A veterinarian abroad: Tanzania

In a second travel log from Bond LSC researcher Cheryl Rosenfeld, learn about the wildlife she encountered in Tanzania this summer. Through the North American Veterinary Community (NAVC), Rosenfeld furthered her veterinary education while encountering wildlife in their natural habitat. See more about the first leg of her trip to Rwanda here

By Cheryl Rosenfeld

In the early morning hours, our group flew from Kigali, Rwanda to the Serengeti in Tanzania. As we began the descent to the dirt runway, we glimpsed our first sight of wildebeest and the awe-inspiring Serengeti plains and I soon boarded “tano,” Swahili for the fifth 4×4 in our convoy. “Tano” soon came to have special meaning, as there are many groupings of five to see in Tanzania: “The Big Five, The Ugly Five, etc.” Emanuel, whose life-long ambition was to attend college to be a guide, led us to see all of these groups of five and then some.

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Cheryl Rosenfeld

From the time we pulled away from the meeting spot, I started photographing animals on one side of the vehicle, but it seemed even more intriguing ones would appear on the other side of the road.

When the NAVC and our veterinary guide, Dr. Carol Walton, organized this trip, it was anticipated that the wildebeest would be in the Western corridor of the Serengeti but she was wrong. It’s no longer the case that the location of the wildebeest migrations can be projected with accuracy. Our lecture the first evening in Tanzania discussed how the wildebeest know to migrate and why past modeling of their migratory pattern is no longer accurate. Theories for the migratory nature of these animals include their ability to smell rain and/or changes in calcium concentrations in the soil. Wildebeest rely heavily on calcium to produce sufficient milk to nurse their calves that expend considerable energy keeping up with the herd.

In the past, the rains, like the wildebeest migration, would occur in similar sites and times throughout the year. Climate change has likely contributed to the rainfall in these sites being less reliable and correspondingly, compromised forecasting where the wildebeest will be located throughout the year. This year the wildebeest decided instead to migrate to the central Serengeti region. Thus, the next day we set off on an over-three-hour journey to this region.

While driving to find wildebeest we came upon new animals and birds including Coke’s Hartbeest, several Masai giraffe, and topis, which seemed to be splattered with oil. Finally, the wildebeest herds starting increasing in size until it reached a crescendo. As far as one could look in all directions there were wildebeest: males, females, and an abundance of baby calves. Eating alongside them were many zebras and their babies, with brown fuzzy fur along their back-end. It was the most amazing spectacle any of us had witnessed.

After seeing the vast wildebeest herds, we then came upon the elephants and lions, along with their babies. In the safety of the vehicle, we watched them engage in their natural behaviors for which no zoo experience can replicate. Both species were incredibly affectionate to the offspring and each other. In the case of the lionesses, each time the females, who were likely related, caught up with another that they had not seen in a short while would lead to emotional bouts of jumping on each other, caressing and licking. It was hardly the acts of a deadly predator. Yet, their existence rests on the wildebeest and other prey. With the wildebeest in this area, it seemed all life was flourishing at this time. A true paradise.

However, even paradise is subject to outside threats. One such threat is the massive poaching of elephants in Tanzania and surrounding African countries with 40,000 being killed last year alone. Prior to 2013, Tanzania had a “shoot to kill” policy for those caught poaching elephants or other endangered species. However, this rule has since been relaxed with the elephant numbers now in severe decline. At this unsustainable rate of poaching, the African elephant may go extinct in the wild in the next few decades.

While we did see some groups of elephants, the size of each matriarch-led group seemed less than those depicted in Sir David Attenborough and National Geographic documentaries. Moreover, one elephant that we came across, which I affectionately referred to as “Stumpy,” bore sad evidence of this brutal practice: He lost part of his trunk in a poacher’s snare. Without a full trunk, this elephant exhibited great difficulty grasping various plant items to place in his mouth.

Our subsequent travel took us to the famous “Olduvai (which should actually be Oldupai) Gorge,” one of the most famous paleoanthropological sites, including the Leakeys’ famous discovery. From there we traveled to the Ngorongoro Crater, a gigantic fracture of the earth’s crust that provides habitat for some 30,000 animals, including the most endangered black rhinoceros that only has 20 to 30 left in this area. The difference between the black and white rhino lies not in their coat color but a structural difference in their lips with black rhino possessing pointed and prehensile upper lip to browse on twigs and leaves. In contrast, white rhino possess a square upper lip to graze on the grasses below.

When Dr. Walton convinced us to set off at first light, around 6 a.m., our goal was to find one of these amazing creatures. Once again, with Emmanuel’s assistance and eagle eyes, what started out as a black dot far off in the horizon began to morph into a recognizable rhinoceros. In utter delight, we strained our necks and photographed as this beautiful animal continued to move along and forage in the distance. It would be inhumane to allow this animal to go extinct. In the case of the rhino, many Asian countries believe that its horn increases male libido, which has never been proved to be the case. This mistaken notion possibly originated from the fact that male rhinos copulate with females for several hours duration. This behavior is, however, not transferrable to men who consume any part of a rhino.

The list of species we saw in Tanzania continued to grow while we drove around the crater with black-backed and common jackals following alongside our vehicle, eland and grants gazelles grazing in the plains, flocks of greater and lesser flamingoes observed in the distance, and more lion prides and spotted hyenas.

The next day, we had our final farewell lunch at the famous Arusha Coffee Lodge, where US presidents have dined. We then set off on our long journey back to the US.

All of us were impacted by the creatures and sites we saw. One male veterinarian, who seemed gruff and quiet for most of the expedition, put it best the night before we left. He unexpectedly stood up after our last lecture and proclaimed that he signed up for the expedition more as an escape from the daily grind of being a veterinarian. However, the trip made such as impression on him to the point that he realized that part of the veterinarian oath on “relieving animal suffering” should include standing up and advocating on their behalf to prevent their brutal murder, as previously occurred in the case of the gorillas and is ongoing for elephants and rhinos. All of us were moved by his emotional comments and the tears welling up in his eyes. Our group was indeed fortunate to see these majestic animals, while they still exist, in their natural environments. I hope there is a wake-up call for nations to come together to prevent their extinction.

