Duke Research Blog

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Category: Chemistry Page 1 of 6

Big SMILES All Around for Polymer Chemists at Duke, MIT and Northwestern

Science is increasingly asking artificial intelligence machines to help us search and interpret huge collections of data, and it’s making a difference.

But unfortunately, polymer chemistry — the study of large, complex molecules — has been hampered in this effort because it lacks a crisp, coherent language to describe molecules that are not tidy and orderly.

Think nylon. Teflon. Silicone. Polyester. These and other polymers are what the chemists call “stochastic,” they’re assembled from predictable building blocks and follow a finite set of attachment rules, but can be very different in the details from one strand to the next, even within the same polymer formulation.

Plastics, love ’em or hate ’em, they’re here to stay.
Foto: Mathias Cramer/temporealfoto.com

Chemistry’s old stick and ball models and shorthand chemical notations aren’t adequate for a long molecule that can best be described as a series of probabilities that one kind of piece might be in a given spot, or not.

Polymer chemists searching for new materials for medical treatments or plastics that won’t become an environmental burden have been somewhat hampered by using a written language that looks like long strings of consonants, equal signs, brackets, carets and parentheses. It’s also somewhat equivocal, so the polymer Nylon-6-6 ends up written like this: 

{<C(=O)CCCCC(=O)<,>NCCCCCCN>}

Or this,

{<C(=O)CCCCC(=O)NCCCCCCN>}

And when we get to something called ‘concatenation syntax,’ matters only get worse.  

Stephen Craig, the William T. Miller Professor of Chemistry, has been a polymer chemist for almost two decades and he says the notation language above has some utility for polymers. But Craig, who now heads the National Science Foundation’s Center for the Chemistry of Molecularly Optimized Networks (MONET), and his MONET colleagues thought they could do better.

Stephen Craig

“Once you have that insight about how a polymer is grown, you need to define some symbols that say there’s a probability of this kind of structure occurring here, or some other structure occurring at that spot,” Craig says. “And then it’s reducing that to practice and sort of defining a set of symbols.”

Now he and his MONET colleagues at MIT and Northwestern University have done just that, resulting in a new language – BigSMILES – that’s an adaptation of the existing language called SMILES (simplified molecular-input line-entry system). They they think it can reduce this hugely combinatorial problem of describing polymers down to something even a dumb computer can understand.

And that, Craig says, should enable computers to do all the stuff they’re good at – searching huge datasets for patterns and finding needles in haystacks.

The initial heavy lifting was done by MONET members Prof. Brad Olsen and his co-worker Tzyy-Shyang Lin at MIT who conceived of the idea and developed the set of symbols and the syntax together. Now polymers and their constituent building blocks and variety of linkages might be described like this:

Examples of bigSMILES symbols from the recent paper

It’s certainly not the best reading material for us and it would be terribly difficult to read aloud, but it becomes child’s play for a computer.

Members of MONET spent a couple of weeks trying to stump the new language with the weirdest polymers they could imagine, which turned up the need for a few more parts to the ‘alphabet.’ But by and large, it holds up, Craig says. They also threw a huge database of polymers at it and it translated them with ease.

“One of the things I’m excited about is how the data entry might eventually be tied directly to the synthetic methods used to make a particular polymer,” Craig says. “There’s an opportunity to actually capture and process more information about the molecules than is typically available from standard characterizations. If that can be done, it will enable all sorts of discoveries.”

BigSMILES was introduced to the polymer community by an article in ACS Central Science last week, and the MONET team is eager to see the response.

“Can other people use it and does it work for everything?” Craig asks. “Because polymer structure space is effectively infinite.” Which is just the kind of thing you need Big Data and machine learning to address. “This is an area where the intersection of chemistry and data science can have a huge impact,” Craig says.

Love at First Whiff

Many people turn to the Internet to find a Mr. or Ms. Right. But lemurs don’t have to cyberstalk potential love interests to find a good match — they just give them a sniff.

A study of lemur scents finds that an individual’s distinctive body odor reflects genetic differences in their immune system, and that other lemurs can detect these differences by smell.

Smell check: Fritz the ring-tailed lemur sniffs a tree for traces of other lemurs’ scents at the Duke Lemur Center.
Smell check: Fritz the ring-tailed lemur sniffs a tree for traces of other lemurs’ scents. Photo by David Haring, Duke Lemur Center.

