TXBiobytes from Texas Biomed

The birth of a child is typically one of the happiest moments in a family’s life. But for mothers and fathers infected with the Zika virus, pregnancy can be particularly stressful, as they wait to see if their child will suffer the sometimes devastating consequences of infection.

Mosquitos carrying the Zika virus are in the United States and infections are on the rise. Microcephaly appears to be the most devastating consequence and little is known how to stop it.

Scientists at Texas Biomed have begun several projects aimed at understanding the Zika virus and its impact on newborns.

Suzette Tardif, Ph.D., and Jean Patterson, Ph.D., talk about efforts to figure out how the virus works and how scientists can best test therapies to intervene.

Discovered in Uganda in 1947, Zika virus has been impacting lives for more than half a century. While Africans have built up an apparent immunity, the Western Hemisphere was left relatively unscathed until near the end of 2013 when cases of Zika virus and its most dangerous known consequence of infection, microcephaly, were reported in Brazil.

Mosquitos carrying the Zika virus are now in the U.S. Scientists at Texas Biomed have started several projects aimed at understanding this relatively unknown disease and are leading efforts to figure out how the virus works and how best we can test therapeutic strategies.

They hope to:

1. Develop an animal model to determine a timeline for infection and answer the questions: how long will Zika last in the body? When will it be most problematic for pregnant women, and how long do men have to wait before having sexual contact?

2. When vaccines and therapies are being developed, test them in animal models that mimic human immune and gestational systems to make sure that the vaccine offers protection against the various strains of the disease and does no harm to mothers or unborn children.

Applying the expertise of Texas Biomed scientists in virology, immunology, genetics, and pregnancy in several different nonhuman primate models will help lead to a better understanding of how Zika virus impacts fetal development. Texas Biomed scientists believe that different nonhuman primate models for this disease have the potential to reveal unique consequences of Zika virus infection.

Zika virus is a long-term health issue for the United States, and it is imperative we know more.

Dr. Cheeseman and his team are coming up with new ways to look at different strains of malaria.

Alieu Dia, Ph.D. and Ian Cheeseman, Ph.D., use flow cytometry to study malaria parasites.

Malaria is a mosquito-borne disease that kills hundreds of thousands of people around the world every year. Scientist Ian Cheeseman, Ph.D., of Texas Biomed specializes in the genetics of the parasite that causes malaria. His newest study published in the journal Genome Biology and Evolution was recently highlighted in the Editors Choice section of the prestigious journal Science.

“At the basic level we simply do not know what’s in a malaria infection, even though this has profound implications for how we think about treating and eradicating this disease,” Cheeseman said.

Using various technologies, these scientists are literally cracking open cells and using single cell DNA sequencing to discover previously unknown characteristics of malarial infections.

Texas Biomedical Research Institute in San Antonio is a new focal point for TB research, with scientists studying the disease from dozens of angles, researching new therapies and a better way to vaccinate people against the insidious infection that targets the lungs.

Tuberculosis is an ancient health threat that’s still claiming several thousand lives each day around the globe. It’s the world’s deadliest infectious disease. And TB isn’t just a third world concern. It’s an American problem, too. The World Health Organization Global TB Strategy aims to eradicate TB by 2035.

In 2016, Bexar County had one of the four highest rates of TB in the state, along with Harris, Dallas, and Hidalgo Counties. Texas, California, Florida and New York have the highest rates of tuberculosis in the U.S.

Eusondia Arnett, Ph.D., and a team of researchers are working on TB at Texas Biomed.

The new President/CEO of Texas Biomed, Larry Schlesinger, M.D., is a globally-recognized expert researcher in the TB field. He is joined at Texas Biomed by Joanne Turner, Ph.D. and Jordi Torrelles, Ph.D. Between the three of them and their team members, these scientists are poised to make real progress in their collaborative work.

With their expertise in both lab and animal research, the new Tuberculosis research team at Texas Biomed is a unique asset for South Texas.

SAN ANTONIO (February 26, 2015) – New research that focuses on the mechanism by which Ebola virus infects a cell and the discovery of a promising drug therapy candidate was published tomorrow, February 27, 2015, in the journal Science. Dr. Robert Davey, scientist and Ewing Halsell Scholar in the Department of Immunology and Virology at Texas Biomedical Research Institute announced today that a small molecule called Tetrandrine derived from an Asian herb has shown to be a potent small molecule inhibiting infection of human white blood cells in vitro or petri dish experiments and prevented Ebola virus disease in mice.

The latest outbreak of Ebola virus disease has caused the death of more than 8,600 people worldwide and created an international crisis that has shown few signs of stopping, continuing to infect thousands in West Africa. Ebola virus causes hemorrhagic fever in humans and currently has no approved therapy or vaccine. Scientists at Texas Biomed have been working in the Institute’s Biosafety Level 4 containment laboratory for more than 10 years to find a vaccine, therapies and detection methods for the virus.

Davey and his team have been working for more than five years on identifying and finding therapy targets for Ebola virus disease. Davey’s research has focused on stopping the virus before it has a chance to enter or interact with cellular factors, as that is a critical first step to combatting infection.

Ebola virus begins its entry into a cell by first binding to several types of cell surface proteins. Then the virus is taken into the cell and follows an endosomal route, ord membrane-bound route that transports the virus to various cell compartments.

From previous studies, Davey said that during this endosomal process, he knew that calcium signaling in cells, which allow cells to transmit electrical charges to one another, controls many of the processes in the cell and was important for Ebola virus infection.

“We were not able, however, to pinpoint the mechanisms involved in this process,” Davey explained. “With this research, we discovered that two pore channels (TPCs) are the key calcium sensor involved in Ebola virus infection. These TPCs essentially need to be turned on in order for the virus to function properly.”

Two pore channels are unusual calcium channels found in endosomes that control the way endosomes move through cells and the environment of the cells. Davey compared TPCs to traffic cops and air conditioners, helping direct the endosomes and any virus it might be carrying through the cell and making the endosomes and its passengers more comfortable along the way.

Davey and his team were able to show the critical role of two pore channels in Ebola virus infection, which has not previously been shown in any other virus.

In addition to identifying this critical mechanism to infection, Davey’s team also showed that drugs targeting this interaction show some efficacy as potential treatments against Ebola virus disease.

In the study, Davey’s team determined that existing drugs currently used to treat high blood pressure have an ability to turn this key calcium sensor on and off. Working with a group in Munich, Germany and Southwest Research Institute, the team tested several small molecules to see which was most effective at turning the sensors off thus prohibiting Ebola virus from moving any further through the cell.

The team found Tetrandrine protected mice from disease without obvious side effects and was the best candidate for further animal testing, because it was the most potent compound tested, gave little evidence of cytotoxicity and required a smaller dose to be effective and tolerated.

“When we tested in mice, the drugs stopped virus replication and saved most of them from disease,” Davey said.

Essentially,