Carbon Nanotube-based Sensor Detects Nitrosamines in Air
A collaboration between environmental science and engineering researchers and biomedical researchers from the MIT SRP has led to the development of a carbon nanotube (CNT) based sensor that enables detection of nitrosamines in air. The sensor was developed by Dr. Maggie He of Prof. Timothy Swager’s laboratory in collaboration with Prof. John Essigmann and Dr. Robert Croy. The approach utilizes functionalized CNTs that can bind nitrosamines spanning across gold electrodes. Specific binding of nitrosamines to the CNTs produces a change in current proportional to the level of chemical in the air. These inexpensive sensors present opportunities for improved remediation efforts at the Olin Chemical Superfund site in Wilmington MA, and they were featured in an article by Chemical & Engineering News, as an NIEHS Paper of the Month, and in an NIEHS SRP Research Brief article and podcast.
Brown University SRP Director Prof. Robert Hurt Presented at Friday Forum Seminar Series
On February 21, 2020, Prof. Robert Hurt (Program Director and Project 4 PI for the Brown University SRP) visited MIT to give a lecture as part of the Friday Forum seminar series. This lecture was co-sponsored by the MIT SRP and Center for Environmental Health Sciences (CEHS). Prof. Hurt provided an overview of the Brown SRP and discussed the program’s research on graphene-based nanomaterials. In particular, Prof. Hurt’s team is developing nanomaterials for advanced barrier technologies to prevent exposure to toxic contaminants. During his talk, he emphasized the cross disciplinary work of the Brown SRP. As one example, Prof. Hurt’s engineering team works closely with Prof. Agnes Kane’s team of toxicological researchers in order to evaluate the risks associated with exposure to relevant nanomaterials. Together, these complementary engineering and biological research projects will lead to development of safer, more effective barriers against environmental toxicants. During his visit, Prof. Hurt (center) discussed graphene-based materials and their potential uses with Prof. Timothy Swager (MIT SRP Projects 1 and 2; left) and Bevin Engelward (MIT SRP Director; right).
The Data Management and Analysis Core Takes off at MIT
With support from the NIEHS, MIT SRP is developing new infrastructure that enables data to be combined in new ways and that ensures FAIR practices. An exciting development is the ability to upload metadata in real time for wide ranging data sets, including environmental as well as biological data. The new Data Management Core will build off of the open access SEEK platform to create a system where researchers from vastly different fields can share and interpret each other’s metadata, facilitating collaborations that are key to SRP success.
MIT Bidirectional Engagement with the Passamaquoddy Tribe
On August 2, 2019, a team from MIT SRP visited stakeholders in Maine, including A.E. Hodsdon Consulting Engineers in Waterville, ME, the group that oversees the drinking water treatment facility for the Passamaquoddy Tribe at Pleasant Point. The district is known as the Passamaquoddy Water District (PWD) and facility’s water source, Boyden Lake, has been known for years to be very challenging. The lake is small and shallow with a several residential homes on it and the treatment facility draws it water from a small impoundment area located downstream from the lake.
Drs. Jennifer Kay, Kathy Vandiver, and Bevin Engelward met with engineer Mark McCluskey and company president Al Hodsdon, who provided a technical overview of challenges that PWD faces in maintaining the standards for this public water supply. The facility is supervised by Hodsdon’s because the district doesn’t have a licensed operator. Seasonal changes and weather-related events produce high levels of organic material, discoloring the drinking water and raising the tribe’s concern about water purity and safety. Additionally, the PWD’s published water quality tests have exceeded the state standards for trihalomethanes (THMs) from time to time, triggering public notices that last for three months and increasing fears about water quality. THMs are commonly formed in water containing organic material that is treated with high levels of chlorination to overcome microbial risk. At our Hodsdon meeting, the MIT team pointed out that conditions that produce THMs also produce of N-nitrosodimethylamine (NDMA), one of MIT’s contaminants of concern. Our discussion with the Hodsdon engineers led the MIT team to conclude that a follow-up trip to Maine with the goal of testing for NDMA at several locations in the PWD district would be supported and welcomed.
In addition to visiting the engineers in Waterville, the MIT SRP team also met with the newly elected Vice Chief of the Passamaquoddy Tribe at Pleasant Point, Maggie Dana. At this meeting, Drs. Jennifer Kay, Kathy Vandiver, Bevin Engelward, and John Essigmann met with Brownfields Coordinator Dale Mitchell and members of the Sipayik Environmental Department, including Director Marvin Cling, Water Quality Manager Billy Longfellow, and Ecology Coordinator Chris Johnson. Overall, tribal members are still quite concerned about ongoing issues with the municipal PWD water supply, in particular the frequent water discoloration and PWD notices of THMs exceedances. The Passamaquoddy expressed a continuing interest in collaborations with MIT scientists in water quality studies.
The MIT SRP is well-positioned to assist with water quality testing as members of the MIT team have previously partnered with Sipayik Environmental Dept. members (named above) in a citizen science project testing for metals, including lead and arsenic in PWD water and well water used by the Passamaquoddy tribe. This successful research collaboration between MIT and the Passamaquoddy Environmental Dept. was both a capacity-building and trust-building experience. Tribal households received back their individual results for lead and arsenic levels in their drinking water with recommendations for how to reduce their exposures. This study laid the groundwork for a future partnership with our Passamaquoddy colleagues to address additional water quality concerns such as NDMA.