Viruses as Vehicles: Finding what drives

Graduate students Yuleam Song and Dan Salamango inoculate a bacteria culture in Johnson's lab. The inoculation takes a small portion of a virus and multiplies the sample, allowing researchers to custom-make viruses.

Graduate students Yuleam Song and Dan Salamango inoculate a bacteria culture in Johnson’s lab. The inoculation takes a small portion of a virus and multiplies the sample, allowing researchers to custom-make viruses.

By Madison Knapp | Bond Life Sciences Center summer intern

Modern science has found a way to turn viruses —tiny, dangerous weapons responsible for runny noses, crippling stomach pains and worldwide epidemics such as AIDS— into a tool.

Gene therapy centers on the idea that scientists can hijack viruses and use them as vehicles to deliver DNA to organs in the body that are missing important genes, but the understanding of virus behavior is far from exhaustive.

Marc Johnson, researcher at the Christopher S. Bond Life Sciences Center and associate professor of molecular microbiology and immunology in the MU School of Medicine, has been building an understanding of viral navigation mechanisms which allow a virus to recognize the kind of cell it can infect.

Johnson’s research specifically explores the intricacies of the viral navigation system and could improve future direction of gene therapy, he said.

 

Marc Johnson (left) with a post doctoral student that works in his lab. The lab does important research on the basic function and mechanisms of viral navigation and transport.

Marc Johnson (left) with Dan Salamango, a graduate student that works in his lab. The lab does important research on the basic function and mechanisms of viral navigation and transport.

Turning a virus into a tool

Conceptualized in the 1970s, gene therapy was developed to treat patients for a variety of diseases, including Parkinson’s, leukemia and hemophilia (a genetic condition that stops blood from clotting).

To treat disease using gene therapy, a customized virus is prepared. A virus can be thought of as a missile with a navigation system and two other basic subunits: A capsule that holds the ammunition and the ammunition itself.

The viral genetic material can be thought of as the missile’s ammunition. When a cell is infected, this genetic material is deployed and incorporated into the cell’s DNA. The host cell then becomes a factory producing parts of the virus. Those parts assemble inside the cell to make a new virus, which then leaves the cell to infect another.

The capsule is made of structural protein that contains the genetic material, and the navigation system is a protein that allows the virus to recognize the kind of cell it can infect.

 

Viral navigation

Gene therapy uses viruses to solve many problems by utilizing a virus’ ability to integrate itself into a host cell’s DNA; to do this successfully, researchers need to provide a compatible navigation component.

In the body, viruses speed around as if on a busy highway. Each virus has a navigation system telling it which cells to infect. But sometimes if a virus picks up the wrong type of navigation system, it doesn’t know where to go at all.

“What you can do is find a virus that infects the liver already, steal its navigation protein and use that to assemble the virus you want to deliver the gene the liver needs,” Johnson said. “You can basically take the guidance system off of one and stick it onto another to custom design your virus.”

But this doesn’t always work because of incompatibility among certain viruses, he said.

Johnson and his lab are working to understand what makes switching out navigation proteins possible and why some viruses’ navigation systems are incompatible with other viruses.

“I’m trying to understand what makes it compatible so that hopefully down the road we can intelligently make others compatible,” Johnson said.

 

The right map, the right destination

Johnson creates custom viruses by introducing the three viral components—structural protein, genetic material, and navigation protein—to a cell culture. The structural protein and genetic material match, but the navigation component is the wild card. It could either take to the other parts to produce an infectious virus, or it could be incompatible.

Johnson uses a special fluorescent microscope to identify which viruses assembled correctly and which didn’t.

A successful pairing is like making a match. If a navigation protein is programmed to target liver cells, it’s considered a successful pairing when the virus arrives at the liver cell target location.

The scope of gene therapy continues to widen. Improved mechanisms for gene therapy, and greater knowledge of how a navigation protein drives a virus could help more people benefit from the vehicles viruses can become.

Johnson uses several high-profile model retroviruses, including human immunodeficiency virus (HIV), which affects an estimated 35 million people worldwide each year, according to the World Health Organization.

Understanding nuances of HIV in comparison to other viruses allows Johnson to pick out which behaviors might be common to all retroviruses and others behaviors that might be specific to each virus.

Johnson said his more general approach makes it easier to understand more complex viral features.

“If there are multiple mechanisms at work, it gets a little trickier,” Johnson said. “My angle is more generic, which makes it easier to tease them apart.”

Supervising editor is Paige Blankenbuehler

Researchers flex new muscle in SMA drug development

By Paige Blankenbuehler

Lauren and Claire Gibbs share contagious laughter, ambition and a charismatic sarcasm.

Both are honor students at Shawnee Mission East High School in a Kansas City suburb.

They also share a neuromuscular disease called spinal muscular atrophy (SMA), designated as an “orphan disease” because it affects fewer than 200,000 people in the U.S.

However, the landscape for individuals with SMA is quickly changing with the development of new drugs.

More than 7 million people in the United States are carriers (approximately 1 in 40) of the so-called “rare” neurodegenerative disease, SMA.

 

Lauren,17 (left) and Claire, 16 (right), say their shared SMA diagnosis has strengthened their relationship and presented them with opportunities to travel and share their experiences. | Photo provided by the Gibbs family.

Lauren,17 (left) and Claire, 16 (right), say their shared SMA diagnosis has strengthened their relationship and presented them with opportunities to travel and share their experiences. | Photo provided by the Gibbs family.

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Faces of SMA

The success of therapeutics in lab experiments provides a new layer of hope for individuals and families living with the disease.

Lauren, now 17, fit the criteria for SMA Type III, while Claire, now 16, showed symptoms of a more severe manifestation of the disease, SMA Type II.

Lauren and Claire Gibbs were diagnosed on the same day.

Despite their numerous similarities, the biggest disparity between them is mobility.

Claire uses a power wheel chair while Lauren is able to use a manual chair. It’s not unusual to see Lauren being pulled along in her chair, playfully hanging onto the back of Claire’s motorized chair.