From just one whiff, these primates are able to tell which prospective partners have immune genes different from their own. The ability to sniff out mates with different immune genes could make their offspring’s immune systems more diverse and able to fight more pathogens, said first author Kathleen Grogan, who did the research while working on her Ph.D. with professor Christine Drea at Duke University.

The results appeared online August 22 in the journal BMC Evolutionary Biology.

Lemurs advertise their presence by scent marking — rubbing stinky glands against trees to broadcast information about their sex, kin, and whether they are ready to mate.

Lemurs can tell whether a mate’s immune genes are a good genetic match by the scents they leave behind.
Lemurs can tell whether a mate’s immune genes are a good genetic match by the scents they leave behind. Photo by David Haring, Duke Lemur Center

For the study, Grogan, Drea and colleagues collected scent secretions from roughly 60 lemurs at the Duke Lemur Center, the Indianapolis Zoo, and the Cincinnati Zoo. The team used a technique called gas chromatography-mass spectrometry to tease out the hundreds of compounds that make up each animal’s signature scent.

They also analyzed the lemurs’ DNA, looking for differences within a cluster of genes called MHC that help trigger the body’s defenses against foreign invaders such as bacteria and viruses.

Their tests reveal that the chemical cocktail lemurs emit varies depending on which MHC types they carry.

To see if potential mates can smell the difference, the researchers presented lemurs with pairs of wooden rods smeared with the bodily secretions of two unfamiliar mates and observed their responses. Within seconds, the animals were drawn to the smells wafting from the rods, engaging in a frenzy of licking, sniffing, or rubbing their own scents on top.

In 300 trials, the team found that females paid more attention to the scents of males whose immune genes differed from their own.

MHC genes code for proteins that help the immune system recognize foreign invaders and distinguish “friend” from “foe.” Since different genetic versions respond to different sets of foreign substances, Grogan said, sniffing out genetically dissimilar mates produces offspring more capable of fighting a broad range of pathogens.

Just because females spent more time checking out the scents of dissimilar males doesn’t necessarily make them more likely to have kids together, Grogan said. Moving forward, she and her colleagues plan to use maternity and paternity DNA test results from wild lemurs living in Beza Mahafaly Reserve in Madagascar to see if lemur couples are more different in their MHC type than would be expected by chance.

Similar results have been found in humans, but this is the first time the ability to sniff out partners based on their immune genes has been shown in such distant primate kin, said Grogan, who is currently a postdoctoral fellow at Pennsylvania State University.

“Growing evidence suggests that primates rely on olfactory cues way more than we thought they did,” Grogan said. “It’s possible that all primates can do this.”

This research was supported by the National Science Foundation (BCS #0409367, IOS #0719003), the National Institutes of Health (F32 GM123634–01), and the Duke University Center for Science Education.

CITATION: “Genetic Variation at MHC class II Loci Influences Both Olfactory Signals and Scent Discrimination in Ring-Tailed Lemurs,” Kathleen E. Grogan, Rachel L. Harris, Marylène Boulet, and Christine M. Drea. BMC Evolutionary Biology, August 22, 2019. DOI: 10.1186/s12862-019-1486-0

Post by Robin A. Smith

Nature Shows a U-Turn Path to Better Solar Cells

The technical-sounding category of “light-driven charge-transfer reactions,” becomes more familiar to non-physicists when you just call it photosynthesis or solar electricity.

When a molecule (in a leaf or solar cell) is hit by an energetic photon of light, it first absorbs the little meteor’s energy, generating what chemists call an excited state. This excited state then almost immediately (like trillionths of a second) shuttles an electron away to a charge acceptor to lower its energy. That transference of charge is what drives plant life and photovoltaic current.

A 20 Megawatt solar farm ( Aerial Innovations via wikimedia commons)

The energy of the excited state plays an important role in determining solar energy conversion efficiency. That is, the more of that photon’s energy that can be retained in the charge-separated state, the better. For most solar-electric devices, the excited state rapidly loses energy, resulting in less efficient devices.

But what if there were a way to create even more energetic excited states from that incoming photon?

