Ah, December—a month suffused with light-filled holidays, presents, parties . . . and the spread of colds and flu. This playful image uses a festive approach to the serious science of understanding and finding ways to combat the flu virus.
This is the third post in a new series highlighting NIGMS’ efforts toward developing a robust, diverse and well-trained scientific workforce.
It’s not every day that you’ll hear someone say, “I learned more about parasites, and I thought, ‘This is so cool!’” But it’s also not every day that you’ll meet an undergraduate researcher like 21-year-old Priscilla Del Valle.
Del Valle’s interest in studying infectious diseases and parasites is motivating her to pursue an M.D./Ph.D. focusing on immunology and pathogenic microorganisms. Currently, Del Valle is a junior at The University of Texas at El Paso (UTEP)’s BUILDing SCHOLARS Center . BUILDing SCHOLARS, which stands for “Building Infrastructure Leading to Diversity Southwest Consortium of Health-Oriented Education Leaders and Research Scholars,” focuses on providing undergraduate students interested in the biomedical sciences with academic, financial and professional development opportunities. Del Valle is one of the first cohort of students selected to take part in this training opportunity.
BUILD scholars receive individual support through this training model, and Del Valle says she likes “the way that they [BUILDing SCHOLARS] take care of us and the workshops and opportunities that we have.”
Born in El Paso, Texas, Del Valle moved to Saltillo, Mexico, where she spent most of her childhood. Shortly after graduating from high school, she returned to El Paso to start undergraduate courses at El Paso Community College (EPCC), to pursue an M.D. Del Valle explains that in Mexico, unlike in the United States, careers in medical research are not really emphasized in the student community or in society, so she did not have firsthand experience with research.
Del Valle discovered her passion for research when she was assigned a project on malaria as part of an EPCC course. She was fascinated by the parasite that causes malaria. “It impressed me how something so little could infect a person so harshly,” she says. Continue reading
Over the past decade, scientists and clinicians have eagerly deposited their burgeoning biomedical data into publicly accessible databases. However, a lack of computational tools for sharing and synthesizing the data has prevented this wealth of information from being fully utilized.
In an attempt to unleash the power of open-access data, the National Institutes of Health, in collaboration with the Howard Hughes Medical Institute and Britain’s Wellcome Trust, launched the Open Science Prize . Last week, after a multi-stage public voting process, the inaugural award was announced. The winner of the grand prize—and $230,000—is a prototype computational tool called nextstrain that tracks the spread of emerging viruses such as Ebola and Zika. This tool could be especially valuable in revealing the transmission patterns and geographic spread of new outbreaks before vaccines are available, such as during the 2013-2016 Ebola epidemic and the current Zika epidemic.
An international team of scientists—led by NIGMS grantee Trevor Bedford of the Fred Hutchinson Cancer Research Center, Seattle, and Richard Neher of Biozentrum at the University of Basel, Switzerland—developed nextstrain as an open-access system capable of sharing and analyzing viral genomes. The system mines viral genome sequence data that researchers have made publicly available online. nextstrain then rapidly determines the evolutionary relationships among all the viruses in its database and displays the results of its analyses on an interactive public website.
The image here shows nextstrain’s analysis of the genomes from Zika virus obtained in 25 countries over the past few years. Plotting the relatedness of these viral strains on a timeline provides investigators a sense of how the virus has spread and evolved, and which strains are genetically similar. Researchers can upload genome sequences of newly discovered viral strains—in this case Zika—and find out in short order how their new strain relates to previously discovered strains, which could potentially impact treatment decisions.
Nearly 100 interdisciplinary teams comprising 450 innovators from 45 nations competed for the Open Science Prize. More than 3,500 people from six continents voted online for the winner. Other finalists for the prize focused on brain maps , gene discovery , air-quality monitoring , neuroimaging and drug discovery .
nextstrain was funded in part by NIH under grant U54GM111274.
Do you like to find new uses for old things? Like weaving old shirts into a rug, repurposing bottles into candle holders or turning packing crates into tables? Katie Gostic, a University of California, Los Angeles (UCLA) graduate student, likes finding new uses for old data. She channeled this interest when she analyzed existing data to study whether childhood exposure to flu affects a person’s future immunity to the disease.
