DNA

Genetic link in primate points to source of adaption and longevity in capuchins

March 2, 2021 By Lauren Hines in Research Tags: capuchins, DNA, genetics

Cebus Imitator — As part of an international collaboration, principal investigator Wes Warren helped study capuchins in Costa Rica. | Photo contributed by Amanda D Melin, Bond LSC.

By Lauren Hines | Bond LSC

Through monkey poop and three years of work researchers from all over the world sequenced the Panamanian white-faced capuchin genome for the first time and devised novel methods to sequence many more wild capuchin genomes.

These monkeys have large brains for their small size and can live past 50. Wes Warren — Bond Life Sciences Center principal investigator — helped sequence the genome to find more answers about their unique brain-to-body ratio and long lifespans as part of the study. This work published Feb. 16 in Proceedings of National Academy of Science looks deeper at the genetic connections to these adapted traits.

“Other species of nonhuman primates don’t have that long lifespan, so the capuchin is a nice model and a different group of nonhuman primates to study that question,” Warren said.

Warren first got involved in his previous job at Washington University in 2017 when Amanda Melin, former principal investigator at Washington University, approached him about building the capuchin genome.

His main role in the study was in directing the genome assembly and using this genetic blueprint to analyze different types of selection pressures that impacted the genome.

Selection pressures are environmental or social factors that make it harder for species to survive and reproduce. Yet, when a small percentage of these species do survive — possibly due to a certain gene — their populations can explode. Afterward, that particular gene becomes widespread across the new population.

“There’s a whole variety of selection pressures that are brought to bear on a species genome, and a lot of that is driven by the environment,” Warren said. “The beauty of this experiment is there are two very distinct populations of capuchins in Costa Rica.”

The study looked at two groups: one in the southern lowland evergreen rainforest where rainfall and fruit are plentiful and another in the northern lowland tropical dry forest where periodic droughts occur.

A gene that affects kidney and water maintenance in the body became a particular interest in their analysis. That could be necessary for survival for the northern population who faced a dry climate and needed to conserve water.

“We can speculate that [these genes are] associated with this adaptation,” Warren said. “We don’t know for sure, and we make that point in the paper. It’s more of a discussion about this is a possibility, and these are real signals of selection. We’re not sure exactly if we can directly correlate them with an adaptation to a dry, hot climate, but it certainly makes biological sense.”

Warren and the other researchers discovered the gene, among others, by lining up genetic codes of capuchins and other mammals to find matching sets of nucleotides. This allowed researchers to identify known and novel genes, like the ones related to brain size and longevity.

Mike Montague, who previously worked under Warren while they were at Washington University, believes the correlation between brain size and longevity is due to genetics.

Genomes between capuchins and other animals showed differences that seemed to be tied to brain development, size and metabolizing mechanisms. Large brains require lots of fuel, so an efficient system for processing sugars would also be needed.

“Having an understanding of these genes and why they’re different in capuchins might be linked to these larger genetic pathways, [which] allow the capuchin to have this large brain,” Montague said.

As for longevity, researchers identified some genes associated with DNA damage response, metabolism, cell cycle and insulin signaling. While damage to DNA is thought to be a major contributor to aging, aging-related genes also deal with growth and development. This means researchers can’t be sure if the identified genes correlate with longevity.

While some genes found are associated with human cognition and large brain size in humans, they can’t be directly linked to human genes without further examination.

Researchers wouldn’t have been able to identify these genes and sequence the genome without a new technique developed by Joe Orkin, the study’s lead author. Orkin’s new technique, FecalFACS, isolated the DNA in capuchin feces of the animal’s intestinal cells.

Since capuchins are an endangered species, scientists can’t kill or capture them for study. Instead, they had to analyze their feces. The trouble was researchers originally had to cipher between the DNA of the food the capuchins ate and the DNA of the capuchin in feces. Orkin’s new technique allows them to sort that information easily.

