October 2020

#IAmScience Mona Kacher

October 30, 2020 By Lauren Hines in #IAmScience Tags: spinal muscular atrophy

By Lauren Hines | Bond LSC

Years ago, when career technician Mona Kacher was still in school, her science teacher asked their students who wanted to dissect a salamander first. Some students were hesitant, others excited, but no one more excited than Kacher who had already raised her hand.

Originally, Kacher was a medical technician in an Army hospital lab. However, when she left the Army, she was encouraged by her then father-in-law to apply for a senior research position at Dalton Cardiovascular Research Center. There, the lab manager asked if she knew anything about the chemistry analyzer they had just bought.

She knew it inside and out.

“So, that started an unintentional career in research, and I’ve stayed with it ever since,” Kacher said.

In her 31 years at Mizzou, Kacher has been bouncing around campus as a senior technician and research specialist working in various labs and disciplines.

“As you know, PIs sometimes lose their funding or funding comes and goes,” Kacher said. “So, I’ve had to piece together a career on campus, moving around a little bit.”

Kacher has worked in oncology, veterinary pathobiology, diabetes, hypertension, Lyme disease, HIV-AIDS and malaria research. She has been listed as a co-author of 20 scientific manuscripts that also include her data.

“Mona’s wide variety of disciplines that she has been exposed to throughout her career absolutely helps strengthen the Lorson lab,” said Chris Lorson, principal investigator at Bond Life Sciences Center. “She is able to draw on techniques she has performed in the past and apply them to various research needs.”

Kacher has been at the Chris Lorson lab at BLSC for the past two years. She’s the only technician there, so she assists others and helps teach methods and procedures to graduate and undergraduate students. Kacher also maintains five mice colonies for Lorson’s gene therapy work regarding Spinal Muscle Atrophy (SMA).

SMA is a genetic disorder that occurs in children missing the survival motor neuron-one gene. The disorder is the leading genetic cause of infantile death worldwide and causes muscle weakness, respiratory failure and premature death.

“SMA has likely affected members of my own family,” Kacher said. “It’s a very sad situation for a lot of families, and working in research that may directly improve the outcomes of the lives for some of these little sick children is very rewarding.”

Kacher is currently working on projects that test treatment methods for SMA and other neurodegenerative diseases. In these projects, infant mice the size of gummy bears receive a spinal injection with the treatment. Spinal injections are also involved in some projects.

“She is focused and hard-working,” Lorson said. “She understands the need for flexibility in the world of research and will persevere until the task is completed. She has a wonderfully positive attitude and a genuine concern for the well-being of those around her.”

Similar to how her research reaches a range of disciplines, her interests are just as varied.

Kacher and her wife started a business named, Shivers Shaved Ice and Shivers Coffee & Donuts in 2017. They owned it for several years until Kacher went back to MU.

In addition, Kacher likes to make jewelry and art. She also plays guitar and used to sing at weddings and in the Columbia Chorale. She still sings with MU’s Choral Union.

All of this creativity seeps into BLSC where she has colorful toys on her desk and a rainbow of organizers on lab shelves.

“Gosh, well, I think I’ve certainly brightened up the lab,” Kacher said.

With so many positions across campus, Kacher believes this one will be her last. She plans on retiring in a few years.

“I enjoy a lot of variety in life,” Kacher said. “So, being able to contribute data and small pieces of information in this field or that field, knowing that all the little pieces together are what makes a cure or moves scientists into the next direction for studying that disease or that condition is very rewarding.”

Using improved technology to create an Immune Cell Atlas

October 28, 2020 By Becca Wolf in Research Tags: agriculture, gene expression, RNA

Ashley Meyer | photo by Mariah Cox, Bond LSC

By Becca Wolf | Bond LSC

When given an opportunity to use the newest technology, one has to take it.

Ashley Meyer, the lab supervisor of the Wes Warren lab at Bond Life Sciences Center, recently started using the improved technology of single cell RNA sequencing to create an Immune Cell Atlas for chickens. This search browser of sorts allows people to search for cells and gene expression in chickens.

“It would be a platform for researchers to have a baseline of what should be normal, and then be able to run comparative experiments to say ‘Okay, if we challenge this chicken with this disease, what biological response are we seeing?’ Which can help you then understand the disease better,” Meyer said. “Like, ‘How is it being transmitted? How is this chicken reacting to it?’”

Poultry is one of the largest agricultural industries in Missouri, so it is important to keep chickens healthy.

“The Immune Cell Atlas will help us analyze tissues and will help us perform the single cell RNA sequencing on them to ask what’s normal and what’s diseased so that we can see what’s happening,” Meyer said. “It will also allow us to see which chickens are more susceptible than others or how the progression diseases happen.”