Lauren is participating in a clinical trial with ISIS-SMNRx a compound developed by Isis Pharmaceuticals, a leading company in the antisense drug discovery and development based in Carlsbad, Calif. Lauren feels that she has gained stamina and a greater ability to walk  — a feat that wasn’t routine just five years ago.

Prior to the trial, Lauren was able to walk only for short distances.

Time and Natalie Gibbs with their daughters Lauren, 17 (left) and Claire, 16 (right) in Washington D.C. The family have been visible advocates in the fight for a cure for spinal muscular atrophy. | Photo provided by the Gibbs family.

Tim and Natalie Gibbs with their daughters Lauren, 17 (left) and Claire, 16 (right) in Washington D.C. The Gibbs have been visible advocates in the fight for a cure for spinal muscular atrophy. | Photo provided by the Gibbs family.

 

Bringing New Hope

A new experimental drug developed by researchers at the Christopher S. Bond Life Sciences Center, is bringing hope to individuals with the orphan disease affecting one in 6,000 people.

Christian Lorson PhD, investigator in the Bond Life Sciences Center and Professor of Veterinary Pathobiology at the University of Missouri, has been researching SMA for seventeen years and has made a recent breakthrough with the development of a novel compound found to be highly efficacious in animal models of disease. In April, a patent was filed for Lorson’s compound for use in SMA.

Lorson’s therapeutic, an antisense oligonucleotide (a fancy name for a small molecule therapeutic that falls under the umbrella of gene therapy), repairs expression from the gene affected by the disease. The research was published May in in the Oxford University Press, Human Molecular Genetics.

The drug developed by Lorson’s lab is conceptually similar to ISIS-SMNRx already in clinical trial developed by Isis Pharmaceuticals and a team of investigators at Cold Spring Harbor Laboratory headed by Dr. Adrian Krainer.

Antisense drugs are not a new practice, but their wide-spread adoption seems to be on the cusp with recent success stories like the commercialization of an FDA-approved antisense compound produced by Isis in 2013 called Kynamro for the treatment of homozygous familial hypercholesterolemia, a high cholesterol disorder that is passed down through families.

 

Science behind success

The National Institutes of Health has listed SMA as the neurological disease closest to finding a cure. Discoveries made by the Lorson Lab have contributed significantly to current scientific understanding of the disease mechanisms and to the advances being made in finding an effective treatment for SMA.

These antisense therapies work because of the genetic makeup of SMA —the genetics are incredibly clear: a single, specific gene called Survival Motor Neuron 1  (SMN1) has been pinpointed as the cause of SMA.

SMA is a neurodegenerative disorder, meaning muscles become weaker over time due to sick or dying neurons.

These neurons become less functional because of low levels of the SMN.

Remarkably, the disease can be reversed in animal models of disease if the nearly identical duplicate gene, SMN2, can be “turned on” to compensate for low SMN levels.

Lorson’s antisense oligonucleotide therapeutic provides incredible specificity because it hones in on a specific genetic target sequence within SMN2 RNA and allows proper “editing” of the RNA encoding the SMN protein. The strategy is to “repress the repressor,” Lorson said.

The SMA-specific defect lies at the RNA step – the “cutting and splicing” of important RNA sequences does not happen efficiently in SMN2 RNAs because of a several “repressor” signals.

“The final chapter of the book — or the final exon — is omitted,” Lorson said. “But the exciting part is that the important chapter is still there – and can be tricked into being read correctly: if you know how.”

The new, antisense oligonucleotide seems to know how to get the job done.

The existence of such similar genes as SMN1 and SMN2 in humans creates a rare genetic landscape lending itself especially to a therapeutic development for SMA.

Humans are unique in this duplication — something Lorson calls a “genetic happenstance” that, on an evolutionary scale, may as well have happened yesterday.

Why humans have developed this redundant gene is unknown.

Thalia Sass, a University of Missouri biology major, genotypes samples in Christians Lorson's lab that conducts research on spinal spinal atrophy.

Thalia Sass, an MU biological sciences major, genotypes samples in the Lorson Lab where spinal muscular atrophy is researched.

 

Timing is everything

In addition to the developments of new SMA therapeutics, Lorson and his lab sought to answer an important biological question concerning the disease: When can a therapeutic be administered and still show some degree of efficacy?

Lorson’s research found that the earliest administration of a treatment provided the best outlook— extending the survival of laboratory mice by 500 to 700 percent, “a profound rescue,” according to his research published in April in the Oxford University Press, Human Molecular Genetics.

A near complete, 90 percent rescue was demonstrated in severe SMA mouse models. But even when the therapeutic was administered after the onset of SMA symptoms, there was still a significant impact on the severity of the disease.

“If you replace SMN early and get (a therapeutic) to cells that are important to the disease, you correct it,” Lorson said. “This provides hope that patients who have been diagnosed will still see some therapeutic benefit even if it is clear that the best results will likely come from early therapeutic administration.”

In Lorson’s study it’s definitive that the earlier a therapeutic can be administered, the better the outcome for individuals with SMA.

“This really points towards a strong push for neonatal screening,” Lorson said. “Infant screening would likely be incredibly beneficial for SMA and that’s something that the SMA community is really excited about.”

 

A breakthrough for families

On June 2, Lauren and Claire Gibbs attended a routine, annual rehab appointment with Dr. Robert Rinaldi, MD, division of pediatric rehabilitation medicine and attending physician at Children’s Mercy Hospital in Kansas City, Mo Dr. Rinaldi is not associated with the Isis clinical trial.

The appointment was like a reunion among close friends — Rinaldi began seeing Claire and Lauren Gibbs 16 years ago, the first year that he began working at the hospital and when the girls were one- and two-years-old, respectively.

The girls did all of the routine tests —measuring strength of grip and breathing, and assessing range of movement with the occupational and physical therapists.

A little later, Rinaldi sat with Natalie Gibbs, Lauren and Claire’s mother and a relentless advocate for advancement in SMA awareness.