“We observe this really beautiful population structure to these capuchins that live in this particular area,” Warren said. “We could not have got that… this larger number really let us get a very accurate portrayal of the population structure and how related they are to each other.”

Now that the paper has been published, the study’s next steps include expanding the sample beyond the two populations and investigating the functions of the newly discovered genes in other animals.

“There’s just a host of different questions that you could ask, now that we have this one particular genome added to the collection of other genomes for different primates,” Montague said.

More information about the study can be found in, “The genomics of ecological flexibility, large brains, and long lives in capuchin monkeys revealed with fecalFACS.” The study was published on Feb. 16 in Proceedings of the National Academy of Sciences.

Probing for answers

May 25, 2020 By Lauren Hines in Research Tags: DNA

By Lauren Hines | Bond LSC

Disease diagnosis takes money, time and technology — something rural communities don’t always possess. Kwaku Tawiah, a fifth-year graduate student, and researchers in the Burke lab are creating a probe that can diagnose and inhibit viral diseases cheaply, in less time and without electricity.

“With some of these infections, the faster you’re able to detect it, the better,” Tawiah said. “So, one of my motivations in grad school was to come up with some of these assays that don’t require all this time for experimentation.”

Some rural communities, like Tawiah’s hometown in Ghana, don’t have the electricity to operate diagnostic machines or the resources to afford them. The probe helps solve this problem.

The probe is a structure made up of a single strand of DNA that can fold into a unique 3D shape, which can recognize and bind to the surface protein of a virus.

“It’s a string of DNA, right?” Tawiah said. “What is unique about these probes is you can easily attach other things to the string of DNA.”

Tawiah and other researchers attach fluorescent molecules to the end of the DNA strand so when it binds to the surface protein, they can detect the virus.

Tawiah’s paper on the probe that can detect and inhibit Marburg, a cousin of the Ebola virus, will be submitted for peer review within a few weeks.

Even though Tawiah is graduating, other students in the lab want to expand the application of the probe.

Since virus surfaces have similar structures, the probe can be modified to detect and inhibit other viruses such as COVID-19.

“The beauty of what I do on the platform that we build is that it can be translated to other viruses,” Tawiah said. “So, with the platform for detection, you can essentially do the same thing for COVID, but you have to have the surrogate COVID virus particles…”

Currently, researchers in the lab are waiting for the particles and know the probe can bind to the virus, but they don’t know where exactly it can bind to.

“The lab is interested in using other techniques to find out where exactly the probe binds to on the surface of the virus,” Tawiah said.

While Tawiah is leaving to start his post doctorate in July to further develop low cost diagnostic methods, the Burke lab is continuing to probe for more answers.

DNA Day

April 25, 2019 By Danielle Pycior in Events and speakers Tags: DNA

A time to celebrate the thing that makes us who we are

By Danielle Pycior | Bond LSC

In 1865, after a decade long search into patterns of inheritance, Gregor Mendel discovered how individuals receive traits from their parents. Through working with pea plants, he found that genes come in pairs and are inherited as distinct units. He tracked those genes through dominant and recessive traits. Like many vital scientists throughout history, Mendel wasn’t appreciated in his own time due to his unpopular ideas. Now seen as the “father of genetics,” Mendel is recognized as the scientist who began the genetics revolution.

Screen Shot 2019-04-25 at 3.08.28 PM — Gregor Mendel

“There’s been an immense amount of progress even in the last two decades,” Warren said.

While one cell’s DNA unraveled is around 1.2 miles in length, the entire DNA strand in a human body is equivalent to 120 billion miles, twice the diameter of the solar system.

“What fascinates me is decoding the genetic blueprint of life, comparing it to other closely related species and trying to understand how that species is unique and different,” Warren said.

Throughout his career, Warren has been able to work closely with what he calls the ‘blueprint for life.’ Through incredible scientific advancements, he’s been able to decode the genomic code of various species, paving the way for understanding and discovery.

