Jonathan Hardy is an associate professor in MSU’s Department of Microbiology and Molecular Genetics. He was recruited from Stanford to join MSU’s Institute for Quantitative Health Sciences and Engineering. Dr. Hardy has a B.S. in cell and molecular biology from the University of Washington and a Ph.D. in microbiology and immunology from Stanford University.
The Hardy Lab
The Hardy laboratory studies bacterial infections that affect children. Bacteria cause a wide range of pediatric diseases, from painful earaches to life-threatening meningitis, and these infections not only harm children but also cost billions of dollars in health care annually. Because many bacterial pathogens are becoming resistant to antibiotics, it is crucial to understand the basic biology of these organisms, and how they infect our bodies. We use the techniques of molecular imaging to study bacterial pathogens. These tools allow us to monitor the organism in ways that conventional methods cannot, visualizing and quantifying bacteria over time, both in culture and in live animals. In this way, we can study the process of infection as it occurs, without destroying the culture sample or harming the animal.
One of our most important tools is in vivo bioluminescence imaging (BLI). To image bacteria with BLI, we genetically tag the organism with genes encoding the production of light (bioluminescence). The light from the bacteria can then be detected with a CCD camera, even in a live animal. This method allows us to locate and measure bacterial infection without interfering in the process, enabling us to reveal events not seen using classical procedures.
Some bacteria grow rapidly in the body, whereas others may remain dormant for years before reawakening to cause disease. By monitoring bacterial pathogens non-invasively in live animals over time, we can observe the infection whether or not symptoms are present. Using BLI to image the deadly foodborne bacterial pathogen Listeria monocytogenes, which preferentially infects pregnant women and can cause meningitis in the newborn, we were able to observe the bacteria hiding in the bodies of mice without causing disease. This event was occurring in the lumen of the gallbladder. The discovery was completely unexpected and had never been observed before imaging. Years later, it was confirmed that this event occurs in humans, by researchers at the Pasteur Institute in Paris.
Prenatal infection in women can cause subsequent neurodevelopmental disorders in the child, such as cerebral palsy, schizophrenia and even autism. We are using imaging to study prenatal infection in mice, in the hope of understanding how this occurs. We have used BLI to observe infection progressing in pregnant mice, without affecting the process of birth, and allowing us to test behavioral changes in the offspring. In combination with other techniques such as MRI and ultrasound, we have accessed windows into the growth of the live fetus in the effort to understand this mysterious process and reveal how infection can subtly impact the development of the brain.
Molecular imaging has changed our view of bacterial infection, and the Hardy lab is fortunate to be located in the amazing environment of IQ, where we have found people and resources that have greatly expanded the horizons of our research.