ASU spaceflight research pioneer receives top NASA science award

August 4, 2011

Microbiologist uses spaceflight platform to usher in new era of innovative research

Cheryl Nickerson, a microbiologist at Arizona State University’s Biodesign Institute received the Exceptional Scientific Achievement Medal – NASA’s most prestigious commendation for outstanding contributions to science.
"It is a distinct honor and privilege that my biological research in support of the U.S. Space Program has been acknowledged by NASA in such a prestigious format," said Nickerson. "It is the goal and passion of my team to use the microgravity environment of spaceflight as an innovative research platform to unveil novel cellular and molecular mechanisms directly relevant to disease progression that cannot be observed here on Earth. I am excited with the potential of this work to both mitigate the risk of infectious disease to the crew during future exploration missions, as well as for development of novel strategies to diagnose, treat and prevent infectious disease for the general public." Download Full Image

It has been an exciting and tumultuous few weeks for both NASA and Nickerson. On July 8, her most recent experiment – designed to study the effects of spaceflight on a new type of vaccine – rocketed toward the International Space Station aboard the space shuttle Atlantis, on its emotional final journey.

"It is always an unbelievably exhilarating experience to watch your science launch on a Shuttle, but this final mission of the Shuttle program evoked a particularly wide range of emotions," said Nickerson. "While we will profoundly miss this fleet of incredible vehicles and gratefully acknowledge their amazing scientific accomplishments, we also realize that Shuttle has paved the way for a series of next generation spaceflight vehicles. These vehicles, including commercial craft, will continue Shuttle’s legacy of carrying experiments into space, thereby providing scientists with routine, reliable and affordable access to the unique microgravity research platform."

Nickerson has been using spaceflight or spaceflight analogues to study microbial behavior since 1998. In an audacious series of experiments, she was able to validate her early hunches about the responses of certain microorganisms to conditions of reduced gravity. Initially intrigued by the well-known fact that astronauts are immunocompromised during spaceflight and could thus be more susceptible to infection, Nickerson pondered the
effects of reduced gravity  on the disease-causing capacity or virulence of human pathogens.

"The findings from our initial spaceflight experiments were surprising and revealed that the food-borne pathogen, Salmonella, became more virulent when cultured in the microgravity environment of spaceflight," said Nickerson. "Equally surprising, we found that spaceflight globally altered the gene expression of Salmonella in key ways that were not observed during culture on Earth, leading  to the identification of a master switch that regulates this response.

We also found that spaceflight altered the virulence characteristics of other bacterial pathogens, and that they used the same master switch to regulate their responses as did Salmonella."

Nickerson also proposed a mechanism for the profound microbial changes observed under low gravity – a reduction in a physical force known as fluid shear, exerted by liquids as they flow over cell surfaces. Not only was reduced fluid shear a plausible trigger for the changes in virulence and accompanying gene expression Nickerson observed, it
 provided a tantalizing clue about how pathogens might switch their virulence on and off during the normal infection
process on Earth. Microorganisms, including pathogens, are known to encounter regions of low fluid shear during their migrations through the body during the infection process, including in the gut, respiratory passages, and the urogenital tract.

Importantly, these spaceflight-based discoveries are directly applicable to the general public, and the information from these studies is being used to develop novel therapeutics against Salmonella and other infectious agents to reduce human mordibity and mortality on Earth.

The Exceptional Scientific Achievement Medal is awarded to both government and non-government individuals for accomplishments that are “far above others in quality or excellence – a rare, outstanding, clearly superior achievement.”

Nickerson’s path-breaking investigations using the unique platform of spaceflight clearly fit NASA’s stringent criteria for this important award.

According to Duane L. Pierson, Chief Microbiologist at NASA’s Johnson Space Center: “Dr. Cheryl Nickerson has pioneered ground and spaceflight research on microbial pathogens resulting in the most significant advancements to our understanding of microorganisms in the microgravity environment of space.  Her contributions have provided invaluable knowledge of the delicate balance of host-microbe interactions that ultimately determines the difference
between health and disease.”

Mark Uhran, Assistant Associate Administrator of the International Space Station is similarly enthusiastic about Nickerson’s contributions and the intense commitment she brings to her research: “Without any doubt, Dr. Cheryl Nickerson has consistently been among our top scientific performers in the field of  space-based microgravity research. Her impeccable attention to scientific quality and keen appreciation for the benefits of applications-oriented
research distinguishes her clearly in the field.”

Although the last mission of Atlantis on July 18th marked the space shuttle’s swan song, Nickerson says that work will
continue at the International Space Station due to a newly signed Space Act Agreement between NASA and ASU's Biodesign Institute.

