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Pigs pave the way for advancements in IVF treatment

New research makes IVF four times more efficient to create pigs like this for genetics research and breeding in labs like that of Randy Prather at MU. | Photo by Nicholas Benner.

New research makes IVF four times more efficient to create pigs like this for genetics research and breeding in labs like that of Randy Prather at MU. | Photo by Nicholas Benner.

Research quadruples speed and efficiency to develop embryos 

By Samantha Kummerer | Bond LSC

What started as a serendipitous discovery is now opening the door for decreasing the costs and risks involved with in vitro fertilization (IVF).

And it all started with cultured pig cells.

Dr. Michael Roberts’ and Dr. Randall Prather’s laboratories in the University of Missouri work with pigs to research stem cells. During an attempt to improve how they grew these cells, researchers stumbled across a method to improve the success of IVF in pigs.

“Sometimes you start an experiment and come up with up with a side project and it turns out to be really good,” Researcher Ye Yuan said.

Their discovery doubles the number of piglets born and speeds up the entire IVF process by 400 percent, which significantly increases both the efficiency of experiments and their potential application to other species. The journal Proceedings of the National Academy of Sciences published their work July 3 in its online early edition.

 

From the beginning:

The Prather lab in the MU Animal Sciences Research Center uses genetically modified pig embryos to improve pig production for agriculture and also to mimic human disease states, such as cystic fibrosis. Roberts’ team in the Bond Life Sciences Center occasionally collaborates with Prather’s lab to produce genetically modified pigs for this valuable research. However, the efficiency of producing these pigs is very low because it depends on multiple steps.

First, scientists remove oocytes (“eggs”) and the “nurse” cells that surround them from immature female pig ovaries and place the eggs in a chemical environment designed to mature the eggs, allowing them to be fertilized in vitro with sperm from a boar. This process creates zygotes, which are single-celled embryos, that are allowed to develop further until they become hollow balls of cells called blastocysts about six-days later. These tiny embryos are then transferred back into a female pig with the hopes of achieving a successful pregnancy and healthy piglets.

However, Roberts said the chance of generating a successful piglet after all those steps is very low; only 1-2 percent of the original eggs make it that far.

The quality of the premature eggs and the process of maturing them significantly reduces the rate of success.

“In other words, all this depends on having oocytes that are competent, that is they can be fertilized, form blastocysts and initiate a successful pregnancy,” Roberts explained.

Normally, researchers overcome the low success rate by starting out with a very large number of eggs, but this takes lots of time and money.

So, lab researchers, Ye Yuan and Lee Spate, began tinkering with the way the eggs were cultured before they were fertilized, making use of special growth factors they used when culturing pig embryonic stem cells.

Yuan and Spate added two factors called fibroblast growth factor 2 (FGF2) and leukemia inhibitory factor (LIF).

This combination helped more than the use of just a single factor and so they decided to add a third factor, insulin-like growth factor 1 (IGF1).

Together the three compounds create the chemical medium termed “FLI”.

“It improved every aspect of the whole process,” Roberts said. “It almost doubled the efficiency of oocyte maturation in terms of going through meiosis. It appeared to improve fertilization and it improved the production of blastocysts.”

In all, the use of FLI medium doubles the number of piglets born and quadruples the efficiency of the entire process from egg to piglet.

While the researchers are still figuring out why the three factors work together so well, Roberts believes it has to do with the fluid that surrounds the immature eggs while they are still in the ovary.

Roberts explained that unusual metabolic changes happen in the eggs and their nurse cells when the three components are used in combination but not when they are used on their own. These components are also found in the follicular fluid surrounding the egg when it is in the ovary.

However, follicular fluid actually contains factors that hinder egg maturation until the time is right, so it would seem counterintuitive to add the fluid to a chemical environment aimed at maturing the eggs. However, when freed from the other components of follicular fluid, the three growth factors act efficiently to promote maturation.

“It just creates this whole nurse environment for that egg. Once you’ve done that you’ve sort of patterned them to do everything else after that properly — fertilization, development of that fertilized egg to form a blastocyst, and the capability of those blastocysts to give rise to a piglet,” Roberts said.

Researchers hope the FLI medium can be translated beyond genetically modified pigs.

“If we could translate this to other species it could be more meaningful,” Yuan explained.

For the cattle industry, FLI has the potential to decrease the time between generations in highly prized animals.

Currently, if an immature dairy cow has desirable traits, the industry has to wait a year or so for that cow to mature and for its eggs to be collected. Using FLI medium immature eggs could be retrieved when the prized female is still a calf. After fertilizing them with semen from a prized bull, production of more cows with desirable traits could be achieved in a shorter amount of time.

The potential implications of this discovery aren’t just for farm animals.

Yuan said if this treatment could be applied to humans it would be a big help for both the patient and the whole field of human IVF.

Currently, in vitro fertilization for humans comes with high costs and risks.

“You try to generate a lot of eggs from the patients by using super-high doses of expensive hormones, which is not necessarily good for the patient and can, in fact, be risky. ” Roberts explained.

