Researchers are one step closer to understanding HIV
By Danielle Pycior | Bond LSC
Usually, the human immune system is good at recognizing infected cells and then killing them, but in the case of the human immunodeficiency virus (HIV), the virus has ways to hide. One of the ways is by using a viral protein called Vpu.
Vpu helps HIV survive by hiding the fact that it is infected from its host cells. For the past few years, researchers at the University of Missouri have helped uncover how this works.
“If you delete Vpu, those virus-infected cells are killed more efficiently,” said Marc Johnson, a Bond LSC scientist and professor in the Department of Molecular Microbiology and Immunology at the MU School of Medicine.
Understanding the Basics
Johnson and his lab study the connection between viruses and their hosts, trying to understand how viruses convince the host to allow them to keep replicating. In the case of HIV, Johnson and his colleagues discovered that Vpu only functions with the help of B TrCP, another protein.
“The virus doesn’t do anything by itself,” Johnson said. “It only has nine genes, while we have 30,000. It works by tricking its host genes to doing its bidding for it.”
Yul Eum Song, a graduate researcher in Johnson’s lab, explained that CRISPR technology allowed them to alter the genome to see how the proteins operate. CRISPR is a gene editing technique adapted from the DNA of bacteria that allows scientists to add, remove or edit specific locations in a genome.
“So, we use this to target and knock out genes to see if they’re necessary for the mechanism of HIV,” Song said.
They used CRISPR to remove the two types of B TrCP strands from the genome to see if Vpu would still hide HIV without its help.
“CRISPR has lots of applications, but the simplest, and the one I use is basically just molecular scissors that you can put into cells. It will make cuts in the genome wherever you want,” Johnson said.
By removing a certain gene, researchers can see how cells will react with and without certain proteins. In this case, Johnson and his team discovered that without either type of B TrCP strand expressed in the genome, Vpu couldn’t function, so it couldn’t avoid being killed by the immune system.
The magnitude of the HIV problem
“Thirty-five million people are infected with HIV. There are more people living with HIV today than ever in history, and the number keeps going up every year because once they’re infected, they’re infected for life,” Johnson said.
Johnson said that in terms of public health, HIV is a huge concern. Though treatments have gotten substantially better, they can have nasty side effects and don’t always work for everyone, sometimes resulting in death.
“By understanding the mechanisms of HIV, researchers can help combat the virus and create treatments,” Song said.
Both researchers pointed out how discoveries in the area of HIV can translate into other fields. The knowledge that virologists researching HIV find can help other scientists figure out what questions to ask and what functions to look for.
“We’ve learned about the cell and how our own cells work by studying the virus, but the virus is constantly utilizing and counteracting in ways that we’re still figuring out,” Johnson said.
Looking forward, Johnson and his lab are trying to find compounds that will block Vpu, and consequently allow the immune system to kill the HIV infected cells. Though the virus can never be completely removed from someone’s system, virologists search for treatments that can target and kill those cells that are expressing HIV.
“Part of the process is nailing down how VPU works, and a big part of what my lab is doing now is actually screening and testing compounds that do block VPU activity,” Johnson said. “That means if you have an infected virus, you treat them with this compound, and then they behave just like VPU was not there.”
By understanding how various proteins function in cells, researchers can get closer to understanding ways to combat viruses, and closer to understanding the micro-complexities that exist inside the human body.
This research was published in the Journal“Viruses” in Oct. 2018 and was funded by the National Institute of Allergy and Infectious Disease of the National Institutes of Health.
Male Amami spiny rats have the rare distinction of not having a Y chromosome. Scientists at MU’s Bond Life Sciences Center are trying to decipher how exactly their sex is determined during development. | photo by Asato Kuroiwa, Hokkaido University
By Roger Meissen | Bond LSC
Joint press release by University of Missouri and Hokkaido University
What causes rats without a Y chromosome to become male?
A look at the brains of an endangered spiny rat off the coast of Japan by University of Missouri (MU) Bond Life Sciences Center scientist Cheryl Rosenfeld could illuminate the subtle genetic influences that stimulate a mammal’s cells to develop as male versus female in the absence of a Y chromosome.
The root of the answer is in the chromosomes of this particular mammal. Males of the Amami spiny rat (Tokudaia osimensis) are not like most therian mammals — a name used to group animals that give live birth including placental mammals and marsupials. Unlike in most mammals, these males have no Y chromosome, which has been shed over eons of evolution. And they only have one X chromosome.
“I’d been interested in these rats for many years now, and it’s unclear how sexual differentiation of the gonads and brain occur in this species since both males and females have a single X chromosome,” said Cheryl Rosenfeld, lead author on the study and an MU researcher.
Since most mammals inherit chromosomes from both parents — an X from our mother and either an X or Y chromosome from our father — the only way to develop as male is to inherit a Y chromosome. That male chromosome contains a sex-determining region Y (SRY) gene that stimulates male sexual differentiation in many mammalian species, including humans. SRY triggers the fetus to become male by producing a protein that binds DNA, which leads to development of testes and subsequent production of testosterone. This steroid hormone then stimulates development of the rest of the male reproductive tract. This surge in testosterone from the testes also programs masculinization of the brain.
Naturally, this got Rosenfeld curious about how the absence of a Y chromosome and SRY might affect gene expression differences in male and female Amami spiny rats. In collaboration with Asato Kuroiwa from Hokkaido University Takamichi Jogahara of the Frontier Science Research Center in Japan, and Scott Givan, associate director of the MU Informatics Research Core Facility, her laboratory received brain samples from both males and females of this species.
They took those brains, isolated the RNA from them and sequenced the samples of the male and females to compare transcripts between the two sexes. Transcripts are the step between a gene and a protein, essentially a piece of RNA that encodes the information to make a particular protein. Subtle variations in the resulting RNA can change the final protein, giving rise to alternative forms that can exhibit increased or decreased potency. Investigators found major differences between males and females.
“Several different transcripts or isoforms encode the same gene, and while there might be, for example, 10 transcripts for a particular gene, some transcripts are more potent than others and have more effect in individual cells,” Rosenfeld said. “When we compared males to females, there were several hundred more transcripts upregulated in males than females. Our thought is that since both have the same sex chromosomes, the resulting differences could be originating from the fact that the males might have more of one of the more potent transcripts.”
Expression differences in such transcripts might also arise due to epigenetic changes, which are alterations that affect the turning on/off of certain DNA regions but without affecting the DNA itself. Potentially, in females, these more effective transcripts are not expressed because of such epigenetic changes.
