January 9, 2012 Posted by khelgeson in Explore, Health, Montana, Regional, Stories
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Mountain Outlaw: Fighting infection

Story and photos by Tyler Allen Explorebigsky.com contributor

The 1918 flu pandemic, one of the greatest natural disasters in human history, killed between 50–100 million people. By the time it ran its course, 3–6 percent of the world’s population had died from this strain of influenza or from secondary infections.

Today, after nearly a century of biomedical advances and vaccine development, a strain with similar virulence could still impact tens of millions of people. This is due to the instability of the influenza virus and its tendency to spread and evolve rapidly.

In the Molecular Biosciences Building on the campus of Montana State University-Bozeman, Allen Harmsen and researchers in the Harmsen Lab are investigating a new therapy that could fight a potential modern flu pandemic, using viral-like particles called protein cage nanoparticles.

Produced from proteins of an Archaean microorganism that lives in deep sea vents, these protein capsules produce a temporary immune response in the lungs of mice, similar to that generated by an attacking virus.

Unlike an actual virus, these nanoparticles don’t create inflammation in the lung tissue, which compromises oxygen exchange with the blood and can be permanent.

Investigators in the Harmsen Laboratory introduce protein cage nanoparticles to mice bred specifically for biomedical research, and then inoculate the test subjects with a pathogen. Using a Flow Cytometer—a powerful instrument capable of analyzing several thousand particles a second— the researchers map and analyze theimmune-response cells as they attack the invading pathogen.

Harmsen has been researching this therapy for about five years. While nanoparticles are being investigated as a vaccine delivery platform elsewhere, his is the only lab looking into them as a broad spectrum vaccine. Harmsen got the idea while working with fellow MSU scientists Trevor Douglas and Mark Young on a project that used protein cage nanoparticles as a drugdelivery method.

Effective influenza vaccines have been available for over 60 years, but the flu virus still kills 250,000–500,000 people worldwide annually and causes 3–5 million cases of severe illness. During the 2010-2011 flu season, 287 cases of influenza were reported in Montana, with 40 hospitalized.

There have been three pandemic years in the last century. During each, tens of millions died from influenza. The pandemics are caused by a new strain of the virus spreading from animals to humans, or by an existing human virus that picks up new genes from an animal strain.

Since vaccines only work against a particular strain, influenza’s ability to mutate rapidly makes it challenging for researchers to develop a vaccine before a new strain spreads and becomes pandemic. “A significant influenza outbreak like 1918 is very likely to occur again, and this could give researchers time [to develop a vaccine],” Harmsen said.

The temporary immune response created by the nanoparticle therapy lasts up to five weeks in mice, Harmsen says. The hope is that eventual clinical trials will reveal a similar immune response in humans.

Because this immune response is not virus-specific, the lungs can fight any pathogen introduced during this period. Since many deaths from influenza result from secondary infection as the body’s defenses are depleted, this could be an important weapon in the fight against flu mortality.

The Molecular Biosciences Building is home to a number of laboratories working on treatments and vaccines to infectious diseases, including Streptococcus, Staphylococcus and Salmonella. Cuttingedge science is expanding here, and with it, Southwest Montana is growing as a player in global health.

Using nanoparticles to fight MRSA

Aga Apple received some bad news when she arrived in Bozeman to start her doctoral work at MSU . She couldn’t begin her Ph.D. program because the school she attended in Poland, Adam Mickiewicz University, didn’t require the same core classes as most American universities. While this only resulted in five weeks of additional coursework, Apple had to delay her program an entire year. In the meantime she fell in love with Southwest Montana.

After completing her Ph.D. in autoimmunity at MSU , and then her post-doctoral work in ovarian cancer at Dartmouth, Apple returned to Bozeman for a second post-doc. Her research now looks at how protein cage nanoparticles could be used to fight off bacteria, especially MRSA (Methicillin-resistant Staphylococcus aureus). MRSA was first discovered in the United Kingdom in 1961 and is found worldwide. It can kill swiftly, and is especially troublesome in hospitals, where patients have open wounds or invasive devices.

Because bacteria like MRSA reproduce and evolve quickly, they’re capable of developing resistance to the antibiotics used to fight them. Apple is looking for a cell-based approach to fight these dangerous bacteria, using nanoparticles rather than drugs.

Since people who die from influenza are often killed by a secondary bacterial infection due to exhausted immune systems, this work is very closely linked with the Harmsen Lab’s flu research. Since MRSA is capable of killing its host within 24 hours of infection, the implications of nanoparticles as a defense against these drugresistant bacteria could be significant.

Committed to Research

Because of MSU’s commitment to research, particularly in biomedical sciences, the university attracts competitive researchers and their correlating funding dollars. The university was awarded over $100 million in research funding last fiscal year.

Built in 2003, the Molecular Biosciences Building houses a state-of-the-art facility where grants from organizations such as the National Institute of Health and National Institute of Allergy and Infectious Disease help fuel biomedical research.

This story was first published in the winter 11/12 issue of Mountain Outlaw magazine.