Meyer and the Warren lab are some of the first researchers to apply this technology to chicken based research.

Single cell RNA sequencing (RNAseq) allows Meyer to sequence the RNA of an individual cell which provides in-depth data. This can be done using single cell RNAseq which uses the entire cell, or it can be done using single nuclei RNAseq which uses just the nucleus of a cell. This profiles gene expression in cells that make up a tissue to get data on a cellular level to understand the composition of cells.

It is important to target the RNA because it is the messenger that brings instructions from the DNA for controlling the synthesis of proteins. RNA is commonly synthesized in the nucleus of a cell.

“We’re some of the first people to get our hands on some avian single cell data, specifically looking at nuclei. My job is a lot of optimizing these protocols to isolate these nuclei,” Meyer said.

Using nuclei allows Meyer to use samples that have been frozen, collected in other locations, etc., which provides more flexibility.

Isolating the nuclei through RNAseq allows Meyer to identify different cell types based on genes being expressed in a cell in an organ such as a spleen or lung. This information can then be added to the Immune Cell Atlas.

Meyer is a part of a team working on this project including two master’s students, a bioinformatics analyst, and principal investigator, Wes Warren, at Bond LSC, as well as a bioinformatics analyst who works remotely from Santa Cruz, California.

While the team is working from around the country, they are all connected by a common goal.

“Things have been pretty hectic, the break with the COVID quarantine kind of paused everything and then when we got back it just kind of took off, we’ve generated a couple data sets just in the last month or so,” Meyer said.

Having started this research about six months ago, they still have a way to go. Meyer and her collaborators are currently focused on analyzing five to six immune system organs, and plan on expanding in the future.

Since single cell RNAseq is so new, it can be challenging being one of the first labs to use it at MU and in the avian community.

“Since it’s still newer, everyone’s still figuring out how it works,” Meyer said. “Everybody’s determining their own way of analyzing the data. We’re working through the hiccups of everything, and not having years and years of research to guide us can be challenging; however, also exciting because then we can find what works and what doesn’t work which is the whole point of science.”

While challenging, it is rewarding. Meyer hopes that in the future once they have created the chicken Immune Cell Atlas, they are able to expand to other animals.

“It’s exciting to be part of something that’s newer and having something that could be beneficial for other researchers,” Meyer said. “I am a huge advocate for sharing science and teaching science so creating something to aid other research is super empowering for me.”

Learning From History

October 26, 2020 By Lauren Hines in Research Tags: extracellular ATP, plant signaling pathways

Sung-Hwan Cho, a research scientist in the Gary Stacey lab, checks in on the arabidopsis plants that he uses in his purinergic signaling experiments. | photo by Lauren Hines, Bond LSC.

By Lauren Hines | Bond LSC

Until the 1990s, the presence and significance of extracellular ATP, a nucleotide that normally provides energy to a cell, in animal cells was highly contested for decades. Now, the Gary Stacey lab at Bond Life Sciences Center is using that history lesson to explore ATP’s role in plant cells.

Let’s say you have $100 in your pocket. As you’re walking down the street, you throw dollar bills over your shoulder. Sounds ridiculous, right?

Much like these dollar bills, ATP is the currency of cells. When the idea of animal cells dispensing ATP outside the cell to trigger danger signals came out in the 1970s, the scientific community thought it was wasteful and therefore the idea was ridiculed.

“The idea of throwing money over your shoulder is a very good analogy because that’s a good way to influence people,” said Stacey, a principal investigator at Bond LSC. “Give them a financial incentive. It’s the same thing with ATP. The idea is that this is the currency of the cell, but they’re putting it outside the cell in order to signal and influence interactions with their environment or other cells.”

This process of ATP receptors on the cellular membrane bonding with molecules to send signals and communicate between cells is called purinergic signaling.

The term was coined by retired neurobiologist Geoffrey Burnstock in the 1970s when he discovered it in animals; however, Burnstock’s findings were met with skepticism. It wasn’t until 20 years later when the first ATP receptor in animal cells was discovered that his idea gained acceptance.

Today, animal cell purinergic signaling has been used to make drugs that target diseases and develop drug therapies. As for purinergic signaling in plant cells, the research is just beginning. Much like what Burnstock faced, this new research is met with skepticism.

“It was clear to me that if we really wanted to establish this so that people would believe it, we had to get the receptor,” Stacey said.

In 2014, the Stacey lab reported its first ATP receptor called P2K1. Earlier this year, they found another one called P2K2.