“Certainly, we know the biology is different — physically they’re different, morphologically they’re different, but at some genetic level we know they’re very similar,” Warren said. “So how does that change in the variation of the genetic blueprint result in that individual species having a very different phenotypic profile than a closely related species?”

But this rapid advance in the modern era moved much slower after Mendel’s initial discoveries. It wasn’t until the 1900s that Mendel’s work was rediscovered and taken seriously, and by the 1940s, Oswald Avery, an immunochemist, discovered DNA to be the transforming factor of genes. A paper he published outlining this assessment then inspired Erwin Chargaff, who discovered that DNA composition is species specific.

Screen Shot 2019-04-25 at 3.08.47 PM — Rosalind Franklin

A few years later, James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin discovered the double-helix structure of DNA. By 1962, the three men won the Nobel Prize for Physiology and Medicine for the discovery. Though the high-resolution X-rays Franklin took of DNA fibers led to the discovery of the double-helix structure, she was not awarded along with the three men, having died of cancer a few years earlier. Over the next six decades, scientists discovered rapid DNA sequencing techniques, various diseases associated with certain genetic markers, ways of cloning animals, how to decode chromosomes and many other revolutionary advancements.

DNA is something that connects every species on the planet. On the outside, it might look like we are extremely different, but on the inside, biological systems allow for each of our existence in a way that is relatively similar throughout any species. Warren enjoys understanding and dissecting the micro levels of that existence to understand how it influences who we and other species are.

“I absolutely think it’s important to look back into the past to understand where we’ve come from and also to learn from mistakes that we’ve made,” Warren said. “The forward-thinking process has to happen today, and we have to learn from what we’ve done in the past to strategize for the future,” Warren said.

In the future, Warren predicts personalized medical experiences where each person’s genomes are on file for doctors to see, helping to anticipate needs and revolutionize the way doctors are able to treat diseases. A century ago, it would have been unfathomable for scientists to image the profound advancements the field has seen, and yet they have only begun to see what is possible.

#IAmScience Kris Budd

November 22, 2017 By Allison Scott in #IAmScience Tags: DNA

Kris Budd, a Ph.D. candidate in Lori Eggert’s lab, works with Bond LSC to track elephant DNA in Southeast Asia. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because I have the ability to transform the fate of endangered species.”

If someone had told Kris Budd that she’d be investigating elephant feces on daily basis in her Ph.D. program, she wouldn’t have bought it. If they’d said she’d realize it’s a passion of hers, she would’ve been in shock.

As a third year Ph.D. candidate in Lori Eggert’s lab, Budd is able to do meaningful work that is helping endangered elephants through feces.

“I always wanted to work with an endangered species,” Budd said. “I’ve always been excited about this, and the more you find out about elephants, the more you love them.”

Budd receives samples of elephant dung from Southeast Asia, and singles out the elephant DNA from the other species present in the sample — most commonly microbes and insects, but sometimes even goats and humans.

“You have to be aware that there can be DNA from anything that walked by that day,” Budd said. “We have to use specific tools to make sure we just get the elephant DNA.”

“After processing, we use the Genomics Technology Core Facility in Bond LSC, which isn’t an easy task since we typically run hundreds of samples several times for a single study.” Budd said. “But they always do it with grace.”

Budd then uncovers the genetic makeup with the help of the Informatics Research Core Facility (IRCF) and meetings with members of Chris Pires’ lab in Bond LSC.

From there, Budd is able to input the DNA into a system and keep track of the elephants overseas. They, however, become way more than numbers to her.

“They might just be a sample in your data, but you get to know the elephants,” Budd said. “Elephants are so much more. There are so many different elements to them — genetics, behavior, and ecology. Their evolutionary history and family structure tells a story, all seen through feces.”

Her work is about to get a lot more hands-on next semester, as Budd will be traveling overseas to collect samples herself.

