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Michigan State University Superfund Research Program
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MSU Superfund Research Program Newsletter

The MSU Superfund Research Program is pleased to send you the fifth edition of our electronic newsletter. Please take a moment to read over our recent activities.  

For more information on the MSU Superfund Research Program, please visit: http://iit.msu.edu/superfund2013/index.html.

In This Newsletter:

Research Spotlight

Sudin Bhattacharya, Ph.D., Michigan State University
Dr. Timothy Zacharewski, Ph.D., MSU
Dr. Sudin Bhattacharya, Assistant Professor in the Departments of Biomedical Engineering and Pharmacology & Toxicology, as well as the Center for Research on Ingredient Safety at MSU, is co-Investigator for Core A of the MSU Superfund Research Program: Computational Modeling of Mammalian Biomolecular Responses.

Even four decades after its discovery, the aryl hydrocarbon receptor (AHR), a ligand-inducible transcription factor (TF) that is activated by the persistent environmental contaminant 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like chemicals, remains an enigmatic molecule with a controversial endogenous role. Ligand-activated TFs, like the AHR, underlie most of the major cellular stress response pathways. The inactivated TFs are typically sequestered in the cytoplasm or nucleus. Upon activation by its ligand (endogenous or exogenous molecule), the TF is able to bind specific response elements in the promoter regions of target genes and activate or inhibit coordinated expression of suites of genes. However, only a small subset of target genes in TF-governed pathways are regulated in this “classical” manner.

Dr. Bhattacharya’s group is working to unravel the structure and dynamics of the molecular networks underlying activation of the AHR pathway. Using gene expression and genome-wide AHR binding data sets generated by Dr. Timothy Zacharewski’s group in Project 3 of the MSU Superfund Research Program, they have shown that the classical model of direct target gene regulation accounts for only about 10% of gene perturbations in TCDD-exposed mouse liver. Dr. Bhattacharya’s group has used publicly available databases of TF-gene interactions to show that the AHR pathway does not act in isolation, but is instead embedded in a hierarchical network comprised of multiple gene regulatory interactions. Genes in this network bound by similar groups of TFs show similar expression patterns, thus establishing a link between gene co-regulation and co-expression. Furthermore, co-regulated gene clusters activated distinct groups of downstream biological processes, with the AHR-bound genes enriched for metabolic processes and AHR-unbound genes primarily activating immune processes. This ongoing work illustrates how the application of bioinformatic and statistical tools for reconstruction and analysis of the transcriptional regulatory cascades can significantly advance our scientific knowledge of the underlying adverse cellular responses to environmental toxicants.

Society of Toxicology Annual Meeting Awardees 


The Society of Toxicology held their annual meeting in Baltimore, Maryland, March 12 - 16, 2017. Several MSU Superfund affiliates were honored: 
  • A paper by Rance Nault, Kelly Fader, and Dr. Timothy Zacharewski (Project 3) titled, "Pyruvate Kinase Isoform Switching and Hepatic Metabolic Reprogramming by the Environmental Contaminant 2,3,7,8-Tetrachlorodibenzo-p-dioxin," was awarded Honorable Mention in the SOT Toxicological Sciences Paper of the Year category. 
     
  • Jiajun (Brian) Zhou (Project 1) received third place for his student presentation, "Suppression IgM Response by 2,3,7,8-Tetrachlorodiobenzo-p-Dioxin (TCDD) Involves Impairment of Immunoglobulin Secretion by Human Primary B," by the Immunotoxicology Specialty Section of the SOT. He also was awarded the Ronald and Sharon Rogowski Fellowship for Food Safety and Toxicology for the summer of 2017.
     
  • Kelly Fader (Project 3) was the recipient of two awards from the Mechanisms Specialty Section of the SOT, the Carl C. Smith Graduate Student Award - Second Place and the Sheldon D. Murphy Student Travel Award for her abstract, "Hepcidin Deficiency, Systemic Iron Overloading, and Heme Accumulation in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Elicited Hepatotoxicity."

