Tag: spectroscopy

Ashley James wins 2023 Klein Award for studying mercury poisoning

Ashley James (Ashlyn George)

Ashley James is fascinated by her toxicology research because it combines biology, chemistry, physics and morbid topics like poisonings that affect the environment and world health. She also loves the unexpected twists. “We’ve been surprised so many times by what we’ve found. It’s been a fun, wild ride,” she said.

As a PhD student and now postdoctoral research fellow from the University of Saskatchewan, James’ research on mercury poisoning in animals and humans uses X-rays produced by the Stanford Synchrotron Radiation Lightsource (SSRL) at the Department of Energy’s SLAC National Accelerator Laboratory.

For her work, James will receive the 2023 Melvin P. Klein Scientific Development Award during the 2023 SSRL/LCLS Annual Users’ Meeting held at SLAC September 24-29.

“The SSRL-based research of Dr. James addresses a global health question with breakthrough discoveries while demonstrating state-of-the-art methodology for her discipline, thus bearing all the hallmarks of ‘outstanding research accomplishments by a new investigator’ that the award is intended to recognize,” wrote her PhD supervisors Graham George and Ingrid Pickering, Canada Research Chairs and professors at the University of Saskatchewan, in a nomination letter for the award.

James said she felt surprised, excited and honored by SSRL when she found out about winning the award. “It’s awesome to be included in the list of Klein awardees, alongside the diverse projects and incredible scientists who’ve won in the past,” she said.

Re-thinking the Minamata mass poisoning

As a PhD student, James studied the mass poisoning of thousands of people who ingested mercury by eating tainted fish and shellfish from the Minamata Bay in Japan during the late 1950s and 1960s. This famous, deadly tragedy was caused by a chemical plant dumping mercury-contaminated industrial waste into the bay – as demonstrated by a physician working for the factory who fed cats food laced with the industrial waste to confirm that it was responsible for the neurological disease.

Because the chemical plant used inorganic mercury in its processes, scientists initially believed that the contaminated waste contained inorganic mercury. The idea was that this inorganic mercury was transformed in the environment into a common and more toxic form of organic mercury called methylmercury.

James and her collaborators investigated the Minamata poisoning by studying preserved samples from a cat in the historic study. First, they showed that the mercury in the cat’s brain tissue was mostly organic by performing studies at SSRL’s X-ray spectroscopy (XAS) beamline 7-3 and high-energy-resolution fluorescence detection (HERFD-XAS) beamline 6-2, with help from SLAC scientists Matthew Latimer, Thomas Kroll and Dimosthenis Sokaras.

“These synchrotron techniques allowed us to look at historical samples with X-ray eyes to determine what mercury compounds existed in the cat’s brain tissue, which then told us a lot about its toxicology,” explained James. “HERFD-XAS has been particularly useful because its higher resolution enhances the shape of the mercury spectra, so we can fit the complex mixture of compounds with more confidence.”

The team then used computer-based calculations to model the chemical plant’s processes. Instead of methylmercury, their computational chemistry studies predicted that the factory released a different organic mercury compound called alpha-mercuri-acetaldehyde, whose toxicology has not been studied. Their findings challenged the long-standing view of what form of mercury poisoned the human population in Minamata.

The ensuing controversy attracted media attention and some scientific criticism, which was a bit overwhelming and stressful for James as an early-career PhD student. However, she handled it like a veteran, according to her nomination letters. Her supporters described the criticism published in letters to the journal as personal and unscientific. And they praised James’ response as excellent and surgically precise.

“Science is meant to create debate and it certainly did that,” said James. “But our main point was that it is important to study the toxicology of organic mercury compounds other than methylmercury, because they may have important environmental and health impacts.”

Comparing acute and chronic mercury poisoning in humans

Her second PhD research project investigated the more prevalent issue of chronic mercury exposure due to a lifetime of eating marine fish with low levels of methylmercury, which can lead to as much as ten times higher concentrations of mercury in the brain. Specifically, she used the same X-ray spectroscopy techniques and SSRL facilities as the Minamata project to study brain samples from residents of the Seychelles islands.

She compared these results to similar beamline studies on two historic acute organic mercury poisoning cases, which involved a short-term exposure of large concentrations of organic mercury. All brain tissue samples for her PhD work were acquired through her collaborators at the University of Rochester.

“We wanted to see if there was a difference in the chemical form of mercury found in chronic versus acute human exposure cases,” said James. “Honestly, we found the complete opposite of what we expected.”

