Pathfinder Innovation Project—Using Zebrafish to Quickly Screen Air Pollution Sources for Potential Impact on Heart Health

By Aimen Farraj

Fine particulate matter (PM)—a tiny mass of solid and liquid matter floating in the air—comes from sources that emit air pollution including automobiles, power plants and forest fires, and is also formed by the interaction of other air pollutants.  PM is everywhere and exposure levels are largely determined by how close one is to an emitting air pollution source.

Many studies have shown that PM’s health effects stem largely from its impact on the heart, driving people to the hospital and making diseases like heart failure worse.  These health effects are caused by chemicals within particulate matter, which vary depending on the air pollution source.  No two air sheds are alike, resulting in endless numbers of unique PM samples with little information on their potential to affect health. Traditional methods for assessment are just too slow and impractical.

In 2013, our team applied for a Pathfinder Innovation Project (PIP) to develop an approach to rapidly assess the cardiotoxicity potential of PM from different sources. The PIP program is an internal competition for EPA scientists to receive time to explore their biggest ideas in environmental research. The goal of this work is to identify PM sources and PM components that cause cardiovascular effects on a larger scale to expedite risk determinations associated with exposure to different air sheds.

an illustration of a zebrafish

Two day-old wild type zebrafish used for heart rate determinations

To do this, we developed a zebrafish model to assess cardiotoxicity of PM from different sources.  Zebrafish are tropical freshwater fish that have uncanny similarities in cardiac function with humans and their small size makes them ideal for rapid testing.  The zebrafish model we developed is based on measurement of a simple health metric, i.e. heart rate, in hundreds of fish in a 96-well plate. Since the early days of the project, we have demonstrated that this model can be used to quickly assess cardiac impacts of PM exposure.

Now the team is working to refine all aspects of the model, including increased automation to permit rapid heart rate determinations and to expand the number of PM sources assessed.  If successful, this effort may accelerate the pace at which PM toxicity information is acquired, link health effects to specific air pollution sources, and inform strategies to target and reduce PM sources linked to highest potency components.

 

Pathfinder Innovation Project Team: Aimen Farraj, Stephanie Padilla, Alan Tennant, Rory Conolly, David DeMarini, Ian Gilmour, Mike Hays, Najwa Haykal-Coates, Wayne Cascio, Mehdi Hazari, and Oak Ridge Institute for Science and Education student Kyle Martin

 

About the Author: Dr. Aimen K. Farraj is in his eleventh year as EPA’s Principal Investigator in the Environmental Public Health Division.  His research interests include the study of the adverse cardiovascular effects of air pollution and development of better predictive tools for risk assessment.

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.

Pathfinder Innovation Project – Harnessing Smart Web Technology for Sustainable Chemicals

By David E. Meyer, Ph.D.

graphic: a man and woman hold up beakers under the sentence"pathfinder innovation presents: meet the innovatorsHave you ever stopped to think how your smartphone can find a nearby place to eat or reroute you to avoid a traffic jam down the road? It’s because your phone is able to simultaneously locate and retrieve relevant linked open data streams based on what you’ve told it, understand what the data means based on how it is stored, and ultimately help you with your decision. If EPA and other federal data sources were stored in a similar way, a computer could better manage the large amounts of data needed to evaluate the sustainability of chemicals.

four profile pictures of the team members

Pictured: David E. Meyer (top left), Wesley Ingwersen (top right), Michael Gonzalez (bottom left) and Jane Bare (bottom right)

In 2014, our team (pictured left) applied for a Pathfinder Innovation Project (PIP) to study the use of smart web technology and data mining to improve the process of evaluating chemical sustainability. The PIP program encourages EPA scientists to think “outside the box” to solve challenging problems and rewards them with the necessary time and resources to develop their visions into viable solutions. The goal of this work is to develop an automated application to gather and manage necessary life cycle assessment (LCA) data –how a product is produced, used, and handled at the end of its life—to evaluate the environmental sustainability of chemicals.

To do this, we first identified EPA data sources and developed a method to apply the data for use in LCA. We described what the data means through the creation of an LCA ontology. An ontology is a vocabulary that describes data within a conceptual model and enables a computer to understand why and how the data are needed. The resulting method has been peer-reviewed and holds the potential to identify and generate LCA data much faster and cheaper than what has typically been done. The PIP program has supported this work every step of the way based on its importance in advancing the way EPA applies LCA research to other environmental challenges. Private companies that are required to report this kind of data will also benefit from this faster approach by reducing the time they spend processing data requests.

