‘Stepping into Science’ Highlights Variety of Scientific Careers

NIAID’s RML Campus Hosts Day-Long High School Program

Introducing local students to biomedical science and research has long been a feature of outreach programs at NIAID’s Rocky Mountain Laboratories in Hamilton, Montana.  However, realizing that traditional laboratory science – aka “bench research” – isn’t for everyone, RML staff recently invited two dozen area high school students to experience not only traditional research but also the lesser-known careers that make bench research possible.

Where bench science can be slow and methodical – scientists may spend their entire career investigating the same problem – jobs that support bench research often vary greatly from project to project. Both types of careers are rewarding and exciting – but appeal to different types of people.

“Stepping into Science,” held this spring at the RML campus, was the idea of Kamryn Cregger, who began postbaccalaureate research work at RML in August 2023. Cregger says she quickly realized that RML had amazing resources to benefit area students, and she hoped to provide them with a similar type of opportunity that she experienced as a high schooler in rural Maryland. Cregger enrolled in a biomedical leadership program that led to a pharmaceutical internship, two years of lab training, and ultimately a bachelor’s degree in plant sciences from the University of Tennessee.

Now working on tickborne disease projects at RML – and helping local middle-school students through RML’s Biomedical Research After School Scholars program – Cregger wanted to find a way to connect with college-bound high schoolers.

“With all of the scientists and staff members on site, why not show the local students what kinds of jobs there are in science in addition to bench work?” she thought. Making those types of connections also could establish the RML group as long-term mentors for students applying for college, internships, or career positions.

After a few months of planning meetings, coordinating with RML volunteers, and finding out what most appealed to students and faculty from Hamilton and Corvallis high schools – the groups arrived for the whirlwind day of activities at RML.

“Throughout the day,” Cregger said, “students asked questions about careers, RML research, medical school application processes, the differences in academic versus government research and even vaccine development!” Students received a campus tour, overview of the types of research done in the different laboratory groups and rotated through three hands-on demonstrations by virologists, animal care staff and  microscopists.

A team of RML virologists worked together to demonstrate biosafety knowledge, proper laboratory skills, such as pipetting, working in a biosafety cabinet, and dressing in personal protective equipment (PPE). They even designed a way for students to participate in a fun research-based game.

The three microscopists – Forrest Hoyt, Sophia Antonioli-Schmit and Bryan Hansen – all discussed their remarkable journeys from local high schools to RML.

In the animal care segment, “We taught them about animal husbandry, histology technicians, biologists and veterinarians,” veterinary pathologist Carl Shaia said. “Someone in each of those positions described their duties, education and how they came to RML. We also briefly touched on pay, the importance of benefits and the impact of student debt for higher education.”

RML biologist Tara Wehrly’s daughter participated in the events. Wehrly said she appreciated how the activities gave her daughter a greater understanding of the work she does.

“My daughter knows I work here, and I talk about scientific matters, but until she was on campus, it was more of an abstract concept,” Wehrly said. “I feel that Kamryn (Cregger) found the right people to give enthusiastic, informative presentations communicating the fun parts of their jobs to this group of teenagers. The discussions the kids had with post-bacs and post-docs gave them information about potential career paths that they might not have considered prior to this.”

Cregger and other event organizers already are discussing where to take the idea next, starting off with hopes of continuing the program for years to come. RML would like to inspire generations of science-loving people “and is honored to help guide the students down whatever path they choose,” according to Cregger. 

NIAID Raises Awareness to Malaria-like Diseases in W. Africa

Dengue, Zika, Chikungunya Viruses in Mali; Disease Likely Misdiagnosed

NIAID scientists and colleagues have identified dengue, Zika and chikungunya viruses in the West African country of Mali, where health care providers likely misdiagnose patients with illness from those viruses due to unavailable diagnostic tools. Because malaria is the most common fever-causing illness in rural sub-Saharan Africa, most medical workers presume patients with a fever have malaria. The primary cause of all four infectious diseases is a mosquito bite.

Records from the Malian Health Information System show that about one-third of all patient visits to health care facilities are related to malaria, with 2.37 million clinical cases.

A new study from NIAID’s Rocky Mountain Laboratories and the University of Sciences, Techniques and Technologies in Mali aims to help spread information to medical workers about the existence of the additional viral diseases. Ideally, circulating the information will help them obtain the necessary diagnostics.

The study, published in The American Journal of Tropical Medicine and Hygiene, involved 600 residents, 200 from each of the southern Malian communities of Soromba, Bamba and Banzana. The scientists detected antibodies to dengue virus in the blood of 77.2% of the residents tested; to Zika virus in 31.2%, and to chikungunya virus in 25.8%. They detected at least one of the three viruses in 84.9% of participants, meaning just 15.1% tested negative to any of the three viruses.

Evidence of the parasites that cause malaria was found in 44.5% of those tested. Unlike malaria, however, where most cases are found in children under age 14, residents over age 50 were most likely to have been exposed to dengue, Zika or chikungunya viruses. 

“Despite the high exposure risk to dengue virus in southern Mali, dengue fever cases have rarely been reported,” the researchers write. “This is likely due to the lack of diagnostic testing and the biased clinical focus on malaria in the region. Awareness of dengue virus as a cause of febrile illness needs to be urgently established in medical communities as an important public health measure.”