The human body uses a chemical process called demethylation as a defense mechanism to slowly turn organic mercury into less toxic inorganic mercury. The researchers therefore thought people showing no evident symptoms of mercury poisoning would have mostly inorganic mercury that had been demethylated, James explained. Instead, they found individuals with chronic exposure had low concentrations of mercury in their brains, but it was entirely organic.

Similarly, the scientists predicted individuals after acute poisoning would have less time to demethylate the mercury, meaning they would have high levels of organic and low levels of inorganic mercury. Instead, they found complex mixtures with low concentrations of organic and high concentrations of inorganic mercury.

“The takeaway of this crazy twist is that it could be misleading to use acute exposure studies to understand the vast majority of human exposures that are chronic in nature,” said James. “Over a billion people worldwide depend on fish as their primary or sole source of protein. So, better understanding the ramifications of ingesting fish that may contain low levels of mercury is an important global food security question.”

As a postdoc, James is extending her mercury toxicology research. She is now studying the role of metals in multiple sclerosis using a diverse range of SSRL X-ray spectroscopy and X-ray imaging beamlines.

“Dr. James’ remarkably impactful research is further distinguished by her use of an incredible range of different techniques — from advanced X-ray spectroscopy methods at SSRL to quantum chemistry, alongside more conventional toxicology methodology,” said George and Pickering. “This work represents one of the very first demonstrations of these techniques to her field.”

The Klein award is named in honor of the late Melvin P. Klein, a world-renowned biophysicist at Lawrence Berkeley National Laboratory and the University of California, Berkeley and a longtime user at SSRL.

For questions or comments, contact the SLAC Office of Communications at communications@slac.stanford.edu.

SSRL is an Office of Science user facility.

This is a a reposting of my news feature courtesy of SLAC National Accelerator Laboratory.

SLAC’s Riti Sarangi wins 2021 Farrel W. Lytle Award

Ritimuka “Riti” Sarangi is this year’s Lytle Award recipient. (Jacqueline Ramseyer Orrell/SLAC National Accelerator Laboratory)

Ritimukta “Riti” Sarangi, a senior scientist at the Department of Energy’s SLAC National Accelerator Laboratory, is the latest recipient of the Farrel W. Lytle Award, which recognizes important contributions to synchrotron science and efforts to support users at the Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science user facility.  

Since its inception in 1998, the Farrel W. Lytle Award has been given annually to SSRL staff members and users from around the world.

“Farrel is a legend in X-ray spectroscopy science. He has made contributions to every aspect of X-ray instrumentation, measurement and analysis,” Sarangi said. “I was completely unaware of my nomination and was thrilled when I received the email” notifying her of the award.

Sarangi started running experiments at SSRL in 2001, when she was a graduate research assistant at Stanford University. After earning her PhD in chemistry, she joined the SSRL staff in 2007. She is currently a senior member of the Structural Molecular Biology group at SSRL and a hard X-ray spectroscopist.

In a nomination letter for the award, Graham George, the Canada research chair in X-ray absorption spectroscopy at the University of Saskatchewan, praised Sarangi’s contributions in research, user support, outreach and leadership. “While SSRL scientific staff includes many outstanding individuals, even among this strong competition Riti stands out,” he wrote. “I have heard Riti described by senior SSRL management as an ‘anchor at SSRL,’ and I think that this description is an accurate one.”

Catalyzing discoveries

Sarangi uses X-ray spectroscopy techniques to study the fundamental properties of enzymes, molecules produced by a living organism that act as a catalyst to bring about specific biochemical reactions. Much of her research focuses on metalloenzymes, a broad group of enzymes with one or more metal ions in their active site, where other molecules bind and undergo a chemical reaction.

“Metalloenzymes perform a wide range of chemical transformations from electron transfer to small molecule activation to more complex molecular transformations,” explained Sarangi. “My goal is to apply X-ray methods towards understanding the structural and electronic details of these metal-containing active sites to shed light on the functional details of metalloenzymes and related systems.”

She is particularly interested in understanding methyl coenzyme M reductase (MCR), a unique nickel-containing enzyme responsible for the generation of 1 billion metric tons of methane annually.

Methane is the main component of natural gas and accounts for almost a quarter of U.S. energy consumption, but it is also a potent greenhouse gas. Understanding the mechanistic aspects of methane activation and synthesis is, therefore, imperative from fundamental, applied-energy, economic and environmental perspectives, Sarangi said.

Sarangi investigates metalloenzymes like MCR using modern X-ray spectroscopic tools and advanced computer simulations that model the quantum physics underlying chemical reactions.