These eggs are then collected, fertilized, and the best-looking embryo transferred back to the patient. As in pigs, this overall process isn’t all that efficient. The hope is that the treatment of the patient with hormones can be minimized if immature eggs are collected directly from the ovary by using an endoscope and matured in FLI medium, allowing them to be just as competent as those retrieved after high hormone treatment.

“The idea is it would be safer for the woman, it would be cheaper, and it might even achieve a better success rate,” Roberts said.

The team still has some time before knowing for sure if FLI medium is applicable in other mammals.

Yuan said the focus is now on understanding the mechanism behind how the three compounds work so well together.

For now, preliminary data are being collected with mice and a patent is awaiting approval. Still, the team has high hopes for this almost accidental finding.

“Whenever you’re doing science, you’d like to think you’re doing something that could be useful,” Roberts said. “I mean when we started this out it wasn’t to improve fertility IVF in women, it was to just get better oocytes in pigs. Now it’s possible that FLI medium could become important in bovine embryo work and possibly even help with human IVF.”

 

Michael Roberts is a Bond LSC scientist and a Curators’ Distinguished Professor of Animal Science, Biochemistry and Veterinary Pathobiology in the College of Agriculture, Food and Natural Resources (CAFNR) and the College of Veterinary Medicine. He is also a member of the National Academy of Sciences.

Randall Prather is a Curators’ Distinguished Professor of Animal Science in the College of Agriculture, Food and Natural Resources (CAFNR) and Director of the National Institutes of Health funded National Swine Resource and Research Center.

#MeetScienceTwitter

How an MU student helped start a Twitter trend and how social media is advancing science.

By Mary Jane Rogers | Bond LSC

In the modern age, science isn’t a solitary endeavor.

You might be a tweet away from connecting with scientists about their work, as one MU student recently proved.

Dalton Ludwick, an MU doctoral student in entomology, helped spur a hashtag trend to connect real scientists with none other than Bill Nye.

If you follow any scientists on Twitter, you may have come across the hashtag #BillMeetScienceTwitter while scrolling through your feed. Thousands of scientists on Twitter introduced themselves to the famous TV host of Bill Nye the Science Guy using the hashtag. By May 22, a mere three days after the hashtag started, more than 27,000 scientists and experts had tweeted at Nye.

#BillMeetScienceTwitter was born from a Twitter discussion between Ludwick, London-based zoologist Dani Rabaiotti and New Zealand-based marine biologist Melissa Marquez.

Bill Nye Saves the World

“Bill Nye Saves the World” is a television show currently streaming on Netflix hosted by Bill Nye. The first season explores topics such as climate change, alternative medicine and video games.

The original sentiment behind the hashtag was something scientists have long been discussing — that Nye’s television show doesn’t include a diverse array of science experts to answer questions outside Nye’s specialty. On Season One of his show, a majority of the experts Nye invited were comedians, supermodels and Hollywood stars, like Karlie Kloss and Zach Braff.

We were curious about the origins of this campaign, so we reached out to Ludwick, one of the creators of the hashtag.

MU Bond LSC Tweet Dalton Ludwick Response

Ludwick regularly uses social media to reach out and connect with other scientists. He meets other scientists on Twitter, shares ideas and often turns that conversation into a real-life, professional relationship on a global scale.

Dalton Ludwick

Dalton Ludwick, a Ph.D candidate in Entomology at MU and one of the creators of #BillMeetScienceTwitter.

“I talk to people from the UK, Australia and New Zealand on social media,” he said. “It’s a great way to connect with people.”

Social media is a game changer for scientists who once felt walled off from the broader world. It can be a great way to connect with people doing similar research, track grants and jobs, share exciting breakthroughs, and follow conferences.

Jared Decker, an assistant professor in the College of Agriculture, Food and Natural Resources at MU, is another avid social media user on campus. He uses Facebook, Twitter and YouTube accounts to connect with other science professionals and academics, as well as his public — mainly beef and cattle producers and farmers.

Jared Decker

Jared Decker, an assistant professor in the College of Agriculture, Food and Natural Resources at MU.

“Just the other night I was writing a grant and one of the reviewers had a specific criticism,” he said. “So, I got on Twitter and asked my question. A colleague of mine was online in Australia and was able to respond to make sure we were meeting the guidelines.”

Jared Decker

Scientists used to have to walk down the hall to ask a colleague, or play phone tag with someone abroad.

“You can’t do that at 1 a.m.,” said Decker, “but you can go on Twitter.”

Many scientists believed that Nye’s television show wasn’t utilizing his vast array of science connections to find experts in specific fields of science.

“If you ask me about biology or oncology, I probably shouldn’t answer because that’s not my area of expertise,” said Ludwick.

In response to a tweet by Rabaiotti, Mike Stevenson was the first to ask if anyone had reached out to Nye on Twitter. Ludwick replied to that conversation with the hashtag #BillMeetScienceTwitter, which was meant to show Nye the diversity of scientists on social media.

