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You may know them as the zebra danios or even GloFishTM in your home aquarium, but it turns out that zebrafish have an important role to play in bettering our understanding of nanomaterial toxicity— that is, zebrafish along with cutting-edge investigative work performed by researchers in the Harper Nanotoxicology Laboratory. On the forefront of nanomaterial toxicology research, assistant professor Dr. Stacey Harper was recently named the 2014 recipient of the Savery Outstanding Young Faculty Award. This honor is designed to “recognize outstanding contributions through teaching, research, international, and/or extended education activities of a young faculty member in the College of Agricultural Sciences at Oregon State University” and has been awarded since 1994. Dr. Harper is on the faculty of both the environmental and molecular toxicology department in the College of Agricultural Sciences (CAS) and the environmental engineering department in the School of Chemical, Biological and Environmental Engineering (CBEE).
Key to being awarded this honor is Harper’s strong record of achievement and recognition since becoming an assistant professor at Oregon State in 2009. In her first year at OSU she was named a Signature Researcher of the Oregon Nanoscience and Microtechnologies Institute (ONAMI) and, in 2011, was selected as an Outstanding New Environmental Scientist (ONES) by the National Institute of Environmental Health Sciences (NIEHS), receiving a five-year, $1.9 million award. In 2012, Harper was honored with the L.L. Stewart Faculty Scholars Award, which recognizes an outstanding faculty member at Oregon State University and provides resources to stimulate creative advancements in teaching, research, and extended education.
The Harper Lab, housed in the Agricultural and Life Science building on Oregon State’s Corvallis campus, is headed by Dr. Harper and managed by Harper’s husband, biologist Bryan Harper. Bryan is the lab’s research coordinator and takes charge of the day-to-day business of running the lab, enabling Stacey to keep her attention and focus on ongoing nanotoxicology research. The Harper Lab was bustling with activity this summer, with a staff of sixteen students participating in the research efforts, including four graduate students and several undergraduates, many from the University Honors College. Truly an interdisciplinary laboratory setting, students working there represent a variety of departments, including biology, chemistry and toxicology, as well as chemical, biological, and environmental engineering. Says Dr. Harper, “I believe our research benefits from the interdisciplinary nature of our researchers, including the differences in style and background expertise that Bryan and I bring to the team.”
Researchers in the lab ascertain a material’s relative toxicity using bioassays, which are accomplished by exposing fertilized zebrafish eggs to a solution of nanomaterials at the embryonic stage and then visually observing the effects on their growth over the next five days as they develop into tiny, but fully-formed, transparent fish. One benefit of this work is that it enables toxicological screening to be performed early in a product’s development, rather than after the fact. By using this analysis method, a product developer can “tweak” a formulation, submit several different formulas for testing via bioassay, obtain results in a very short time, and use these test results to select the formulation that has the least potential for harm. The quick turnaround and relatively low cost of these bioassays are some of the reasons for their popularity. In spite of the fact that this testing is generally not a regulatory requirement, it is valued as a cost-effective method for eco-conscious manufacturers to improve the environmental friendliness of their products.
One relatively new innovation in the lab is the development of the “nanocosm”, a major contribution by environmental engineering graduate student Fan Wu and biologist Bryan Harper. Much smaller than a traditional microcosm, this tiny ecosystem-in-a-bottle includes zebrafish, daphnia, algae and bacteria. The team is finding that testing nanomaterials in the nanocosm can sometimes yield different results than when testing is performed on any of the individual species alone. Looking at how nanomaterials affect these small, contained environments adds an important additional layer of information in toxicity testing.
As you might imagine, all these rapid testing strategies generate large amounts of data, and this has lead Dr. Harper into the world of informatics. Results from the numerous bioassays are added to a data repository, the Nanomaterial-Biological Interactions (NBI) Knowledgebase, housed on the Corvallis campus at the Northwest Alliance for Computational Science & Engineering (NACSE) in the Kelley Engineering Center. This data, which includes over 150 bioassays performed on a wide range of nanomaterials, is made available to the public and is used by government, industry and academic toxicology researchers. Harper’s goal is that she and other researchers will create predictive hazard determination models related to the behavior of nanomaterials, based on structure-activity relationships that are identified through analysis of the repository data. According to Harper, “Sharing our data in this way has led to a number of great collaborations with other research groups interested in figuring out what specific features of nanomaterials can be modified to alter biological impacts. We have been working with modelers at Pacific Northwest National Laboratories and the Center for Environmental Implications of Nanotechnology at the University of California Los Angeles to develop some of the first models that will enable us to predict where a nanoparticle will go in the environment and what it will do when it gets there. Our data has been incorporated into the Nanomaterial Registry, an NIH-funded informatics effort to compile data on the biological impacts of nanomaterials, and is being used to support a European Union nanoparticle safety collaboration platform called NanoPUZZLES”.
The Harper Lab is unique in that its funding comes from a wide diversity of sources, including the National Institutes of Health, the US Department of Agriculture (USDA) and the National Science Foundation (NSF). In addition, some work in the Harper Lab is performed at the request of investigators from both commercial and government organizations. One major supporter of the lab has been ONAMI through the Safer Nanomaterials and Nanomanufacturing Inititative. Support from ONAMI helped to fund the initial development of the NBI and also provided significant lab start-up funds. “They really helped us to hit the ground running,” says Bryan Harper. In addition, Dr. Stacey Harper’s numerous awards in the past few years have been a big help in moving her research forward quickly, with a snowball effect. For example, Oregon State University Research Office awarded a Research Equipment Reserve Fund (RERF) grant that allowed the lab to purchase a BD Accuri C6 flow cytometer, which was instrumental in landing the lab’s recent NSF funding. The flow cytometer enables the Harper Lab researchers to quickly and efficiently measure the effects of nanomaterials on the smaller nanocosm organisms, which typically number into the millions.
Clearly, the Harper Lab is onto something. Eco-conscious manufacturers are increasingly recognizing the value of toxicity testing during the product development stage, and new predictive models are being developed by researchers around the world, through analysis of the data accumulating in the NBI Knowledgebase. The research results and the data analysis capabilities made possible through the work of Dr. Stacey Harper are poised to have a major impact on our understanding of nanotoxicology.
For more information:
The Harper Nanotoxicology Lab – http://nanolab.oregonstate.edu
The NBI Knowledgebase – http://nbi.oregonstate.edu
The ONAMI Safer Nanomaterials and Nanomanufacturing Inititative – http://greennano.org