Using a very efficient photosynthesizing bacterium as their inspiration, a team of Duke chemists that included graduate students Nick Polizzi and Ting Jiang, and faculty members David Beratan and Michael Therien, synthesized a “supermolecule” to help address this question.

“Nick and Ting discovered a really cool trick about electron transfer that we might be able to adapt to improving solar cells,” said Michael Therien, the William R. Kenan, Jr. Professor of Chemistry. “Biology figured this out eons ago,” he said.

“When molecules absorb light, they have more energy,” Therien said. “One of the things that these molecular excited states do is that they move charge. Generally speaking, most solar energy conversion structures that chemists design feature molecules that push electron density in the direction they want charge to move when a photon is absorbed. The solar-fueled microbe, Rhodobacter sphaeroides, however, does the opposite. What Nick and Ting demonstrated is that this could also be a winning strategy for solar cells.”

Ting Jiang
Nick Polizzi

The chemists devised a clever synthetic molecule that shows the advantages of an excited state that pushes electron density in the direction opposite to where charge flows. In effect, this allows more of the energy harvested from a photon to be used in a solar cell. 

“Nick and Ting’s work shows that there are huge advantages to pushing electron density in the exact opposite direction where you want charge to flow,” Therien said in his top-floor office of the French Family Science Center. “The biggest advantage of an excited state that pushes charge the wrong way is it stops a really critical pathway for excited state relaxation.”

“So, in many ways it’s a Rube Goldberg Like conception,” Therien said. “It is a design strategy that’s been maybe staring us in the face for several years, but no one’s connected the dots like Nick and Ting have here.”

In a July 2 commentary for the Proceedings of the National Academy of Sciences, Bowling Green State University chemist and photoscientist Malcom D.E. Forbes calls this work “a great leap forward,” and says it “should be regarded as one of the most beautiful experiments in physical chemistry in the 21st century.”

Here’s a schematic from the paper.
(Image by Nick Polizzi)

CITATION: “Engineering Opposite Electronic Polarization of Singlet and Triplet States Increases the Yield of High-Energy Photoproducts,” Nicholas Polizzi, Ting Jiang, David Beratan, Michael Therien. Proceedings of the National Academy of Sciences, June 10, 2019. DOI: 10.1073/pnas.1901752116 Online: https://www.pnas.org/content/early/2019/07/01/1908872116

Don’t Drink the Tap

Have you ever questioned the quality of the water you drink every day? Or worried that cooking with tap water might be dangerous? For most of us, the answer to these questions is probably no. However, students from a Bass Connections team at Duke say we may want to think otherwise.

Image result for image of water

From bottle refilling stations to the tap, drinking water is so habitual and commonplace that we often take it for granted. Only in moments of crisis do we start worrying about what’s in the water we drink daily. The reality is that safe drinking water isn’t accessible for a lot of people.

Image result for pink hog farm water
Pig waste discoloring lagoon water

Images like this hog farm motivated the Bass Connections project team DECIPHER to take a closer look at the quality of water in North Carolina. On April 16 they presented their concerning findings from three case studies looking at lead contamination, coal ash impoundments, and aging infrastructure at the Motorco Music Hall.

Motorco in Durham. The talk was inside, though.

Nadratun Chowdhury, a Ph.D. student in Civil and Environmental Engineering, investigated lead contamination in water. Lead is an abundant and corrosion-resistant material, making it appealing for use in things like paint, batteries, faucets and pipes. While we’ve successfully removed lead from paint and gasoline, a lot of old water pipes in use today are still fashioned from lead. That’s not good – lead is very toxic and can leach into the water.

Just how toxic is it? Anything over a blood-lead level concentration of fifty parts per billion – fifty drops of water in a giant Olympic swimming pool – is considered dangerous. According to Duke graduate student Aaron Reuben, this much lead in one’s blood is correlated with downward social mobility, serious health concerns, diminished capacity to regulate thoughts and emotions, and hyperactivity. Lower income and minority areas are more at risk due to the higher likelihood of owning contaminated older homes.

Rupanjali Karthik, a Master of Laws student, conducted research on the intersection of water and aging infrastructure in Orange County. Breaks in water pipes are common and can result in serious consequences, like the loss of 9 million gallons of drinkable water. Sometimes it takes 8 or 9 months just to find the location of a broken pipe. In 2018, the UNC-Chapel Hill water main break caused a huge shortage on campus and at the medical center.

