Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Chemistry (Page 1 of 7)

3D Virus Cam Catches Germs Red-Handed

A 3D plot of a virus wiggling around

The Duke team used their 3D virus cam to spy on this small lentivirus as it danced through a salt water solution.

Before germs like viruses can make you sick, they first have to make a landing on one of your cells — Mars Rover style — and then punch their way inside.

A team of physical chemists at Duke is building a microscope so powerful that it can spot these minuscule germs in the act of infection.

The team has created a new 3D “virus cam” that can spy on tiny viral germs as they wriggle around in real time. In a video caught by the microscope, you can watch as a lentivirus bounces and jitters through an area a little wider that a human hair.

Next, they hope to develop this technique into a multi-functional “magic camera” that will let them see not only the dancing viruses, but also the much larger cell membranes they are trying breech.

“Really what we are trying to investigate is the very first contacts of the virus with the cell surface — how it calls receptors, and how it sheds its envelope,” said group leader Kevin Welsher, assistant professor of chemistry at Duke. “We want to watch that process in real time, and to do that, we need to be able to lock on to the virus right from the first moment.”

A 3D plot spells out the name "Duke"

To test out the microscope, the team attached a fluorescent bead to a motion controller and tracked its movements as it spelled out a familiar name.

This isn’t the first microscope that can track real-time, 3D motions of individual particles. In fact, as a postdoctoral researcher at Princeton, Welsher built an earlier model and used it to track a bright fluorescent bead as it gets stuck in the membrane of a cell.

But the new virus cam, built by Duke postdoc Shangguo Hou, can track particles that are faster-moving and dimmer compared to earlier microscopes. “We were trying to overcome a speed limit, and we were trying to do so with the fewest number of photons collected possible,” Welsher said.

The ability to spot dimmer particles is particularly important when tracking viruses, Welsher said. These small bundles of proteins and DNA don’t naturally give off any light, so to see them under a microscope, researchers first have to stick something fluorescent on them. But many bright fluorescent particles, such as quantum dots, are pretty big compared to the size of most viruses. Attaching one is kind of like sticking a baseball onto a basketball – there is a good chance it might affect how the virus moves and interacts with cells.

The new microscope can detect the fainter light given off by much smaller fluorescent proteins – which, if the virus is a basketball, are approximately the size of a pea. Fluorescent proteins can also be inserted to the viral genome, which allows them to be incorporated into the virus as it is being assembled.

“That was the big move for us,” Welsher said, “We didn’t need to use a quantum dot, we didn’t need to use an artificial fluorescent bead. As long as the fluorescent protein was somewhere in the virus, we could spot it.” To create their viral video, Welsher’s team enlisted Duke’s Viral Vector Core to insert a yellow fluorescent protein into their lentivirus.

Now that the virus-tracking microscope is up-and-running, the team is busy building a laser scanning microscope that will also be able to map cell surfaces nearby. “So if we know where the particle is, we can also image around it and reconstruct where the particle is going,” Welsher said. “We hope to adapt this to capturing viral infection in real time.”

Robust real-time 3D single-particle tracking using a dynamically moving laser spot,” Shangguo Hou, Xiaoqi Lang and Kevin Welsher. Optics Letters, June 15, 2017. DOI: 10.1364/OL.42.002390

Kara J. Manke, PhDPost by Kara Manke

Hidden No More: Women in STEM reflect on their Journeys

Back when she was a newly-minted Ph.D., Ayana Arce struggled to picture her future life as an experimental physicist. An African American woman in a field where the number of black women U.S. doctorates is still staggeringly small, Arce could not identify many role models who looked like her.

“I didn’t know what my life would look like as a black postdoc or faculty member,” Arce said.

But in the end, Arce – an associate professor of physics at Duke who went on to join the international team of physicists who discovered the Higgs Boson in 2012 — drew inspiration from her family.

“I looked to the women such as my mother who had had academic careers, and tried to think about how I could shape my life to look something like that, and I realized that it could be something I could make work,” Arce said.