When the team – including MU student Madison Ortega who is in the MU Maximizing Access to Research Careers/Initiative for Maximizing Student Diversity (MARC/IMSD) program — looked closer, they realized many of the transcripts expressed in males encode for various zinc finger protein genes. In males, these genes can be turned on by SRY and are thought to significantly influence sex development.
“What we think might be happening is the males might be turning on all these other zinc finger transcripts that may compensate for the absence of SRY, so they influence undifferentiated gonad to become a testes and help program the brain to be male. Without these zinc finger protein transcripts, female sexual differentiation of the gonad and brain might result,” Rosenfeld said. “It’s possibly it’s more of a potential gradient within these rodents, where you have to turn on all these other zinc finger protein transcripts in males to stimulate male sexual differentiation and compensate for the absence of SRY.”
With the potential extinction of Amami spiny rats on the horizon, furthering this research has a degree of urgency.
“By elucidating more of the mechanisms in this endangered species, I think it might help us save the species or facilitate them being bred in captivity,” Rosenfeld said.
She hopes this research will continue with her team fully sequencing the genome of the Amami spiny rats to look more closely at what’s going on and how that might lead to a better understanding of the nuances of how animals without a Y chromosome undergoes male sexual differentiation.
“If you move outside the mammals, there are all sorts of sex chromosomes and exceptions like the duckbill platypus who has five sets of X and Y, and they can’t find differences between males and females,” Rosenfeld said. “People are focused on sex chromosomes and the SRY gene that they might be forgetting other contributing factors. By understanding these anomalous species, it opens up the idea that the mechanisms regulating gonadal and brain sexual differentiation are quite complex and not fully understood.”
For scientists, studying a disease presents a puzzle looking for an answer, but there are real people behind the research that may one day cure the illnesses that turned their lives upside down. Chris Lorson and Monir Shababi work on one of these puzzles in Bond LSC.
Find out more about their work and the faces behind SMARD, a rare, often fatal, genetic motor neuron disease in the following story courtesy of the College of Veterinary Medicine.
Monir Shababi, an assistant research professor in veterinary pathobiology, and Christian Lorson, Bond LSC principal investigator, College of Veterinary Medicine professor and associate dean for research and graduate studies, have invested countless hours during the past five years to solving a cruel medical mystery. A family who has endured the agonizing ordeal of having two children born with the same disease has invested funding for the research being conducted at MU’s Bond Life Sciences Center.
Meet the Sims family: mother, Jill Sims, MD; daughter, Caroline; father, Eric, an associate professor of economics at Notre Dame; daughter, Molly; and daughter, Catherine, who turned 5 in August. Catherine is living with a rare genetic disorder called Spinal Muscular Atrophy with Respiratory Distress, or SMARD. The Sims had another child, Bobby, who was born in 2012 and died of SMARD after a month of life.
The disease is called spinal muscle atrophy with respiratory distress, or SMARD. SMARD is a progressive motor neuron disease that has no treatment or cure. At least, not yet.
Shababi, PhD, and Lorson, PhD, and the Sims family — mother Jill, father Eric, grandparents Grant and Patricia — have teamed up in an effort to change that.
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The disease is so rare that it is largely unknown, even to most medical professionals. When you are the parent of a child with SMARD, you are in a daily, nonstop, life-and-death struggle.
It is exhausting. It is frustrating. It is a battle that requires an endless reserve of endurance and willpower. And, it requires cutting-edge, scientific discoveries that are just coming to light at MU’s Bond Life Sciences Center.
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Catherine Sims lives on a ventilator and needs around-the-clock care. Yet, now age 5, her life is a victory.
“Our first daughter was born healthy, so we had no idea that we carried such a terrible disease,” Jill Sims says. “Then, our second child, Bobby, — who is named after my dad — was born very small, which was unusual given our family history, and he was very quiet as an infant. Those were the only things I noticed. He was three weeks old and we were driving back from Thanksgiving at my parents’ house. I fed him and put him in his car seat. I checked on him 30 minutes later and he had died. He had aspirated. The disease causes the diaphragm not to work, so he couldn’t breathe and eat at the same time.”
Despite requiring mechanical ventilation and around-the-clock care, Catherine attends school, enjoys family outings and participates in activities as much as possible.
Bobby Sims, born Oct. 31, 2012, died on Nov. 30, 2012. His death was attributed to unknown respiratory failure, and he was considered a victim of Sudden Infant Death Syndrome (SIDS). Catherine Sims was born in August 2013; her diagnosis came four months later.
“I went on to have Catherine next, and then we knew something was up,” Sims says. “Catherine was very similar to Bobby, very small and very quiet. That, of course, led us to figure out something was going on.
“In the period of time when Catherine was having problems and was hospitalized but undiagnosed, Catherine had a test done that put her group of symptoms into a specific category of neuromuscular diseases,” Sims says. “A good friend of mine Googled that category and the search produced a WordPress blog that Lisa Porter Werner had contributed to.”
The blog contained personal stories of families who had children with a disease named SMARD. The goal of the blog was to put SMARD on the radar, for families who didn’t have a diagnosis and needed to find answers as well as find support. Porter Werner had posted her own family’s story.
“My friend forwarded me Lisa’s particular story regarding her two children with SMARD, and the story almost identically matched my own,” Sims recalls.
Porter had read extensively and combed the internet for information and cases similar to those of her children. Porter eventually found a modicum of information about something called SMARD, which had been diagnosed in approximately 60 children.
“Lisa Porter’s blog contained the personal stories of families who had children with SMARD,” Sims recalls. “My friend forwarded me Lisa’s particular story regarding her two children with SMARD, and the story almost identically matched my own.
Living with SMARD, a progressive motor neuron disease, means Catherine needs 24/7 care from her family and home-health attendants.
“The Werner’s first daughter died at six weeks of age. It was called a SIDS case; she just died in her sleep,” Sims says. “They had Silas, their son who is living with SMARD, shortly thereafter and she put him in a sleep study when he was three weeks old. She said, ‘No, my daughter didn’t just die. There was a reason.’ It turned out that Silas was having major breathing problems during sleep.
“I was convinced after reading about Lisa’s family that my two children had SMARD as well, and I asked Catherine’s doctors to test her for it,” Sims says. “Catherine’s test came back positive four weeks later. A year or so later, I connected with Lisa through a Facebook group for families with children with SMARD. We began talking more, once my in-laws funded SMARD research at the Jackson Lab, and continued to talk once we found out about Dr. Shababi’s paper that came out in 2016.”