Excess fluoridation is also an issue caused by aging infrastructure. In February 2017, a combination of human and machine error caused an excessive fluoride concentration coming out of an Orange County Water Treatment Plant. People were advised not to use their water even to shower. A UNC basketball game had to move locations, and stores were completely swept of bottled water.

Another issue is that arsenic, a known carcinogen, is often used as the fluoridation agent. We definitely don’t want that in our drinking water. Fluoridation isn’t even that necessary these days when we have toothpaste and mouthwash that supports our dental health.

Tommy Lin, an undergraduate studying Chemistry and Computer Science, topped off the group’s presentation with findings surrounding coal ash in Belmont, NC. Coal ash, the residue after coal is burned in power plants, can pollute rivers and seep into ground water, affecting domestic wells of neighboring communities. This creates a cocktail of highly concentrated heavy metals and carcinogens. Drinking it can cause damage to your nervous system, cancer, and birth defects, among other things. Not so great.

The group’s presentation.

Forty-five plastic water bottles. That’s how much water it takes Laura, a Belmont resident, to cook her middle-sized family Thanksgiving. She knows that number because it’s been her family’s tradition the past three years. The Allen Plant Steam Station is a big culprit of polluting water with coal ash. Tons of homes nearby the station, like Laura’s, are told not to use the tap water. You can find these homes excessively stockpiled with cases on cases of plastic water bottles.

These issues aren’t that apparent to people unless they have been directly impacted. Lead, aging infrastructure, and coal ash all pose real threats but are also very invisible problems. Kathleen Burns, a Ph.D. student in English, notes that only in moments of crisis will people start to care, but by then it may be too late.

So, what can people do? Not much, according to the Bass Connections team. They noted that providing clean water is very much a structural issue which will require some complex steps to be solved. So, for now, you may want to go buy a Brita.

Will Sheehan
Post by Will Sheehan

Teaching a Machine to Spot a Crystal

A collection of iridescent crystals grown in space

Not all protein crystals exhibit the colorful iridescence of these crystals grown in space. But no matter their looks, all are important to scientists. Credit: NASA Marshall Space Flight Center (NASA-MSFC).

Protein crystals don’t usually display the glitz and glam of gemstones. But no matter their looks, each and every one is precious to scientists.

Patrick Charbonneau, a professor of chemistry and physics at Duke, along with a worldwide group of scientists, teamed up with researchers at Google Brain to use state-of-the-art machine learning algorithms to spot these rare and valuable crystals. Their work could accelerate drug discovery by making it easier for researchers to map the structures of proteins.

“Every time you miss a protein crystal, because they are so rare, you risk missing on an important biomedical discovery,” Charbonneau said.

Knowing the structure of proteins is key to understanding their function and possibly designing drugs that work with their specific shapes. But the traditional approach to determining these structures, called X-ray crystallography, requires that proteins be crystallized.

Crystallizing proteins is hard — really hard. Unlike the simple atoms and molecules that make up common crystals like salt and sugar, these big, bulky molecules, which can contain tens of thousands of atoms each, struggle to arrange themselves into the ordered arrays that form the basis of crystals.

“What allows an object like a protein to self-assemble into something like a crystal is a bit like magic,” Charbonneau said.

Even after decades of practice, scientists have to rely in part on trial and error to obtain protein crystals. After isolating a protein, they mix it with hundreds of different types of liquid solutions, hoping to find the right recipe that coaxes them to crystallize. They then look at droplets of each mixture under a microscope, hoping to spot the smallest speck of a growing crystal.

“You have to manually say, there is a crystal there, there is none there, there is one there, and usually it is none, none, none,” Charbonneau said. “Not only is it expensive to pay people to do this, but also people fail. They get tired and they get sloppy, and it detracts from their other work.”

Three microscope images of protein crystallization solutions

The machine learning software searches for points and edges (left) to identify crystals in images of droplets of solution. It can also identify when non-crystalline solids have formed (middle) and when no solids have formed (right).

Charbonneau thought perhaps deep learning software, which is now capable of recognizing individual faces in photographs even when they are blurry or caught from the side, should also be able to identify the points and edges that make up a crystal in solution.