Adrienne Stiff-Roberts, Fay Cobb Payton, Kyla McMullen, Robin Coger and Valerie Ashby on stage at the Hidden Figures No More panel discussion.

Adrienne Stiff-Roberts, Fay Cobb Payton, Kyla McMullen, Robin Coger and Valerie Ashby on stage at the Hidden Figures No More panel discussion. Credit: Chris Hildreth, Duke Photography.

Arce joined five other African American women faculty on the stage of Duke’s Griffith Film Theater March 23 for a warm and candid discussion on the joys and continuing challenges of their careers in science, technology, engineering and math (STEM) fields.

The panel, titled “Hidden Figures No More: Highlighting Phenomenal Women in STEM,” was inspired by Hidden Figures, a film which celebrates three pioneering African American women mathematicians who overcame racial segregation and prejudice to play pivotal roles in NASA’s first manned space flight.

The panel discussion was spearheaded by Johnna Frierson, Director of the Office of Diversity and Inclusion at the Pratt School of Engineering, and co-sponsored by the Duke Women’s Center. It was followed by a free screening of the film.

Though our society has made great strides since the days depicted in the film, women and minorities still remain under-represented in most STEM fields. Those who do pursue careers in STEM must overcome numerous hurdles, including unconscious bias and a lack of colleagues and role models who share their gender and race.

“In my field, at some of the smaller meetings, I am often the only black woman present at the conference, many times I’m the only black person at all,” said Adrienne Stiff-Roberts, an Associate Professor of Electrical and Computer Engineering at Duke. “In that atmosphere often it can be very challenging to engage with others in the way that you are supposed to, and you can feel like an outsider.”

Valerie Ashby and Ayana Arce onstage at the Hidden Figures No More panel discussion

Valerie Ashby and Ayana Arce shared their experiences. Credit: Chris Hildreth, Duke Photography

Stiff-Roberts and the other panelists have all excelled in the face of these challenges, making their marks in fields that include physics, chemistry, computer science, mechanical engineering and electrical engineering. On Thursday they shared their thoughts and experiences with a diverse audience of students, faculty, community members and more than a few kids.

Many of the panelists credited teams of mentors and sponsors for bolstering them when times got tough, and encouraged young scientists to form their own support squads.

Valerie Ashby, Dean at Duke’s Trinity College of Arts and Sciences, advised students to look for supporters who have a vision for what they can become, and are eager to help them get there. “Don’t assume that your help might come from people who you might expect your help to come from,” Ashby said.

The importance of cheerleading from friends, and particularly parents, can never be overestimated, the panelists said.

“Having someone who will celebrate every single positive with you is a beautiful thing,” said Ashby, in response to a mother seeking advice for how to support a daughter majoring in biomedical engineering. “If your daughter is like many of us, we’ll do 99 great things but if we do one wrong thing we will focus on the one wrong thing and think we can’t do anything.”

Women in STEM can also be important and powerful allies to each other, noted Kyla McMullen, an Assistant Professor of Computer and Information Science at the University of Florida.

“I have seen situations where a woman suggests something and then the male next her says the same thing and gets the credit,” McMullen said. “That still happens, but one thing that I see help is when women make an effort to reiterate the points made by other women so people can see who credit should be attributed to.”

With all the advice out there for young people who are striving to succeed in STEM – particularly women and underrepresented minorities – the panelists advocated that everyone to stay true to themselves, above all.

“I want to encourage everyone in the room – whether you are a budding scientist or woman scholar – you can be yourself,” Ashby said. “You should make up in your mind that you are going to be yourself, no matter what.”

Kara J. Manke, PhD

Post by Kara Manke

Closing the Funding Gap for Minority Scientists

DURHAM, N.C. — The barriers to minority students in science, technology, engineering and math (STEM) don’t go away once they’ve finished school and landed a job, studies show. But one nationwide initiative aims to level the playing field once they get there.

