Frozen Poo Pill a Possible Cure to Clostridium difficile Infections

First used in the 1950s, the fecal transplant has steadily gained street-cred since its introduction as a potential cure to the fierce bacterial infection caused by Clostridium difficile.

C. difficile is a gastrointestinal illness that causes around 14,000 deaths in the US every year.

A team at Massachusetts General Hospital recently published a study in JAMA highlighting a new method of storage for fecal transplants, essentially turning them into a frozen pill that can last for up to 250 days.

The basic idea of a fecal transplant is this: Healthy feces contain a mix of good bacteria that, when reintroduced back into the body, reequips the intestine to fight the C. difficile infection and allow the gut to function properly.

In the past, fecal transplant administration seemed like a fairly uncomfortable procedure — invasive at one of two ends. To get the necessary bacteria into the gut, patients could endure either a tube that went into their nose and down to their digestive tract, or an enema. Now, researchers at Massachusetts General Hospital in Boston have encapsulated the essential fecal material and tested this “poo pill” in a small study of 20 people.

The 20 patients ranged in age from 11 to 89 years old and each had suffered repeated cases of C. Difficile infection. Over the course of two days, each patient ingested 30 frozen capsules, 15 each day, and in 14 out of 20 patients, the infection was eliminated. In the remaining patients, the infection went away after a second round of 30 pills.

But the purpose of the pill wasn’t just to ease treatment protocol. It also allowed researchers to test ways to store the treatment for convenient use in the future. They found that freezing the pill to give to later patients was a viable option, making fecal transplants a simpler and safer medical tool.

Now, researchers are working towards a larger study with the frozen poo pills and hope to replicate the success they saw in the preliminary 20 patients.

An edible bacterial transplant is still unappetizing, but benefits seem to vastly outweigh the gross-factor. I just don’t, for the life of me, understand why they chose to store the fecal material in clear capsules. It looks exactly like how it sounds—like a frozen poo pill.

Sex-Geckos Sent to Space for Experiment

Of all the things I think about, my ability to reproduce in zero gravity ranks somewhere between “There’s a very small chance I’ve thought of this,” and “What.” But fortunately for me, and the rest of humanity that doesn’t actively contemplate space sex, a team of Russian scientists have wondered for us.

Actually, “wonder” is a bit of an understatement. These scientists rocketed five geckos (one male and four females) into space on a satellite called Foton-M4 with the intention of monitoring “the effect of microgravity on sexual behavior.” In other words, they wanted to see if geckos could do it mid-float in space. I like to think that as the Russian scientists waved the geckos goodbye, they said “Do it for science.”

This wasn’t just a can-they-do-it-in-space mission, though. The geckos had company aboard Foton-M4. It hosted a multitude of life-in-space experiments, with subjects ranging from fruit flies to fungus to microbes.

But why, Russia?

For the benefit of our great, great, great grandchildren’s great, great, great grandchildren. They wanted to test the waters of space life and specifically, the possibility of procreation for future humans—naturally, they thought to extrapolate from geckos.

To be fair, they didn’t just fling lusty geckos into orbit on any old satellite; they flung lusty geckos into orbit in a satellite that had, what they hoped, was sure-fire sex appeal.

In the experiment, Gecko-F4, the very first objective was to “create the conditions for sexual behavior.” How do you set the mood for gecko sex? Only science knows. In their efforts to witness the moments of facilitated gecko intimacy, they installed cameras. But I’m sad to say, these professional scientists didn’t get to sit around and watch until something naughty happened, because shortly after the initial launch, the signal was lost.

After a stressful three days, Russia’s space agency regained a connection with Foton-M4 on July 28^th. Side note: I turned 22 that day — best birthday present ever. But much to my dismay, one month later the satellite came prematurely crashing back to earth, and when researchers inspected the satellite, they found all five love geckos dead. Scientists suspect that part of the heater in the satellite broke and the poor critters froze to death. No one knows if they ever got it on.

Scientists on the experiment tried to console the public by shifting attention to the fruit flies that were also aboard Foton-M4 — they survived and procreated. I’m sure many people took solace in that.

It’s funny to see what types of news gain traction. This topic—gecko sex in space—took a firm hold of the public internationally; NPR, CNN, NBC, The Guardian, The BBC; they all covered it. It was all over the place and there were actual feelings involved. I even read an article that compared Gecko-F4 to the Apollo 13 mission. And I agree, they’re very similar. Except in Apollo 13 a brave group of astronauts overcame tremendous obstacles and returned safely to earth, and in Gecko-F4, Russians shot sex-lizards into space, lost them, and they died.

New Research Shows Sea Otters Help Fight Global Warming

It may sound absurd to think that sea otters could be a key to combating global warming. But it’s true. The findings of a new study on the subject even floored UCSC’s Jim Estes, one of the study’s leading researchers.