Scientists from both academia and industry came together to collect half a million images of protein crystallization experiments into a database called MARCO. The data specify which of these protein cocktails led to crystallization, based on human evaluation.

The team then worked with a group led by Vincent Vanhoucke from Google Brain to apply the latest in artificial intelligence to help identify crystals in the images.

After “training” the deep learning software on a subset of the data, they unleashed it on the full database. The A.I. was able to accurately identify crystals about 95 percent of the time. Estimates show that humans spot crystals correctly only 85 percent of the time.

“And it does remarkably better than humans,” Charbonneau said. “We were a little surprised because most A.I. algorithms are made to recognize cats or dogs, not necessarily geometrical features like the edge of a crystal.”

Other teams of researchers have already asked to use the A.I. model and the MARCO dataset to train their own machine learning algorithms to recognize crystals in protein crystallization experiments, Charbonneau said. These advances should allow researchers to focus more time on biomedical discoveries instead of squinting at samples.

Charbonneau plans to use the data to understand how exactly proteins self-assemble into crystals, so that researchers rely less on chance to get this “magic” to happen.

“We are trying to use this data to see if we can get more insight into the physical chemistry of self-assembly of proteins,” Charbonneau said.

CITATION: “Classification of crystallization outcomes using deep convolutional neural networks,” Andrew E. Bruno, et al. PLOS ONE, June 20, 2018. DOI: 10.1371/journal.pone.0198883

 

Post by Kara Manke

Looking at Cooking as a Science Experiment

From five-star restaurants to Grandma’s homemade cookies, cooking is an art that has transformed the way we taste food. But haven’t you ever wondered how cooking works? How in the world did people discover how to make Dipping Dots or Jell-O?

Patrick Charbonneau is an Associate Professor of Chemistry here at Duke and last Friday he gave a delicious talk about the science of cooking (with samples!).

Patrick Charbonneau, Duke Chemist and Foodie

Around 10,000 years ago humans discovered that by fermenting milk you could turn it into yogurt, something that is more transportable, lasts longer, and digests easier. In the 1600s a new cooking apparatus called the “bone digester” (pressure cooker) allowed you to cook things faster while enhancing the flavor. When the 1800s came around, a scientist named Eben Horsford discovered that adding an acid with sodium bicarbonate creates baking powder. Soon enough scientific and kitchen minds started to collaborate, and new creations were made in the culinary world. As you can see, a lot of fundamental cooking techniques and ingredients we use today are a product of scientific discoveries.

Old-school pressure cookers. Forerunners of the Instant Pot.

Whisked Toffee

Freezer toffee, AKA caramel

A huge part of cooking is controlling the transformation of matter, or “a change in phase.” Professor Charbonneau presented a very cool example demonstrating how controlling this phase shift can affect your experience eating something. He made the same toffee recipe twice, but he changed it slightly as the melted toffee mixture was cooling. One version you stick straight in the freezer; the other you whisk as it cools. The whisked version turns out crumbly and sweeter; the other one turns into a chewy, shiny caramel. The audience got samples, and I could easily tell how different each version looked and tasted.

Charbonneau explained that while both toffees have the same ingredients, most people prefer the crumbly one because it seems sweeter (I agreed). This is because the chewier one takes longer to dissolve onto your taste buds, so your brain registers it as less sweet.

I was fascinated to learn that a lot of food is mostly just water. It’s weird to think a solid thing could be made of water, yet some foods are up to 99% water and still elastic! We have polymers — long repeating patterns of atoms in a chain — to thank for that. In fact, you can turn almost any liquid into a gel. Polymers take up little space but play a vital role in not only foods but other everyday objects, like contact lenses.

Charbonneau also showed us a seemingly magical way to make cake. He took about half a Dixie cup of cake batter, stuck a whipping siphon charged with nitrous oxide inside it for a second, then threw it in the microwave for thirty seconds. Boom, easy as cake. Out came a cup full of some pretty darn good fluffy chocolate cake. The gas bubbles in the butter and egg batter expand when they are heated up, causing the batter to gel and form a solid network.

Professor Charbonneau is doing stuff like this in his class here at Duke, “The Chemistry and Physics of Cooking,” all the time.

In the past ten years a surge in science-cooking related classes has emerged. The experiments you could do in a kitchen-lab are so cool and can make science appealing to those who might normally shy away from it.