Dani Rabaiotti original tweet

Rabaiotti – a Ph.D candidate at University College London, who studies the effects of climate change on wild dogs in Africa – was the first to introduce herself to Nye.

First #BillMeetScienceTwitter post

Overall, the tweets and engagement have been overwhelmingly positive.

Maryam Zaringhalam Dr. Solomon David Katherine Crocker Laura Skates Amanda L. Glaze Anne A Madden, Ph.D

We decided to tweet at Nye too!

MU Bond LSC

“What we were actually trying to do was reach out and offer assistance in areas outside the expertise of Bill and Neil,” said Ludwick. “We wanted to show the diversity of people doing science, as well as the diversity of the science that we do. More than 50 percent of the people tweeting on #BillMeetScienceTwitter were women — certainly not just a bunch of nerdy men in lab coats!”

Ludwick adds that the hashtag wasn’t intended as an attack on Bill Nye or Neil deGrasse Tyson, another scientist celebrity with broad reach. Instead, the point was to let them know that fellow scientists exist and can be a great source for accurate scientific information.

Nye responded to the hashtag, and even took the time to retweet and reply to his favorite posts.

Bill Nye Response to Hashtag Bill Nye Response 2 Bill Nye Response 1

Overall, the hashtag was a huge success, brought awareness and engaged scientific topics. But more than that, it shows how responsive and positive the scientific community can be. Some news articles noted that the campaign was “trolling in the politest way possible.”

“The scientific community on Twitter is really welcoming,” Decker said. “It doesn’t matter if you’re a first year science student or an endowed professor. People don’t treat you any differently.”

And an online presence is vital for scientists and their careers. In 2007, BioInformatics LLC conducted a survey of 1,510 scientists with regard to how they used social media. They found:

  • 77% of life scientists participated in some type of social media
  • 50% viewed blogs, discussion groups, online communities, and social networking as beneficial to sharing ideas with colleagues
  • 85% saw social media affecting their decision-making

For junior scientists or researchers who are just getting started, Decker has some advice.

“Tweeting out at conferences is a good way to practice taking in an idea and getting it back out there in written form,” Decker said. “Instead of taking notes, tweet out what you would have written down.”

#BillMeetScienceTwitter also helped bridge the gap between scientists and the public. Ludwick said that this hashtag helped flip the public perception that scientists are only old men in lab coats on its head.

“People were saying, ‘Hey, I’m going to show my daughter this and inspire her,’” Ludwick said.

Ludwick also thinks that, in general, social media makes him better at communicating science to the public.

“Twitter is a great way to break things down and stop using scientific jargon,” he said. “I think it has helped me personally and it’s great practice.”

Decker agrees with Ludwick’s assessment.

“The first few months on the job it felt like I was back in Spanish class,” he joked. “I was taking the science jargon and doing mental gymnastics to translate it into the language a lay person would understand. But, now I’m fluent in both!”

So, think twice the next time you consider social media to be a waste of time. Whether it’s a hashtag that brings issues to the attention of science celebrities, platforms that connect scientists at a global level or posts that make research more accessible, social media has done a pretty cool job of advancing science.

The Necessity of Fungi

Graduate Researcher Sarah Unruh explores the essential role of fungi in orchid germination

Sarah Unruh

Graduate Researcher Sarah Unruh | photo by Emily Kummerfeld, Bond LSC

By Emily Kummerfeld | Bond LSC

The blooms of orchids are unmistakably beautiful, and how they reproduce has fascinated biologists for centuries.

But, orchids might not even exist if not for the help of fungus. Up to 30,000 species of orchids require the intervention of fungi since their seeds do not contain the necessary nutrients to sprout.

Sarah Unruh, a fifth-year biological sciences PhD student in the lab of Bond LSC’s Chris Pires, seeks to discover and record the specific types of fungi utilized by many orchid species. By studying their specific genetic expressions, she hopes to uncover what allows these fungi to interact with orchids in this way, how these fungi are related to each other and what genes each organism is expressing with and without each other.

Blooming orchid

A blooming orchid in the Tucker greenhouse. Although this orchid grows in a pot, like most species of orchid it is an epiphyte and naturally grows on tree branches. | photo by Emily Kummerfeld, Bond LSC

“The main question for me is, what is the nature of this relationship? Is it more mutualistic or parasitic? You don’t often get something for nothing, so why is the fungus participating in this relationship? Most fungi that live in plant roots receive carbon from the plant. Orchid fungi are doing the opposite and that is weird. I want to know how this relationship works,” Unruh says.

Unruh first studied orchid evolution and how each orchid species related to each other genetically. “My assumptions of what a plant was were so violated by orchids and it still fascinates me! So many orchid species grow on trees, many don’t have leaves, some species never even turn green or photosynthesize.”