"Our work to date merely builds the foundation from which a tremendous amount of research still needs to be accomplished. I am confident that  spaceflight platforms, such as the International Space Station National Laboratory and commercial spacecraft, will provide exciting, ground-breaking discoveries in a variety of biomedical fields that
will translationally advance human health and quality of life for many years to come."

Britt Lewis

Communications Specialist, ASU Library

Chemicals used to fight pests may affect human development

August 4, 2011

An arsenal of chemicals are used to effectively battle noxious pests. The costs to human health from pesticide exposure, however, have not received adequate scientific attention.

Rolf Halden, a researcher at Arizona State University’s Biodesign Institute, joined forces with with key collaborators from other major research institutions, to study two particularly pervasive pesticides, examining their levels in utero and the effects of these chemicals on newborns. The group’s research – the first of its kind to examine the health implications of two leading pesticides during fetal development – recently appeared in the journal Environmental Science & Technology. Download Full Image

Due to the widespread use of pesticides, humans are exposed to an assortment of these chemicals throughout their lives. Chlordane and permethrin, two common chemicals, are the focus of Halden’s multi-institutional team involving Arizona State University, Johns Hopkins University, the National Cancer Institute and Emory University.

Chlordane, having been identified as a likely human carcinogen, was banned from use in 1988. It remains a human health issue long after its discontinued use, however, as it is known to persist in the environment along with other such organohalide chemicals, Halden stresses: “Chlordane is just one of many mass produced organohalides that are detectable in the U.S. environment, where they cause ecological and human health concerns, due to their inherent persistence, toxicity and strong tendency to bioaccumulate in living organisms, including humans.”

Permethrin, known as a pyrethroid insecticide, doesn’t share chlordane’s long-term persistence in the environment, but is nevertheless of serious health concern. It is one of the most broadly used pesticides today—applied for commercial and residential insect control, for food and feed crops, on clothing and as part of mosquito abatement programs.

The health effects from environmental contaminants like chlordane and permethrin are a matter of growing concern, particularly during sensitive stages of fetal development.  Halden notes that the human immune system is vulnerable to changes caused by such chemicals. White blood cells including lymphocytes (T and B cells), natural killer (NK) cells and monocytes, which can mature into macrophages and migrate to other tissues, are all part of the complex fabric of immunity.  

Previous in vitro studies have shown that chlordane and permethrin can affect the delicate immune system in both humans and animals. For example, chlordane has been shown to reduce the effectiveness of NK cells to attack and kill tumor cells. Further, migration of cells to sites of inflammation—a process known as chemotaxis—is also inhibited following chlordane exposure.  Other immune functions associated with tumor-fighting processes and auto-immunity may be disrupted as a result of elevated chlordane levels.

Permethrin also affects immune function, acting to inhibit cell signaling of T helper lymphocytes and modifying antibody production, macrophage function, cell death and cellular immune responses.

Despite existing data implicating chlordane and permethrin in immune system interference, the effects of these two chemicals on immune activity during fetal development has not previously been studied. Working in conjunction with the Center for Disease Control, Halden and collaborators set out to investigate whether in utero exposure to chlordane or permethrin is associated with changes in cytokine levels at birth.

Cytokines are signaling proteins that play a critical role in the immune system, particularly during the processes of inflammation and infection. Halden and his colleagues measured serum levels of nine cytokines in newborns, comparing these with recorded birth weight, length, head circumference and gestational age. They also measured umbilical cord serum from 300 newborns at the Johns Hopkins Hospital, analyzing these for permethrin, chlordane and PBUT—a chemical often used in commercial preparations of permethrin, to enhance the chemical’s insecticidal properties.

Results of the study showed a clear correlation between higher chlordane concentrations and lower levels of a particular cytokine, labeled IL-12. This cytokine is linked with an inflammatory immune response and its reduced levels suggest impairment of this response. The team concludes that such changes in IL-12 could be associated with a decreased ability in newborns to resist infection or combat tumor formation.

Permethrin levels in serum were also associated with cytokine alterations, though in this case, levels of the cytokine IL-10 decreased in response to the pesticide. IL-10 is an anti-inflammatory cytokine, so its reduction may be associated with increased inflammation as well as an increase in allergic reactions, which are typically moderated by IL-10. Decreased levels of this cytokine may trigger diseases associated with increased inflammation, including various allergies and asthma.

Changes in growth parameters or gestational age of newborns did not appear to be correlated with chlordane or permethrin serum levels. Nevertheless, the results of the study were significant and represent the first compelling association between chlordane and permethrin exposure and levels of inflammatory cytokines in the fetus.

Britt Lewis

Communications Specialist, ASU Library