Another cool thing I learned at the stations outside of Charbonneau’s talk was that Dipping Dots are made by dripping melted ice cream into a bowl of liquid nitrogen. The nitrogen is so cold that it flash-freezes the ice cream droplet into a ball-like shape!

Post by Will Sheehan

Will Sheehan

Stretchable, Twistable Wires for Wearable Electronics

A new conductive “felt” carries electricity even when twisted, bent and stretched. Credit: Matthew Catenacci

The exercise-tracking power of a Fitbit may soon jump from your wrist and into your clothing.

Researchers are seeking to embed electronics such as fitness trackers and health monitors into our shirts, hats, and shoes. But no one wants stiff copper wires or silicon transistors deforming their clothing or poking into their skin.

Scientists in Benjamin Wiley’s lab at Duke have created new conductive “felt” that can be easily patterned onto fabrics to create flexible wires. The felt, composed of silver-coated copper nanowires and silicon rubber, carries electricity even when bent, stretched and twisted, over and over again.

“We wanted to create wiring that is stretchable on the body,” said Matthew Catenacci, a graduate student in Wiley’s group.

The conductive felt is made of stacks of interwoven silver-coated copper nanotubes filled with a stretchable silicone rubber (left). When stretched, felt made from more pliable rubber is more resilient to small tears and holes than felts made of stiffer rubber (middle). These tears can be seen in small cavities in the felt (right). Credit: Matthew Catenacci

To create a flexible wire, the team first sucks a solution of copper nanowires and water through a stencil, creating a stack of interwoven nanowires in the desired shape. The material is similar to the interwoven fibers that comprise fabric felt, but on a much smaller scale, said Wiley, an associate professor of chemistry at Duke.

“The way I think about the wires are like tiny sticks of uncooked spaghetti,” Wiley said. “The water passes through, and then you end up with this pile of sticks with a high porosity.”

The interwoven nanowires are heated to 300 F to melt the contacts together, and then silicone rubber is added to fill in the gaps between the wires.

To show the pliability of their new material, Catenacci patterned the nanowire felt into a variety of squiggly, snaking patterns. Stretching and twisting the wires up to 300 times did not degrade the conductivity.

The material maintains its conductivity when twisted and stretched. Credit: Matthew Catenacci

“On a larger scale you could take a whole shirt, put it over a vacuum filter, and with a stencil you could create whatever wire pattern you want,” Catenacci said. “After you add the silicone, so you will just have a patch of fabric that is able to stretch.”

Their felt is not the first conductive material that displays the agility of a gymnast. Flexible wires made of silver microflakes also exhibit this unique set of properties. But the new material has the best performance of any other material so far, and at a much lower cost.

“This material retains its conductivity after stretching better than any other material with this high of an initial conductivity. That is what separates it,” Wiley said.

Stretchable Conductive Composites from Cu-Ag Nanowire Felt,” Matthew J. Catenacci, Christopher Reyes, Mutya A. Cruz and Benjamin J. Wiley. ACS Nano, March 14, 2018. DOI: 10.1021/acsnano.8b00887

Post by Kara Manke

MRI Tags Stick to Molecules with Chemical “Velcro®”

An extremely close-up view of Velcro

In the new technique, MRI chemical tags attach to a target molecule and nothing else – kind of like how Velcro only sticks to itself. Credit: tanakawho, via Flickr.

Imagine attaching a beacon to a drug molecule and following its journey through our winding innards, tracking just where and how it interacts with the chemicals in our bodies to help treat illnesses.

Duke scientists may be closer to doing just that. They have developed a chemical tag that can be attached to molecules to make them light up under magnetic resonance imaging (MRI).

This tag or “lightbulb” changes its frequency when the molecule interacts with another molecule, potentially allowing researchers to both locate the molecule in the body and see how it is metabolized.

“MRI methods are very sensitive to small changes in the chemical structure, so you can actually use these tags to directly image chemical transformations,” said Thomas Theis, an assistant research professor in the chemistry department at Duke.

Chemical tags that light up under MRI are not new. In 2016, the Duke team of Warren S. Warren’s lab and Qiu Wang’s lab created molecular lightbulbs for MRI that burn brighter and longer than any previously discovered.

A photo of graduate students Junu Bae and Zijian Zhou in front of a bookshelf.