Typically the muscles of individuals with SMA deteriorate over time, but together they inspected the definition of a new calf muscle on Lauren’s left leg.

For a young woman with Type III SMA — this means she can walk for short distances with little discomfort but still uses her wheel chair a majority of the time — Lauren’s new calf muscle is a remarkable achievement.

clinicaltrialinfoboxAs Lauren continues to participate in the ISIS antisense therapy clinical trial, her conditions continue to improve dramatically, even with the late administration of the therapy — in her case, 16 years after her diagnosis and onset of effects.

Lauren believes her ability and stamina for walking have increased significantly.

“Quite frankly my jaw almost hit the ground when she stood up — the change was that impressive to me,” Rinaldi said.

Rinaldi, also the co-director of the Nerve and Muscle Clinics at the hospital, had last seen Lauren two years ago. He said the Lauren he saw during a routine rehab appointment in June was like seeing a new person altogether.

“The way she stood up from the wheel chair — how quickly she did that with no support — her posture when she was standing up was more upright, her pelvis was in a much better position, her core was straighter,” Rinaldi said. “It struck me immediately how much better she looked.”

Lauren Gibbs is the first of Rinaldi’s patients to have participated in the ISIS clinical trial.

“It’s moving very fast in this field,” Rinaldi said. “I think the technology that’s evolving in research is opening up more avenues for investigation for us and there’s a big desire to find a cure for these types of diseases.”

The progress has rewarded the Gibbs family’s advocacy in SMA awareness and they’ve been able to set new goals they didn’t imagine were possible when the diagnoses for Lauren and Claire were made. Natalie Gibbs is a long-time member of Families of SMA and is currently on their Board of Directors.

The organization Families of SMA is currently providing funding to Lorson to advance this research area.

“We’re able to see first hand — and our physician who has been watching them for sixteen years has seen — that everything we’re doing in the clinical trials is really making a difference,” Natalie Gibbs said.

Over the course of their daughters’ lives, Natalie and her husband Tim Gibbs say a shift in momentum has accelerated the technology and research toward finding a cure for SMA.

“I am really impressed with the progress Lauren has made with the trial and how well Claire is doing overall,” Natalie Gibbs said. “Even though it’s a progressive and very devastating type of disease, I feel like we’re really conquering it.”

 

Link to publications:

Therapeutic window study:  http://www.ncbi.nlm.nih.gov/pubmed/24722206

University of Missouri ASO:  http://hmg.oxfordjournals.org/content/early/2014/04/29/hmg.ddu198.full.pdf+html

For more information on spinal muscular atrophy, visit FightSMA.org and fsma.org

 

At the Bond LSC, the wall wears the plants

The unusual red color of the Lobelias leaves stand out among 200 other species that thrive in the 20-foot plant wall at the Bond Life Sciences Center | Paige Blankenbuehler

The unusual red color of the Lobelias leaves make them stand out among 200 other species that thrive in the 20-foot plant wall at the Bond Life Sciences Center | Paige Blankenbuehler

Story by Madison Knapp | Bond Life Sciences summer intern

A hidden treasure on the University of Missouri’s campus is a living and breathing work of art.

In the Christopher S. Bond Life Sciences Center, a 20-foot plant wall stands as a towering tribute to the diversity of plant life and coexistence of species — a botanical landscape of more than 200 individual plants from 40 to 50 species including many ferns, vines, perennials, orchids and geraniums.

The display continues to be a visual reminder of the building’s interdisciplinary nature – much like the plants within the wall, the Bond Life Sciences Center facilitates the coexistence and collaboration between an array of researchers within its walls.

One plant cascades down the wall and stands out more than most — it looks more like a large insect than any type of plant typically seen in such displays.

Tillandsia is a genus of succulent plant native to Central America that can undergo long dry spells. The wiry plant thrives on the stone beside the plant wall without the help of a pot of soil, and is seemingly absent an essential, anatomical feature of most flora — roots.

With leaves more like Medusa's hair, Thallandsia are rootless plants mounted on stone  alongside the plant wall. | Paige Blankenbuehler

With leaves more like Medusa’s hair, Thallandsia are rootless plants mounted on stone alongside the plant wall. | Paige Blankenbuehler

They still have tiny root protrusions, but the mass is minuscule compared to the thick leaves, which take up and store water and nutrients, rather than the root system which handles that work in most plants.

Approximately 60 Tillandsias pepper the plant wall, including a few mounted directly onto the stone wall with a special kind of non-toxic rubber cement manufactured by Davis Farms based out of San Diego.

The strange plant was added to the green tapestry by Jason Fenton, an office support associate at the Bond Life Sciences Center. He first noticed the rootless plants in Belize while on a trip there in 2003 and had been growing them at his home.

“I think they’re really beautiful and distinctive,” Fenton said. “They help give variety to the wall.”

The rootless plants require special treatment — just a little extra attention from facilities manager, Jim Bixby, who waters the Tillandsias with a spray bottle once a week.

The wall started with a vision from Jack Schultz, director of the Bond Life Sciences Center. The execution and maintenance of the feature is credited to Bixby, who has honed the project since 2010.

After trying several watering systems, Bixby found one that worked. He hung rows of pots with modified flat sides and tailored a simple, drip irrigation system made for easy watering along a grid.

Within the diverse landscape and after additions of a variety of plants over the years, Bixby has seen competition between several of the species.

The wall favors the ferns, which have taken over much of the space, crowding out other plants for the eastern sunlight that flows through the windows, Bixby said.

Several long-stemmed species have found ways to cope, however; venturing out between the ferns’ curtain-like fronds to get their fair share of sunlight.

Supervising editor: Paige Blankenbuehler

The 20-foot tall plant wall outside of Monsanto Auditorium in the Bond Life Sciences Center is a nod to coexistence and diversity. | Paige Blankenbuehler

The 20-foot tall plant wall outside of Monsanto Auditorium in the Bond Life Sciences Center is a nod to coexistence and diversity. | Paige Blankenbuehler

A veterinarian abroad: Rwanda

While summer brings a slower pace for many researchers, others use it as an opportunity to learn for their profession and network with others in their field.