As an undergraduate student at Princeton University, Gostic was originally pursuing a degree in engineering. Her focus shifted to biology after taking an infectious disease modeling class. Gostic’s background in math and programming allows her to take large, complex pre-existing data sets and reanalyze them using new tools and methods. The result: Information that wasn’t accessible when the data were first collected.
Now a graduate researcher in the ecology and evolutionary biology lab of James Lloyd-Smith , Gostic studies infectious diseases. The lab builds mathematical models to investigate zoonotic diseases—diseases that animals can transmit to humans but that humans don’t frequently spread between each other. Examples include diseases caused by Leptospira, a type of bacteria that infects household pets and many other animals, and monkeypox, a virus whose transmission to humans is increasing since the eradication of smallpox. The lab also studies bird flus, a category of flu viruses that infect birds and other animals and only occasionally jump to people. A very small number of cases of human-to-human transmission of bird flus have been recorded. However, if a bird flu virus mutated in a way that allowed it to spread among humans, it could cause a pandemic. Continue reading
- Go to http://fred.publichealth.
- Select “Get Started”
- Pick a state and city
- Play both simulations
To help the public better understand how measles can spread, a team of infectious disease computer modelers at the University of Pittsburgh has launched a free, mobile-friendly tool that lets users simulate measles outbreaks in cities across the country.
The tool is part of the Pitt team’s Framework for Reconstructing Epidemiological Dynamics, or FRED, that it previously developed to simulate flu epidemics. FRED is based on anonymized U.S. census data that captures demographic and geographic distributions of different communities. It also incorporates details about the simulated disease, such as how contagious it is.
Just as you might turn to Twitter or Facebook for a pulse on what’s happening around you, researchers involved in an infectious disease computational modeling project are turning to anonymized social media and other publicly available Web data to improve their ability to forecast emerging outbreaks and develop tools that can help health officials as they respond.
Mining Wikipedia Data
“When it comes to infectious disease forecasting, getting ahead of the curve is problematic because data from official public health sources is retrospective,” says Irene Eckstrand of the National Institutes of Health, which funds the project, called Models of Infectious Disease Agent Study (MIDAS). “Incorporating real-time, anonymized data from social media and other Web sources into disease modeling tools may be helpful, but it also presents challenges.”
To help evaluate the Web’s potential for improving infectious disease forecasting efforts, MIDAS researcher Sara Del Valle of Los Alamos National Laboratory conducted proof-of-concept experiments involving data that Wikipedia releases hourly to any interested party. Del Valle’s research group built models based on the page view histories of disease-related Wikipedia pages in seven languages. The scientists tested the new models against their other models, which rely on official health data reported from countries using those languages. By comparing the outcomes of the different modeling approaches, the Los Alamos team concluded that the Wikipedia-based modeling results for flu and dengue fever performed better than those for other diseases. Continue reading
News articles this weekend reported an uptick in flu cases in many parts of the country. When will your area be hardest hit? Infectious disease experts at Columbia University have launched an influenza forecast Web site that gives weekly predictions for rates of flu infection in 94 U.S. cities. The predictions indicate the number of cases in Chicago; Atlanta; Washington, D.C.; and Los Angeles will peak this week, with New York City, Boston, Miami and Providence peaking in following weeks. The forecasts are updated every Friday afternoon, so check back then for any changes.
The forecasting approach, which adapts techniques used in modern weather prediction, relies on real-time observational data of people with influenza-like illness, including those who actually tested positive for flu. The researchers have spent the last couple of years developing the forecasting system and testing it—first retrospectively predicting flu cases from 2003-2008 in New York City and then in real time during the 2012-2013 influenza season in 108 cities.
“People have become acclimated to understanding the capabilities and limitations of weather forecasts,” said Jeffrey Shaman , who’s led the flu forecasting project. “Making our forecasts available on the Web site will help people develop a similar familiarity and comfort.” Shaman and his team are hoping that, just as rainy forecasts prompt more people to carry umbrellas, an outlook for high influenza activity may motivate them to get vaccinated and practice other flu-prevention measures.