“I think more and more people are working on purinergic signaling in plants,” Stacey said. “I think we will see a big explosion of people working in this area. Just as is the case with the animal field, the plant field is really going to take off now that we actually know what the receptors are.”

Currently, the Stacey lab is trying to understand how these receptors work. Research scientist Sung-Hwan Cho from the Stacey lab took over the project regarding P2K1.

“The ATP study in animals is just half a piece of the puzzle,” Cho said. “You need to find the other half of the piece. For 40 years, many labs have already studied this, but in plants, there’s just been a few.”

Research done by the Stacey lab has shown that although not much is known about purinergic signaling in plants compared to in animals, purinergic signaling can impact plant growth, development, defense against diseases and stress tolerance. Cho is currently studying how P2K1 impacts certain metabolic pathways in plants.

In another experiment done by the lab, they found that mutants without the ATP receptor that experienced stress did not grow smaller while plants that did have the receptor and experienced stress grew smaller.

“That says the purinergic signaling is what’s mediating the stress response,” Stacey said. “That is affecting the development of the plant in response to stress… So, if we understand this better then maybe we can make plants that are more drought and stress-tolerant and grow better.”

#IAmScience Karl Kerns

October 24, 2020 By Becca Wolf in #IAmScience Tags: animal science, bioinformatics

By Becca Wolf | Bond LSC

It’s all about the journey and Karl Kerns has been places.

Originally from a small town in southwestern Iowa, Kerns did his undergrad years at Iowa State University (ISU), taking internships in Maryland, Texas, southeast Asia, and southern Australia, among other places that focused on animal physiology and fertilization.

“I do like traveling just in the sense of vacation. I like having a purpose while traveling. It’s hard for me to sit back and relax and be in vacation mode,” Kerns said.

This focus and determination eventually brought him to Mizzou where he completed his postdoctoral fellowship in the Dong Xu lab at Bond Life Sciences Center this past spring, co-advised with Peter Sutovsky and Susanta Behura in the Division of Animal Sciences. Kerns was initially attracted to MU for his doctoral training because of the reputation of the animal sciences’ reproductive physiology program, but he then joined Bond LSC to continue his research during his USDA NIFA Postdoctoral Fellowship.

“MU is a world class institution. There are not many places that offer the resources we are fortunate to have here with the combination of animal science, veterinary medicine, and the resources of a research hospital system,” Kerns said. “And it’s not just equipment resources, but also intellect and the people that we [Bond LSC] have, it really provides an atmosphere that lets you dig into science a little bit deeper than you can anywhere else.”

This atmosphere at Bond LSC has aided Kerns in his current position as a newly-minted faculty member at ISU.

“It set me up for success. Especially in the middle of COVID right now, there’s not a lot of faculty positions available, so to get a faculty position when all those other positions were being halted, it speaks volumes to the training I received here,” Kerns said.

Kerns began teaching this fall semester, teaching Anatomy and Physiology labs twice a week.

Going back to his alma mater as a professor was not exactly the homecoming Kerns expected.

“It’s a very odd timeframe coming back during COVID when the buildings are not bustling with students and faculty.”

In the Xu lab, Kerns worked on bioinformatics and artificial intelligence with graduate students. They were able to incorporate machine and deep learning analysis with high throughput, single cell phenotyping, looking at multi-million cell data sets for bioimage analysis.

“There are multiple times that you step back from the microscope or from the computer after doing data analysis and you have so much awe and admiration for how all these intricate biological functions have to come together to support life,” Kerns said. “That is what fuels me.”

Kerns’ first publication at Mizzou was about how zinc, a vital micronutrient, helps regulate fertility in pigs, cattle, and humans.

“Research in the life sciences is extraordinarily rewarding because there is a time between initial discovery and publication that just you and your co-authors know this little piece of how life as we know it functions, previously unknown from the start of time,” Kerns said.

While he enjoys special moments like these in the lab, Kerns has been enjoying his time in the classroom with students during this isolating time of the pandemic as well.

“It’s my duty, being taxpayer funded in the training that I got, to make sure I teach the next generation,” Kerns said, “Let them have a taste of the cutting-edge technologies I learned at Mizzou and cutting-edge research findings that we found. The academia system is all about having people that are experts in a set area and passing it down to the next generation to expand on.”

Along with teaching, Kerns is also doing research at ISU. He is currently working on analyzing the fertility of boars and bulls to see what helps predict their fertility. Significant amounts of research and improvements focus on the female side of reproduction but not male, so by improving male fertility, Kerns will be able to help livestock producers and stakeholders improve their efficiency.

Kerns has big plans for his research in the future.