Bond LSC researcher Cheryl Rosenfeld recently traveled to Africa to further her learning as a veterinarian. This continuing education gives her the opportunity to learn the newest techniques in the field and network with others to learn what’s current and on the collective minds in veterinary medicine.  Through the North American Veterinary Community (NAVC), Rosenfeld has now gone on three expeditions where participants observe animals in their natural, exotic environments, attend nightly lectures and learn more about the humans near these animals. 

Previous expeditions led Rosenfeld to the Galapagos Islands and the Florida Keys, but her June 2014 trip started in Rwanda and ended in Tanzania. Here’s the first of two entries where Rosenfeld shares here experience. 

By Cheryl Rosenfeld

The fate of animal populations is generally intertwined with the predicament of humans in the area. Nowhere is this truer than in Rwanda. Most people know Rwanda for Dian Fossey’s work with the mountain gorillas and the genocide of more than 1 million Hutus and Tutsis that happened 20 years ago in 1994. In this 100-day period, an average of six individuals were killed per minute. Children that survived were often orphaned and many surviving women suffered being raped and exposed to HIV infection. In all, many still require extensive medical and psychological care. On our flight and checking into our hotel was a medical team from Harvard Medical Center that was there as part of the Clinton Foundation to assist in the medical needs.

We saw the history that continues to shape the country when we first visited a genocide memorial site just outside of Kigali where thousands of individuals were brutally murdered and the Kigali Genocide Museum that was partially funded by an English Jewish Holocaust survivor. The history of the conflict is rooted partially in Western influence that infused a social division. Prior to Europeans colonization, Hutus and Tutsis lived in relative peace and individuals could go back and forth between these two groups. The original difference was that Tutsi individuals owned more than 10 cows. The differential treatment and classification adopted by Europeans began to trigger conflict between the two groups. Prior indicators, including extensive propaganda, were ignored by the United States and United Nations. The museum includes two stained glass windows that depict the evidence that genocide was imminent and failure by other nations to prevent this tragedy. Genocide isn’t unique to Rwanda, though, and the displays describe the commonalities on their sad origins in other countries throughout history.  Outside the museum, there are several mass graves where fresh flowers are placed on a routine basis.

I was originally hesitant about traveling to Rwanda because of this history, but am very glad I took the chance. The Rwandan government has worked hard to turn around and instill pride in the country. Their economy is one of the fastest growing in Africa with construction of new businesses and hotels in Kigali. Moreover, the government has placed a ban on plastic bags and hired teams of individuals to keep the country clean. One Saturday a month, all Rwandans, including the President, are expected to participate in clean-up day, which becomes a convivial social event. While there is still sadness in the eyes of many individuals I met, I also saw hope of something better, which was inspiring to witness.

We were soon off to learn about the mountain gorillas that are now the pride of the country. During Dian Fossey’s time, she battled to prevent poaching of these magnificent and intelligent creatures. The country now realizes the worth of preserving and propagating the mountain gorilla populations. In a reasonable and safe way, they developed a tourist industry to view the various troops of gorillas. It currently costs $750 to spend one hour with the mountain gorillas. The government has restricted access to prevent gorilla habituation and stress from too many tourists.

We spent two days with different troops. While waiting in the morning to find out which troop we were responsible for trekking, we were entertained by local dancers. I regrettably made the mistake of indicating I felt fit to track the one of ten groups that was at the furthest distance.

The group that was involved in trekking the first day was called “Snow” in Kinyarwanda. I believe they received this name because they inevitably reside high in the mountains, which used to have snow. As we set off on our hike, many children came out to say “MooRahHoh”- hello in Kinyarwanda and asked for us to take their picture. We were informed that we should easily return before lunch, and therefore were only provided a package of peanuts. Unfortunately, it took us longer to hike through the forests that transitioned from bamboo to masses of stinging nettles and did not return to the hotel until 6:30 p.m. After more than three hours of hiking and our eyes finally fell upon our first mountain gorilla, the silverback of the group. Even knowing that this was the ultimate goal, we were not prepared for this amazing experience of being so close to a creature in the wild that resembled us.

We had the opportunity to meet the rest of the troop, including several 3 to 4 month old babies that were quite entertaining. The enclosed photos and videos only provide a sliver of the spectacle that we were privileged to be part of these two days of gorilla trekking that made our hunger and continued burning sensation on our face and legs from stinging nettles well worth it.

Hearing danger: predator vibrations trigger plant chemical defenses

Experiments show chewing vibrations, but not wind or insect song, cause response

As the cabbage butterfly caterpillar takes one crescent-shaped bite at a time from the edge of a leaf, it doesn’t go unnoticed.

This tiny Arabidopsis mustard plant hears its predator loud and clear as chewing vibrations reverberate through leaves and stems, and it reacts with chemical defenses. Plants have long been known to detect sound, but why they have this ability has remained a mystery.

University of Missouri experiments mark the first time scientists have shown that a plant responds to an ecologically relevant sound in its environment.

“What is surprising and cool is that these plants only create defense responses to feeding vibrations and not to wind or other vibrations in the same frequency as the chewing caterpillar,” said Heidi Appel, an investigator at MU’s Bond Life Sciences Center and senior research scientist in the Division of Plant Sciences in the College of Agriculture, Food and Natural Resources.

Heidi Appel, investigator at MU’s Bond Life Sciences Center and senior research scientist in the Division of Plant Sciences in the College of Agriculture, Food and Natural Resources, and Rex Cocroft, a professor of Biological Sciences in MU’s College of Arts and Science, found that plants create chemical responses specifically to predator chewing vibrations.

Heidi Appel, investigator at MU’s Bond Life Sciences Center and senior research scientist in the Division of Plant Sciences in the College of Agriculture, Food and Natural Resources, and Rex Cocroft, a professor of Biological Sciences in MU’s College of Arts and Science, found that plants create chemical responses specifically to predator chewing vibrations.

Appel partnered with Rex Cocroft, an MU animal communication expert who studies how plant-feeding insects produce and detect vibrations traveling through their host plants.