“While spectroscopy provides an experimental window into specific properties about your system, quantum simulation methods provide additional information about structure, bonding and reactivity properties,” she said. “Experiments answer the what and theory answers the why given this specific what.”

Her nominators noted the powerful and unusual nature of her combined methodology. Stephen Ragsdale, professor of Biological Chemistry at the University of Michigan, wrote, “Riti’s approach is continuing to close the gap between experimental and computational aspects of X-ray spectroscopy. It is also absolutely crucial in understanding the complex biological systems that we and others are studying.”

In one recent study, Sarangi and colleagues combined a variety of experimental and theoretical techniques to uncover how enzymes help synthesize methane, revealing a surprising way the enzyme binds to the chemical it converts to methane. Ragsdale called the research “an extraordinary feat.”

Supporting users

Sarangi does a lot more than groundbreaking research, spending much of her time supporting the SSRL user community. “Riti is engaged at every level with user support and is someone who is not afraid to get her hands dirty,” George wrote.

For example, she developed a computer cluster for implementing various theoretical packages that simulate, interpret or augment experimental X-ray spectroscopy data.

“When I started at SSRL in a user support role, I realized these theoretical tools were rarely leveraged by our biological user community and therefore the full potential of their X-ray datasets was often not realized,” said Sarangi. “While I have continued to apply theoretical tools to my own research program, I have also established and made available a high-speed computational cluster to the entire bio-spectroscopy and bio-inspired catalysis user community.”

She has also been crucial to keeping SSRL running during the COVID-19 pandemic, her nominators said.

“She played a pivotal role in generating online access programs and coordinating communication and timeline details so users could continue to accomplish our science during the time when SSRL was closed for visitors,” Timothy Stemmler, assistance vice president for research and professor of pharmaceutical sciences at Wayne State University, wrote in a letter. “Her efforts to allow online access will surely transform how data is collected at the entire lab moving forward, and will lead to many future discoveries, he wrote.

The nominators also applauded Sarangi’s mentoring, training and recruitment of the next generation of scientists. “She has clear skills in organizing and delivering training content and this sets her apart as not just an amazing colleague, but an amazing educator,” wrote Stemmler.

Envisioning the future

Looking forward, Sarangi thinks the lessons learned during the pandemic suggest that more researchers could work remotely – something she said accelerated her scientific and operational engagement with staff, users and collaborators. In 20 years, she expects SSRL X-ray science to become an automated and high-throughput experience that integrates multiple complementary X-ray and non-X-ray measurements.   

She is also leading efforts to plan the future of structural science at lightsources, based on a series of workshops whose reports will develop a robust case for investing in X-ray science.

“This is no easy task and has required mastering the details of techniques adjacent to her expertise, diplomacy in bringing diverse ideas in different disciplines together, and hard work,” wrote Edward Snell, chief executive officer of the Hauptman-Woodward Medical Research Institute, in a nominating letter.

George also praised Sarangi’s leadership and vision. “I have had the distinctive privilege of knowing Farrel quite well, and I am certain that he would approve of this nomination,” he wrote. “The SSRL Users’ executive committee would be hard pressed to find a better candidate.”

The award will be presented to Sarangi at the 2021 SSRL/LCLS Annual Users’ Meeting during the plenary session on September 24. 

For questions or comments, contact the SLAC Office of Communications at communications@slac.stanford.edu.

This is a reposting of my news story, courtesy of SLAC National Accelerator Laboratory.

Stanford graduate student Aisulu Aitbekova wins 2021 Melvin P. Klein Award

Aisulu Aitbekova

Aisulu Aitbekova, a 2021 doctoral graduate from Stanford University, discovered her passion for research when she traveled from Kazakhstan to the U.S. for a summer internship as a chemical engineering undergraduate. She said that experience inspired her to go to graduate school.

After earning a master’s in chemical engineering at the Massachusetts Institute of Technology, she continued her studies at Stanford University under the supervision of Matteo Cargnello, an assistant professor of chemical engineering and Aitbekova’s doctoral advisor. Much of her thesis work involved beamline studies at the Stanford Synchrotron Radiation Lightsource (SSRL) at the Department of Energy’s SLAC National Accelerator Laboratory.  

Now, Aitbekova has been selected to receive the 2021 Melvin P. Klein Scientific Development Award, which recognizes outstanding research accomplishments by undergraduates, graduate students and postdoctoral fellows within three years of completing their doctoral degrees.