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In order to know what SMARD is, it is important to know what it is not. Despite the obvious similarities in name, spinal muscular atrophy (SMA) and spinal muscular atrophy with respiratory distress have sharp differences.
Both conditions affect the lower motor neuron cells of the spinal cord that control voluntary muscle activities like walking, talking, breathing and swallowing. Both are sometimes characterized as “like ALS in babies.”
SMA, which can range from type 1-4, is caused by mutations in or the absence of the SMN1 gene. SMA typically causes weakness in the core first and the baby or child may present as hypotonic, or having low muscle tone — sometimes called floppy baby syndrome. Babies or children with SMA may eventually develop respiratory compromise over time.
SMA is the leading genetic killer of infants; one in 40 people are carriers of SMA.
SMARD, in contrast, is extremely rare. The exact number of cases is unknown, but it has clearly occurred in more than the approximately 100 children worldwide who now carry that tragic diagnosis. SMARD is branded an “orphan” disease, a term commonly applied to any debilitating medical condition that affects fewer than 200,000 Americans. There is little information and few resources available regarding SMARD.
The Sims sisters: Catherine, a SMARD survivor, with older sister Molly and younger sister Caroline. Catherine is standing with the aid of a device.
SMARD is a genetic disease, caused by mutations or loss of the IGHMBP2 gene, Immunoglobulin MU-binding protein 2. The condition is inherited in a recessive pattern, meaning both parents must be carriers of the gene mutation and each parent must pass along a copy of the mutation in order for the child to be affected. In essence, every time two carriers have a baby, there is a one in four chance their child will be affected.
Onset of the disease usually occurs suddenly, in what seems to be an otherwise healthy baby, typically between 6 weeks and 6 months of age. Once the diaphragm is paralyzed, the infant must depend on their accessory muscles to breathe. These muscles also weaken as the disease progresses, until the child needs mechanical ventilation.
Many children die in the first year of life, often in their sleep or from a respiratory illness. Past the age of 1 year, almost all children living with SMARD require a tracheostomy, a ventilator and a wheelchair.
Simply put, SMA usually presents as a hypotonic or “floppy” baby who gradually develops respiratory distress. SMARD presents as a baby in respiratory distress who gradually becomes hypotonic.
SMA and SMARD share a similarity in that both are monogenic disorders, conditions caused by mutations or loss of a single gene. Shababi and Lorson have an established history of working with SMA. Now, their focus is SMARD.
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“In 2009 and 2010, a lab at the Ohio State University used a viral vector to introduce the SMN gene in SMA mice,” Shababi, the CVM researcher, says. “The viral vector does not contain the necessary genes required for the virus to cause infectious disease. You can replace viral genes with the specific gene you want and keep only the part of the virus that is required to enter the body, find its receptor and produce the desired protein from the gene it carries.
“They (researchers at Ohio State) put a human SMN gene into a viral vector — adeno-associated virus 9 (AAV9) — that has the potential to pass the blood brain barrier in humans. This virus has the capability to enter into the brain, the spinal cord, muscles and peripheral organs,” Shababi continues. “The AAV9 virus carrying the SMN gene was injected into SMA mice. They were able to rescue the affected mice. That was a huge step toward treating SMA. That vector is currently in Phase 2 clinical trials with AveXis/Novartis.
“With SMARD, there is also a single gene involved in the disease — the IGHMBP2 gene,” Shababi continues. “So, we took a human IGHMBP2 gene, in the form of cDNA, and placed it into the same AAV9 vector and injected it into the brain of SMARD pups that were 2 days of age. Our virus did the job and the SMARD mice were cured.”
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Catherine and older sister Molly sporting festival face paint.
“Dr. Shababi posted a paper, I believe in March 2016, that reported the results of her work on SMARD,” Sims says. “Lisa found the paper and contacted Dr. Shababi and had a wonderful reception. They had several very long conversations about what Monir was doing, what she had already been doing, and they immediately had a strong connection.
“Dr. Shababi was very personable over the phone, and was very passionate and very approachable about her work,” Sims relates. “Sometimes, it’s hard to get ahold of people, but Monir answers her own phone, and she was very clear with Lisa about what had already been done, which was pretty cool for us because we didn’t know — we didn’t realize how much work Dr. Shababi and Dr. Lorson had already done on SMARD. We were impressed by how much of a handle they already had on the disease. They were ahead of the game. That was great news for us on the family side; at the time, we were aware of only one other lab in the country — the Jackson Lab in Maine — doing work in this area. We couldn’t believe that, wow, there’s a second lab and they are already in gear, they already have a lot of good things going.
“Then, Lisa got me in the loop with Monir, and I talked to her a few times,” Sims continues. “They were having a funding issue, which is not surprising because of how rare the disease is. When we first learned about the work being done at the Jackson Lab, my in-laws agreed to fund SMARD research at Jackson. After learning what Dr. Shababi and Dr. Lorson were doing, I talked to my in-laws again and asked if they would be interested in funding Monir’s research. My father-in-law and I had a few conversations with Monir and Chris Lorson, and then my in-laws decided to do another fund, this time at Missouri, that started this past December.”
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“If you look back a number of years, there has been a gene therapy on the translational side that has had exceptionally powerful results in SMA,” says Lorson. “AveXis now has a Phase 2 clinical trial going for their gene therapy product, which has the potential to be very impactful. It has demonstrated efficacy in SMA, but also provides an important proof of principle for gene therapy as a whole. So, it was really exciting to know that there’s only one gene responsible for each of these horribly devastating diseases, SMA and SMARD. It allows you to consider following a similar path. Knowing that, Monir started developing a project that was gene therapy, gene replacement for SMARD.
“Whenever I talk about this, I give about 110 percent of the credit to Monir,” Lorson explains. “Monir has really been the driver of this entire project. Originally, I said, ‘Monir, I’d really like you to develop this gene therapy for SMARD, I think it’s a really exciting area of research. I’ll check back in about six months.’ When I did, we had the mice, we had the vector and she was doing the experiments. That’s exactly the kind of gumption that you hope to find. She did all of that. My role was to say, ‘Good job, Monir!’
“She was the first author on an important paper in Molecular Therapy published in 2016,” Lorson continues. “Based upon that, and the level of excitement, people found her. Through Facebook and Facebook friends, they started to communicate back and forth. Monir is driving it. Monir is doing it.