With support from a 3-year, $500,0000 grant from the National Science Foundation, assistant professors and postdoctoral fellows who come from underrepresented minorities are encouraged to apply by May 5 for a free grant writing workshop to be held June 22-24 in Washington, D.C..

It’s no secret that STEM has a diversity problem. In 2015, African-Americans and Latinos made up 29 percent of the U.S. workforce, but only 11 percent of scientists and engineers.

A study published in the journal Science in 2011 revealed that minority scientists also were less likely to win grants from the National Institutes of Health, the largest source of research funding to universities.

Based on an analysis of 83,000 grant applications from 2000 to 2006, the study authors found that applications from black researchers were 13 percent less likely to succeed than applications from their white peers. Applications from Asian and Hispanic scientists were 5 and 3 percent less likely to be awarded, respectively.

Even when the study authors made sure they were comparing applicants with similar educational backgrounds, training, employers and publication records, the funding gap persisted — particularly for African-Americans.

Competition for federal research dollars is already tough. But white scientists won 29 percent of the time, and black scientists succeeded only 16 percent of the time.

Pennsylvania State University chemistry professor Squire Booker is co-principal investigator of a $500,000 initiative funded by the National Science Foundation to help underrepresented minority scientists write winning research grants.

“That report sent a shock wave through the scientific community,” said Squire Booker, a Howard Hughes Medical Institute investigator and chemistry professor at Pennsylvania State University. Speaking last week in the Nanaline H. Duke building on Duke’s Research Drive, Booker outlined a mentoring initiative that aims to close the gap.

In 2013, Booker and colleagues on the Minority Affairs Committee of the American Society for Biochemistry and Molecular Biology decided to host a workshop to demystify the grant application process and help minority scientists write winning grants.

Grant success is key to making it in academia. Even at universities that don’t make funding a formal requirement for tenure and promotion, research is expensive. Outside funding is often required to keep a lab going, and research productivity — generating data and publishing results — is critical.

To insure underrepresented minorities have every chance to compete for increasingly tight federal research dollars, Booker and colleagues developed the Interactive Mentoring Activities for Grantsmanship Enhancement program, known as IMAGE. Program officers from NIH and NSF offer tips on navigating the funding process, crafting a successful proposal, decoding reviews and revising and resubmitting. The organizers also stage a mock review panel, and participants receive real-time, constructive feedback on potential research proposals.

Participants include researchers in biology, biophysics, biochemistry and molecular biology. More than half of the program’s 130 alumni have been awarded NSF or NIH grants since the workshop series started in 2013.

Booker anticipates this year’s program will include more postdoctoral fellows. “Now we’re trying to expand the program to intervene at an earlier stage,” Booker said.

To apply for the 2017 workshop visit http://www.asbmb.org/grantwriting/.  The application deadline is May 5.

s200_robin.smith

Post by Robin Smith

The Road to a Tastier Tomato

This week, I discovered that I’ve lived life deprived of a good tomato.

As a tomato-lover, I was surprised to learn from Professor Harry Klee of the University of Florida that the supermarket tomatoes I’ve enjoyed throughout my 18-year existence are all flavorless compared to the tomatoes of the past. He spoke at Duke as a guest of the University Program in Genetics and Genomics on Feb. 28.

It turns out that commercial tomato growers, by breeding more profitable (i.e. higher-yield, redder-color, larger-fruit) tomato varieties over the past 50 years, inadvertently excluded what Klee believes is the most important tomato trait of all:

Commercial tomato growers have bred larger, redder tomatoes that are less flavorful than heirloom and older varieties. Image courtesy of Harry Klee.

Flavor.

Apparently, I was one of very few people unaware of this issue. The public outcry in response to the increasing flavorlessness of commercial tomatoes began over a decade ago, when Klee first began to study tomato genetics.