This focus soon evolved into her interest in the relationship between orchid plants and fungi. Fungi are neither plants nor animals, and have their own branch on the eukaryotic family tree. They are nonetheless essential to plant biology, “eighty percent of plant species have beneficial fungi in their roots,” says Unruh.

Many orchids are technically classified as epiphytes, which means they grow on the surface of another plant and get all their food and water needs from the air, rain and what accumulates nearby. That doesn’t leave a lot of extra nutrients to put into seeds, which typically need the store of food to sprout and grow its first leaves.

Germinating orchids seeds

Germinating orchids seeds. A small mass of fungus is placed in the Petri dish to assist in germination. | photo by Emily Kummerfeld, Bond LSC

That’s where fungi come into play. Some types of fungi can even germinate several species of orchids, and studying the DNA sequences of these fungi could be vital in the future for endemic endangered orchids and their associated fungi. “I’ve always been interested in relationships between organisms or symbioses,” says Unruh, “the fact that orchid seeds need fungi to survive was too weird not to research.”

"Super Fungus"

Tulasnella calospora, nicknamed the “Super Fungus”. This type of fungus can germinate several species of orchids. | photo by Roger Meissen, Bond LSC

But the process of studying fungi DNA is not a simple one.

“In order to look at their genomes, I need to grow a lot of fungi and then grind it up and add certain substances to isolate only the DNA. I send this DNA to a facility called the Joint Genome Institute where they send it through a machine that spits out a file with a list of lots of small pieces of the genome – like puzzle pieces. I then use computer programs to put the pieces together and try to assign a function to each gene.”

So, the established relationship between fungus and seed helps the orchid, but it’s not known what the fungus is getting out of this arrangement. One idea, based on recent published research, is the fungi receives a certain form of nitrogen from the orchid seeds. Another experiment Unruh is working on is growing the orchid seeds by themselves through special media, growing the fungus by itself, or growing them together. She then measures the gene expression to see if there are big differences when the plant or fungus is alone or together. “This will help answer my question of how mutually beneficial this association is,” says Unruh.

The data collected from this research will form the bulk of her PhD thesis. However, there remains many questions regarding the relationship between orchids and fungus that Unruh would like to explore in the future, such as which fungi are best for reintroducing endangered orchid species or what other roles fungi play in their environment. “I foresee fungi, especially plant and fungal relationships, becoming the focus of more and more research in the future.”

In 2014, Unruh received a three-year National Science Foundation (NSF) Graduate Research Fellowship. More recently, she has received a grant from the Joint Genome Institute to sequence 15 full genomes of orchid fungi.

A step into summer research

Jacqueline Ihnat

Jacqueline Ihnat, one of the 12 Cherng Summer Scholars, outside Dr. Cornelison’s lab at the Bond Life Sciences Center.

Sometimes the most learning occurs outside of the classroom.

For Jacqueline Ihnat, an opportunity to pursue research at the Bond Life Sciences Center this summer will give her that chance. She recently became one of 12 Cherng Summer Scholars, a full-time, ten-week program within the Honors College at MU.

“Doing research helps keep me focused on the bigger picture,” Ihnat said. “Sometimes in class we learn things that don’t seem entirely relevant or useful, but being part of a research lab allows me to apply some of the knowledge that I gain in the classroom.  It’s a daily reminder of why I’m learning what I am.”

Jacqueline Ihnat’s passion for science started in high school. Her high school biology teacher ignited that love by teaching her how to struggle through difficult problems and concepts. Now, Ihnat is an MU pre-med student with a major in business management and a minor in Spanish.

Since Ihnat is fascinated with cells and how our bodies function, she’ll be studying the role of specialized stem cells in muscle regeneration and how they interact with muscle fibers — specifically the role of Eph-A3, a type of cell-surface receptor. This project will take place in the lab of Dawn Cornelison, a Bond LSC biologist who will be mentoring Ihnat this summer.

DSC_3313.jpg

Jacqueline Ihnat as she pipettes samples in Dr. Cornelison’s lab in Bond LSC. | photo by Mary Jane Rogers, Bond LSC

Each muscle in the body is unique in its length, fiber organization and fiber type patterning, so Ihnat hopes to explore why two types of muscle — fast and slow twitch muscle — develop and regenerate to maintain each specific muscle fiber-type composition.

When a muscle is damaged from exercise or injury, a muscle’s stem cells, or “satellite cells,” will multiply, move towards the injury and form new muscle, replacing the damaged fiber. There is no research that determines if “fast” satellite cells create fast fibers and if “slow” satellite cells create slow fibers, and Ihnat hopes to tackle that question this summer. This kind of research gives scientists a deeper understanding of degenerative muscle diseases such as ALS, which could lead to more effective treatments and therapies.

The Cherng Summer Scholars program is supported by a gift from Andrew and Peggy Cherng and the Panda Charitable Foundation. The Cherng’s are the founders of Panda Express, a well-known restaurant chain. These scholarships support individually designed theoretical research, applied research or artistry projects under the mentorship of an MU faculty member.