In a nomination letter for the award, SLAC Distinguished Staff Scientist Simon Bare praised Aitbekova’s initiative. “She has quickly become proficient in the application of X-ray techniques available at the synchrotron at SLAC. This proficiency and mastery include everything from operating the beamline to analyzing and interpreting the data,” he wrote.

Aitbekova said she felt “absolutely thrilled and grateful” to all of her mentors when she found out about winning the award.

“I’m so thankful for my PhD advisor Matteo Cargnello. My success would not have been possible without his mentorship,” Aitbekova said. “I’m also particularly grateful to Simon Bare, who I consider to be my second advisor. His continuous excitement about X-ray absorption spectroscopy has been the driving force for my work at SSRL.” 

Catalyzing change

Aitbekova said she is passionate about finding solutions to combat climate change. She designs materials to convert harmful pollutant gases into useful fuels and chemicals. To perform these chemical transformations, she develops catalysts and studies their properties using X-ray absorption spectroscopy (XAS). Catalysts are substances that increase rates of chemical reactions without being consumed themselves.

“I have identified that a catalyst’s size, shape and composition profoundly affect its performance in eliminating these gases,” but exactly how those properties affect performance remains unknown, she said. “This problem is further complicated by the dynamic nature of catalytic materials. As a catalyst performs chemical transformations, its structure changes, making it challenging to precisely map a catalyst’s properties to its performance.”

To overcome these barriers, she engineers materials the size of one ten-thousandth the diameter of a human hair and then tracks how they change during reactions using XAS.

In one study, Aitbekova and her colleagues engineered a catalyst using a combination of ruthenium and iron oxide nanoparticles, which they think act in a tag-team fashion to improve the synthesis of fuels from carbon dioxide and hydrogen. Using a prototype in the lab, they achieved much higher yields of ethane, propane and butane than previous catalysts.

Switching gears

While engineering catalysts that convert carbon dioxide into chemicals, she developed a new approach for preparing materials, where small particles are encapsulated inside porous oxide materials – for example, encapsulating ruthenium within a sheath of iron.

However, Aitbekova recognized a completely different application for this new approach: creating a palladium-platinum catalyst that works inside a car’s emission control system.

To eliminate the discharge of noxious emission gases, cars are equipped with a catalytic converter. Exhaust gases pass into the catalytic converter, where they are turned into less harmful gases. The catalysts inside these units are platinum and palladium metals, but these metals gradually lose their efficiency due to their extreme working conditions, she said.

“My platinum and palladium catalysts show excellent stability and performance after being subjected to air and steam at 1,100 degrees Celsius, the harshest operating environment automotive exhaust emission control catalysts could be subjected to,” explained Aitbekova. “Further improvements in these materials and successful testing under true exhaust conditions have a potential to revolutionize the field of automotive exhaust emission control.”

Her nominators agreed, citing it as the highlight of her graduate career.

“This work, currently under review for publication, is truly the remarkable result of Aisulu’s hard work and experience in pivoting from one area to another to make an impact and of her ability to connect multiple fields and solve important problems,” Cargnello wrote.

Amplifying impact

Despite this success, Aitbekova is already focused on how to make an even greater impact through mentoring and future research.

Her nominators all applauded her passion and commitment to mentor the next generation of STEM scholars, as demonstrated by mentoring “a countless number of undergraduates” according to Cargnello and by exchanging letters with middle school students from underrepresented groups.

Part of this passion, Cargnello and others wrote, stems from her experiences growing up in a highly conservative environment with the understanding that homemaking would be her eventual job. Aitbekova’s nominators wrote that they admired the fact that she made her way to Stanford and has acted as an ambassador for the values and principles of diversity and inclusion.

Aitbekova said she embraces the role. “Since my first summer research experience in the USA, I’ve wanted to serve as a bridge to science and graduate school to those who, like me, didn’t have access to such knowledge and resources.”

She will continue to act as a bridge in her next endeavor as a Kavli Nanoscience Institute Prize Postdoctoral Fellow at Caltech, where she plans to expand her work of converting carbon dioxide into fuels by running the chemical transformations with solar energy. That will “bring society one step closer to sustainable energy sources,” she said.

Bare and others praised her drive to make an everyday impact. “She has a natural passion for wanting to understand the physical principles behind the phenomena that she has observed in her research. But this passion for understanding is nicely balanced by her desire to discover something new, and to make a real difference — the practicality that is often missing in someone early in their career,” wrote Bare.

The award will be presented to Aitbekova at the 2021 SSRL/LCLS Annual Users’ Meeting during the plenary session on September 24. 

This is a reposting of my news story, courtesy of SLAC National Accelerator Laboratory.