Metabolomics Core

From Sample to Source

February 16, 2021 By Lauren Hines in Research Tags: cancer, Metabolomics Core

Metabolite screening looks to better understand cancer

Metabolomics Lab — Research scientist Rajarshi Ghosh in the Lloyd W. Sumner lab loads samples into the Nuclear Magnetic Resonance (MNR) spectrometer for analysis. | Photo by Lauren Hines, Bond LSC.

By Lauren Hines | Bond LSC

Doctors take blood or urine samples to see what’s going on in the body of a patient, and that’s not all that different from what metabolomics scientists do when looking at metabolites.

“[The doctor] may profile 20 or 30 compounds to try to understand what’s going on with your physical health and well-being,” said Lloyd W. Sumner, director of the MU Metabolomics Center. “Well, that’s what we do but on a larger scale. Instead of analyzing 20 or 30, we’re analyzing hundreds to thousands of individual chemicals, specifically metabolites, that are in your body. This provides a high-resolution biochemical phenotype for our subjects.”

Even though metabolites are relatively small molecules compared to DNA and proteins, they play a big role in every organism.

Metabolites serve as energy sources and building blocks that are the end products of our cellular processes. These molecules can tell researchers in the Metabolomics Center at Bond Life Sciences Center a lot about what goes on in the bodies of plants and animals and offers potentially great opportunities in precision health.

One specific example happened in July 2020 when the Metabolomics Center and the Rat Resource and Research Center highlighted what looking at metabolites can do in a new publication.

“We were able to show from the metabolic profiles that we could predict [colon] cancer or the tumor load [in rats] well in advance,” Sumner said. “Thus, metabolomics is a very powerful diagnostic and prognostic tool that we were just beginning to realize, and we would ultimately like to move metabolomics into the clinical medical arena as well and use it in personalized medicine.”

However, researchers were asking a different question at first.

“We’ve always thought about the gut microbiome,” said James Amos-Landgraf, associate professor of veterinary pathobiology at the Rat Resource Center. “What is the mechanism behind [the bacteria in the gut] influencing cancer development? And one of the possibilities certainly could be the metabolites that are being produced by those bacteria.”

Researchers took two genetically identical sets of rats, which were genetically susceptible to cancer, and introduced different microbiomes in each group. Then, they analyzed the metabolites in the rat feces and blood.

“What was interesting to us was that at one month of age, there were metabolites that could predict at four months whether or not they had more tumors or less tumors,” Amos-Landgraf said. “That was somewhat independent of the microbiome, so it certainly correlated slightly with what microbiome was there, but it was more about what those bacteria were actually producing.”

Now, researchers have to identify the metabolites in the profile to better understand the biochemistry and mechanism of cancer proliferation. However, only a few percent of metabolites have been identified to date. The Metabolomics Center continuous to expand its efforts in metabolite identification by measuring the size, charge and structure of these molecules.

“Metabolomics is really crucial to understanding the role of the gut microbiome,” Amos-Landgraf said. “Understanding both what the gut is producing and how our body responds to that is going to be crucial. So, moving forward that’s the direction we’re taking.”

According to the Centers for Disease Control and Prevention, cases of colon cancer have decreased in older populations due to screenings. Those screenings allow doctors to remove benign tumors before they spread. Additional diagnostics can potentially further decrease cases.

Researchers like Amos-Landgraf and Sumner see the metabolites that were present in the less susceptible animals as acting as a potential preventative. While very long down the road, the metabolites could be used as a screening technique to predict cancer in people.

“Cancer is kind of a flagship focal area for me because it’s a very metabolically dysregulated disease,” Sumner said. “Trying to understand that process will hopefully lead to new information and better health overall.”

While the paper has not been peer-reviewed yet, readers can find out more about this study in Integrated Metabolome and Transcriptome Analyses Provide Insight into Colon Cancer Development by the Gut Microbiota. The work stemmed from Differential Susceptibility to Colorectal Cancer Due to Naturally Occurring Gut Microbiota, which is also available to read.

#IAmScience Zhentian Lei

December 11, 2020 By Becca Wolf in #IAmScience Tags: Metabolomics Core

By Becca Wolf | Bond LSC

Columbia has been very different than Ardmore, Oklahoma, for Zhentian Lei. But the move from the Samuel Roberts Noble Foundation, a nonprofit agricultural research center, to Bond Life Sciences Center has been a good one for the researcher.

“I like it here much better,” Lei said. “The town that we used to live in Oklahoma is very small and at least 100 miles from other universities. So, it wasn’t convenient to collaborate or visit other labs. It’s not like here where you can just walk across the campus to another building and talk to other researchers.”

Lei first came to MU five years ago when the Lloyd Sumner lab moved here.

“The most attractive thing is that there are so many PI’s and research groups on campus that you can work with,” Lei said. “Our previous institute was a nonprofit research institute that focused on agriculture, and we have done a lot of agriculture and plant science work, but now we have people working in animals, medicine, etc. that we can collaborate with. That opens an exciting window for us, we can have a lot more collaborations and opportunities.”

Here at Bond LSC, Lei is the assistant director of the University of Missouri Metabolomics Center and assistant research professor of biochemistry. On the second floor of Bond LSC, he and other researchers perform targeted and non-targeted metabolite profiling on samples such as plant tissues, cancer tissues, and blood samples. These small molecules are the product of chemical reactions in cells, and their study gives us a window into how cells in the body or in a plant contribute to an organism’s inner workings or diseases.

