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Description: The human gastrointestinal (GI) microbiome, often viewed as a complex organ itself, influences homeostasis and is implicated in many human diseases. In the last several years, researchers have made great strides in mechanistically understanding the physiological connection between the microbiome and our health. Researchers have even engineered “smart” probiotic bacteria to survey the GI tract and detect and/or treat disease. Engineering probiotic bacteria to function in this complex environment is a challenge, as the cells must recognize disease-specific molecular cues and execute desired functions, all while carrying out their native activities. We are engineering commensal strains of E. coli, those that normally reside in our GI tract, to recognize wounds and pathogens by detecting molecular signals such as hydrogen peroxide, nitric oxide, and various bacterial quorum sensing molecules. We are now building molecular “surveillance” strains that act as a network to ensure desired functions only occur when there are robust and well-defined signals. In this project, we are engineering bacteria and will test the resulting network to ensure that positive responses occur and only in a well-controlled manner. Our UM Scholar will test the ability of the engineered bacteria to detect molecular signals and work in concert with helper strains to coordinate a response. We will carry out this work in lab tests (in vitro), not in animals or humans. Specifically, our Scholar will assess whether the assembled cells can convert hydrogen peroxide signals, indicative of wounds and infections, into the delivery of granulocyte macrophage colony-stimulating factor (GMCSF), a potential drug for Crohn’s disease.
Faculty Lead: William Bentley, Professor, UMCP Fischell Department of Bioengineering, 301-405-4321, bentley@umd.edu. Dr. Bentley is Director of the Robert E. Fischell Institute for Biomedical Devices. His lab resides on the 5th floor of Clark Hall in College Park. Website: https://bentley.umd.edu/
Additional Notes from the Project Leadership: Skills/Experience to be gained: Participating students will be trained in techniques of cell culture, microelectronics, microfluidics, molecular biology (RNA/DNA purification/characterization, PCR, etc.) and microscopy.
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