For young scientists who are just starting to conduct research and struggling to feel successful, Ihnat has a few words of motivation.

“My high school biology teacher always said that research is 30 years of frustration and disappointment followed by 30 seconds of elation when you finally make a breakthrough,” she said. “Patience is key.”

From neuroscience to negotiations

Neuroscientist and former Secretary of State science adviser to speak at Life Sciences Week
By Eleanor C. Hasenbeck | Bond Life Sciences

Frances Colon

Frances Colón has spent the past decade representing the United States all over the world on topics ranging from climate change to the advancement of women scientists. She will reflect on that experience in her talk at 3:30 p.m. Monday, April 11 in Monsanto Auditorium. | Photo courtesy of Frances Colón

A career in science doesn’t only mean working in a lab, and no one knows that better than Frances Colón.

Colón, a neuroscientist by training and policy maker by trade, will speak about how scientists can become more involved in policy without abandoning the laboratory bench.

During her Missouri Life Sciences Week lecture “My path to science citizenship,” Colón will talk about her transition from the lab to policy. She’ll speak 3:30 p.m. Monday, April 10, in Monsanto Auditorium.

“I think scientists need to realize that they have a broader set of skills than they give themselves credit for that can be applied to the service of the community and their country in many different ways,” said Colón. “I think we’re living in a time where our country needs scientists to get engaged at every level. That doesn’t mean they need to leave a career in academia to go into policy, but it could certainly mean involvement everywhere from the community level to the national level.”

After receiving a doctoral degree in neuroscience and studying how nerve cells mature at Brandeis University, Colón first got involved in making policy as an American Association for the Advancement of Sciences policy fellow. She then served as science and environment adviser for western hemisphere affairs for more than three years before she became deputy science and technology adviser to the Secretary of State, a position she served in until January.

As deputy science adviser, she led efforts to reengage Cuba in scientific collaboration after U.S. policy regarding Cuba shifted. She also coordinated climate change policy for the Energy and Climate Partnership of the Americas, and she worked to advance women and girls in science, technology, engineering and math. Today, she looks to use platforms outside of the government to accomplish the same missions.

Colón said of her career thus far, she is most proud of the work she’s done to educate women in opportunities in STEM careers.

“A lot of these countries started to realize that they can’t tackle a lot of the biggest challenges they’re confronting, from climate change to energy security, without having all of their best talent at the table. That required providing equal opportunity for women and men to achieve these positions,” Colón said. “We worked a lot on finding opportunities for girls to discover STEM careers and to help countries plan out what their STEM capacity building activities could be.”

These activities included things like the two-week camps for girls in South America and Africa, where they learned about coding and genetics with help from corporate partners.

Colón holds a doctorate from Brandeis University, and a bachelor’s degree in biology from the University of Puerto Rico. She was a delegate to the National Committee on U.S.-China Relations’ Young Leaders Forum, and a graduate of the National Hispana Leadership Institute. Last year, she was named one of the 20 most influential Latinos in technology by CNET en Español.

Colón will speak at 3:30 Monday, April 10 in Monsanto Auditorium as part of Missouri Life Sciences Week.

Hanson to explain why broken metabolites matter at Life Sciences Week

By Jinghong Chen | Bond Life Sciences Center

Andrew Hanson, right, will speak Friday, April 14 in Bond LSC's Monsanto Auditorium as the 2017 Dr. Charles W Gehrke speaker. | Photo by University of Florida, Institute of Food and Agricultural Sciences

Andrew Hanson, right, will speak Friday, April 14 in Bond LSC’s Monsanto Auditorium as the 2017 Dr. Charles W Gehrke speaker. | Photo by University of Florida, Institute of Food and Agricultural Sciences

People often think of metabolism as a perfect network. But that assumption is simply not accurate.

Andrew Hanson, an eminent scholar and professor at the University of Florida, describes the misunderstanding as “the power of a paradigm.” American biochemist Albert Lehninger spread the misunderstanding in his classic textbook “Biochemistry”, in which the message he communicated to generations of students was: metabolism is a beautiful machine that functions flawlessly.

Hanson challenges this “metabolism is perfect” paradigm using illustrations from different kinds of organisms in his lecture. He will speak in Bond LSC’s Monsanto Auditorium at 1 p.m. Friday April 14, during the 33rd annual Missouri Life Sciences Week.

For every living organism, metabolism is the sum of every chemical reaction that occurs to maintain life. This sum contains all the metabolites — small molecules created at each level of cell processes and final products — that share a part in the growth, development, reproduction and running of cells and whole organisms.

However, enzymes can make mistakes; many chemical compounds in cells are unstable and undergo spontaneous reactions. The consequences of enzyme errors and chemical side-reactions are, at best, unwanted and sometimes toxic, so organisms have developed mechanisms – damage-control systems – to deal with the consequences of damage.

Hanson’s lab has studied metabolite damage and the damage-control systems that plants and microorganisms employ to cope. But the impact of metabolic problems also reaches into the human domain, causing disease from failure or mutation of damage repair enzymes. “It matters in aging humans and animals a great deal, because aging is the result of cumulative damage,” Hanson said.