From his research, Klee has drawn several important, unexpected conclusions, chief among them:

1: Flavor has more to do with smell than taste;

2: Lesser-known biochemical compounds called “volatiles” influence the flavor of tomatoes more than sugars, acids, and other well-known, larger compounds;

3: These “volatiles” are less present in modern tomato varieties than in tastier, older, and heirloom varieties;

But fear not—

4: Tomatoes can be back-bred to regain the genes that code for volatile compounds.

In other words, Klee has mapped the way back to the flavorful tomatoes of the past. His work culminated in a cover story of the Jan. 27 issue of Science. The corresponding paper describing the analysis of over 300 tomato strains to identify the chemicals associated with “good” and “bad” tomatoes.

Dr. Harry Klee and collaborators in his lab at the University of Florida. Image courtesy of Harry Klee.

To prove that modern tomatoes have less of the compounds that make them tasty, Klee and his team recruited a panel of 100 taste-testers to rank 160 representative tomato varieties. According to Klee, the team “developed statistical models to explain the chemistry of ‘liking’ [tomatoes],” then narrowed down the list of compounds that correlated with “liking” from 400 to 26. After tracing these 26 compounds to genetic loci, they used whole-genome sequencing to show that these loci are less expressed in modern tomatoes than in “cerasiforme” (i.e. old) and heirloom tomato varieties.

Further studies showed that tomato weight is inversely correlated with sugar content—in other words, “a gigantic fruit doesn’t taste as good,” Klee said.

If Klee can convince tomato growers that consumers value flavor over size, color, and quantity, then he might just single-handedly put flavorful tomatoes back on the shelves. Nevertheless—and despite the publicity surrounding his work—Klee understands it make take a while before commercial tomato growers see the light.

Klee and his team of scientists have genetically mapped the way back to the tasty tomatoes of the past. Image courtesy of Harry Klee.

“Growers get no more money if the tomato tastes good or bad; they’re paid for how many pounds of red objects they put in a box…[but] we can’t just blame the modern breeders. We’ve been selecting bigger and bigger fruit for millennia, and that has come at the cost of reducing flavor,” Klee said.

Post by Maya Iskandarani

3D-Printable Material Sets Terminator’s Eyes Aglow

Pumpkins just not cutting it for you this year?

If you want a unique, hand-made Halloween decoration – and happen to have access to a 3D printer – Duke graduate student Patrick Flowers has just the project for you: this 3D-printed Terminator head, complete with shining, blood-red eyes.

Flowers, a PhD candidate in Benjamin Wiley’s lab, is not spending his time studying early eighties action flicks or the Governator’s best break-out roles. Instead, he and his labmates are working hard to brew up highly-conductive, copper-based materials that can be 3D printed into multilayer circuits – just like the one powering this Terminator’s glowing LED eyes.

Their latest copper concoction, which they have named “Electrifi,” is about 100 times more conductive than other materials on the market. The team has a taken out a provisional patent on Electrifi and also started a company, named Multi3D, where 3D-printing aficionados can purchase the material to include in their very own devices.

Micro CT scan of the 3D Terminator head

This X-ray view of Terminator’s head, collected with Duke SMIF’s Micro CT scanner, shows the embedded 3D circuit powering his LED eyes.

Creating a conductive, 3D-printable material is a lot trickier than just throwing some copper into a printer and going to town, Flowers said.

“Copper is really conductive originally, but if you try to extrude it out of a hot nozzle like you have to do in order to do this 3D printing, then it quickly loses all its properties,” Flowers said. And conductive materials that can stand the heat, like silver, are too expensive to use on any sort of scale, he added.

To bring the benefits of 3D printing to the world of electric circuits, Flowers and his labmates are experimenting with mixing copper with other materials to help it stay conductive through this extrusion process.

“This lab has a long history of working with copper – copper nanowires, copper particles, copper nanoparticles – so we’ve got a lot of little tricks that we use to maintain the conductivity,” Flowers said.

The team is currently testing the limits of their new material and plans to publish their findings soon. In the meantime, Flowers is busy exploring the other capabilities of Electrifi — outside of plastic android noggins.