“It is an ideal collaboration, that grew out of conversations between two people working in different fields that turned out to have an important area of overlap,” said Cocroft, a professor of Biological Sciences in MU’s College of Arts and Science. “At one point we began to wonder whether plants might be able to monitor the mechanical vibrations produced by their herbivores.”

While Appel focused on quantifying “how plants care and in what ways,” Cocroft worked to capture inaudible caterpillar chewing vibrations, analyze them and play them back to plants in experiments that mimic the acoustic signature of insect feeding, but without any other cues such as leaf damage.

Cocroft used specialized lasers to listen to and record what the plant hears.

“Most methods of detecting vibrations use a contact microphone, but that wasn’t possible with these tiny leaves because the weight of the sensor would change the signal completely,” said Cocroft.

This cabbage butterfly caterpillar munches on an Arabidopsis leaf adjacent to  a leaf where a piece of reflective tape bounces back a laser beam used to detect the vibrations created by its chewing. Roger Meissen/Bond LSC

This cabbage butterfly caterpillar munches on an Arabidopsis leaf adjacent to a leaf where a piece of reflective tape bounces back a laser beam used to detect the vibrations created by its chewing. Roger Meissen/Bond LSC

The laser beam reflects off a small piece of reflective tape on the leaf’s surface to measure its deflection, minimizing contact with the plant. The laser’s output can also be played back through an audio speaker, allowing human ears to hear the vibrations produced by the caterpillar.

Moved by the sound

Recording the sound is just the start.

You can’t put headphones on a leaf, so tiny piezoelectric actuators – essentially a tiny speaker that plays back vibrations instead of airborne sound – is required.

“It’s a delicate process to vibrate leaves the way a caterpillar does while feeding, because the leaf surface is only vibrated up and down by about 1/10,000 of an inch,” Cocroft said. “But we can attach an actuator to the leaf with wax and very precisely play back a segment of caterpillar feeding to recreate a typical 2-hour feeding session.”

Appel and Cocroft tested whether these chewing sounds could create more chemical defenses in the plants and whether these feeding recordings primed defenses when played before an actual caterpillar ate part of a leaf.

“We looked at glucosinolates that make mustards spicy and have anticancer properties and anthocyanins that give red wine its color and provide some of the health benefits to chocolate,” Appel said. “When the levels of these are higher, the insects walk away or just don’t start feeding.”

The researchers played 2 hours of silence to some Arabidopsis plants and 2 hours of caterpillar-chewing noises to others. They then chose three leaves around the plant, and allowed caterpillars to eat about a third of each leaf.  After giving the plants 24 to 48 hours to respond to the caterpillar attack, they harvested the leaves for chemical analysis.

When they found higher levels of glucosinolates in the plants that were exposed to chewing vibrations, they knew they were on the right track.

A similar second experiment went further, testing whether the plants would simply respond to any vibration, or whether their response was specific to chewing vibrations. In this case Appel analyzed anthocyanins, which again were elevated – but only when plants had been exposed to chewing vibrations but not to vibrations created by wind or the sounds of a non-harmful insect.

Past echoes and future promise

While the past is littered with suggestions that people talk to their plants, Appel and Cocroft hope their work is shifting the focus on plant acoustics towards a better understanding of why plants can detect and respond to vibrations.

“The field is somewhat haunted by its history of playing music to plants. That sort of stimulus is so divorced from the natural ecology of plants that it’s very difficult to interpret any plant responses,” Cocroft said. “We’re trying to think about the plant’s acoustical environment and what it might be listening for, then use those vibrational sounds to figure out what makes a difference.”

The National Science Foundation seems to agree with the merit of their endeavor, awarding a grant to extend this project.

The next step includes looking at how other types of plants respond to insect predator sounds and pinpointing precisely what features of the sounds trigger the change in plant defenses.

These questions aim to further basic research understanding of how plants know what’s going on to respond appropriately to their environment. This could one day lead to ways to create better plants.

“Once you understand these things you can mess around with it in plant breeding through conventional methods or biotech approaches to modify plants so they are more responsive in the ways you want to make them more resistant against pests,” Appel said. “That’s the practical application one day.”

This research was published online in the journal Oecologia July 1, 2014 and will appear in print in its August issue.

Nerve cell communication mechanisms uncovered, may lead to new therapeutic approaches for neurodegenerative diseases

 

Story by Madison Knapp/ Bond Life Sciences summer intern

Simple actions like walking, swallowing and breathing are the result of a complex communication system between cells. When we touch something hot, our nerve cells tell us to take our hand off the object.

This happens in a matter of milliseconds.

This hyperspeed of communication is instrumental in maintaining proper muscle function. Many degenerative diseases affecting millions of people worldwide result from reduced signaling speed or other cellular miscommunications within this intricate network.

Michael Garcia, investigator at the Christopher S. Bond Life Sciences Center and associate professor of biology at the University of Missouri, conducts basic research to answer fundamental questions of nerve cell mechanics.

“In order to fix something, you need to first understand how it works,” Garcia said.

Garcia’s research illuminates relationships between nerve cells to find factors affecting function.  His goal is to provide insight on fundamental cellular mechanisms that aren’t fully understood.

Garcia’s research has been funded partly by the National Science Foundation and National Institutes of Health.

Technological advancements have made it possible to better understand disease development in the human body to create more effective treatments. Alas, a scientist’s work is never finished— when the answer to one question is found, ten more crop up in its wake.

Garcia’s research, which appeared in several journals including Human Molecular Genetics andthe Journal of Neuroscience Research initially sought to shed light on the neuronal response to myelination, the development of an insulating border around a nerve cell, called a myelin sheath, which is critical in rapid communication between cells.

Eric Villalon, a graduate student in Michael Garcia's lab at the Bond Life Sciences Center, examines results. The Garcia Lab is answering news questions in cell mechanics. | PAIGE BLANKENBUEHLER

Eric Villalon, a graduate student in Michael Garcia’s lab at the Bond Life Sciences Center, examines results. The Garcia Lab is answering news questions in cell mechanics. | PAIGE BLANKENBUEHLER

How it works: Rebuilding cell theory

Garcia’s early research disproved a long-standing hypothesis concerning this cellular feature.