“Once we optimize male fertility, we can start taking superior genetics to third world countries that need a good protein source that can grow in their particular climate — we know protein is a source of complete amino acids that provides better cognitive function for people — and also provide a source of financial security for their families as well. It’s a win-win,” Kerns said.

Until then, Kerns plans to continue teaching and doing research. His science journey has taken him many places so far, and his is not stopping there.

“Science is always changing,” Kerns said. “When we say, ‘what does the science say?’ The science only says our current interpretation of it. In the grand scheme, we have so much more to learn. Every day we’re learning more about our world and not uncommonly disproving what we used to hold to as true because of new techniques now available to us.”

Four months in, Baker lab hits the ground running and won’t be stopping anytime soon

October 19, 2020 By Lauren Hines in Research Tags: cancer, cell sheets, copper

Post doctorate Harim Tavares from the Baker lab works in “the hood,” which is a space used to prevent researchers and other outside factors from contaminating cells.

By Lauren Hines | Bond LSC

Saliva is often something people take for granted.

It helps break down food, maintain teeth and keep the oral cavity feeling comfortable. But head and neck cancer patients lose those benefits when chemotherapy treatments damage their salivary glands.

Olga Baker set out to research tissue regeneration for these cancer patients by collaborating with the Michael Petris and Gary Weisman labs after setting up shop four months ago as a new principal investigator at Bond Life Sciences Center.

Together, the Petris and Baker labs are looking at the role of copper in salivary gland damage.

“Nobody has asked what happens to copper metabolism during and after head and neck radiation,” Baker said. “Is copper related to the fibrosis that is developing in those patients, so they don’t make saliva? We don’t know. So, we are answering different questions…. We don’t have any data yet, but what we have is immunofluorescence studies showing that those copper transporters are present in salivary glands from mice and humans.”

If the two labs can learn how copper connects to salivary gland tissue regeneration, Baker can get a step closer to helping patients.

The Baker and Petris labs just published a paper with help from the Proteomics Center and the MU Molecular Interactions Core in the journal of Dental Research. Post doctorate Harim Tavares from the Baker lab is the leading author.

The study used synthetic networks of crosslinked polymer chains that can take in large amounts of water called, smart hydrogels. The smart hydrogels were used in the same mouse model as the cell sheets and promoted tissue regeneration on mouse salivary glands. The paper explored how different materials like smart hydrogels can improve tissue regeneration.

Baker’s other focus takes on cancer and tissue regeneration from a different angle in her collaboration with the Weisman lab.

“Dr. Weisman’s group has studied the mechanisms of salivary gland dysfunction for over 30 years, so between these two groups the tools are in place to provide a translational approach to understand and treat salivary gland disorders,” said Jean Camden, a senior research associate in the Weisman lab.

The two labs just submitted a paper on mouse submandibular glands and cell sheets, which are plastic-like sheets where cells grow and detach once it reaches a certain temperature. Kihoon Nam from the Baker lab is the corresponding author. The study transplanted submandibular gland cell sheets into a wounded mouse to see if cells could be transferred.

“We believe that is a good proof of concept for future use in radiation studies,” Baker said.

The Baker lab uses cell sheets with the Weisman lab to study the role of the P2Y2 receptor in salivary gland regeneration. P2Y2 is a plasma membrane receptor that binds the molecules outside of cells and serves as signals to trigger an action.

The Weisman lab previously showed that P2Y2 receptor activation encourages salivary gland cells to migrate together and form a unit capable of secreting saliva.

“At this time, we don’t know what the role of P2Y2R is in the cell sheets,” Camden said. “That is an aim we proposed in a recent TRIUMPH proposal.”

The TRIUMPH initiative — The Translational Research Informing Useful and Meaningful Precision Health initiative — is a pilot grant funding opportunity through the Missouri School of Medicine.

As if two collaborations weren’t enough, Baker is also working on saliva substitutes. The lab just submitted a grant to fund the project.

“If we get the money, we will be able to make a far better saliva substitute as compared to the Biotine, or Aquoral, or Oasis,” Baker said. “Those are the three leading brands. So, hopefully, we can make something better here at MU and commercialize the product.”

#IAmScience Alana Rodney

October 16, 2020 By Lauren Hines in #IAmScience Tags: animal science, cancer, MARC/IMSD

By Lauren Hines | Bond LSC

Research assistant Alana Rodney walked into her high school science class a few years ago expecting to fill another credit. However, it was there that she found her love of genetics.

“I just remember doing the lab and I learned how to use a pipette,” Rodney said. “I was like, ‘Oh, my goodness. This is so cool.’”

Fast forward to now and Rodney just completed her undergraduate degree in May 2019. And she’s not stopping there as she now pursues a master’s in animal science, genetics and genomics to create better treatments for common diseases and cancers.