Plants are also afflicted by metabolite damage. Under environmental stress such as high temperature or water loss, the error rate of enzymes and rates of unwanted chemical reactions can go up.

The understanding of metabolite damage could also advance metabolic engineering, which is a purposeful manipulation by combining metabolic pathways and DNA techniques to produce desired products. After creating new pathways in an organism, it may fail to cope with the abnormal reactions produced by the new pathways. To fix the problem, the only solution might be to install the required damage control enzymes.

Hanson’s lab hopes to identify new or unsuspected damage reactions, and enzymes that repair or prevent damage. They also are working to connect with metabolic engineering groups that install modified pathways in plants and microbes to study sources of damage and propose solutions.

Metabolism is not perfect. However, after studying its imperfection for years, Hanson concluded, “life is put together in a very beautiful and even more powerful way than we first realize. It makes a lot of mistakes, but it also fixes them so well that we do not even notice them.”

Hanson’s lecture on “Fixing or safely trashing broken metabolites and why it matters” is this year’s Charles W. Gehrke distinguished lecture. Gehrke, a longtime MU professor of Biochemistry, was selected by NASA to analyze rocks retrieved from the first moon landing for any traces of extraterrestrial life. He died in 2009.

Hanson’s lecture is free and open to the public as part of Missouri Life Sciences Week. It occurs at 1:00 on Friday, April 14 in Bond LSC’s Monsanto Auditorium. See more about events during the week at bondlsc.missouri.edu/life-sciences-week.

Pork without the Pig

Genovese's study

This screenshot of a supplemental video included in Genovese’s study shows cells contracting in response to a neurotransmitter. | photo courtesy of the Nicholas Genovese

What if you could have pork without the pig? Nicholas Genovese’s cultured meat could provide a more environmentally friendly meat
By Eleanor C. Hasenbeck | MU Bond Life Sciences Center

Scientists are one step closer to that reality. For the first time, researchers in the Roberts’ lab at Bond Life Sciences Center at MU were able to create a framework to make pig skeletal muscle cells from cell cultures.

In vitro meat, also known as cultured meat or cell-cultured meat, is made up of muscle cells created from cultured stem cells.

As a visiting scholar at the University of Missouri, Nicholas Genovese mapped out pathways to successfully create the first batch of in vitro pork. Genovese also said it was the first time it was done without an animal serum, a growth agent made from animal blood.

According to Genovese, his research in the Roberts Lab was also the first time the field of in vitro meats was studied at an American university.

“I feel it’s a very meaningful way to create more environmentally sustainable meats, which is going to use fewer resources, with fewer environmental impacts and reduce need for animal suffering and slaughter while providing meats for everyone who loves meat,” Genovese said.

The research could have environmental impacts. According to the United Nation’s Food and Agriculture Organization, livestock produce 14.5 percent of all human-produced greenhouse gas emissions. Livestock grazing and feed production takes up 59 percent of the earth’s un-iced landscape. Cultured meat takes up only as much land as the laboratory or kitchen (or carnery, the term some members of the industry have coined for their facilities) it is produced in. It uses energy more efficiently. According to Genovese, three calories of energy can produce one calorie of consumable meat. The conversion factor in meat produced by an animal is much higher. According to the FAO, a cow must consume 11 calories to produce one calorie of beef for human consumption.

And while Michael Roberts, the lab’s principal investigator, is skeptical of how successful in vitro meat will be, he said the results could yield other benefits. Researchers might be able to use a similar technique as they used to create skeletal muscle tissue to make cardiac muscle tissue. Pork muscles are anatomically similar to a human’s and can be used to model treatments for regenerative muscle therapies, like replacing tissue damaged by injury or heart attacks.

“I was interested in using these cells to show that we could differentiate them into a tissue. It’d been done with human and mouse, but we’re not going to eat human and mouse,” Roberts said. “The pig is so similar in many respects to humans, that if you’re going to test out technology and regenerative medicine, the pig is really an ideal animal for doing this, particularly for heart muscle,” he added.

While you won’t find in vitro meat in the supermarket just yet, Genovese and others are working toward making cultured meats a reality for the masses. Right now, producing in vitro meat is too costly to make it economically viable. Meat is produced in small batches, and the technology needed to mass-produce it just isn’t there yet.  Genovese recently co-founded the company Memphis Meats, where he now serves as Chief Scientific Officer. The company premiered the first in vitro meatball last year, at the hefty price tag of $18,000.

“We are rapidly accelerating our process towards developments of technology that we hope will make cultured meats accessible to everyone within the not-so-distant future,” Genovese said.

Nicholas Genovese was a member of the Roberts lab in Bond LSC from 2012 to 2016. The study “Enhanced Development of Skeletal Myotubes from Porcine Induced Pluripotent Stem Cells” was recently published by the journal Scientific Reports in February 2017.