“AAV9 is in clinic for a number of other diseases, but every time you put a new gene in, you have to go through the Food and Drug Administration,” Lorson says. “That’s why the process isn’t as simple as it might appear to be. Every single time you change that vector — that gene delivery vehicle — you have to get it approved.”
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“My in-laws have been very generous, but you need a lot of capital to do this research,” Jill Sims says. “SMARD is so rare that progress will probably come only from academic research. You really need a lot of support and you need a lot of funding from various sources. Right now, our life continues the same. It’s great that everybody is doing this great research, but you need so much more for a cure. That’s what everybody wants; we want our kids to be normal.
“A day in the life of someone with SMARD is very difficult,” Sims says. “There’s a lot that has to be done to have a normal life, and there are a lot of obstacles to that, so you’re constantly trying to overcome those.
“This disease is devastating,” Sims continues. “It can take away every basic human function: the ability to sit, crawl, stand, walk, talk, swallow, feed oneself, clean oneself, use writing utensils and so on. The disease also makes the person more likely to have respiratory problems since they can’t breathe or even cough on their own. It is hard as a parent. Every day we live with the potential fatality of this disease. If their trach tubes come out, they cannot breathe. These trachs sit in their windpipes, held in by ties, like a tight necklace. It is not secure.
“You may go months without anything happening then, all of a sudden, it’s coming out. When that happens, she may only have 60 or so seconds to live,” Sims says. ”You have to have someone always watching them, either a specially trained nurse or a parent, who is a trained caregiver.
“That’s the hard part that we always live with,” says Sims. “Yes, she looks good, and she goes to school, and she’s in activities, to some degree. We adapt everything so she can do as much as possible. But, she is living with a fatal disease that is non-treatable. We basically just manage her symptoms. We know very well that we could lose a second child. That’s what is hardest on us. Even though there are these great advances, she is alive because of amazing machines. Every day presents the chance that she could die.
“When we take Catherine places, there are always at least 10 machines that go with her,” Sims says. “Everything just takes longer. We have a special van with a lift, because she’s in a wheelchair. You are in the thick of trying to make what is not normal to be normal.
“You can’t just pick up your child and go, you can’t feed them a different way, or put a different outfit on them,” Sims continues. “Those are the silly things I took for granted having had a healthy child before. I just did her hair, brushed her teeth, and put her in whatever, and fed her whatever I wanted. Catherine cannot do that. It’s the small things that you take for granted, and there are so many ‘small’ things. We are fortunate to have excellent in-home nursing care, but this also means that my husband and I have had to sacrifice a lot of our privacy. And, I’ve had to give up a lot of my mothering, because I have someone else that always needs to know what I’m doing. That’s hard.
“So, we want a cure,” Sims states. “We are all in. We are always fighting the disease. Our goal would be to have a cure as fast as possible, because the older the kids get, the less chance you have of curing them. This is a neurologic disease; it is hard to get those nerves back. We realize that our kids may be too old. Catherine will be 5; Lisa’s Silas is 8 or 9. They’re kind of old. The ideal time would be right at birth or shortly thereafter. So, that’s what we want. We want the big places — the big funding sources — to realize how important this is, even though it affects only a small number of people.”
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“Our gene therapy vector is a very powerful tool,” Lorson says. “It is early days, in terms of trying to push it to the clinic, but we’re trying to do all the important pre-clinical questions.
“There are a number of questions you have to ask,” Lorson continues. “When do you deliver that kind of vector? Does it work only if you do it right at birth, before disease develops? Can you correct the disease, in other words, once the research animals have the disease, can you bring them back to more of a normal state? Or, once that happens, is it just too late for something like gene therapy? We want to deliver what they want to see, in terms of working hard and getting results out. That is what we are trying to do.
“I want to say, ‘Thank you,’ in the biggest way possible to the Sims family,” Lorson says. “Their generosity is really amazing. We consider this an exceptional honor. We want to be the best stewards they could possibly find, of their trust and of their funds. People go out and raise these funds — in some cases, through car washes and bake sales — so you have to put a particularly high value on those dollars. My fondest hope is that we do that every day.”
If you would like to help in the battle against diseases that could someday be relieved through gene therapy, please visit this page.
It takes a lot to move a discovery from lab bench to an application that can provide therapeutic benefits to those suffering from disease.
Bond LSC’s Chris Lorson is making moves to bridge that gap with the start of Shift Pharmaceuticals. With its formation in March 2017, Lorson adds co-founder and Chief Science Officer of the company to his list of titles that include Bond LSC investigator, professor of veterinary pathobiology and associate dean for research and graduate studies.
Shift Pharmaceuticals builds off of years of progress the Lorson Lab has made in understanding spinal muscular atrophy (SMA), which is the leading genetic cause of infant deaths. The disease causes neurons to die, leading to muscle failure, including those that affect walking, arm movement, and respiratory function. While SMA is technically a rare disease, it is remarkably common, affecting nearly 1/10,000 births.
“It’s a devastating disease for patients and families; while the primary defect in is nerves, this leads to problems in muscles, bones, and other vital systems,” Lorson said. “Historically, the majority of kids who develop SMA do not survive beyond 3-5 years.”
Lorson knew his research had potential for drug development, and MU’s Office of Technology Management & Industry Relations (OTMIR) pursued patent protection for the technology. This process helps safeguard the innovations resulting from the research and allows MU to better attract commercial interest to develop and market medical treatments originating from the technology. But it took a partnership with co-founder Steve O’Connor to get the ball rolling. O’Connor is MU’s Entrepreneur in Residence and has significant experience in starting drug development businesses and now serves as CEO of Shift.
“I never knew how to start a company,” Lorson said. “I would argue most academics don’t – this isn’t part of our traditional training. I sat around not knowing what to do, realizing I had this thing that could do a lot, but the practical steps of setting up a biotech start-up were beyond me.”
“Steve thought this technology sounded really cool, so in late March he submitted paperwork and by the end of March we were a company. Shift’s first grant was submitted 3 days later.”
The goal of Shift Pharmaceuticals is to move their lead compound into the clinic for SMA.
“When you look at the disease, it’s not just one cell type and not just one clinical type of patient,” Lorson said. “It really is a disease that is complex and the idea is to bring more options to the fight.”