“I want to eventually study cancers in humans and disease treatments for different types of cancers and other diseases that affect people in general, but especially the Black community because that’s really important to me,” Rodney said.

Rodney plans on eventually applying what she learns from the genome of cats to humans, especially cancer research.

“Cancer definitely has had a big effect on my family,” Rodney said. “A lot of people in my family have breast cancer and other types of diseases. I do think some of that is due to the environment that my family was in. I know that has a direct effect on the genetics of a person. So, some of this hits close to home for me.”

Rodney entered the world of research as an undergrad through the Initiative for Maximizing Student Diversity (IMSD) program. It is now called the Maximizing Access to Research Careers (MARC) program.

“The IMSD/MARC program is also one of the main reasons that I am in science right now,” Rodney said.

IMSD/MARC helps develop the research and professional skills of students from underrepresented groups by paying students to work in labs and exposing them to research.

“The IMSD/MARC program gave me a real sense of community in science,” Rodney said. “I was with a bunch of other students who have similar debt and probably wouldn’t be in grad school if it wasn’t for that program. It really gave me the motivation and push I needed to keep going even when school got hard. Having a community to really say, ‘Okay, let’s study. Okay, let’s talk about it.’”

For the past year, Rodney has been in the Wes Warren lab at the Bond Life Sciences Center working on bioinformatics and experiments for her thesis project.

“She’s been a joy to work with, and she’s very hungry to learn,” said Warren, a primary investigator at Bond LSC. “That’s what I really value in anybody that I work with.”

Rodney recently submitted her first paper to the journal Scientific Reports where she was the first author. The paper explored the effectiveness of whole-exome sequencing, (WES) which is a cost-effective strategy that sequences coding regions in DNA.

WES is usually used on human diseases that express multiple observable characteristics called, phenotypes. This makes it hard to classify which disease it is. WES also helps to identify alleles in genes that cause certain diseases.

In this instance, WES was applied to the DNA of diseased cats and was compared to the DNA of healthy cats as a baseline. WES discovered new variants — differences from the norm — for certain kidney disease in cats.

“That puts it out into the literature so that veterinarians and scientists that are interested in investigating that particular disease now have a candidate they can pursue,” Warren said.

The new variants were labeled as potential causative alleles of the kidney disease in cats.

“That was a nice paper to show that whole-exome sequencing in cats is possible, and that is a viable way to get data on the disease from the cats versus whole-genome sequencing. So basically, the paper just showed the effectiveness of whole-exome sequencing.”

Other strategies like whole genome sequencing cost more and provide slower results, so demonstrating WES as an effective option for research can help further the field.

In addition to her experiments, Rodney loves introducing children to the world of science.

“I’m really passionate about outreach and working with the youth and supporting them,” Rodney said. “I like to do science outreach, so I’ll go to elementary schools and talk with kids in the neighborhood, and if they want to do a science experiment, I’ll do it with them.”

Maybe in one of those science classrooms, Rodney can inspire a new student to pursue a field they love, just like her.

Regulators Classify Gene-Edited Rice Varieties with Disease Resistance as Equivalent to Conventional Varieties

October 14, 2020 By Roger Meissen in Research Tags: CRISPR, Danforth Plant Science Center, rice

Crops resist bacterial leaf blight; ruling clears path to provide smallholder farmers with a safe, affordable option for preventing destructive disease

Columbia and St. Louis, MO, October 14, 2020 – The Healthy Crops team, with support from the Bill & Melinda Gates Foundation, have used gene editing tools to develop new varieties of disease-resistant rice that regulators in the United States and Colombia have determined are equivalent to what could be accomplished with conventional breeding. Bacterial blight can reduce rice yields by up to 70 percent, with the heaviest losses typically experienced by smallholder rice growers in low and middle-income countries. This has a profound impact on farmer productivity and economic mobility. The Healthy Crops team turned to gene editing to develop disease-resistant varieties as a way to provide farmers with a safe, affordable, effective solution.

“We first set about to understand the gene the bacteria use to make the plant vulnerable to its disease,” said Bing Yang, PhD, a researcher with the University of Missouri Bond Life Sciences Center professor, Division of Plant Sciences and member, Donald Danforth Plant Science Center in St. Louis. “We then used our CRISPR technology precisely to remove the element in the gene to avoid the pathway the pathogen takes that makes the plants susceptible to blight.”

The team used gene editing to create rice lines in elite varieties that are comparable to naturally occurring variants. These lines can resist infection by bacterial leaf blight, which leads to major losses for one of the world’s most important food crops. The rulings from the United States Department of Agriculture (USDA) and the corresponding authority in Colombia, the Instituto Colombiano Agropecuario (ICA), clear the way for field tests to select the best material for distribution to breeders in the U.S. and Colombia.