“We’re going in the spring and we’ll teach local technicians how to go about collecting samples,” Budd said. “We’ll collect a lot of samples of our own while we’re there, too.”

Budd will be able to determine what is happening with the elephant populations in Southeast Asia more closely then.

“There’s a big push with critically endangered species to translate data into something that can help them,” Budd said. “The samples I’m working on from Myanmar are actually an extinct population, but we want to re-wild similar elephants in the same location.”

Essentially, that would require Budd to find a genetically similar elephant population that would be most likely to thrive in the same environment.

While actually implementing the re-wild process won’t happen for a while, Budd is certain about the influence of Bond LSC in the elephant re-wilding’s future success.

“My work wouldn’t be possible without the people who work at Bond LSC,” Budd said.

Dr. Burke wins Distinguished Professor Award

November 14, 2017 By Samantha Kummerer in Research Tags: DNA, RNA

Donald Burke-Agüero stands in his office in Bond LSC, holding a model of an RNA protein structure. Burke-Agüero studies the bio-chemical functions of RNA, and how those functions might be able to be artificially designed or replicated. | Phillip Sitter, Bond LSC

By Samantha Kummerer | Bond LSC

“He’s a triple threat in science,” Bond Life Sciences researcher David Pintel said.

Donald Burke’s combination of scientific excellence, caring mentorship and devotion to the University of Missouri led Pintel to nominate Burke for the 2017 William H. Byler Distinguished Professor Award.

The university agreed, awarding him the honor in October.

The University-wide accolade recognizes a faculty member for their “outstanding abilities, performance, and character.” When Pintel read this description he said he instantly thought of Burke.

This is the first time a faculty member from Bond LSC has won the award. Pintel said the award shows the quality of people here and the department is proud of him for receiving it.

Burke is a Molecular Microbiology & Immunology professor. His lab in Bond LSC studies RNA, the molecule used to help cells copy genetic information from DNA.

For Burke, the award is an honor.

“You always try to do everything you can to contribute to making the place great and you don’t do it for the purpose of being recognized, yet when the recognition happens, it’s nice,” he said.

Burke’s lab hosts students from the high-school to post-doctoral level. For each member, Burke said he tries to figure out their motivation. He starts by just asking questions and is able to align their goals and his.

“You can’t just say ‘This is what we do in my lab, deal with it.’ You can’t do that,” Burke elaborated, “Yes, it’s a lot of work and a lot of effort, but it has ceased being a burden for me. Now, I think of it as a new fun challenge.”

He said that challenge has paid off because every student that has gone through his lab has taken his science in new directions.

Pintel said this connection Burke has with his students is easy to see.

“People in his lab love him and, to me, that’s always a good sign,” Pintel said. “When I see people in a lab like that, I know it’s a good environment. That always means something good is going on.”

During their time in his lab, Burke tries to teach his students the importance of working as a team as well as learning understand the research process.

“Some of the things I’m most proud of aren’t necessarily the most impactful research, but the things where I know the struggle that went into solving the puzzle that was in front of us,” he explained. “The thrill of the chase may not be as interesting to the rest of the world but you know how hard that person worked and how many false leads there were.”

Recently, Burke has expanded his passion for motivating others to a new area. In July, Burke became the Interim Chair of Molecular Microbiology & Immunology.

“Now that he’s the interim chair he is trying to provide the same kind of supportive environment for the department that he’s been doing for his lab,” Pintel said.

Burk said he wants to help other faculty members achieve their goals and prioritize tasks. He is also involved in a new faculty search where he works to ensure the applicant pool reflects those that might be wanting to apply by removing language that may prevent people from applying.

“Again, I want to help find what obstacles can be in their way and get rid of those before it slows them down,” Burke said restating his passion for helping others achieve excellence.

Donald Burke-Aguero is an MU professor in the Department of Molecular Microbiology & Immunology. He received his bachelors’ degree from the University of Kansas and his Ph.D. from the University of California, Berkeley. Burke joined the MU community in 2005.