With the start of any new business, money is always a necessity. Funding from the advocacy group CURE SMA provided the initial funding for the discovery of this compound, while several other foundations including FightSMA, the Gwendolyn Strong Foundation, and Muscular Dystrophy Association have further contributed to the pre-clinical development. MU’s OTMIR negotiated an option agreement with Shift, giving them the exclusive rights to the technology, which helped them obtain a recent $2.73 million grant from the Department of Defense Congressionally Directed Medical Research Program (CDMRP). This will move the company toward the first phase of investigating a new drug.
The root of SMA
Lorson has spent most of his scientific career chasing the underlying causes of SMA.
That search focused in on a few key genes in those suffering from the disease. Two genes — named survival motor neuron-1 and -2 (SMN1 and SMN2, respectively) — are central to SMA development. In patients, SMN1 is mutated and doesn’t process enough of a key protein (SMN) that helps neurons function. While SMN2 acts as a backup gene for this function, a miniscule change in the SMN2 gene causes it to make less SMN protein than required by the body.
In 2016, the Lorson Lab at Bond LSC produced a compound that increases the lifespan of SMA mice . They targeted the back-up gene, SMN2, to produce more functional protein and discovered an increase of protein causing a significant lifespan extension in treated mice. This discovery showed promise for creating a cure for those with SMA.
Shift Pharmaceuticals will be working on developing a drug that builds off Lorson’s work and targets all forms of SMA.
Shift’s first two employees, Mizzou alumnus Paul Morcos and UMKC alumnae Diane Beatty, will help move toward that goal. With Morcos in research and development and Beatty negotiating regulatory affairs, the company hopes to move the drug toward FDA approval.
Thanks to the recent Department of Defense grant, the next step looks to testing in larger animals and at things Lorson did not consider before.
“The experiments we will be doing are not academic in nature, rather, they are focused on the singular goal of preparing our lead compound for an FDA submission. From a traditional academic lab perspective, these might sound rather boring,” Lorson said. “All of these things are not things you do in an academic setting, but that is exactly the point. This is drug development, not the quest for another paper.”
Within the Business Incubator, MU will provide space for the company as well for their research. This sort of partnership is just another part that may one day help translate vital basic research into future treatment.
“Almost everybody has the possibility of doing something that is translational, it is just envisioning it in a different way,” Lorson said.
Cheryl Rosenfeld recently worked with the FDA to study genetic effects of BPA. Her results were published in Epigenetics in July 2018. photo by Roger Meissen | Bond LSC
By Roger Meissen | Bond LSC
After a decade of work, Cheryl Rosenfeld is no stranger to bisphenol A (BPA), and her most recent study challenges the dangers posed by developmental exposure the chemical.
Her results continue to raise concerns about how BPA can potentially turn on or off genes in animals and subsequent effects on that early exposure can have on the development and brains of rats. Their research was published in the journal Epigenetics in July.
Rosenfeld and the University of Missouri joined experts from University of Cincinnati and FDA researchers as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity, or CLARITY-BPA Consortium project. This collaboration is one of several across the United States meant to judge the chemical’s effect using standardized protocols established by the FDA to determine whether BPA exposure, especially during perinatal life, leads harmful effects.
“This is the first study published since a February 2018 BPA statement that challenges the FDA assertion that there is no concern for BPA,” Rosenfeld said. “We’ve shown using the FDA models and studies done right there at their facility that, indeed, early life exposure to BPA can result in gene expression and epigenetic changes that persist into adulthood.”
The study looked at gene expression changes in two brain regions — the hippocampus and the hypothalamus. The hippocampus is associated with long-term learning and memory and the hypothalamus plays a large role in hormone production that influence both the endocrine and nervous systems and affects diverse behaviors, including socialization, sexual behaviors, and appetite control.
Partners at the FDA/National Center for Toxicological Research fed Sprague-Dawley groups of rats — a standardized animal model in this research — diets of BPA, the synthetic estrogen present in birth control pills, ethinyl estradiol, or a chemical-free diet during a developmental period.
The brains from these animals were sent to Rosenfeld’s laboratory, who took biopsies from specific regions of the brain. They used these samples to evaluate whether a group of 10 genes, shown to be affected by BPA exposure in other studies, was affected by this exposure. They also examined the DNA methylation patterns for the promoters of three of these genes to determine whether prior BPA exposure led to persistent epigenetic changes. Epigenetic modifications do not affect the DNA sequence itself but gene and/or eventual protein expression.
Investigators determined that for several of the genes examined BPA exposure altered the expression pattern relative to animals not exposed to either chemical. Sex differences in gene expression in these two brain regions exists in normal animals, and such differences might thus contribute to masculinization or feminization of the brain manifesting as differences in various behavioral patterns, such as male or female sexual behavior. However, previous exposure to BPA abolished many of these gene expression differences between males and females, suggesting that it could disrupt male- and female-typical behaviors. For a gene, brain derived neural factor (BDNF), involved in learning and memory, BPA exposure led to increased methylation of its promoter, which could affect the expression of this key gene. Hippocampal expression of several genes was associated with prior performance in a test designed to measure learning and memory.
“It has become increasingly apparent that BPA can act as a weak estrogen, but what we’re seeing in these results is that it can elicit other effects in addition to those mirroring estrogen and likely independent of estrogen receptor pathways,” Rosenfeld said.
Initiatives like this and other CLARITY-BPA studies aim to answer questions that may later inform government regulators on how to limit or balance the health effects of manufactured chemicals that end up in the environment and may affect human and animal growth in previously unknown ways. With more than 15 billion pounds of BPA were estimated to be produced in 2013, its ubiquitous use in making plastics, lining cans and other manufacturing is of concern. Rosenfeld hopes a closer look at its epigenetic effects may lead to better regulation of the chemical.
“When people are thinking about the effects of BPA, they need to be thinking about it on a molecular scale,” she said. “These results might be subtle, but they can lead to dramatic consequences with long-standing, irreversible changes. Once BPA exposure resculpts an animal’s brain through DNA methylation and other epigenetic changes, it may be permanent.”
MARC/IMSD Director Brian Booton poses with the 2018 MARC/IMSD fellows. photo by Roger Meissen | Bond LSC
By Allison Scott | Bond LSC
Research at the undergraduate level offers more than meets the eye. With students from every year of their undergraduate careers working in Bond LSC, it’s a great opportunity to acquire skills and experience.
Linda Blockus, head of the Undergraduate Research office in 150 Bond LSC, advises students to get started early and be proactive.
“I encourage students who are interested in research to talk to people and network,” Blockus said. “Talk to your professors, advisors and other students to find out what is available. Then, pursue those opportunities.”