The improvements were accomplished via gene editing, which did not introduce any DNA into the plants and focused on “promoter regions” in three genes that are targeted by the causative agent of rice blight, the bacterium Xanthomonas oryzae pathovar oryzae. The research was described in an article in Nature Biotechnology in 2019.

Yang is just one member of the research consortium, headed by Humboldt Professor Wolf B. Frommer from Heinrich Heine University Düsseldorf (HHU), that has worked more than four years on this research. Six research institutions on three continents were involved including the University of Missouri, Donald Danforth Plant Science Center, University of Florida, the Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT) in Colombia, the Institut de Recherche pour le Développement (IRD) in France and the International Rice Research Institute (IRRI) in the Philippines.

In the wake of the ruling from U.S. and Colombian officials, the new blight-resistant varieties can now be used to introduce the resistance trait into many different types of rice via standard breeding strategies. Additional testing and breeding work is expected to take place in multiple locations that are favorable for growing tropical rice varieties.

“It’s exciting to use science and technology to do to help farmers protect and improve their rice production,” Yang said. “We hope to work closely with the local institutions in the next phase to introduce these into the varieties of rice small farmers use.”

The Healthy Crops Team has no commercial interest in its work. Its goal is to ensure disease- resistant rice varieties are accessible and affordable, especially for smallholder farmers who depend on rice production to support their families.

About The Donald Danforth Plant Science Center
Founded in 1998, the Donald Danforth Plant Science Center is a not-for-profit research institute with a mission to improve the human condition through plant science. Research, education and outreach aim to have impact at the nexus of food security and the environment, and position the St. Louis region as a world center for plant science. The Center’s work is funded through competitive grants from many sources, including the National Institutes of Health, U.S. Department of Energy, National Science Foundation, and the Bill & Melinda Gates Foundation. Follow us on Twitter at @DanforthCenter.

About Bond Life Sciences Center

Founded in 2004, the Christopher S. Bond Life Sciences Center was designed with teamwork in mind, fostering collaborations between scientists of diverse disciplines and backgrounds. From cancer and HIV to plant science and informatics, our researchers work together to move basic science forward and lay the groundwork for a better world. Learn more at bondlsc.missouri.edu.

Finding a Link between Xenoestrogens and Autism

October 12, 2020 By Becca Wolf in Research Tags: Autism Spectrum Disorder, biochemistry, mice

California mice | photo by Roger Meissen, Bond LSC

By Becca Wolf | Bond LSC

It’s hard to see a family member treated differently because of a behavior disorder, but those with relatives diagnosed with Autism Spectrum Disorder (ASD) know its impact. Since it affects how people act, communicate, and learn, people with ASD often get bullied or feel left out because of these behaviors.

Sarabjit Kaur, a former undergraduate researcher in the Cheryl Rosenfeld lab at the Bond Life Sciences Center, witnessed this stigma firsthand growing up with a brother who is autistic. Going to college, she knew she wanted to do something that made a difference in understanding ASD.

In Kaur’s final year at MU, she conducted a correlational study to see the effect of xenoestrogens on the microbiome-gut-brain axis and autistic behavior.

“The dramatic rise in ASD suggests that there’s an environmental component to this because genetics don’t change that fast,” Kaur said, “We know that steroid hormones play an important role in brain development. That’s why we suspect that endocrine disruptors such as the xenoestrogens, BPA [bisphenol A] and genistein, might be an important contributor to this disease.”

Xenoestrogens like BPA are often called “forever chemicals” because they don’t readily break down in the environment. Since we use millions of tons of manufacturing plastics, as food can linings and in things like receipts, our exposure can add up. While genistein is naturally found in plant products such as soybeans and coffee, both are common in our environment and affect the body in some way.

To start, Kaur tested the effects of the chemicals on California mice. She found that mice exposed to genistein were more likely to exhibit repetitive behaviors and socio-communicative disturbances. Mice with a low dose of BPA resulted in more frequent repetitive behaviors compared to those with a higher dose. These social communicative deficits were dose dependent autistic-like behaviors, showing that there is a possible correlation between these xenoestrogens and ASD.

In this study, Kaur also found that there are sex dependent effects of these xenoestrogens. BPA and genistein affected female and male mice differently. Exposed female mice resulted in different types of metabolites relative to control such as amino acids or glucose involved in carbohydrate metabolism, but in males the protein metabolism was affected by BPA and genistein relative to the control group.