Chemical persuasion

Scientists prove parasite mimics key plant peptide to feed off roots
By Roger Meissen | Bond LSC

A nematode (the oblong object on the upper left) activates the vascular stem cell pathway in the developing nematode feeding site (syncytium) on a plant root. | contributed by Melissa Mitchum

A nematode (the oblong object on the left) activates the vascular stem cell pathway in the developing nematode feeding site (syncytium) on a plant root. | photo by Xiaoli Guo, MU post-doctoral research associate

When it comes to nematodes, unraveling the root of the issue is complicated.

These tiny parasites siphon off the nutrients from the roots of important crops like soybeans, and scientists keep uncovering more about how they accomplish this task.

Research from the lab of Bond LSC’s Melissa Mitchum recently pinpointed a new way nematodes take over root cells.

DSC_4307.jpg

Melissa Mitchum | photo by Roger Meissen, Bond LSC

“In a normal plant, the plant sends different chemical signals to form different types of structures for a plant. One of those structures is the xylem for nutrient flow,” said Mitchum, an associate professor in the Division of Plant Sciences at MU. “Plant researchers discovered a peptide signal for vascular stem cells several years ago, but this is the first time anyone has proven that a nematode is also secreting chemical mimics to keep these stem cells from changing into the plant structures they normally would.”

Stem cells? Xylem? Chemical mimics?

Let’s unpack what’s going on.

First, all plants contain stem cells. These are cells with unbridled potential and are at the growth centers in a plant. Think the tips of shoots and roots. With the right urging, plant stem cells can turn into many different types of cells.

That influence often comes in the form of chemicals. These chemicals are typically made inside the plant and when stem cells are exposed to them at the right time, they turn certain genes either on or off that in turn start a transformation of these cells into more specialized organs.

Want a leaf? Expose a stem cell to a particular combination of chemicals. Need a root? Flood it with a different concoction of peptides. The xylem — the dead cells that pipe water and nutrients up and down the plant — requires a particular type of peptide that connects with just the right receptor to start the process.

But for a nematode, the plan is to hijack the plant’s plan and make plant cells feed it. This microscopic worm attaches itself to a root and uses a needle-like mouthpiece to inject spit into a single root cell. That spit contains chemical signals of its own engineered to look like plant signals. In this case, these chemicals — B-type CLE peptides — and their purpose are just being discovered by Mitchum’s lab.

“Now a nematode doesn’t want to turn its feeding site into xylem because these are dead cells it can’t use, so they may be tapping into part of the pathway required to maintain the stems cells while suppressing xylem differentiation to form a structure that serves as a nutrient sink,” Mitchum said. “To me that’s really cool.”

This means these cells are free to serve the nematode. Many of their cell walls dissolve to create a large nutrient storage container for the nematode and some create finger-like cell wall ingrowths that increase the take up of food being piped through the roots. For a nematode, that’s a lifetime of meals for it while it sits immobile, just eating.

But how did scientists figure out and test that this nematode’s chemical was the cause?

Using next generation sequencing technologies that were previously unavailable, Michael Gardner, a graduate research assistant, and Jianying Wang, a senior research associate in Mitchum’s lab, compared the pieces of the plant and nematode genome and found nearly identical peptides in both — B-type CLE peptides.

“Everything is faster, more sensitive and we can detect things that had gone undetected through these technological advances that didn’t exist 10 years ago,” Mitchum said.

To test their theory, Xiaoli Guo, postdoctoral researcher and first author of the study in Mitchum’s lab synthesized the B-type CLE nematode peptide and applied it to vascular stem cells of the model plant Arabidopsis. They found that the nematode peptides triggered a growth response in much the same way as the plants own peptides affected development.

They used mutant Arabidopsis plants engineered to not be affected as much by this peptide to confirm their findings.

“We knocked out genes in the plant to turn off this pathway, and that caused the nematode’s feeding cell to be compromised. That’s why you see reduced development of the nematode on the plants.”

This all matters because these tiny nematodes cost U.S. farmers billions every year in lost yields from soybeans, and similar nematodes affect sugar beets, potatoes, corn and other crops.

While this discovery is just a piece of a puzzle, these pieces hopefully will come together to build better crops.

“You have to know what is happening before you can intervene,” Mitchum said. “Now our biggest hurdle is to figure out how to not compromise plant growth while blocking only the nematode’s version of this peptide.”

Mitchum is a Bond LSC investigator and an associate professor of Plant Sciences in the College of Agriculture, Food and Natural Resources. The study Identification of cyst nematode B-type CLE peptides and modulation of the vascular stem cell pathway for feeding cell formation” recently was published by the journal PLOS Pathogens in February 2017.

Growing a more nourishing future

Nga Nguyen

Nga Nguyen, a doctoral candidate in MU’s Division of Plant Sciences, observes samples of a model plant species, Arabidopsis thaliana, in the Mendoza-Cózatl lab at Bond Life Sciences Center on Feb. 7, 2017. | photo by Eleanor C. Hasenbeck, Bond LSC

Nga Nguyen hopes to apply her research to increase nutrient contents in crop plants
By Eleanor C. Hasenbeck | Bond LSC

Plants smell better than animals, at least to Nga Nguyen. That’s one reason why she decided to study them.

