Shravika Talla
Tutku Tazegul
Genetics, Cell Biology, and Development College of Biological Sciences December 2019 Mentor: Anthony Baughn Mentor's Department: Microbiology and Immunology
Biomedical Engineering College of Science and Engineering May 2019 Mentor: David Odde Mentor's Department: Biomedical Engineering
Antibiotic para-Aminosalicylic Acid Selectivity in Mycobacterium Tuberculosis
Development and Use of an Image Processing Algorithm to Analyze Glioma Cell Protrusion Dynamics
Infectious disease-causing Mycobacterium tuberculosis has been known to become increasingly resistant to antibacterial drugs, leading to a potential public health problem regarding the treatment of patients with tuberculosis. para-Aminosalicylic acid (PAS) is a structural analog of para-aminobenzoic acid (PABA), a compound used in the folate biosynthesis pathway for bacteria, that has an additional hydroxyl group. PAS has been found to inhibit the folate biosynthesis pathway of M. tuberculosis, but not in other bacteria such as E. coli. In E. coli, PAS is used in lieu of PABA. Still, the mechanistic basis for PAS selectivity in M. tuberculosis can be further examined. Here we show that the enzyme dihydrofolate reductase (DHFR) in M. tuberculosis accounts for this selectivity. It has also been shown that PAS antagonizes the activity of multiple drugs used to treat patients with HIV. These data suggest that PAS selectivity for M. tuberculosis is due to the DHFR enzyme. These results elucidate why M. tuberculosis is susceptible to the clinically used antibiotic PAS. With the rise of drug resistant strains, this information can be applied to understand the resistance to antifolates. Furthermore, knowledge that PAS reduces the function of HIV treatment drugs shows implications for HIV patients infected with M. tuberculosis.
The Odde Lab is in the process of developing a cell migration simulator in an effort to predict cell migration patterns and incorporate cell migration consideration into glioblastoma therapies. The simulator models a cell as a central body with multiple modules as a “motor-clutch� system that migrates through a cyclic process of cell membrane protrusion, adhesion of these protrusions to a substrate, force transmission of myosin motors through the protrusions, and rear-release of the protrusion-substrate adhesions. Although the cell migration simulator has successfully predicted certain cell migration patterns, there are some biophysical parameters associated with cell migration that are not well understood. My project focuses on refining and improving a software program that automatically tracks cell protrusions, and using this software to collect and analyze experimental data from cells in different environments (varying substrate stiffnesses, chemotherapy drugs). I have been using this experimentally collected data to elucidate the physical rules that cell protrusions follow, and will implement these rules into future versions of the cell migration simulator.
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