These processes occur in the microbiome-gut-brain axis, which is the feedback loop where microbes communicate to the central nervous system through channels involving nervous, endocrine, and immune signaling mechanisms.

Exposure to xenoestrogens may be inducing epigenetic changes through altering gene/protein expression, without changing the DNA sequence itself.

“The results get super complicated because there has been dose dependent effects, both sex dependent effects and treatment dependent effects,” Kaur said.

Scientists use California mice as a model for behavior research because of their relationship similarities to humans. They are social creatures, both parents care for their young, and the male and female mate for life. This gives insight as to how BPA and genistein may impact humans.

“We wanted to do this in an animal model because we could help inform our epidemiology colleagues,” Kaur said, “So those that do work with humans, this could help them see what they are looking for as in terms of a diagnosis tool.”

In the future, doctors could look at the bacterial population or the metabolites in the microbiome-gut-brain axis to determine if a child is autistic.

“I just hope, this research will help my brother and people like him. That’s what research is all about, to help advance. Hopefully, we could give people a fresh, healthy start in the beginning of their lives,” Kaur said.

“It would mean a lot to many if in the future people could help their friends, family members, or their siblings that go through ASD,” Kaur said, “It would really help even if we could alleviate the symptoms or give people a fresh start.”

For more information, check out the December 2020 edition of Scientific Reports article, “Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.”

#IAmScience Norma Castro-Guerrero

October 9, 2020 By Becca Wolf in #IAmScience Tags: Legume, nutrition

By Becca Wolf | Bond LSC

If you like your work, you won’t ever work a day in your life.

That’s the case for Norma Castro-Guerrero, a research scientist in David Mendoza’s lab at Bond Life Sciences Center. Having a good attitude and making the most of everything is something she strives to do.

“I wake up every day and I am already thinking about what I need to do,” Castro-Guerrero said. “Time flies by during the day. I think that’s a way to know that you love what you do.”

She first witnessed this attitude in action from a principal investigator (PI) in her undergraduate studies at the Universidad Nacional Autónoma de México (UNAM) in her hometown of Mexico City, Mexico. This PI soon became an influential role model in Castro-Guerrero’s life.

“She was such a strong woman and full of enthusiasm for science,” Castro-Guerrero said, “She was so supportive, ‘You’re a woman and you will do great, getting the best grades and publishing papers.’ From there, I think it was very natural to me to keep studying and publishing during my Ph.D. and postdoctorate.”

Castro-Guerrero has implemented this enthusiasm in the Mendoza lab, where she oversees research projects and students. As a senior scientist, she trains the students on how to run a successful lab. She knows firsthand how important an encouraging environment can be for student growth.

“What you want to teach them is how important it is to have a healthy environment to achieve their goals. It’s not only teaching them the techniques or basics, it’s also that they feel comfortable and happy in the lab because they will be more efficient,” she said.

The Mendoza lab gives her the opportunity to express this enthusiasm. Castro-Guerrero enjoys the freedom she has to study her own ideas. Everyone is encouraged to make decisions and solve problems they feel are important.

Castro-Guerrero currently focuses on studying micronutrients in legumes like common bean and soybean, crops used in communities that suffer from nutrient deficiencies. She is looking at what mechanisms the legumes are using compared to other crops that make them accumulate more of these elements. Understanding the key factors will be useful to design better crops.

“Some people’s diet depends on these seeds, so improving them is a perfect vehicle to improve their health,” Castro-Guerrero said.

To further this study, Castro-Guerrero and her team have collaborated with people in South Africa and Mexico to improve the well-being of communities. Helping others motivates her, and this project is rewarding in more ways than one.

Aside from science, Castro-Guerrero’s other passion in life is traveling. And here at Bond LSC, she was able to combine these two passions.

In the past several years, Castro-Guerrero was able to travel to Asia and Africa to discuss research the Mendoza lab is working on at symposiums and other events.

“I really enjoy that people notice what we are doing in Missouri. They know that in the middle of United States we’re doing this great science, and they look for collaboration with us,” Castro-Guerrero said. “So, when you go there and they say start dropping names of people in this building [Bond LSC], we know we are in the right place. Being able to see the recognition not only the university but your own building is getting outside the country, I really enjoy that.”

Castro-Guerrero gets as much as she can out of her international science trips. “I know how people work in Mexico and in the United States. There are differences and it’s very enriching to see how other places work. Their dynamics, their strategies, you learn from them. I think it’s neat to be able to interact with other scientific communities,” Castro-Guerrero said.

“In my lab, the students observe you doing this, talking, writing, discussing, and they want to follow you like I did with my PI in the past,” Castro-Guerrero said, “You see them get excited that they’re working on at Bond LSC. And we are happy and proud of that.”