“I was blown away. We got all the data together, looked at the results, and I was like, ‘Whoa! Are you sure? Go back and run those numbers again.’”

But in the end, it checked out. Suddenly, sea otters were every conservationist’s dream come true. After 40 years of collecting data, UCSC researchers Estes, Chris Wilmers and their colleagues had uncovered a new link between the universally adored furball and what many consider Earth’s most imminent danger.

Estes and Wilmers studied sea otters and their effect on kelp beds in a region stretching from Vancouver Island to the edge of Alaska’s Aleutian Islands. After comparing otter-dense and otter-scarce areas, they found that kelp flourished in the former.

“It blew my mind. It was just incredible to see these two completely different ecosystems as a consequence of loss of sea otters,” says Estes.

Equipped with data on kelp density and net primary production (measured in units of carbon absorbed per area, per time), and the rate at which kelp absorbs CO2, Estes and Wilmers only needed to piece them all together.

“It was really a very simple, almost back-of-the-envelope calculation. It was just doing all the accounting to know how much carbon is there with and without sea otters,” says Wilmers.

With an appetite for kelp-destructive sea urchins, hungry otters yield thicker kelp beds which, in turn, absorb more carbon from the atmosphere. Otters on the hunt force sea urchins into hiding and allow the kelp beds to thrive, photosynthesize and essentially suck out copious amounts of CO2. This top-down, predator-prey effect is known as a trophic cascade, and is the basis of the suspected connection between predators and the cycling of CO2. If predators suppress herbivores, plants prosper and stimulate the carbon cycle, decreasing CO2 in the atmosphere. Essentially, it’s environmental dominoes.

The study found that kelp beds with a robust sea otter population had up to 12 times the absorbance capacity than kelp in sea-otter scant regions. In fact, if the entire planet was composed of a sea otter-kelp ecosystem, sea otter-induced carbon reduction would rank solidly in the 5-10% range.

Though this incredible correlation paints sea otters as something of a furry superhero, they can’t do it alone. With sea otters as their poster-child, Estes and Wilmers’ study illuminates the global effect apex predators can have on the carbon cycle.

“From a global perspective, the effect of sea otters is miniscule, but it points to the fact that predators can have a pretty dramatic effect in their own ecosystem,” says Wilmers. “There are predators everywhere, so globally, the effect of predators can be pretty significant.” Their research suggests that, while a predator-prey balance is key in species interactions, it more importantly underlies the collective harmony of our ecosystems’ carbon cycle.

After finding the astounding sea otter-carbon correlation in the ocean, many researchers have turned their attention to land, searching for sea otter-analogous predators in a terrestrial ecosystem. Wilmers himself is looking into that possibility, targeting wolves as a focal point for his potential future research.

Telomere Structures Unfold to Reveal Possible Anti-Cancer Therapy

Scientists have long fought cancer with their biggest, baddest research tactics — but big and bad only go so far. A new, potential approach involves working in a more concealed space: within the ends of our chromosomes. Biochemist Michael Stone, an assistant professor at the University of California, Santa Cruz, and his colleagues are tackling cancer research with, literally, a twist of biophysics. Stone’s lab probes inside the tips of chromosomes to stretch and bend DNA, watching how each strand reacts to invasive prodding.

Warping DNA requires specific and precise instruments. These adjustments in structure are so minuscule, less than one billionth of a meter, that only special microscopes can detect the changes. Stone’s lab is applying a pair of novel techniques — fluorescence microscopy and “magnetic tweezers” — to contort DNA precisely and, at the same time, account for each infinitesimal change in structure.

The magnetic tweezers and fluorescence microscopy duo are stirring new ideas about how folded structures in our cells may serve as the next major drug target for cancer therapies.

“We have this unique niche where we’re not only up on the biology, but we also have these specialized techniques,” Stone says. “We study how our genetic material behaves as just that, a material. That’s not the way we’re typically taught to think about DNA.”

The cells in our bodies carry a genetic blueprint tucked into compact pieces of DNA called chromosomes. A cap at the end of each chromosome protects the DNA from being damaged. These protective ends, called telomeres, play a key role in differentiating between chromosomes that end naturally with telomeres, and chromosomes that have damaged ends without telomeres. Scaled to fit in your hand, a chromosome would appear much like a shoelace, with the telomere acting as the plastic tip that keeps the lace from unraveling.

Every time our cells divide and copy, each telomere loses a bit of its length. Shortening telomeres essentially act as an hourglass for the life span of the cell. The chromosome divides and shrinks until it becomes a health risk to the cell, at which point, it enters a death phase. Though “death phase” sounds fairly ominous, it’s actually what’s keeping our cells in check. Every cell division is an opportunity for chromosomal mutation. The cell’s limited lifespan, caused by telomere shortening, restricts mutation and genetic damage.