It isn’t all as intimidating as it might appear. Students have a number of resources available to find out more about research on campus.
“There’s no one way to get involved,” Blockus said. “Students can go directly through our website, undergradresearch.missouri.edu, come to our office or go to their professors.”
That’s exactly what students involved in the Freshman Research in Plant Sciences (FRIPS) program have done. Sarah Unruh, a Ph.D. student who serves as a Graduate Student Coordinator for the program, boasts of the program’s ability to guide research-minded students along their path at Bond LSC.
“They do 10 hours of research in lab,” Unruh said. “We try to give them skills that are helpful moving forward, so things like finding papers and keeping up with a lab notebook.”
Each of the students selected for the program works in a lab they find the most interesting, but the program assists with those relationships to help students adjust to the process.
“Students lead the way in which lab they go to,” Unruh said. “They interview with different faculty, but we facilitate the match-making.”
Those interactions and networking opportunities open doors down the line.
“I think what they get the most out of FRIPS is that they’re actually doing science, so they get an idea of what it looks like,” Unruh said. “They’re making connections on a different level than just the classroom with teaching assistants and professors.”
Jenna Bohler — one of the students involved in FRIPS this year — has benefited from its connection-facilitating.
“Paula McSteen, Norman Best and Jenn Brown have taught me so much this year in particular,” Bohler said. “They’ve been great resources whenever I’ve had questions.”
Bohler is about to finish her FRIPS experience and can attest to the program’s influence on her first year at Mizzou.
“I knew coming into college I wanted to be involved in research, and FRIPS allowed me to get involved really early so I have four years instead of two or three,” Bohler said.
And it’s not only helpful in the lab.
“What I’ve learned from FRIPS has helped with my classes,” Bohler said. “I learn things before I’m taught them in class, which makes them easier to understand.”
Some FRIPS students have even extended their research opportunities beyond their freshman year.
“Students have used their time wisely in the lab and then gone on to do summer research programs,” Unruh said.
For those who aren’t freshman but find themselves interested in research, there are a number of programs available.
The Society of Undergraduate Researchers in Life Sciences (SURLS) is a group of undergraduate researchers who meet twice a month to explore the options they have within their field. It helps participants to network, meet people with similar interests and better understand a number of components of research.
Alec Wilken, a junior bioscience major who works in the Holliday lab in the medical school, served as the vice president and will be the president for his senior year. He’s been part of SURLS since he was a freshman and has seen first-hand how it’s shaped his path in the field of research.
“SURLS helped me find what I was interested in,” Wilken said. “We have professors come in, and we visit labs, which helps undergraduates grasp how interesting research on campus really is.”
SURLS provides students with the opportunity to grow throughout their undergraduate careers.
“I stayed in SURLS after joining my lab because it became a vehicle that helped me be better in my lab,” Wilken said.
The organization’s impact has allowed Wilken to uncover the path he wants his career to take, as he now plans to earn a Ph.D.
“I found a home in research, and SURLS helped me do that,” Wilken said.
For those with plans to pursue a Ph.D. in their future, MU’s Maximizing Access to Research Careers/Initiative for Maximizing Student Diversity (MARC/IMSD) program is the perfect fit.
The grant is funded by the National Institutes of Health (NIH), but at Mizzou there’s the addition of Express to the program’s title. It stands for Exposure to Research for Science Students, which emphasizes the scientific aspect of the program.
Brian Booton, is the undergraduate director for MARC/IMSD-Express at Mizzou, acknowledges the prestige that goes along with being an MARC/IMSD scholar.
“It’s a highly selective grant,” Booton said. “There are only 49 programs in the country.”
With stiff competition for the program at universities across the nation, it’s important to focus on the students’ experiences.
“The ways in which IMSD-Express helps students is more than just research,” Booton said. “We try to expose students to the different pathways where further education can take them.”
Part of that is through the way the weekly meetings breakdown.
“I break programing down into three areas: personal, academic and professional development,” Booton said.
Doing so helps guide students in the right direction because it is set up to further their education by developing skills for success.
But it’s not all lectures and typical meetings. MARC/IMSD-Express offers a peer mentorship program for underclassmen apprentices to be paired with upperclassmen fellows.
“Even if you have a professor you really admire, there’s some distance there,” Booton said. “Someone that’s only two years older than you is more relatable; it’s spending time with your future self.”
The various research opportunities at Mizzou make it possible for students to supplement their classroom learning in a way unlike any other.
“It’s part of your education,” Blockus said. “Taking advantage of research is a great way to set yourself up for the future.”
For more information and to apply for these opportunities, visit:
Scientists are seeing changes in vocal patterns in the grandoffspring of California mice exposed to endocrine disrupting chemicals like BPA. Photo by Roger Meissen | Bond LSC
Endocrine disruptors alter baby mice calls generations later
By Roger Meissen | Bond LSC
The sounds can seem like a mix between a bird tweet and a high-pitched scream to us, but these vocalizations that baby California mice make are essential to how they communicate with their parents and siblings.
Exposure of grandparent mice to bisphenol A (BPA) and related endocrine disrupting chemicals (EDCs) may alter that communication in their grandoffspring, potentially affecting the communication between pups and their parents and the resulting parental care provided to them.
According to a new study, MU Bond Life Science Center’s Cheryl Rosenfeld and an interdisciplinary team of researchers from the US and Germany looked at how this communication alters from normal patterns across multiple generations of California mice.
“We specifically wanted to see if grandparents were exposed, would that affect the communication of the grandoffspring?” Rosenfeld said. “What we saw was that in some cases, some aspects of their vocalizations became even more pronounced. It might be a response to multigenerational exposure to EDCs or they might be calling more because they aren’t receiving sufficient parental care in an effort to say, ‘hey, you’re neglecting me; please pay attention and provide warmth and nutritional support to me.’”
Studies from Rosenfeld previously found that BPA caused lax parenting and neglect in first-generation mice when their parents were developmentally exposed to the chemical. This chemical acts as an endocrine disruptor and mimics the effect of hormones like estrogen in animals, altering their development. BPA is prevalent in the environment because it’s heavily used in manufacturing and leaches out of our plastics, linings of food cans and dozens of other sources.
The study showed female babies tended to make shorter calls out to parents early on after being born, but as they aged they called out more, and male babies made longer calls in early postnatal periods and spoke more as they aged. These patterns were different from controls not exposed to the chemicals.
