TXBiobytes from Texas Biomed

Ebola VirusNIH Image Gallery

Can an infection with a parasitic disease increase the risk of developing a deadly virus? That's the question under study at Texas Biomed, where Staff Scientist Olena Shtanko, Ph.D. is conducting work as part of a study funded by the National Institutes of Health.

Olena Shtanko, Ph.D.

The hypothesis under study is that people who have acute malarial infection may experience some protective effects against Ebola infection. On the flip side, patients who have been infected with malaria but are no longer in the acute phase of the disease may be more susceptible to Ebola infection.

Knowing whether this is true could lead to more targeted therapies and also open the door to new discoveries about the interplay of other infectious diseases.

Ebola and malaria are both endemic in Africa.

Marie-Claire Gauduin, Ph.D.

Growing up in Africa, Marie-Claire Gauduin, Ph.D. witnessed firsthand the devastation caused by HIV, the virus that causes AIDS. She decided to study science and work on ways to combat this global killer. Her heart still breaks for the way the African people have suffered in the AIDS epidemic.

HIV Infecting a Human CellCourtesy: NIH Image Gallery

Now, as a Texas Biomed scientist, she is studying ways to combat HIV, the virus that causes AIDS. Dr. Gauduin and her team came up with a patented way to create a vaccine. It's a genetically-engineered vaccine strategy to prevent HIV infection that targets the outer layers of body structures that are the first site of contact for the virus.

Designed to be a single dose that lasts a lifetime, the vaccine will lead to the continual production of disease-fighting cells without being eliminated by the immune system. The experimental vaccine is directed to what are known as the musocal layers of the epithelium in the genital and rectal areas where the virus enter the body.

    

  

Marie-Claire Gauduin, Ph.D., in Africa

Another feature of the vaccine system is that it could be adapted to other infections.

Now, Dr. Gauduin is working on another approach to vaccinating against HIV using a different virus that targets the same area of the body HPV (human papilloma virus).

Dr. Gauduin has more than 25 years of experience in HIV/AIDS research and medical microbiology.

Photo by Kathy West Studios

The Institutional Animal Care and Use Committee (IACUC) is appointed in accordance with the Animal Welfare Act and the Policy on Humane Care and Use of Laboratory Animals. But it’s more passion than legal obligation that guides this group.

The IACUC Committee at Texas Biomed makes extraordinary efforts to ensure the nonhuman primates that the more than 2,000 monkeys that live at the Southwest National Primate Research Center on our campus have the best care possible.

Not only people who work here, but lay people from the community as well help make important decisions about the research conducted on our campus involving the use of animals.

Photo by Kathy West Studios

Xue Li, Ph.D., Shalini Nair, and Tim Anderson, Ph.D.

Malaria is worldwide scourge infecting 200 million people around the world and killing more than 400,000 of them. The parasite is carried by the Anopheles mosquito, particularly in tropical areas like Sub-Saharan Africa and Asia.

Texas Biomed scientists are “particularly interested in the evolution of drug resistance,” said Scientist Tim Anderson, Ph.D., adding that it is “a recurring problem in controlling tropical diseases.”

Artemisinin is a recently discovered drug that is the gold standard for treating malaria, considered instrumental in reducing the number of cases of the infectious disease over the last decade. However, more than 125 mutation variations of drug resistance have emerged in Southeast Asia. Those mutations impact the metabolism of the parasite itself – inhibiting growth rate, for instance.

A recent NIH-funded study published in the journal Antimicrobial Agents and Chemotherapy by Anderson and his team looked at one particular drug resistant variant sequence (called an allele) that is outpacing the others. Anderson’s team wanted to test the idea that successful resistance alleles have fewer adverse consequences for the parasites and, thus, thrived and spread.

Shalini Nair works with malaria parasites in Dr. Tim Anderson's lab.

Senior Research Associate Shalini Nair, who has worked at Texas Biomed for 18 years, was a key part of this project. “I started out by figuring out how to use CRISPR-Cas9 to edit key mutations in the malaria parasite,” Nair explained. CRISPR is short for clustered regularly interspaced short palindromic repeats. It’s a system for genome editing, using the cell’s own DNA repair mechanism to add or delete pieces of genetic material.

To maximize the relevance of their results, the team used “a recently isolated parasite clone from the Thailand-Myanmar border for manipulation rather than a laboratory adapted parasite clone,” the journal article stated.

Malaria parasites grow in flasks of red blood cells.

In a head-to-head comparison between two mutants – one strong and thriving in patients and one not as strong and waning – researchers grew the parasites in flasks of blood cells in the lab. Scientists measure how the mutations impacted the “fitness” of the parasites. In other words, they checked to see if the mutations impacted the metabolism of the more common and less common strains in the expected way. Scientists hypothesized the more common and thriving mutations would have less “fitness cost” to the parasite.