Mammals’ nervous systems are uniquely equipped with myelination, which has been shown to increase conduction velocity, or the speed at which nerve cells pass signals. Low velocity is often associated with neurodegenerative diseases, so research exploring why could later have application in therapeutic technology.

In addition to myelination, cell size makes a big difference in conduction velocity — the bigger the nerve cells, the faster they can pass and receive signals. Garcia’s findings disproved a hypothesis that related myelination to this phenomenon.

The hypothesis, published in a 1992 edition of Cell, claimed that myelination causes a cellular process called phosphorylation which then causes an increase in the axonal diameter (width of the communicating part of a nerve cell), leading to faster nerve cell communication. Garcia found that myelination did cause an increase in axonal diameter, and myelination was required for phosphorylation, but that the two results were independent of one another.

To narrow in on the processes affecting axonal diameter, Garcia identified the protein responsible for growth.

Garcia followed earlier work, showing that one subunit controls whether there is growth at all with myelination, by identifying the domain of this protein that determines how much growth.

After clarifying this part of the process, a question still remains: If not to control myelination, why does phosphorylation happen?

 

Looking forward

Jeffrey Dale, a recent PhD graduate from Garcia’s lab, said current research is in part geared toward finding a connection between phosphorylation and a process called remyelination.

Remyelination could be key to new therapeutic approaches. When a cell is damaged (as in neurodegenerative disease) the myelin sheath can be stripped away. Remyelination is the process a cell goes through to replace the myelin.

Imagine you have a new wooden toy boat, painted and smooth. If you take a knife and whittle away all the paint and then repaint it—even exactly how it was painted before—the boat is not going to be as shiny and smooth as it was before. This is how remyelination works (or rather, doesn’t).  When nerve cells are damaged, the myelin sheath is stripped away and even after the cell rebuilds it, the cell can’t conduct signals at the same speed it was able to before.

“If you can learn what controls myelination, maybe you can improve effectiveness of remyelination,” Dale said.

Garcia said it is possible that revealing the mechanics involved in phosphorylation could lead to better treatments. In context of neurodegenerative diseases, the question why don’t axons function properly might be wrapped up in Garcia’s question: In healthy cells, why do they?

Supervising editor: Paige Blankenbuehler

SoyKB: Leading the convergence of wet and dry science in the era of Big Data

Yaya Cui, an investigator in plant sciences at the Bond Life Sciences Center examines data on fast neuron soybean mutants that are represented on the SoyKB database.

Yaya Cui, an investigator in plant sciences at the Bond Life Sciences Center examines data on fast neuron soybean mutants that are represented on the SoyKB database.

The most puzzling scientific mysteries may be solved at the same machine you’re likely reading this sentence.

In the era of “Big Data” many significant scientific discoveries — the development of new drugs to fight diseases, strategies of agricultural breeding to solve world-hunger problems and figuring out why the world exists — are being made without ever stepping foot in a lab.

Developed by researchers at the Bond Life Sciences Center, SoyKB.org allows international researchers, scientists and farmers to chart the unknown territory of soybean genomics together — sometimes continents away from one another — through that data.

 

Digital solutions to real-world questions

As part of the Obama Administration’s $200 million “Big Data” Initiative, SoyKB (Soy Knowledge Base) was born.

The digital infrastructure changes the way researchers conduct their experiments dramatically, according to plant scientists like Gary Stacey, Bond LSC researcher, endowed professor of soybean biotechnology and professor of plant sciences and biochemistry.

“It’s very powerful,” Stacey said. “Humans can only look at so many lines in an excel spreadsheet — then it just kind of blurs. So we need these kinds of tools to be able to deal with this high-throughput data.”

The website, managed by Trupti Joshi, an assistant research professor in computer science at MU’s College of Engineering, enables researchers to develop important scientific questions and theories.

“There are people that during their entire career, don’t do any bench work or wet science, they just look at the data,” Stacey said.

The Gene Pathway Viewer available on SoyKB, shows different signaling pathways and points to the function of specific genes so that researchers can develop improvements for badly performing soybean lines.

“It’s much easier to grasp this whole data and narrow it down to basically what you want to focus on,” Joshi said.

A 3D-protein modeling tool lends itself especially to drug design. A pharmaceutical company could test the hypothesis and in some situations, the proposed drug turns out to yield the expected results — formulated solely by data analysis.

The Big Data initiative drives a blending of “wet science” — conducting experiments in the lab and gathering original data — and “dry science” — using computational methods.

Testament of the times?

“Oh, absolutely,” Joshi said.

 

Collaboration between the “wet” and “dry” sciences

Before SoyKB, data from numerous experiments would be gathered and disregarded, with only the desired results analyzed. The website makes it easy to dump all of the data gathered to then be repurposed by other researchers.

“With these kinds of databases now, all the data is put there so something that’s not valuable to me may be valuable to somebody else,” Stacey said,

Joshi said infrastructure like SoyKB is becoming more necessary in all realms of scientific discovery.

“(SoyKB) has turned out to be a very good public resource for the soybean community to cross reference that and check the details of their findings,” she said.

Computer science prevents researchers having to reinvent the wheel with their own digital platforms. SoyKB has a translational infrastructure with computational methods and tools that can be used for many disciplines like health sciences, animal sciences, physics and genetic research.

“I think there’s more and more need for these types of collaborations,” Joshi said. “It can be really difficult for biologists to handle the large scope of data by themselves and you really don’t want to spend time just dealing with files — You want to focus more on the biology, so these types of collaborations work really well.

It’s a win-win situation for everyone,” she said.

The success of SoyKB was perhaps catalyzed by Joshi. She adopted the website and the compilation of data in its infant stages as her PhD dissertation.

Joshi is unique because she has both a biology degree and a computer science background. Stacey said Joshi, who has “had a foot in each camp,” serves as an irreplaceable translator.

Most recently, the progress of SoyKB as part of the Big Data Initiative was presented at the International Conference on Bioinformatics and Biomedicine Dec. 2013 in Shanghai. The ongoing project is funded by NSF grants.