“In my undergrad, I studied horticulture,” Nguyen said. “For that you don’t really learn the inside mechanisms of plants, so I decided besides knowing the cultivation techniques, I’d like to also learn about the molecular biology.”

As a fifth year doctoral candidate in the Mendoza-Cózatl lab at Bond Life Sciences Center, she hopes to combine her undergraduate background with her present research in the microbiology of plants to improve the crops of the future.

Nguyen studies how transporter proteins move micronutrients like iron through plants. By understanding how plants move these nutrients in model plants, researchers hope to apply the same understanding and techniques to crops like soy and common beans. Increasing the micronutrient content of these crops could be a useful tool in combatting nutrient deficiencies in areas where people don’t have access to meat and dairy.

But Nguyen says the benefits of studying plants don’t end there. “I hope people pay attention to plant research and study,” Nguyen said.  “If you think about it, it’s not just our food, but our clothing and the materials we use.”

Beginning of a journey

By Jinghong Chen | Bond Life Sciences Center

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Emily Million, a prospective biochemistry graduate student from Truman State University and Kevin Muñoz-Forti of University of Puerto Rico’s Pontifical Catholic University talk at the Graduate Life Sciences Joint Recruitment Weekend on February 4 after looking at posters about many different research programs and projects. | Roger Meissen, Bond LSC

Nick Dietz was not certain where to start his research journey this time last year.

But the atmosphere during a recruitment weekend nearly a year ago convinced him to pick MU over three other offers of admission. He is now a first-year plant sciences Ph.D. graduate student and life sciences fellow at MU.

“It is crucially important for [prospective] graduate students to feel they are going to feel like home, and Mizzou just knocked out that part with the recruitment weekend,” said Dietz.

The Graduate Life Sciences Joint Recruitment Weekend, an annual event since 2010, builds a two-way street between MU faculties and prospective graduate students and helps them to determine whether MU is the place for them to continue their education.

This year, about 35 prospective students with different academic backgrounds participated in the recruitment event.

“Up to this point, the departments only know these [prospective] students on paper,” said Debbie Allen, coordinator of Graduate Initiatives. “But this is an chance for the faculty and staff to meet them in person to get a feel that whether they are going to be a good fit for our program.”

Conversely, the prospective students also gain deeper understanding of MU via tours around the campus and the laboratories, one-on-one interviews with potential advisors and interdisciplinary poster sessions. The event combines recruiting efforts from the division of Biochemistry, Plant Sciences, Molecular Pathogenesis and Therapeutics graduate program, Genetics Area program, MU Information Institute, the Interdisciplinary Plant Group and Life Sciences Fellowship Program.

More than 100 faculty, graduate students and post-doctoral fellows joined the recruitment weekend. They play a valuable role in interacting with the prospective students, as they are the ones who are in the midst of MU life.

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Nick Dietz, a freshman plant sciences graduate student, volunteered as a student ambassador during the the annual Graduate Life Sciences Joint Recruitment Weekend Saturday, Feb. 4. Dietz said last year’s event clinched his decision to attend MU and made him want to help prospective students make their decisions on where to attend. | photo by Roger Meissen, Bond LSC

Dietz joined that effort as a student ambassador. He toured Matthew Murphy, an Illinois College graduate, around the campus and shuttled him to different interviews.

Murphy drove from St. Louis for the recruitment weekend. With a major in biology and a minor in mathematics, he wishes to submerge himself into plant sciences.

During his gap year at the Donald Danforth Plant Science Center after graduation, Murphy learned about the division of Plant Sciences, which is one of the MU’s strongest programs. That eventually got him pumped up to apply for MU.

The recruitment weekend energized him further.

“Every graduate student I have talked to is really helpful and honest,” said Murphy. “They are all saying… how thankful they are to pick Mizzou.”

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Lloyd Sumner, professor of biochemistry and director of MU’s Metabolomics Center in Bond LSC, talks with a prospective graduate student Saturday, Feb. 4, during the annual Graduate Life Sciences Joint Recruitment Weekend. | photo by Roger Meissen, Bond LSC

Lloyd Sumner, an MU professor of biochemistry, is expecting new students to join his lab. He had lunch and one-on-one meetings with the 11 prospective students invited by the biochemistry department, and toured them around his lab to showcase the instrumental resources.

“These are educated young adults with often very grand ideas. It is inspiring to visit with them and to be part of their future goals and careers,” Sumner said.

After six months rotating between different labs, Dietz has not yet decided which research route he will take yet. Nevertheless, he remains certain of one thing: he is enjoying the life here.

“It is a really warm atmosphere,” said Dietz. “I don’t feel I am being used as a labor. Professors actually want me to do well and get a good education.”