The cultures were maintained for 60 days. Then they extracted DNA and amplified it, comparing frequencies of the different mutations.

Xue Li, Ph.D., is a post-doctoral student who compiled the data from the study. “Our results were not the same as our hypothesis,” Li stated. The scientists want to see if there are other mutations in different areas of the genome impacting whether these drug-resistant parasites flourish or fail. The answer may be more complicated than first thought.

Dr. Anderson emphasized that malaria researchers like his team need to understand the process by which parasites adapt to anti-malarials.” If we understand that,” he said, “we are in a far better position to then to develop more effective, evolution proof interventions.”

Smita Kulkarni, Ph.D.

Despite more than three decades’ worth of research, HIV continues to be a major health threat in the U.S. and around the world. Although effective therapies exist that can give HIV-patients a relatively normal lifespan, the life-long treatment poses an enormous financial burden.

That’s why scientists who study the problem of infectious diseases continue to focus on the virus that causes AIDS.

Smita Kulkarni, Ph.D., was recently awarded a $525,000 grant from the National Institutes of Health to conduct research on the interaction between what are called long non-coding RNAs and HIV, a new area of investigation.

Dr. Kulkarni specializes in host-pathogen interactions, specifically involving HIV.

“We have worked on HIV and the impact of host factors on HIV for so long,” Dr. Kulkarni said, “but in reality we’ve looked at only 3% of the genome.”

Scientists have focused exclusively on protein-coding genes. The rest of the human genome -- 97% -- does not code for proteins.

The protein coding genes make RNA messenger molecules that take the coded information from nucleus to cytoplasm where it is translated into proteins. The non-coding RNAs carry out diverse regulatory work in the cells rather than just ferry information.

Artist's rendering of HIV Virus in the bloodstream

“What we found in our preliminary observations is that one of these long non-coding RNAs can inhibit HIV replication,” Dr. Kulkarni explained.

Although this research is in the very early stages, Dr. Kulkarni and her team will try to pinpoint molecular mechanisms which explain how this RNA stops the virus from making copies of itself. Using this novel information, scientists will attempt to come up with a way to use this information against HIV, perhaps opening up a new field for intervention.

Dr. Kulkarni also believes these long-coding RNAs have potential for recruitment in therapies against other infectious pathogens that live inside cells.

Marmosets in the study were monitored with Fitbit-like devices.

What does a monkey wearing a Fitbit-like device have to do with Parkinson's disease? A newly-published study shows marmosets at the Southwest National Primate Research Center can mimic the non-motor symptoms of Parkinson's.

Marmosets are small, New World monkeys that can mimic the sleep disturbances, changes in circadian rhythm, and cognitive impairment people with Parkinson's disease develop.

Associate Scientist Marcel Daadi, Ph.D., leader of the Regenerative Medicine and Aging Unit at the SNPRC, is the lead author of a new study published in the journal PLOS ONE. In addition to monitoring the marmosets, scientists videotaped the animals to document their ability to perform certain tasks and how those abilities were impacted over time by the disease.

By developing an effective animal model that can emulate both the motor and non-motor symptoms of Parkinson’s disease, scientists have a better chance of understanding the molecular mechanisms of the neuro-circuitry responsible for changes in the brain during the course of the disease. Scans like magnetic resonance imaging (MRIs) and analysis after dissections may lead to potential targets for new therapies for patients.

Khamis Tomusange, Ph.D. and Siqi Gong

Texas Biomed scientists say what they've learned in the lab recently is an exciting development on the front lines of the battle against HIV, the virus that causes AIDS.

Using macaques as an animal model, the team showed for the first time that an antibody called immunoglobulin M – called IgM – was effective in preventing infection when the monkeys were exposed to HIV in the mucosal cavity. More than 90 percent of new cases of HIV are caused through exposure to the virus in body cavities during sexual intercourse.

Creating a manmade version of the IgM molecule in the lab and testing it is challenging. Dr. Ruth Ruprecht leads the team which published its findings in a recent journal.

The IgM antibody has multiple arms to catch the virus, making it more efficient in clumping up the virus and keeping it from passing through the mucosal barrier and entering the rest of the body.

For more information on this recent work, click here.

Deepak Kaushal, Ph.D.

The Southwest National Primate Center's Mission is to improve the health of our global community through innovative biomedical research with nonhuman primate. The newest member of the team who will direct this program -- one of only seven of its kind in the country -- is Deepak Kaushal, Ph.D. He comes to Texas Biomedical Research Institute from the Tulane National Primate Research Center in Louisiana. Dr. Kaushal specializes in tuberculosis (TB) research in nonhuman primates.

"I think this is a tremendous opportunity for me to bring my research here and build collaboration with what is already a very strong tuberculosis research team at Texas Biomed," Dr. Kaushal said. "I am also looking forward to the chance to administer a large research center like the SNPRC."