“Exposure of the their grandparents to EDC’s is altering these grandoffspring behaviors and that could have important ramifications to human babies and how EDCs might affect their initial form of communication, crying,” Rosenfeld said. “This follow up work is clearly important because children with autism have communication deficits, as evidenced even in their early crying patterns, and altered social skills. We’re always trying to find animal models like this that might explain whether exposure to environmental chemicals is increasing the incidence of autism or autistic-like signs in animal models.”
California mice are an especially useful model for studying behavior changes, because these mice are monogamous and both mom and dad are essential in rearing their pups, similar to most human societies. This allows scientists to potentially extrapolate their behavior changes to humans.
In this study, both female and male grandparents were fed one of three diets — A BPA diet that contained an environmentally relevant concentration of this chemical, an ethinyl estradiol diet or diet free of any EDCs. Ethinyl estradiol is another disruptor found in birth control that mimics the effect of estrogen in the body. All offspring were fed the chemical-free food after being weaned off the parents. They had babies, and these grandchildren were the generation scientists looked at to study their communication.
The grandchildren were recorded with special microphones that could pick up the calls of the babies in isolation booths. These sounds range from communications humans can’t even hear as they are high in the ultrasonic range- greater than 20,000 hertz- to communications that begin in the range of human hearing and then project into ultrasonic range. When researchers lowered the frequency of these high-pitched calls to a range we can hear they sound like a mix between owl screeches and bird tweets (how the vocalizations appear and sound are included below for the reader to decide for themselves) . They then compared them to normal mice, looking at the length of each call and the pattern of the calls, what they refer to as “syllables.” Each syllable is akin to an individual sentence or phrase in humans.
Audible call from a control starts out in the audible range and extends into the ultrasonic range. Lowering the audio by 10 hertz brings into within human range of hearing.BPA audible call sounds haunting and starts out in the audible range and extends into ultrasonic. Lowering by 10 hertz brings into within human range of hearing.Ultrasonic vocalization from a control is solely within the USV range and sound like bird tweets.The three tick marks are the vocalizations. Lowering the audio by 10 hertz brings into within human range of hearing.BPA ultrasonic call sounds sounds like a bird tweet. Lowering by 10 hertz brings into within human range of hearing.
These calls from BPA exposed mice were compared to the ethinyl estradiol and the mice not exposed to any chemicals.
“We’re seeing clear traits emerge in this F2 generation with the vocalizations and I think it lends credence to the idea that these things could tamper with vocalization patterns, which are incredibly important in how pups communicate with each other and their parents, whether it’s because they are trying to get more attention from exposed parents or what we call multigenerational effects in that the exposure of their grandparents directly affected their later grandoffspring traits.”
The study, “Multigenerational effects of Bisphenol-A or Ethinyl Estradiol Exposure on F2 California Mice (Peromyscus californicus) pup vocalizations,” was funded by the National Institute of Environmental Health Sciences Grant (5R21ES023150) and was published in the journal PLOS One June 18, 2018.
Bond LSC Facility Manager Dana Weir observes a family of rats in one of the vivariums. Photo by Raye Allen
By Madelyne Maag | Bond LSC
You’ve heard of aquariums and terrariums, but probably not of a vivarium before. These enclosed structures take on a whole new meaning when science is brought into the picture.
And little do people know when they walk across the main floor of Bond LSC, they are walking above a city-like work space where the occupants work to improve our lives.
Vivariums functions as cubicles, condominiums and daycare centers for the rodents that live within them. The 10,000 square-foot lab at Bond LSC uses these transgenic rodents to study muscular dystrophy, diabetes, fertility, and oncology research, among other health research areas.
“These rodents are the living, working team that help us learn more about our health.” said Dana Weir, the facility manager from the Office of Animal Resources. “We want to make sure they are well taken care of so Raye Allen’s team works year-round to make sure they are monitored, well-fed, and comfortable in the vivariums.”
Raye Allen, the lab supervisor for Bond LSC’s vivarium, said cleanliness and care are the top priorities in addition to research. Cleaning, transporting, feeding the rodents all require a carefully detailed process.
The 1,700 clear polycarbonate containers are arranged in rows with single, coupled or a small family of rodents within them. Each shoebox-sized rodent condo, is provided with dry cushioned bedding, large quantities of food and water, as well as their own little hiding space. Clean, filtered air is also pumped through the back of their homes.
“These rodents live a cleaner life than you or I could ever imagine.” Weir said.
Each person who enters the lab must wear closed toe-shoes, two sets of nitrile gloves, a white floor-length, long-sleeved button up lab coat, a face mask and hairnet.
“Raye Allen’s team is mindful of everything they touch when handling the rodents or their homes in the lab. We spray everything with bleach to prevent any outside bacteria from contaminating the lab and only handle our rodents under the biosafety hoods present in each room.”
Several university, state and federal regulations ensure the safety and security of Bond LSC’s transgenic rodents. The National Research Council, USDA’s Animal Welfare Act, and University of Missouri’s Institutional Animal Care and Use Committee work together to monitor animal welfare and set standards for lab research on animals.
Weir carefully holds one of the rodents underneath a fume hood. Photo by Raye Allen
The Institutional Animal Care and Use Committee (IACUC) inspects Bond LSC’s vivarium every six months, in order to make sure that containment, handling and safety protocols followed by lab researchers are up-to-date. The IACUC also reviews the purpose of animals being used for each particular research project. A board of faculty members, veterinarians and two non-science community members review justification from lab researchers.
The safety and security of these rodents are the top priority of the researchers working in the labs, but there is also an emotional bond that is formed between them as well.
“Rodents are intelligent and emotional animals, so they learn who their caretakers are very quickly.” said Allen. “They recognize us by the smells we put off and get pretty excited when one of our researchers enters the room to interact with them.”
The researchers like Allen who work with these rodents on a daily basis, care deeply about the rodents as well as the work these furry critters do.
“The bond formed between the animals and their caretakers is equally as important as the research they help us do,” said Weir. “This goes for all of the animal research conducted in Bond as well as other research that is conducted across the Mizzou campus.”
Graduate student Yuleum Song prepares cells for viral infection in the BL-2 hood. | Image by Jennifer Lu, Bond LSC
By Madelyne Maag | Bond LSC
Viruses can be nasty things and scientists have to take precautions.
You might think of researchers in floor-length lab coats, safety goggles, and plastic gloves or even the more extreme look of bulky, yellow hazmat suits similar to what Jim Hopper wear in Stranger Things. But, depending on the type of viruses being handled, these stereotypes aren’t quite the truth.