Short Course: Computational Systems Biology and Dose Response Modeling

The Training Core of the MSU SRP will offer an intensive three day short course, “Computational Systems Biology and Dose Response Modeling,” May 15-17, 2017. Short course students will learn dynamical systems modeling techniques for quantitative investigation of how biological systems respond to perturbations at the cellular level.

The course includes lectures and hands-on computer simulation exercises on:

  • Common network motifs in signal transduction and gene regulatory networks that underlie systems-level cellular behaviors including homeostasis, adaptation, threshold response, binary and irreversible cell fate decisions, and oscillations. 
  • How molecular circuits comprimising genes and proteins give rise to various dynamic and dose-response behaviors. Examples include cellular stress response, cell differentiation, and cell cycle and checkpoint control, etc.
  • Use of these simulation techniques to develop computational models for understanding and predicting nonlinear dose response behaviors of environmental toxicants and drugs. 
Course instructors are Sudin Bhattacharya, MSU, Wan-Yun Cheng, U.S. E.P.A., Rory B. Connolly, U.S. E.P.A., and Qiang Zhang, Emory University. 

For questions regarding the course, please contact, Dr. Qiang Zhang, qiang.zhang@emory.edu.

If you are interested in attending the course, please contatct Kasey Baldwin, kbaldwin@msu.edu

Three MSU SRP Laboratories Collaborate on Experiment


Three laboratories affiliated with the MSU Superfund Project are collaborating to investigate the bioavailability of dioxins when bound to activated carbon. The laboratories of Dr. Norbert Kaminski (Project 1), Dr. Stephen Boyd (Project 6), and Dr. Syed Hashsham (Project 4).

The focus of this ongoing collaboration is on characterizing the properties of activated carbon for the purpose of environmental remediation. Specifically, activated carbon is a material that is becoming more widely used to remediate chemically contaminated soils and sediments due largely to its cost effectiveness versus more traditional cleanup methods such as dredging or excavating. Activated carbon particles are very porous and lipophilic persistent environmental contaminants like dioxins, being very water-insoluble, articulate into the activated carbon and adhere to it. The idea is that the activated carbon will sequester the contaminant in a form that is no longer bioavailable to fish, mammals, and humans.

The collaborative laboratory experiments utilize a mammalian mouse model. Boyd’s group prepared and then orally administered microporous activated carbon adsorbed with dioxins (TCDD). To test the bioavailability of the TCDD, Kaminski’s laboratory assessed modulation of the immune system, a hallmark of TCDD toxicity. Hashsham’s laboratory analyzed the changes in the composition of the microorganisms (i.e., gut microbiome) within the GI tract.

The results from these collaborative experiments show that microporous activated carbon does successfully sequesters TCDD to minimize bioavailability as evidence by a loss of TCDD biological activity in the mouse model.

Community Engagement and Research Translation Cores Work Together to Reach the Tittabawassee River Community


Legacy industrial processes resulted in the contamination of the Tittabawassee River by dioxin-like compounds, which was first identified in the 1980’s and more recently is being remediated. One of the major activities of the MSU Superfund Program has been to work with the community to provide information to help minimize exposure to these contaminants. In the summer of 2016, the Community Engagement Core of the MSU SRP conducted a survey of anglers on the Saginaw and Tittabaswassee Rivers. Although human exposure can occur through a number of pathways, fish consumption is a major concern. To better understand this community’s informational and engagement needs, the current survey evaluated the anglers’ fishing habits, knowledge, and risk perceptions. Participants were also asked about their perceptions of and contact with the Michigan Department of Health and Human Service’s River Walker program whose staff walk along the Saginaw and Tittabawassee Rivers and speak with anglers regarding the risk posed by fish and strategies for avoiding exposure.
 