Science has allowed Castro-Guerrero to wake up every day excited about what it will bring. Whether it is supervising students in the lab, conducting research, or traveling around the world, she is ready for anything.

“I love it, I don’t want to do anything else,” Castro-Guerrero said, then pauses, “Except traveling. But traveling the world while doing science is even better.”

Plant vs. Pathogen

October 7, 2020 By Lauren Hines in Research Tags: plant immune system

Research scientist Jianbin Su studies the immune system in lettuce on the third floor of the Bond Life Science Center.

By Lauren Hines | Bond LSC

Scientist Jianbin Su’s research lately took him outside to look at patches of grass and cracks in sidewalks around Mizzou’s campus, searching for a subject in the wild. He found his subject in the form of wild lettuce.

That search can potentially help Su — a research scientist in the Walter Gassmann lab at Bond Life Sciences Center — better understand the immune system of lettuce and therefore protect it against diseases like Downy Mildew and Xanthomonas, which would increase lettuce crop yield.

Su’s paper under review about how the pathogen effector protein, AvrRps4, interacts with lettuce’s immune system will hopefully soon be accepted in the journal Molecular Plant-Microbe Interactions.

“Scientists in Florida are still focusing on lettuce resistance to Xanthomonas,” Su said. “If we can find a mechanism where lettuce recognizes our protein, this finding can be applied to make lettuce immune to Xanthomonas.”

Xanthomonas causes bacterial leaf spots and is a serious seed-borne disease that results in significant losses for the lettuce industry

To infect a plant successfully, the bacterium must inject 30 to 40 protein effectors, like AvrRps4, in the cell and interact with multiple plant cell functions at once to overcome the host. Effectors for a pathogen can bind to proteins that affect the biological activities of the plant, letting the disease invade the plant, suppress its immune system and allow Xanthomonas to survive.

However, when the plant cell’s receptors recognize the pathogen, it can trigger its immune response. To stop the pathogen from growing, the plant cell initiates a hypersensitive response by killing itself. If the plant can’t stop the pathogen, it will multiply and affect much larger areas of the leaf. This will ultimately destroy the plant tissue and cause the characteristic round, brown dead spots on the lettuce leaves.

“Plants can afford the hypersensitive response because their developmental program isn’t set in stone like in most animals,” said Walter Gassmann, interim director for Bond Life Sciences Center. “They can adjust their growth in real-time…so losing a leaf is not a big deal to a plant, not like us, losing a limb or something like that.”

Wild Lettuce Found on Campus — While studying lettuce immunity, research scientist Jianbin Su took photos of wild lettuce growing on campus. | photo contributed by Jianbin Su.

Once AvRrps4 enters the plant cell, it splits up into two parts: AvRrps4-C and AvRrps4-N. Some plants like flowers, tomatoes and melons only recognize the C part, but lettuce only recognizes the N part of the effector.

“The C part of AvrRps4 has been studied by many labs, and they’ve already found some mechanisms,” Su said. “The C part attacks a group of important proteins that are required for plant immunity. That’s the function of the C part, but the function of the N part is not clear. That’s what I’m focusing on in lettuce.”

Recognition is important because, without it, plant cells can’t respond to fight off the pathogen.

Su is studying lettuce not only because it hasn’t been studied as much, but so far, it’s the only plant that requires recognition of both parts to initiate immunity.

This means lettuce evolved to recognize and attack AvRrps4-C. In turn, the effector evolved by adding a second part to prevent recognition by plants.

This evolutionary choice, if you will, is odd. Instead of getting around the immune response by getting rid of the protein that is recognized, the protein added a second part to itself. This means AvRrps4-N, the original part, must possess a vital function for the pathogen worth keeping.

“That’s why we think this effector arose in nature,” Gassmann said. “It’s because the first part triggered a very strong immune response, something else got tacked on to it to weaken that immune response to give the pathogen a leg up.”

This evolutionary battle can be seen in Mizzou’s very own backyard. Su found five different types of wild lettuce. After testing if the types were able to recognize the N part of the effector, he found two of the five did.

Since some did and others did not, Su thinks the receptor for recognizing the effector has been lost in some wild lettuce types due to evolution and the absence of the pathogen in certain areas.

“We haven’t found the lettuce receptor but based on this information we can narrow it down,” Su said. “Right now, we have 36 candidates. We are already sure that among the 36, there’s 99.999% that there is one receptor that recognizes our protein.”

Su still has much work left to do but, for now, he resubmitted his paper Oct. 5.

“Once we identify the receptors that recognize our protein, our research will go into the next direction, and maybe have some application purpose for our research,” Su said.

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