Lei and researchers in the center analyze samples to figure out what changed in response to things such as treatments and drugs. As assistant director, Lei is responsible for maintenance and making sure that the machines are working.

“When you exercise or when you eat something different, your metabolism would change in response to those things, so the differences are important and we analyze them on a daily basis,” Lei said.

Lei also conducts research of his own. He mostly collaborates with principal investigators (PIs) on campus on method development.

“If we want to analyze something that we have not done before, we have to develop a method. We have to try to make sure that we can detect and quantify correctly without any doubt,” Lei said.

Lei first became interested in metabolomics as he was going through school.

“Metabolites in plants are different. If you taste a banana, the taste will be different from an apple, which is also different from a pineapple, so the differences are caused by secondary metabolites in the plants or in the fruits. They each have their unique set of metabolites,” Lei said. “It is very fascinating when you don’t know what you’re looking at and you want to know why it is the way it is. It’s fascinating and satisfying to be able to quantify and detect the differences.”

While Lei has a good system going in the MU Metabolomics Center currently, he hopes to get some instrument grants from federal funding agencies to update some of the instruments.

“We depend on high-tech instruments to detect compounds and quantify them. If you don’t have those techniques, or if our instruments aren’t ready, you cannot really do much,” Lei said. “In the center we have several high GCMS and LCMS that cost like half a million for one instrument. It is way more expensive than my car.”

GCMS (gas chromatography-mass spectrometry) is an analytical method that identifies substances within a test sample and is commonly used in drug detection, forensics, and identification of unknown samples.

LCMS (Liquid chromatography mass spectrometry) on the other hand is an analytical chemistry technique combining the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. This system is popular in chemical analysis and can be applied in many areas such as biotechnology, environment monitoring, and agrochemical industries.

Having these be up-to-date is important for Bond LSC, and Lei is doing as much as he can to keep them in good order.

“If you don’t have good instruments and you cannot provide good results, researchers may go to other places for services,” Lei said.

Despite working with these challenges, Lei is happy that he is at Bond LSC.

“I really like it here,” Lei said. “The town, the university, and the climate on campus really focuses on researchers, and that is really a plus for us.”

#IAmScience Saurav Sarma

October 11, 2019 By Roger Meissen in #IAmScience Tags: Lloyd Sumner, Metabolomics, Metabolomics Core

By Danielle Pycior | Bond LSC

Saurav Sarma grew up amongst tea plantations and medicinal plants in the northeastern corner of India near Tibet, a state called Assam.

His day-to-day observations of the plants sparked a curiosity that eventually led him to a career looking at the chemical building blocks behind it all in the labs of Lloyd Sumner and the University of Missouri Metabolomics Center at Bond Life Sciences Center.

His interest revolved around the connections between carbon, oxygen, nitrogen and hydrogen, which make up living systems.

“How they’re connected makes all the difference,” he said.

Sarma enjoys working in the metabolomics core because of the incredible facilities and collaboration. Among other things, his job is to look for thousands of molecules to find biomarkers for various diseases.

“The purpose of the core is to profile the small molecules,” he said. “So, for example, a group might want to see the molecular differences between a healthy plant and a diseased one. There are thousands of molecules, so you need sophisticated techniques to profile those molecules because they are otherwise unknown.”

Sarma works with people on and off campus who are curious about the molecules in their areas of research, but he also does data analysis, communication and collaborative research project. He enjoys the diversity of his job, which is focused on how molecules shape our lives.

“Finding something new is always exciting,” he said. “Science can always surprise you.”

While he finds this research to be fascinating, he also enjoys how it can help people and push civilization forward. From health to the economy to agriculture, he said science benefits us in ways we often don’t realize or think about.

“So, it’s not that my work is great, it’s that everybody’s work is great,” he said. “Everything that we use nowadays didn’t come up in one day, it’s from people’s hard work over many years, and maybe someone will benefit from our work in the future.”

Things may not always go as planned, but he doesn’t let that stop him.

“In science, nothing is a failure,” he said. “The knowledge you are generating today is helping researchers in the future, so learning how to deal with failure and keeping an open-mind is important.”

He said that it’s easy to get stuck in mental patterns, and by keeping an open-mind, you’re more likely to see or think of things you might not otherwise see in your own research, in conversations and daily life, too. Many of the most important discoveries of humanity occurred outside of the normal paradigm. And while ‘failure’ can be challenging and frustrating, he said it makes the success more significant.

“As a synthetic chemist, I run a hundred reactions and maybe 10 work and 90 fail,” he said. “So, it helps you to deal with failures, but it also feels great when you reach a goal. You are getting through hurdles and it gives you this satisfaction of getting something done that wasn’t easy to get done.”

He received his undergraduate degree in science, followed by a masters in organic chemistry before making the journey to North Carolina for his Ph.D. in medicinal organic chemistry. After his Ph.D., he arrived at MU in the radiology department for his postdoc. While there, he developed a trimodal drug delivery system called closomer to help minimize the side effects of cancer.

“I was fascinated by working with drug delivery systems, but then again, it was about molecules and their characterization and identification,” he said. “That’s been a binding thing throughout all of my research.”

Apart from science, he loves the classics – literature, music, sports and movies. He’s currently reading “Thousand Splendid Suns.” He also loves hanging out with his four-year-old daughter watching cartoons. “I don’t have any exceptional hobbies,” he said.

A personal career goal of his is to develop sophisticated methods for exploring more of the chemical space that is still unknown, and he hopes to see a greater breakthrough for cancer treatment in his lifetime that allows for less pain and side effects.