Junu Bae and Zijian Zhou, the co-first authors of the paper. Credit: Qiu Wang, Duke University.

In a study published March 9 in Science Advances, the researchers report a new method for attaching tags to molecules, allowing them to tag molecules indirectly to a broader scope of molecules than they could before.

“The tags are like lightbulbs covered in Velcro,” said Junu Bae, a graduate student in Qiu Wang’s lab at Duke. “We attach the other side of the Velcro to the target molecule, and once they find each other they stick.”

This reaction is what researchers call bioorthogonal, which means that the tag will only stick to the molecular target and won’t react with any other molecules.

And the reaction was designed with another important feature in mind — it generates a rare form of nitrogen gas that also lights up under MRI.

“One could dream up a lot of potential applications for the nitrogen gas, but one that we have been thinking about is lung imaging,” Theis said.

Currently the best way to image the lungs is with xenon gas, but this method has the downside of putting patients to sleep. “Nitrogen gas would be perfectly safe to inhale because it is what you inhale in the air anyways,” Theis said.

A stylized chemical diagram of the hyperpolarization process

In the new technique, a type of molecule called a tetrazine is hyperpolarized, making it “light up” under MRI (illustrated on the left). It is then tagged to a target molecule through a what is called a bioorthogonal reaction. The reaction also generates a rare form of nitrogen gas that can be spotted under MRI (illustrated on the right). Credit: Junu Bae and Seoyoung Cho, Duke University.

Other applications could include watching how air flows through porous materials or studying the nitrogen fixation process in plants.

One downside to the new tags is that they don’t shine as long or as brightly as other MRI molecular lightbulbs, said Zijian Zhou, a graduate student in  Warren’s lab at Duke.

The team is tinkering with the formula for polarizing, or lighting up, the molecule tags to increase their lifetime and brilliance, and to make them more compatible with chemical conditions in the human body.

“We are now developing new techniques and new procedures which may be helpful for driving the polarization levels even higher, so we can have even better signal for these applications,” Zhou said.

15N4-1,2,4,5-tetrazines as potential molecular tags: Integrating bioorthogonal chemistry with hyperpolarization and unearthing para-N2,” Junu Bae, Zijian Zhou, Thomas Theis, Warren S. Warren and Qiu Wang. Science Advances, March 9, 2018. DOI: 10.1126/sciadv.aar2978

Post by Kara Manke

How Earth’s Earliest Lifeforms Protected Their Genes

A colorful hot spring in Yellowstone National Park

Heat-loving thermophile bacteria may have been some of the earliest lifeforms on Earth. Researchers are studying their great great great grandchildren, like those living in Yellowstone’s Grand Prismatic Spring, to understand how these early bacteria repaired their DNA.

Think your life is hard? Imagine being a tiny bacterium trying to get a foothold on a young and desolate Earth. The earliest lifeforms on our planet endured searing heat, ultraviolet radiation and an atmosphere devoid of oxygen.

Benjamin Rousseau, a research technician in David Beratan’s lab at Duke, studies one of the molecular machines that helped these bacteria survive their harsh environment. This molecule, called photolyase, fixes DNA damaged by ultraviolet (UV) radiation — the same wavelengths of sunlight that give us sunburn and put us at greater risk of skin cancer.

“Anything under the sun — in both meanings of the phrase — has to have ways to repair itself, and photolyase proteins are one of them,” Rousseau said. “They are one of the most ancient repair proteins.”

Though these proteins have been around for billions of years, scientists are still not quite sure exactly how they work. In a new study, Rousseau and coworkers, working with Professor David Beratan and Assistant Research Professor Agostino Migliore, used computer simulations to study photolyase in thermophiles, the great great great great grandchildren of Earth’s original bacterial pioneers.

The study appeared in the Feb. 28 issue of the Journal of the American Chemical Society.

DNA is built of chains of bases — A, C, G and T — whose order encodes our genetic information. UV light can trigger two adjacent bases to react and latch onto one other, rendering these genetic instructions unreadable.

Photolyase uses a molecular antenna to capture light from the sun and convert it into an electron. It then hands the electron over to the DNA strand, sparking a reaction that splits the two bases apart and restores the genetic information.