MU Scientists Successfully Transplant, Grow Stem Cells in Pigs

New line of pigs do not reject transplants, will allow for future research on stem cell therapies

Story by Nathan Hurst/MU News Bureau

COLUMBIA, Mo. – One of the biggest challenges for medical researchers studying the effectiveness of stem cell therapies is that transplants or grafts of cells are often rejected by the hosts. This rejection can render experiments useless, making research into potentially life-saving treatments a long and difficult process. Now, researchers at the University of Missouri have shown that a new line of genetically modified pigs will host transplanted cells without the risk of rejection.

Roberts, Mike

Mike Roberts, courtesy of MU News Bureau

“The rejection of transplants and grafts by host bodies is a huge hurdle for medical researchers,” said R. Michael Roberts, Curators Professor of Animal Science and Biochemistry and a researcher in the Bond Life Sciences Center. “By establishing that these pigs will support transplants without the fear of rejection, we can  move stem cell therapy research forward at a quicker pace.”

In a published study, the team of researchers implanted human pluripotent stem cells in a special line of pigs developed by Randall Prather, an MU Curators Professor of reproductive physiology. Prather specifically created the pigs with immune systems that allow the pigs to accept all transplants or grafts without rejection. Once the scientists implanted the cells, the pigs did not reject the stem cells and the cells thrived. Prather says achieving this success with pigs is notable because pigs are much closer to humans than many other test animals.

Randall Prather, courtesy of MU News Bureau

Randall Prather, courtesy of MU News Bureau

“Many medical researchers prefer conducting studies with pigs because they are more anatomically similar to humans than other animals, such as mice and rats,” Prather said. “Physically, pigs are much closer to the size and scale of humans than other animals, and they respond to health threats similarly. This means that research in pigs is more likely to have results similar to those in humans for many different tests and treatments.”

“Now that we know that human stem cells can thrive in these pigs, a door has been opened for new and exciting research by scientists around the world,” Roberts said. “Hopefully this means that we are one step closer to therapies and treatments for a number of debilitating human diseases.”

Roberts and Prather published their study, “Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency” in the Proceedings of the National Academy of Sciences.

This study was made possible through grants from Konkuk University in South Korea and the National Institutes of Health.

Roberts has appointments in the MU College of Food, Agriculture and Natural Resources (CAFNR) and the MU School of Medicine and is a member of the National Academy of Sciences. Prather has an appointment in CAFNR and is the director of the NIH-funded National Swine Resource and Research Center.

New screening tool gives scientists more control over genetic research

A tangled spool of yarn represents DNA, while the fingers holding the section represent the insulators just added by MU researchers to improve a scientific, screening tool. | Paige Blankenbuehler

A tangled spool of yarn represents DNA, while the fingers holding the section represent the insulators just added by MU researchers to improve a scientific, screening tool. | Paige Blankenbuehler

Here’s a scenario: You are trying to find a lost section of string in the world’s most massively tangled spool of yarn. Then try cutting that section of yarn that’s deeply embedded in the mess without inadvertently cutting another or losing track of the piece you’re after.

For researchers, this problem is not unlike something they encounter in the study of genetic information in the tangled spool that is DNA.

A new tool will help scientists straighten things out.

The tool, developed by University of Missouri Bond Life Sciences Center investigators helps researchers effectively screen cell behavior by limiting epigenetic silencing, which occurs when a cell packages and stows away important genetic information, much like an accountant puts a client’s information away in a filing cabinet.

The cell can go digging to find that information when it absolutely needs it, but otherwise that information is tucked away and inactive.

Professors of biochemistry Mark Hannink, Tom Mawhinney and research assistant professor Valeri V. Mossine used insulators to develop the piggyBac transposon plus insulators, a better reporter of signaling between cells that makes improved screening possible.

This simple addition to an existing screening tool used in laboratories will help streamline research and contribute to screening products like vitamins and supplements and medicines for authenticity, Hannink said.

This is why the insulator addition to the piggyBac reporter assay by MU researchers is a game changer in the scientific world.

 

How it works

DNA stretches out to nearly 10 feet when it’s uncoiled. That’s 10 feet of your body’s deepest secrets coiled into a microscopic package and tucked away into each and every one of your cells. The human body, by the way, holds an estimated 10 trillion cells. An inconceivable number, right?

Let’s go back to our yarn analogy. You’re trying to find one specific piece to cut but it’s deeply tangled in the mass of yarn. You need to find the piece that you really care about and clamp your fingers onto the yarn to reduce the slack — straighten it out — so you can cut it easily.

Think of your fingers as the insulators.

The insulators of the new piggyBac transposon tool perform the same task of stretching out the DNA so certain expressions through signaling pathways are held open, enabling the investigation of specific genetic material.

Hannink hypothesizes this new reporter could provide answers to questions like: Does an anti-migraine medicine have the component that will relieve that ailment? Does a multi-vitamin deliver all of the nutrients on its label?

“A lot of botanicals are said to have anti-inflammatory benefits,” Hannink said. “By using an assay like this, we can easily determine if they actually do and if so, what molecules in these complex mixtures are in fact the cause of the punitive inflammatory activity.”

 

 

Reproducing results

Replication is a critical part of verifying scientific discovery and epigenetic silencing is a big headache for investigators trying to reproduce results.

Scientists studying genetic material can open certain expressions with other reporter tools but often, the cell will turn expressions off and block signaling pathways, causing an expected result to fail because of epigenetic silencing.

The new assay preserves conditions of an experiment so the same results can be reached. Cell behavior under the same conditions and expressions that were switched on during the experiment will be expressed.

The new version of the reporter assay is being used at the MU Center for Botanical Interaction Studies to understand how botanical compounds affect the immune system and in other research on the central nervous system and on the development of prostate cancer.

This research appeared in the Dec. 20, 2013 edition of PLoS ONE. It was funded by the University of Missouri Agriculture Experiment Station Laboratories and grants from the National Center for Complementary and Alternative Medicines, Office of Dietary Supplements and the National Cancer Institute.