MIT SRP team concluded the tribal visit with a separate meeting with Passamaquoddy Brownfields Coordinator Dale Mitchell to learn more about the Meddybemps Superfund site. This site harbors a wealth of native artifacts dating back more than 8,000 years. The site is located on Meddybemps Lake, a major native trading route and an important Passamaquoddy ancestral home. Today’s tribal elders have named this place “Ntolonapemk” — “My Relatives’ Place.” The tribe feels a great spiritual connection to this place and to their tribal ancestors and they are hoping to acquire this land in the near future. The MIT team expressed an interest in supporting the Passamaquoddy with regard to the assessment of the environmental health risks associated with the Meddybemps Superfund site.
Adaptation of an Animal Mutation Model to Cell Culture Enables Rapid In Vitro Mutagenicity Testing
There is much interest in understanding the mechanisms underlying the complex patterns displayed in mutational spectra, because these spectra will help to illuminate the molecular etiology of genetic diseases, such as cancer. The lambda gpt delta C57BL/6J mouse is an extraordinarily useful model for the probing underlying mechanisms of human cancer, and the mutational spectra of dozens of environmental carcinogens have been characterized using this transgenic animal model. Responding to the need for a high-throughput cell culture model derived from this mouse, Dr. Pennapa Thongararm from the Essigmann lab used lentiviral transformation to produce mouse embryo fibroblast cell lines. She then tested the utility of these cells for studies of the kind of DNA damage (specifically, methylation damage) that is produced by N-nitrosamines, environmental carcinogens that are the focus of MIT SRP research.
Studies by Dr. Thongaram et al., recently published in Chemical Research in Toxicology, show a clear induction of methylation damage-induced mutations, with the predominant mutation being G to A. Based on the chemistry of the DNA damage that is formed by methylating agents, the team predicted that these mutations might be coming from O6-methylguanine, which can mispair efficiently with thymine. To test this possibility, the team used a chemical inhibitor of the protein that repairs O6MeG and queried the resulting mutation pattern. They saw a clear enhancement of the original signature, providing direct evidence that O6MeG is the main driver of mutagenicity from methylating agents, and calling attention to the importance of DNA repair as a key player in suppressing methylation-induced mutations. This work opens doors to studies of methylation damage-induced mutations in vivo where ongoing collaborative work is uncovering the importance of gene-environment interactions as modulators of the risk of cancer from exposure to environmental contaminants. Publication DOI: 10.1021/acs.chemrestox.9b00444
Trainee Spotlight: Dr. Amanda Armijo
Amanda Armijo, a postdoctoral fellow at MIT Professor John Essigmann’s group in the Department of Biological Engineering and Dr. James Fox’s group in the Division of Comparative Medicine, is studying the genotoxic signatures caused by environmental contaminants and how these mutations result in development of liver cancer. Specifically, her research focuses on the mutational patterns induced by the probable human carcinogen, N-nitrosodimethylamine (NDMA). NDMA is key contaminant of the Superfund site in Wilmington, MA, which for many years has contaminated the drinking water from several municipal wells. As part of the MIT Superfund Research Program, Amanda is utilizing a high-fidelity duplex consensus sequencing (DS) method to reveal early onset genetic signatures of environmental toxicant-driven human diseases that occur later in life. Identifying these mutational processes can inform strategies for Superfund site remediation as well as clinical genetic disease early-detection, intervention and prevention.
These experiments are being performed in transgenic C57Bl/6 mice that contain a reporter gene to enable a mutational assessment and high-fidelity sequencing of the changes in the DNA triplets in the reporter gene region. To accomplish this, the transgenic mice are treated with a carcinogenic regimen of NDMA and then liver DNA is analyzed 10 weeks post-exposure (prior to development of cancerous lesions) with DS to produce high resolution mutational spectra (HRMS). DS is a highly accurate method to identify rare, unique mutations present in a heterogenous genetic milieu. Mutational spectra patterns will also be identified in lesions that have fully developed into pathological cancer induced by NDMA. Gene-environment interactions that define inter-individual variations in sensitivity to NDMA will be identified using mutational patterns.
Amanda received her Bachelor’s degree in Microbiology, Immunology, and Molecular Genetics from UCLA. After working as a laboratory technician, she entered graduate school at UCLA in the department of Molecular and Medical Pharmacology where her work focused on the link between nucleotide metabolism and DNA replication stress responses. Her graduate work subsequently led to the preclinical development of a panel of small molecule inhibitors of deoxycytidine kinase as an anti-cancer therapeutic. Amanda successfully defended her dissertation and next attended Cornell University’s College of Veterinary Medicine, receiving a Doctor of Veterinary Medicine degree. Following completion of her DVM, Amanda completed an internship in Laboratory Animal Surgery and Medicine at Tufts University. She is happy to have found a program at MIT that combines her interests in both caring for laboratory animals and in performing important research that can positively impact human health. In her spare time, she enjoys sports, volunteering for spay/neuter clinics, cooking, and spending time with her family.