We are now finishing the development of a prototype that automates the discovery and use of EPA data for LCA. Continuing work will focus on expanding the data discovery tool into a full life cycle data modeling system that is capable of automatically gathering data from a variety of sources, harmonizing (or matching) the data to be consistent with existing chemical life cycle models, applying the data to evaluate chemical sustainability, and sharing the data with anyone who needs it in the future.

Read the blog Transforming Science and Technology with Pathfinder Innovation Projects to learn more about the program.

 

About the Author: David E. Meyer, Ph.D., is a chemical engineer in EPA’s Sustainable Technology Division and Life Cycle Assessment Center of Excellence. David and the LCA team generate data, methods, and tools to support the widespread use of LCA in EPA. The LCA team supports decision makers in various Program and Regional Offices to develop custom LCA approaches for implementing EPA’s policies for sustainability.

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.

Pathfinder Innovation Project – Does the Microbiome Influence More than Just our Gut?

By Tamara Tal

Did you know that tgraphic: a man and woman hold up beakers under the sentence"pathfinder innovation presents: meet the innovatorshere are an estimated 100 trillion microbes living on, and in, the human body? These microbes are everywhere – they coat our skin, live in our hair, and carpet our gut.  The community of bacteria that line our gut, known as the gut microbiota, expands our ability to process food and chemicals far beyond what the human genome encodes, and functions as a so-called “second genome.”

A group photo of the project team.

The project team.
Pictured front: Charles Wood, Tamara Tal (author), Alexander Gearhart . Pictured back: Mark Strynar, Drake Phelps. Not pictured: Doris Betancourt, Nichole Brinkman, Scott Keely, Charlene McQueen, Jeanene Olin, and Jon Sobus

Many studies have reported that microbiota are required for normal development. What’s more, changes to the human microbiome have been associated with multiple diseases like obesity, asthma, diabetes, and multiple sclerosis. Importantly for EPA, some studies are beginning to reveal that microbiota can detoxify or bioactivate environmental chemicals. Basically, those little microbes are doing a lot for us, but we still don’t understand how it all works.

In 2014, our team (pictured left) applied for a Pathfinder Innovation Project (PIP) to study the microbiome and how it relates to chemical safety. The PIP program is an internal competition for EPA scientists to receive time to explore their biggest ideas in environmental research. The key goal of this work is to better understand whether the toxicity of environmental chemicals is modified by gut microbes.

To do this, we developed a zebrafish model to test whether chemical toxicity is reliant on host-associated microbiota. Zebrafish are a small freshwater fish that develop rapidly after birth and are 70% similar in genetic makeup to humans. Since our initial proposal, we have demonstrated that this model can be used to rapidly test whether chemical toxicity is shaped by microbiota by comparing the effects of chemical exposures in sterile and colonized zebrafish. The PIP program has supported this work every step of the way.

A microscopic picture of a zebra fish

4 day old sterile zebrafish larva colonized with fluorescent bacteria (A. veronii HM21: dTomato)

Entering our third cycle of PIPs, the team is now working on a long-term effort that will allow us to learn more about how the microbiome impacts our body’s ability to process chemicals and thereby affect brain development. If we find that resident microbes change the way we process chemicals or that chemical exposures disrupt brain development that is controlled by normal microbial colonization, the way that we assess these chemicals may need to be re-examined.

Read the blog Transforming Science and Technology with Pathfinder Innovation Projects to learn more about the program.

 

About the Author: Tamara Tal is a Biologist in NHEERL’s Integrated Systems Toxicology Division. The Tal lab studies whether host-associated microbiota modify the developmental toxicity of environmental chemicals. The group also works to resolve how early life stage thyroid hormone disruption impacts brain development and function in zebrafish.

 

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.

Transforming Science and Technology with Pathfinder Innovation Projects

By Kevin Kuhn

graphic: a man and woman hold up beakers under the sentence"pathfinder innovation presents: meet the innovatorsSix years ago, I was 2300 miles from home when I received a call from my wife telling me that my baby daughter was about to be born two months early. By the time I landed at home in DC, my daughter was born weighing just under four pounds—small but strong.

At the time, I was too focused on my daughter to see the amazing technology in the hospital that made all the difference: from the tiny tools to the constantly beeping machines keeping track of her vitals.