For labs like that of Marc Johnson in Bond LSC, safety comes from the incomplete nature of the HIV viruses they study. The viruses in Johnson’s lab are defective, meaning they cannot reproduce themselves. It doesn’t mean the virus is completely safe to handle. If it were to come into contact with another living being it would only infect the cells exposed to the virus and could not expand further. With defective strains of HIV, the virus can be grown at biosafety level two.
This level two is one of four levels of biosafety that are used to define how a lab might be physically set up and how its researchers are equipped in order to contain a virus. The levels act as more of a scale than a concrete definition of the lab since the type of virus being handled by a lab can vary.
Johnson, a professor of Molecular Microbiology and Immunology, says that his lab teeters between BSL-2 and BSL-3 depending on what type of virus they are working with.
“Our lab is classified as a BSL-2 (Biosafety Level 2) because we work with pathogens that have a low chance of spreading and a low chance of doing significant damage if they do spread,” said Dr. Johnson. “This simply means that our lab is shut off from anyone outside the lab who might try to come in outside of business hours. We also equip our staff with safety goggles, and gloves while they work with a virus under a Laminar Flow Hood to keep the air sterile.”
The major difference between levels like BSL-2 and BSL-3 often comes down to the type of virus being handled, whether it be something like HIV or a more lethal infection like SARS. The Laboratory for Infectious Disease Research is one of the only facilities on the MU campus, that can be classified as a level three. Because the lab handles airborne viruses, they take extra precautions to regulate air and waste coming out of the facility.
The highest level of biosafety can be identified as BSL4, which typically handles deadly viruses such as Ebola that could cause significant harm if it spread. This is where the terrifying and bulky hazmat suits come into play. The virus being handled in a BSL-4 lab comes with a high risk of researchers being infected if the proper steps are not taken to properly handle or contain the virus.
There are no BSL-4 laboratories in Columbia. In fact, one of the nearest labs won’t be opening its doors until 2022 in Manhattan, Kansas. These levels of safety are simply put in place to protect those who wish to study a virus and further medical research for the rest of the world.
The different levels of Biosafety might seem frightening to some, but there is nothing really to fear. These precautions are put in places just as signs that remind us to wash our hands after using the restroom. They are ways to prevent the contamination and spread of viruses and disease. MU Researchers don’t just have these precautions in place to protect everyone around them. They also have these precautions in place so that viruses like HIV can be better understood and treated by medical professionals around the world.
Shannon King, a Ph.D. candidate in Biochemistry from the Peck Lab in Bond LSC, gives instructions as faculty and students prepare to harvest root samples for later experiments. | photo by MJ Rogers, Roots in Drought Project
By Madelyne Maag | Bond LSC
If you’ve ever sat down on a beach, then there is a good chance that you’ve stretched your fingers into the sand, like a plant spreading its roots underground. By sinking deeper into the sand, your fingers are bound to encounter cool, damp sand, where water is more abundant and available to nourish plant life above it.
“One of the largest factors that affects yield in terms of environmental stresses is water limitation,” said Scott Peck, a plant biochemist at the Bond Life Sciences Center. “With the increasing global population and around 70% of water going to agricultural production, there simply won’t be enough water to sustain the global population that needs it. Therefore, we need to figure out a way to maintain crops with less water production.”
Peck is one of several faculty members working on this project that aims to be a first step in finding a solution for farmers when it comes to drought.
So what makes nodal roots so special? Bob Sharp, the project’s primary investigator, plant physiologist in the Division of Plant Sciences and Director of the IPG, explains that corn needs a significant amount of water to maintain growth. Nodal or crown roots, which can be seen growing out from the cornstalk and into the ground around it, provide the framework of the mature plant’s root system that collects most of the water it needs to thrive. The nodal roots grow to more than six feet into the ground to obtain water.
“Roots are a relatively unexplored part of the plant because they’re underground and difficult to study,” Sharp said. “Roots are also critical in the field because they are the part of the plant that directly experiences the drying soil environment, and can influence how the rest of the plant responds to drought.”
Joined by researchers from MU’s Division of Plant Sciences, Department of Biochemistry, Division of Biological Sciences, Department of Health Management and Informatics, School of Journalism and Bond LSC, Sharp is hopeful that they will be able to understand how the roots are able to continue to grow and survive under drought conditions.
As climate change shifts global weather patterns, droughts have hit various parts of the world more severely. Take 2012 in Missouri for example. By mid-July, all 114 counties had declared a state of emergency due to severe drought and suffered millions of dollars in crop loss.
Despite this being one of the most memorable droughts in recent years, these phenomena are not uncommon and certain crops, like corn, have developed a way to battle drought conditions underground.
From the start of the project in 2016, faculty and students have studied one season of growing and harvesting maize plants in the field, as well as using a novel controlled water deficit imposition system in the lab. In the field, Shannon King, a Ph.D. candidate in Biochemistry who is part of the team, is using a “drought simulator” to impose and maintain drought conditions during inclement weather. It works like a massive, open-ended greenhouse on train tracks. When it begins to rain, the simulator rolls over the cornfield being used for this project to keep water at bay. It is then removed once weather conditions improve.
The Drought Simulator, created by Ph.D. candidate Shannon King, acts as a giant mobile greenhouse. Whenever inclement weather moves in, the greenhouse moves on top of the crop field to protect it from any precipitation. Photo by MJ Rogers, Roots in Drought Project
As the project approaches the halfway mark, the next steps will involve analyses of proteomics, metabolomics, transcriptomics and physiological data from nodal root samples in the lab and field. Once these studies are complete, the team will integrate the datasets using bioinformatics approaches to generate hypotheses on gene candidates and metabolic pathways involved in root growth maintenance under water deficit.
As a Broader Impacts activity of the project, Dr. Sharp and other members of the team will discuss their research at a workshop in the arid environment of northwest China. Here students, postdocs, and faculty will team up with Professor Shaozhong Kang of China Agricultural University to experience first-hand the problems and solutions of agricultural water-use efficiency near the Gobi Desert. The team will also present the importance of the project to the public, farmers, and legislators at the Missouri State Fair.
By understanding the way roots react under drought conditions in a controlled lab setting, in the field in Missouri, and in arid climatic zones across the globe, Sharp hopes that the findings of this project will help improve the ability of plants to find and use water and thereby lessen the global impact of drought on crop productivity.