A ribbon diagram of a photolyase protein

Photolyase proteins use a molecular antenna (green, blue and red structure on the right) to harvest light and convert it into an electron. The adenine-containing structure in the middle hands the electron to the DNA strand, splitting apart DNA bases. Credit: Benjamin Rousseau, courtesy of the Journal of the American Chemical Society.

Rousseau studied the role of a molecule called adenine in shuttling the electron  from the molecular antenna to the DNA strand. He looked at photolyase in both the heat-loving ancestors of ancient bacteria, called thermophiles, and more modern bacteria like E. Coli that thrive at moderate temperatures, called mesophiles.

He found that in thermophiles, adenine played a role in transferring the electron to the DNA. But in E. coli, the adenine was in a different position, providing mainly structural support.

The results “strongly suggest that mesophiles and thermophiles fundamentally differ in their use of adenine for this electron transfer repair mechanism,” Rousseau said.

He also found that when he cooled E. Coli down to 20 degrees Celsius — about 68 degrees Fahrenheit — the adenine shifted back in place, resuming its transport function.

“It’s like a temperature-controlled switch,” Rousseau said.

Though humans no longer use photolyase for DNA repair, the protein persists in life as diverse as bacteria, fungi and plants — and is even being studied as an ingredient in sunscreens to help repair UV-damaged skin.

Understanding exactly how photolyase works may also help researchers design proteins with a variety of new functions, Rousseau said.

“Photolyase does all of the work on its own — it harvests the light, it transfers the electron over a huge distance to the other site, and then it cleaves the DNA bases,” Rousseau said. “Proteins with that kind of plethora of functions tend to be an attractive target for protein engineering.”

Post by Kara Manke

Can Science Explain Everything? An Exploration of Faith

The Veritas Forum, Feb. 1 in Penn Pavilion

I found out about this year’s Veritas Forum an hour before it started — a friend, who two years ago helped me explore Christianity (I grew up non-religious and was curious), mentioned it when we ran into each other at the Brodhead Center.

So, to avoid my academic responsibilities, I instead listened to Duke physics professor Ronen Plesser, a non-practicing Jew, Troy Van Voorhis, a Christian who teaches chemistry at MIT, and moderator Ehsan Samei, a professor of radiology and biomedical engineering at Duke. They discussed the God Hypothesis and how it fit in with their views as hard scientists.

Ehsan Samei

As someone who has relied on the scientific method instead of an omniscient, higher power to understand the natural world, I found it amazing how the speakers used relatable examples to demonstrate their belief that humans cannot explain everything. They started answering the classic question “Why is the sky blue?,” using more and more complex chemistry and physics as answers only led to more questions.

At some point, science-based explanations about how and why molecules move the way they do and where they come from didn’t suffice — at some point, it just seems like something, or someone, is responsible for the unexplainable.

Troy Van Voorhis of MIT

Something that Van Voorhis said particularly stuck in my mind. Reproducibility and objectivity form the “bedrock of science,” but are also it’s “grand limitations.” They are essential to corroborating the results of a scientific study or experiment, but can they really confirm something as scientific truth? When does reproducibility adequately overcome variation in data, and can something be defined as truly objective?

So, I sat there in the audience, thinking about alternatives to explaining morals, ethics, and the feeling of being human since, to paraphrase Plesser, science just doesn’t cut it in these cases. He elaborated on faith after branching off Van Voorhis’ point of view. Plesser’s explanation made the overlap of science and religion become more and more prominent. As someone who also does not practice a religion, I felt that his comparison of faith in science and faith in religion comforting.

Ronan Plesser

Even though I still struggle to fully accept Christ, I was aware of the similarities of the path to scientific and spiritual enlightenment. In science, incessant questioning of our surroundings is necessary to understand the Truths of our world (“otherwise we wouldn’t be publishing papers and we would be out of our jobs!”), as are the calls to God to come down and help people improve themselves. It is impossible, then, to avoid faith entirely since being human inherently involves belief in some sort of system.

I was wowed by the connections that the three men were making between the seemingly divergent areas. I was even more astonished, though, by their emphasis on humility. They exemplified the need for understanding and patience when describing scientific theories and religious ideologies. To be humble is to accept that people have differences and to acknowledge these differences is the only way to reduce conflicts between religion and science.

Post by Stella Wang

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