Along with this effort, the Research Translation Core of the MSU SRP has worked with the Michigan Department of Health and Human Services (MDHHS) to create a Michigan Safe Fish App, which will allow the user to connect with the State Fish Advisory Program as well as the MSU SRP. The purpose of this mobile fish application is to connect the community to information about the risk of toxic chemicals in fish caught in local waters as well as fish consumed from the market. Information on safe portion sizes and allowable frequency of consumption will be available in app; as well as methods of reducing exposure risks when consuming fish, including information on choosing fish low in chemicals, how to clean catches properly, and preparing fish. The app also includes a point system (called Eat 8!) where users can track the amount of fish portions consumed each month. Other features of the app include a “Fish ID” section where users can scroll through pictures of local fish to properly identify their catch. Catch and location can be stored in the database of the app. The app will also provide access to the “Eat Safe Fish Guidelines” provided by the MDHHS. The MI Safe Fish App is currently in the final stages of revision and will be released to the public soon.
Local residents and Delta College students, Trevor Shook and Ashley Logan, sample water from the Tittabawasee River. 

MSU Superfund Virtual Lab Meeting


The Training Core of the MSU Superfund program has held several virtual laboratory meetings this year and will hold two more in March and April. The MSU SRP Virtual Lab meetings feature a different project or core at each meeting. One or two individuals (PI, graduate student, post doc) from each project/core makes the presentation at each meeting. The Training Core’s overall goal with these meetings is to help the graduate students and post docs working on our projects/cores enhance their communication skills and to get to know each other better. Another goal is to promote "cross training" of our trainees across the many disciplines involved in our SRP program. Therefore, PIs are encouraged to provide opportunities for these individuals to present their research during the “Lab Meetings.”

Three meetings this spring have already been held - Rance Nault from Project 3 presented on January 24, Gerben Zylstra from Project 5 presented on February 14, and Jackie Zhuang from the Community Engagement Core presented on March 21. The remaining meeting this spring will take place at B448 Life Sciences Building, MSU at 12 noon Eastern Time and can be joined by Go-To Meeting at https://global.gotomeeting.com/join/594201277, with the Meeting ID: 594-201-277. 

Upcoming Meetings: 
  • April 11, 2017: Research Support Core B: Environmental Molecular Analysis, Presenters: Jim Cole & Beni Chai.

Trainee Spotlight: Jonathan "Brett" Sallach, Ph.D.

(originally posted in SRP ePosted Notes)

Jonathan “Brett” Sallach, Ph.D. is a research associate under the guidance of Dr. Stephen Boyd, Project 6. His current work focuses on evaluating the effects of sorption on the bioavailability of dioxins to both mammals and bacteria.

Collaborating with environmental toxicologists at MSU, Sallach evaluated how activated carbon amendments, an emerging remediation technology, impacts the bioavailability of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in mice using a number of immunoassays. Where other sorbent materials, such as silica and clay, have proven to be ineffective in reducing bioavailability, they have shown that activated carbon has the potential to sequester TCDD in a form that is completely unavailable to the mouse.

TCDD also has the ability to impact the mammalian gut microbiome. Sallach is working on other collaborative efforts to evaluate the effects of activated carbon and TCDD bound activated carbon on the microbial populations and their function within the mammalian digestive system. He is also evaluating how bacterial biodegradation and the use of activated carbon may impact each other as two remediation strategies. This includes investigating the potential toxicity of activated carbon to known dioxin degrading bacteria as well as understanding how sequestration of TCDD by activated carbon may affect their availability to the bacteria.

Sallach was recently awarded a Marie Skłodowska-Curie Fellowship, which supports promising individual researchers to work abroad. With the fellowship, he will continue his training at the University of York in York, England, where he will be evaluating the toxic effects of emerging contaminants in the agro-ecosystem. The ultimate goal of his project is to develop a tool to help predict regions and soils most at risk for the effects of emerging contaminants.
Copyright © *|2017|* *|Michigan State University Superfund Research Program|*, All rights reserved.

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