Leaps forward in science and technology, like those in the hospital that kept my daughter healthy and strong, are important. This is why I care so much about innovation and why I work hard to support EPA scientists foster their big ideas. These ideas, if nurtured, could help develop solutions to our most pressing human health and environmental challenges.

Just a few months after my daughter was born, EPA launched the Pathfinder Innovation Projects competition. By providing funding and time, this internal competition provides EPA scientists the opportunity to be creative and take a chance on their most game-changing ideas. Over the last five years, we have supported 55 amazing projects. Learn more about these projects here.

EPA just announced the sixth cycle of the competition, so our scientists can apply for the opportunity to pursue their most transformative and unconventional ideas. In celebration of another year of Pathfinder Innovation Projects, we’re going to highlight successful projects that have truly embodied the culture of innovation at EPA.

In the upcoming weeks, look out for blogs from these amazing EPA scientists. These will include projects such as modeling the human microbiome for behavioral studies using zebrafish, improving methods for monitoring cardiovascular health, and many more!

These scientists have worked tirelessly to make their best ideas come to life, and I love seeing their research get the attention it deserves.

About the Author: Kevin Kuhn is an advisor to the Chief Innovation Officer in the U.S. Environmental Protection Agency’s Office of Research and Development and manages the Pathfinder Innovation Projects – a competition that provides seed funding for EPA research scientists to pursue high-risk, high-reward research. Learn more about EPA Innovation at: https://www.epa.gov/innovation.

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.

Precisely Right

By Dustin Renwick

Close up image of a the inside of a pill bottle filled with blue pills.During his State of the Union Address a few weeks ago, President Obama outlined his vision for a Precision Medicine Initiative, “a bold new research effort to revolutionize how we improve health and treat disease.” The proposal has received praise from universities, think tanks, and the National Institutes of Health.

One EPA researcher has been at the forefront of this topic for more than a decade already.

Christian Daughton—a recipient of three EPA Pathfinder Innovation Project awards—has focused his research on topics related to precision medicine, more commonly known as personalized medicine.

The basic premise: treatments targeted to the individual instead of the statistically average patient.

In the past, Daughton says, small-town doctors could know their patients and corresponding medical histories, which facilitated individualized treatments, prescriptions and doses. The White House effort updates that historical ideal.

“This new initiative from President Obama is making use of the latest advancements in clinical research to capitalize on making drugs more effective,” Daughton says.

His work at EPA explores the intersection of medicine and the environment. The drugs prescribed in the doctor’s office can eventually end up, in some form, in our waterways. They can contaminate our water resources and harm the species that call those aquatic environments home.

Pharmaceuticals typically enter the environment through human excretion and bathing, as well as improper disposal, such as dumping pills down the drain or tossing them in the trash.

“Human health is intimately connected with the health of the environment,” Daughton says. “If one is ignored, there can be ramifications for the other. But the connections—such as disposing of unused medicine or simply daily excretion and bathing—might not be obvious, and they might not be short-term. That’s why they often escape people’s attention.”

“If you optimize healthcare for treating the patient and the environment as one, you optimize the choice of medication, if any, as well as the dose regimen for the individual patient.”

When doctors tailor precise prescriptions for each patient, they can minimize leftovers, theoretically reduce costs throughout the healthcare system, and succeed in dispersing fewer doses to the environment.

That all adds up to a reduction in the amount of medication that finds its way down a drain or into landfills. Another major advantage: potentially reducing the incidence of recreational use and accidental poisonings among children.

“It’s hard to find any negatives to it other than it’s not easy to implement,” Daughton says.

But the White House has taken a first step toward that reality by making precision medicine a priority.

About the Author: Writer Dustin Renwick is a student contractor with EPA’s Innovation Team and a frequent contributor to “It All Starts with Science.”

Editor's Note: The views expressed here are intended to explain EPA policy. They do not change anyone's rights or obligations. You may share this post. However, please do not change the title or the content, or remove EPA’s identity as the author. If you do make substantive changes, please do not attribute the edited title or content to EPA or the author.

EPA's official web site is www.epa.gov. Some links on this page may redirect users from the EPA website to specific content on a non-EPA, third-party site. In doing so, EPA is directing you only to the specific content referenced at the time of publication, not to any other content that may appear on the same webpage or elsewhere on the third-party site, or be added at a later date.

EPA is providing this link for informational purposes only. EPA cannot attest to the accuracy of non-EPA information provided by any third-party sites or any other linked site. EPA does not endorse any non-government websites, companies, internet applications or any policies or information expressed therein.