arms infectious disease doctors with a whole set of new bugs to track and see if they're associated with disease," he said.

"That's going to be a whole other chapter of work for people to do."

Human waste into plastic?

Imagine you're on your way to Mars, and you lose a crucial tool during a spacewalk.

Not to worry, you'll simply re-enter your spacecraft and use some microorganisms to convert your urine and exhaled carbon dioxide into chemicals to make a new one.

That's one of the ultimate goals of scientists who are developing ways to make long space trips feasible.

Astronauts can't take a lot of spare parts into space because every extra ounce adds to the cost of fuel needed to escape Earth's gravity.

"If astronauts are going to make journeys that span several years, we'll need to find a way to reuse and recycle everything they bring with them," said Dr Mark Blenner, a synthetic biologist from Clemson University in the US, who just presented the strange findings to the American Chemical Society.

"Atom economy will become really important."

The solution lies in part with the astronauts themselves, who will constantly generate waste from breathing, eating and using materials.

Unlike their friends on Earth, Blenner said, these space-farers won't want to throw any waste molecules away.

So he and his team are studying how to repurpose these molecules and convert them into products the astronauts need, such as polyesters and nutrients.

Some essential nutrients, such as omega-3 fatty acids, had a shelf life of just a couple of years.

They'd need to be made en route, beginning a few years after launch, or at the destination.

"Having a biological system that astronauts can awaken from a dormant state to start producing what they need, when they need it, is the motivation for our project."

Blenner's biological system includes a variety of strains of the yeast Yarrowia lipolytica.

These organisms require both nitrogen and carbon to grow.

Blenner's team discovered that the yeast can obtain their nitrogen from urea in untreated urine.

Meanwhile, the yeast obtain their carbon from CO2, which could come from astronauts' exhaled breath, or from the Martian atmosphere.

But to use CO2, the yeast require a middleman to "fix" the carbon into a form they can ingest.

For this purpose, the yeast rely on photosynthetic cyanobacteria or algae provided by the researchers.

One of the yeast strains produces omega-3 fatty acids, which contributed to heart, eye and brain health.

Another strain has been engineered to churn out monomers and link them to make polyester polymers.

Those polymers could then be used in a 3D printer to generate new plastic parts.

Blenner's team was continuing to engineer this yeast strain to produce a variety of monomers that could be polymerised into different types of polyesters with a range of properties.