Research Cores

The strength of the CEHS lies in the quality and breadth of its membership.  The different departments from which our 30 MIT members and one Harvard member are drawn illustrates the breadth of scientific disciplines brought to bear on problems in environmental health sciences in the CEHS. Biological Engineering, Chemical Engineering, Civil and Environmental Engineering, Nuclear Science Engineering, Mechanical Engineering, Electrical Engineering & Computer Science, Biology and Chemistry.  The Harvard faculty member is from the Departments of Epidemiology and Nutrition (David Hunter, also Director of the Harvard Center for Cancer Prevention).

The biological organisms used for study by CEHS members are equally varied, covering almost the entire evolutionary spectrum and, importantly, extending to human population based studies.  Collectively, this group takes advantage of some of the most powerful tools in modern biology from x-ray crystallography to high-throughput functional genomics, from mathematical modeling to microbial and human population based genetics, and from two-photon microscopy to mouse knockout and RNAi technology.  In addition, the Civil and Environmental Engineering faculty provide a fundamental leap from wet-lab and computational based biological research to the external environment, addressing chemical, physical and biological parameters that influence the distribution of toxicants in our environment, in some cases viewing this distribution on a truly global scale.

This Research Core, directed by Peter Dedon, builds upon the historical strength of the Center.  Collectively this group addresses how exposure to DNA damaging agents affects the health of cells, tissues, animals, people and populations, and in particular how these agents cause cancer and contribute to other diseases associated with the aging process. The damaging agents include reactive oxygen and nitrogen species, alkylating agents, and radiation (all ubiquitous in our environment) and the tools used include x-ray crystallography, state-of-the-art mass spectrometry, organic chemistry and biochemistry, bacterial and yeast model organisms, cultured mammalian cells, mathematical modeling of signal transduction pathways, RNAi manipulation of gene expression, transgenic and knock-out mouse model systems, genetic polymorphism detection in human populations, transcriptional profiling, functional genomics and the accompanying bioinformatics required to analyze the data.  The goals are to determine the molecular details of how exposure to environmental agents cause detrimental health effects, and perhaps more importantly to determine the molecular details of how cells, tissues, animals and people ameliorate these detrimental effects.

This Research Core, directed by Linda Griffith, represents an exciting new direction for the CEHS that will bring many of the strengths of the Biological Engineering Department and the emerging Computational and Systems Biology Initiative (CSBi) into the Center. The approaches that will be adopted here include the following: using engineered tissues (such as liver and bone marrow) to monitor and dissect biological responses to toxic environmental agents; linking systematic experiments to quantitative models of cellular responses to damaging agents (the CSBi paradigm as shown in the adjacent figure); developing genomic and proteomic approaches for these systematic measurements; and applying state-of-the-art mechanical engineering to devise new ways of monitoring biological events and single molecule biochemical events. Collaborations between members of this Research Core are already well established. For instance the Griffith lab collaborates with a number of other labs (Samson, Tannenbaum, Essigmann) to apply transcriptional profiling and proteomics to analyze the response of engineered liver tissue to environmental toxicants; one goal is determine how closely the response of engineered tissues recapitulates the response of that tissue in an animal. Ultimately one could imagine using engineered tissues instead of animals to determine whether environmental agents present a health hazard. The Lauffenburger, Tannenbaum, Tidor, and Yaffe labs already collaborate to systematically study and mathematically model apoptosis at the systems biology level, and this approach will be extended to studying apoptosis induced by environmental toxicants.  The So and Engelward Labs have collaborated to use two-photon microscopy for monitoring chromosomal damage as it happens in vivo. The Dedon and So Labs have developed methods to monitor biophysical events on single DNA molecules as these molecules are acted upon by various enzymes relevant to the Environmental Health Sciences.

The mission of this Research Core, directed by David Schauer, is to understand, holistically, the relationships that link ecological processes and human health. This includes the traditional 'fate and transport' model (in which chemical releases are transported and modulated by processes in the ecosystem, thus governingthe extent of human exposure to the chemicals). However, advances over the past decade mandate a broader view of environment-health linkages, in which genomics and ecology play an increasingly prominent and important role. Future advances require better understanding of evolution, gene flow, and ecosystem processes along with progress in chemical and physical modeling and measurement. Gene flow, for example, can affect the distribution of pathogenicity, or the acquisition of antibiotic resistance or biodegradative capability in microbial communities. Ecosystem processes govern the nature of coexisting populations at scales from that of the gut to that of continents, with direct effects on humans at all scales. Examples of projects ongoing in this Core include: the environmental geochemistry of toxic metals, population dynamics of pathogenic and non-pathogenic Vibrio species in natural waters, the ecology of the lower gut and how that influences cancer susceptibility, the ecology and evolution of microorganisms in nature, and studies on arsenic in drinking water in Bangladesh (a result of a tradeoff between chemical toxins and environmentally transported pathogens).  We envision that this Research Core will ultimately represent a bridge from the Systems Biology approach to the Earth System approach in addressing questions related to the effects of environment on human health.