Not all cells divide at the same rate though. Some cells—like stem cells—need to divide more rapidly to successfully function. In these kinds of cells, an enzyme called telomerase makes new telomeric DNA, enabling the rapid divisions by keeping the ends healthy. However, the quick and numerous cell divisions telomerase facilitates can also play a darker role in human health.

Over years of cancer research, scientists have repeatedly come to the same conclusion: telomerase is a fundamental contributor in creating most cancerous cells. The growth of a cancer cell is uncontrolled and its lifespan, virtually immortal. Research has found overactive telomerase in 90% of cancer cells, perpetuating cell growth that develops into tumors.

By tweaking the telomeres’ structure, Stone’s lab at UCSC reaches outside the usual realm of techniques used to study DNA. “My lab is one of the few groups in the world digging deep biophysically into the molecular mechanisms of telomere length maintenance, which is very important in medical biology,” he says.

The magnetic tweezers and a fluorescence microscopy technique called Förster Resonance Energy Transfer (FRET) may look like a convoluted duo to the untrained eye. But the basic ideas are simple: the “tweezers” pull and twist on molecules of DNA, while FRET measures the distances in real time.

The instruments reside in a small, busy lab room. At first sight it’s overwhelming, but it’s a purposeful clutter. What appears to be a haphazard maze of varying sizes of glass is a painstakingly aligned series of laser-guiding lenses and mirrors. Correctly aligned, the optics direct the laser that powers FRET. In other words, it’s the kind of display best kept at arm’s length.

Near the tweezers, a computer screen displays images of the manipulated DNA. With one end of the DNA molecule secured to a glass plate, scientists attach a magnetic bead to the other end and place a larger magnet above the bead. As the large magnet moves closer to the bead, the force on the DNA increases, stretching it further. During this process, FRET measures the fractional changes in length within single molecules by monitoring the interactions between a green donor FRET dye and a red acceptor FRET dye. The amount of energy transfer between the two dyes directly corresponds to the distance between them, making it one of the world’s smallest measuring tapes.

“Basically our lab married these two techniques so we could apply a very stable force and simultaneously monitor it [the DNA structure] on a very small scale,” says Xi Long, the lead graduate student in Stone’s lab.

The researchers focus on what happens in the telomeres of the chromosomes. They zero in on an unusual structure of DNA known as a G-quadruplex. With a structure just as complicated as its name, the G-quadruplex is no simple query. It fascinates researchers because of its propensity to fold and unfold into different forms, like origami on a molecular level. The effects of these folded forms on the level of telomerase activity are profound. In its folded, stable state, the G-quadruplex inhibits telomerase action, making it an intriguing candidate in the cancer therapy world.

Stone’s lab used the paired magnetic tweezers and FRET technique to explore the role of the G-quadruplex in detail. The tweezers stretch specifically dye-labeled DNA molecules in the structure to reveal the lengths at which folding and unfolding occurs. The team has found that the G-quadruplex is surprisingly touchy. Disturbing a single nucleotide could mean its demise. In that way, it’s a lot like Jenga: tamper with one building block and the whole thing collapses.

With such a temperamental structure, the goal is to find a way to keep the G-quadruplex happily stable and folded. Such a tactic could suggest ways to design a new type of cancer therapy. In the lab, scientists have experimented with stabilizing molecules that keep the G-quadruplex folded, blocking overactive telomerase. Replicating that success in cancerous cells — and, ultimately, in patients — will be a long road, Stone acknowledges.

Stone’s lab is keen to share the skills needed to develop and refine these techniques with other labs and researchers. Keeping them secret would eliminate the opportunity for colleagues to contribute their findings to science on a larger scale, says Stone.

“Now, when we report on it in the literature and at meetings, people studying things different than telomere structure are very excited about the methodology,” says Stone. “There are many applications for this sort of technology, reaching much further than just the interests of my lab.”

On a larger scale, Stone strives to explore how the G-quadruplex influences the broader biological roles of telomeres. For example, the lab will study how replication in telomeres differs compared to other segments of DNA. One salient feature of telomere DNA is its high sequence repetition. Repetitive sequences can lead to challenges in replication by confusing DNA polymerase, the replicating protein. A repeat in DNA causes stalling or back-tracking, like a scratch on a CD makes the music skip or stutter.

Stone and his team have studied the G-quadruplex for more than four years. With such a complex focal point, the lab can be an arduous place to work.

“I tell my younger students that you have to enjoy the process of science to be a good scientist. You can’t be completely results-focused,” says Stone. “Experiments are filled with challenges and difficulties. Taking these challenges in stride is just a part of the daily grind of being a research scientist.”

He gestures to a photo of the New York Yankees stadium pinned to his office wall. “Major league baseball hitters fail way more than they succeed,” Stone says. “In fact, the very best hitters fail seven times out of ten. So if you hit .300, you’re doing really well. You might even be MVP of the league. Yet more times than not, you didn’t get a hit. Science is like that. You need to have resilience.”