This work also was funded by NIH’s National Institute of Environmental Health Sciences.
Flu viruses evolve rapidly, often staying one step ahead of efforts to vaccinate against infections or treat them with antiviral drugs. Work led by Jesse Bloom of the Fred Hutchinson Cancer Research Center has uncovered a surprising new flu mutation that allows influenza to infect cells in a novel way. Normally, a protein called hemagglutinin lets flu viruses attach to cells, and a protein called neuraminidase lets newly formed viruses escape from infected cells. Bloom’s lab has characterized a mutant flu virus where neuraminidase can enable the virus to attach to host cells even when hemagglutinin’s binding is blocked. Although the researchers generated the neuraminidase mutant studied in these experiments in their lab, the same mutation occurs naturally in strains from several recent flu outbreaks. There’s a possibility that flu viruses with such mutations may be able to escape antibodies that block the binding of hemagglutinin.
This work also was funded by NIH’s National Institute of Allergy and Infectious Diseases.
Galina Lepesheva knows that kissing bugs are anything but romantic. When the lights get low, these blood-sucking insects begin feasting—and defecating—on the faces of their sleeping victims. Their feces are often infected with a protozoan (a single-celled, eukaryotic parasite) called Trypanosoma cruzi that causes Chagas disease. Lepesheva has developed a compound that might be an effective treatment for Chagas. She has also tested the substance, called VNI, as a treatment for two related diseases—African sleeping sickness and leishmaniasis.
“This particular research is mainly driven by one notion: Why should people suffer from these terrible illnesses if there could be a relatively easy solution?” she says.
Currently, most cases of Chagas disease occur in rural parts of Mexico, Central America and South America. According to some estimates, up to 1 million people in the U.S. could have Chagas disease, and most of them don’t realize it. If left untreated, the infection is lifelong and can be deadly.
The initial, acute stage of the disease is usually mild and lasts 4 to 8 weeks. Then the disease goes dormant for a decade or two. In about one in three people, Chagas re-emerges in its life-threatening, chronic stage, which can affect the heart, digestive system or both. Once chronic Chagas disease develops, about 60 percent of people die from it within 2 years.
The Centers for Disease Control and Prevention (CDC) has targeted Chagas disease as one of five “neglected parasitic infections,” indicating that it warrants special public health action.
“Chagas disease does not attract much attention from pharmaceutical companies,” Lepesheva says. Right now, there are only two medicines to treat it. They are only available by special request from the CDC, aren’t always effective and can cause severe side effects.
Lepesheva’s research focuses on a particular enzyme, CYP51, that is the target of some anti-fungal medicines. If CYP51 can also act as an effective drug target for the parasites that cause Chagas, her work might help meet an important public health need.
CYP51 is found in all kingdoms of life. It helps produce molecules called sterols, which are essential for the development and viability of eukaryotic cells. Lepesheva and her colleagues are studying VNI and related compounds to examine whether they can block the activity of CYP51 in human pathogens such as protozoa, but do no harm to the enzyme in mammals. In other words, her goal is to cripple disease-causing organisms without creating side effects in infected humans or other mammals.
Lepesheva has tested the effectiveness of VNI on Chagas-infected mice. Remarkably, it has worked 100 percent of the time, curing both the acute and chronic stages of the disease. It acts by preventing the protozoan from establishing itself in the host’s body. If it is similarly effective in humans, VNI could become the first reliable treatment for Chagas disease.
It looks like a fluorescent pill, but this image of an E. coli cell actually shows a new potential target in the fight against infectious diseases. The green highlights a protein called TonB, which is produced by many gram-negative bacteria, including those that cause typhoid fever, meningitis and dysentery. TonB lets bacteria take up iron from the host’s body, which they need to survive. New research from Phillip Klebba of Kansas State University and his colleagues shows how TonB powers iron uptake. When TonB spins within the cell envelope (the bacteria’s “skin”) like a tiny motor, it produces energy that lets another protein pull iron into the cell. This knowledge may lead to the development of antibiotics that block the motion of TonB, potentially stopping an infection in its tracks.