The scientists are hoping data from a more in-depth clinical study that just ended will provide additional details about the prevalence of these viruses in Mali. They also are planning to examine patients who have undiagnosed fevers to establish infection rates.

NIAID scientists are investigating dengue, Zika and chikungunya viruses to try and develop preventive and therapeutic treatment options, none of which exist.

Reference: S Bane, et al. Seroprevalence of Arboviruses in a Malaria Hyperendemic Area in Southern Mali. The American Journal of Tropical Medicine and Hygiene DOI: 10.4269/ajtmh.23-0803 (2024).

A NIAID research team has developed an additional nonhuman primate study model for Crimean-Congo hemorrhagic fever (CCHF), providing an alternative for development of critically needed vaccines and therapeutics. They hope the effort, described in a new study published in npj Vaccines, will lead to a widely available replicating RNA-based vaccine that they are testing against CCHF. In some outbreaks CCHF has had a case fatality rate up to 40%.

Cynomolgus macaques (CM), which typically develop mild to moderate CCHF disease, are the preferred model available to study how the virus causes infection and disease in people. During the COVID-19 pandemic, however, CMs were prioritized for other research, and scientists at NIAID’s Rocky Mountain Laboratories (RML) sought to develop an alternative model using rhesus macaques (RM) to continue promising pre-clinical work on a CCHF vaccine.

CCHF virus primarily is spread by Hyalomma ticks throughout Africa, the Middle East, Asia and parts of Europe. The disease, first described in 1944, infects up to 15,000 people annually, according to the World Health Organization. About 1 in 8 of those who are infected develop severe disease, which leads to about 500 deaths each year. A vaccine developed in 1974 in Bulgaria is available in some places but has not been approved by the U.S. Food and Drug Administration or the European Medicines Agency. The World Health Organization lists CCHF virus as a priority pathogen for development of vaccines.

The RML group in Hamilton, Montana, has worked with University of Washington and HDT Bio collaborators in Seattle for about 6 years on developing and evaluating the replicating RNA vaccine platform for SARS-CoV-2 and CCHFV. A collaboration between NIAID, HDT Bio and the University of Texas Medical Branch was recently awarded more than $80 million dollars in funding by the Department of Defense to advance the replicating RNA vaccine for CCHFV and Nipah virus into human clinical trials.

The researchers decided to try and adapt their CM study model to infect RMs. CMs and RMs are the two most commonly used research animals among the 22 different macaque species. RMs infected with CCHFV developed mild-to-moderate disease, similar to the CM model and consistent with mild-to-moderate disease in humans. 

The scientists then used a prime-boost schedule to show that the experimental vaccine provided six infected RMs with a protective immune response that controlled CCHF virus. The results are consistent with their findings using CMs and support continued advancement of this vaccine into human trials.

Future work with the vaccine is planned to try and pinpoint how it triggers immune responses in the animals and provides protection from CCHF virus infection. They also plan to explore which animal models will most accurately predict how the vaccine might act in people.

References:

D Hawman, et al. A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever. npj Vaccines DOI: 10.1038/s41541-024-00887-z (2024).

S Leventhal, et al. Replicating RNA vaccination elicits an unexpected immune response that efficiently protects mice against lethal Crimean-Congo hemorrhagic fever virus challenge. eBio Medicine DOI: https://doi.org/10.1016/j.ebiom.2022.104188 (2022).

E Haddock, et al. A cynomolgus macaque model for Crimean–Congo haemorrhagic fever. Nature Microbiology DOI: 10.1038/s41564-018-0141-7 (2018).

NIAID scientists and colleagues are investigating a potential treatment strategy against Lyme disease that would directly suppress Borrelia burgdorferi, the bacterium that causes the disease. If successful, their idea could reduce or end aggressive broad-spectrum antibiotic treatments that can be drawn-out and destroy the body’s helpful bacteria. The study appears in Frontiers in Antibiotics from scientists at NIAID’s Rocky Mountain Laboratories and colleagues at Purdue University.

The strategy involves the oligopeptide (Opp) transport system that most bacteria use as a secondary nutrition route to move small protein-like peptides through the bacteria. But B. burgdorferi, the researchers learned in a 2017 study, depends on the Opp system for survival, growth, and replication. They subsequently hypothesized that if they could impede the Opp system, maybe the bacterium would stop growing and die.

To test their theory they developed a method to screen 2,240 chemical compounds from a commercial library used for small-molecule drug discovery. They wanted to know if any compounds would bind to a prominent transport system protein known as OppA2. The research team identified eight compounds that did so, and of those, two compounds – C2 and C7 – significantly slowed B. burgdorferi growth, making the Opp system a viable, previously unexplored treatment target.

Next the scientists plan to screen more compounds, hoping to optimize binding to different OppA proteins (there are five to investigate) while still hindering B. burgdorferi growth.

“By targeting a system that appears to be only essential to Borrelia, it is possible that we could vastly improve current treatments by replacing them with a highly specific treatment that could reduce post-treatment complications,” study senior author Ashley Groshong, Ph.D., said.

Reference:

K Holly and A Kataria, et al. Unguarded Liabilities: Borrelia burgdorferi’s complex amino acid dependence exposes unique avenues of inhibition. Frontiers in Antibiotics DOI: 10.3389/frabi.2024.1395425 (2024).