Most of Dr. Kaushal's TB research with animals has involved macaques, but he plans on expanding that work using the baboons and marmosets that are also housed at the SNPRC.

Dr. Kaushal begins his new job as Director of the SNPRC on January 2, 2019.

© Clem Spalding

A baboon from the SNPRC is undergoing an MRI.

Neuropsychiatric diseases affect millions of people and can be disabling. Only about 8% of therapies that work in animal models make it all the way to humans. That's why Texas Biomed scientists are taking part in a study to try and find a better animal model to work with these complex health problems.

The ultimate goal of this research, funded in part by the National Institutes of Health, is to provide evidence for the use of baboons as a preclinical model for neuropsychiatric diseases. This two-year project involves 32 animals from the Southwest National Primate Research Center at Texas Biomed. The idea is to determine a miRNA biomarker signature of structural variation in the brains of baboons.

The animals are being imaged at the Research Imaging institute at the University of Texas Health Science Center at San Antonio.

Melanie A. Carless,  Ph.D., Associate Scientist

Melanie Carless, Ph.D., an Associate Scientist at Texas Biomed, is principal investigator on the study.

Victoria McFarland creates animal enrichment.

The animal enrichment programs at the Southwest National Primate Research Center aim to stimulate species-typical behaviors and promote psychological well-being using social, physical, occupational, feeding and sensory enrichment opportunities, many of which mimic natural behaviors seen in the wild, which we aim to encourage. We also want to prevent or limit the occurrence of abnormal behaviors, which may result from the stress or boredom that sometimes occurs in a captive environment. We use enrichment devices to invite and encourage a wide range of species-typical behaviors that primates living in the wild express. Foraging, locomotion and socializing are all examples of species-typical behaviors.

We have developed an Environmental Enhancement Plan that codifies these principles. Also, a list and description of devices can be found in our Enrichment Device Manual, and recipes for treats are found in our new Enrichment Cookbook.

Almost all of the primates at SNPRC are housed in groups. They spend much of their time interacting socially, including grooming each other. This rich social environment is important for the well-being of all primates, and is particularly critical for developing infants.

For primates that are housed indoors for research, we pair as many individuals as possible. The primates can also see, hear and sometimes touch other primates with which they are not directly housed.

All cages are equipped with some form of structural enrichment, such as climbing structures, perches or swings. Baboons, chimpanzees and other monkeys are very agile. They can jump great distances and walk along a rope or chain with ease. They also like to rest in areas above the ground, where they can get away from others in their group if they wish, or just get a better view of the surroundings.

Monkeys love oranges.

We provide many additional types of structural enrichment, including hanging 55-gallon drums, perches made from PVC or metal pipes, rope and chain swings and tire swings.

The baboon corrals have large culverts and climbing structures that also provide shade. The roofs of most chimpanzee housing areas are made of pipes so that the chimpanzees can brachiate from one area to another.

We provide a stable, nutritionally complete diet and additional fruits, grains and vegetables to all primates. Our feeding enrichment program also includes foods that are not available very often, such as seasonal fruits, pumpkins at Halloween, yogurt or frozen juice treats.

Occupational enrichment includes devices to stimulate problem-solving behavior, motor skills and coordination. Some foods are placed in special devices so that the animal has to spend some time extracting it. For example, balls filled with grain and peanuts must be moved around or shaken so that the food pieces fall out of small holes drilled in the side. Working to acquire food in this manner is similar to foraging for food in the wild.

Feeding devices for chimpanzees include those that require the use of a tool. Our simulated termite mounds are filled with applesauce, oatmeal, spaghetti sauce or other thick liquids. The chimpanzees use straws or sticks to poke down into the pipe and pull out a small amount of food at a time. This is a similar process that wild chimpanzees use to get termites or ants from their nests using twigs.

Many of our enrichment items increase sensory stimuli; the favorite taste of peanut butter, the new smell of a toy or the feel of a kiwi fruit. Some items are given specifically to elicit particular sensations. For example, mirrors can be attached to the wall so the animals can view their neighbors, radios are placed in indoor areas for extra auditory stimuli and televisions are located in many indoor areas for chimpanzees and monkeys to view television shows and children’s and nature videos.

The nonhuman primates enjoy frozen treats inside puzzle balls.

All primates are very good at manipulating their environments. They have opposable thumbs and are very strong and persistent. We provide a wide variety of toys and other objects for our primates to manipulate. Most primates like hard plastic balls. They hold them, sit on them, carry them around and of course, chew on them.

Other durable toys include hollow rubber toys, nylon dog bones and metal rattles attached to the cage. We provide new toys regularly to keep interest high. Sometimes, items that can be destroyed are even more popular. For example, the chimpanzees like to shred and make nests out of paper.