“The circuit inside this guy is really simple, but it does show the capabilities of the material: it is embedded, it shows that I can go down, over, up, out, and go to a couple of eyes,” Flowers said. “Now I want to expand on that and show that you can make these really complicated embedded structures that have multiple layers and multiple components, other than just LEDs.”

adding_battery

Kara J. Manke, PhD

Post by Kara Manke

Cracking a Hit-and-Run Whodunit — With Lasers

The scratch was deep, two feet long, and spattered with paint flecks. Another vehicle had clearly grazed the side of Duke graduate student Jin Yu’s silver Honda Accord.

But the culprit had left no note, no phone number, and no insurance information.

Pump-Probe-Microscope-Pigment

Duke graduate student Jin Yu used laser-based imaging to confirm the source of a large scratch on the side of her car. Paint samples from an undamaged area on her Honda Accord (top left) and a suspected vehicle (top right) gave her the unique pump-probe microscopy signatures of the pigments on each car. The damaged areas of the Honda (bottom left) and the suspected vehicle on right (bottom right) show pigment signatures from both vehicles.

The timing of the accident, the location of the scratch, and the color of the foreign paint all pointed to a likely suspect: another vehicle in her apartment complex parking lot, also sporting a fresh gash.

She had a solid lead, but Yu wasn’t quite satisfied. The chemistry student wanted to make sure her case was rock-solid.

“I wanted to show them some scientific evidence,” Yu said.

And lucky for her, she had just the tools to do that.

As a researcher in the Warren Warren lab, Yu spends her days as scientific sleuth, investigating how a laser-based tool called pump-probe microscopy can be used to differentiate between individual pigments of paint, even if they appear identical to the human eye.

The team is developing the technique as a way for art historians and conservators peer under the surface of priceless paintings, without causing damage to the artwork. But Yu thought there was no reason the technique couldn’t be used for forensics, too.

“The idea popped into my mind — car paint is made up of pigments, just like paintings,” Yu said. “So, if I can compare the pigments remaining on my car with the suspected car, and they match up, that would be a pretty nice clue for finding the suspected car.”

Using a clean set of eyebrow tweezers, Yu carefully gathered small flecks of paint from her car and from the suspected vehicle and sealed them up inside individual Ziploc bags. She collected samples both from the scratched up areas, where the paint was mixed, and from undamaged areas on both cars.

She left a note on the car, citing the preliminary evidence and stating her plan to test the paint samples. Then, back at the lab, she examined all four samples with the pump-probe microscope. Unlike a standard optical microscope, this device illuminates each sample with a precisely timed series of laser pulses; each pigment absorbs and then re-emits this laser light in a slightly different pattern depending on its chemical structure, creating a unique signature.

Optical-Microscope-and-Note

After finding the gash on her Accord (top left), Yu left a note (top right) on the car that she suspected of having caused the accident. Under an optical microscope, samples from damaged areas on the cars show evidence of the same two kinds of paint (bottom). Yu used pump-probe microscopy to confirm that the pigments in the paint samples matched.

The samples from the undamaged areas gave her the characteristic pigment signatures from both of the two vehicles.

She then looked at the paint samples taken from the scratched areas. She found clear evidence of paint pigment from the suspected car on her Honda, and clear evidence of paint pigment from her Honda on the suspected car. This was like DNA evidence, of the automotive variety.

Fortunately, the owner of the suspect vehicle contacted Yu to confess and pay to have her car fixed, without demanding the results of the paint analysis. “But it was reassuring to have some scientific evidence in case she denied the accident,” Yu said.

Yu says she had no interest in forensic science when she started the investigation, but the experience has certainly piqued her curiosity.

“I had never imagined that I can use pump-probe microscopy for forensic science before this car accident happened,” Yu said. “But I think it shows some interesting possibilities.”

Kara J. Manke, PhD

Post by Kara Manke

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