UROP Proceedings 2022-23

School of Science Division of Life Science 17 Understanding the Key Elements of Nucleosome/Chromatin Dynamics Supervisor: ISHIBASHI, Toyotaka / LIFS Student: FISILO, Angelica Cessie / SSCI Course: UROP1000, Summer After the COVID-19 outbreak started, more researchers have sparked interest in manufacturing RNA vaccines. The optimization of mRNA production is needed to deliver the best therapeutics possible. Hence, we proposed the use of thermophilic RNA polymerase. In this UROP1000 project, we will explore the potential of this polymerase to reduce immunogenicity with comparable mRNA efficacy. Using various experimental techniques, we attempted to design, clone, and express the alpha, beta, beta’, omega, and sigma subunits of the bacterial RNA polymerase from three thermophilic bacterial strains: Thermotoga maritima (3109), Pseudothermotoga thermarum (5069), and Caldicellulosiruptor bescii (6725). Through the development of this new RNA polymerase using these bacteria, said RNAP offers a tantalizing glimpse into its potential to transform the landscape of medical therapeutics. Understanding the Key Elements of Nucleosome/Chromatin Dynamics Supervisor: ISHIBASHI, Toyotaka / LIFS Student: HUSEIN, Thomson Christian / SSCI Course: UROP1000, Summer RNA products, such as vaccines, have shown promise; showcased in combating the recent COVID-19 pandemic. As new RNA therapeutics are being produced, we believe that there is a demand for a new RNA polymerase to optimize RNA product purity. Current RNA production methods uses T7 RNA polymerase. Its products have high immunogenicity which decreases efficacy and raises safety concerns. This is caused by the production of double-stranded RNA(ds-RNA) and 3’ surface runoffs which results from T7’s RNAdependent RNAP activity. Eliminating dsRNA is costly and complex due to its similarity to RNA/mRNA. The production of a new thermophilic bacteria RNA polymerase is proposed. Bacterial RNAP offers advantages such as high specificity and limited byproduct formation. Three thermophilic bacteria species (Thermotoga maritama, Pseudothermotoga thermarum, and Caldicellulosiruptor saccharolyticus) were selected, and their RNAP genes will be cloned, expressed in Escherichia coli, and the resulting proteins purified. Receptor Based Drug Development from Chinese Herbal Medicine Supervisor: LI, Ning / LIFS Co-supervisor: XUE, Hong / LIFS Student: KOT, Yung Kei / BIBU Course: UROP2100, Fall UROP3100, Spring Schizophrenia (SCZ) is one of the most severe psychiatric disorders, anxiety is a common symptom in patients with SCZ. L-tetrahydropalmatine (L-THP) and Rudon are the chemicals extracted from Traditional Chinese Medicine (TCM), which are the potential anxiolytic drug candidates. In this report, the anxiolytic effect of Rudon is demonstrated through different animal behavioral tests: elevated plus-maze test, locomotor activity test and tail suspension test using male C57BL/6 mice, the pharmacokinetic study of L-THP with different concentration in human plasma is analyzed by liquid chromatography-mass spectrometry (LC-MS). This study provides critical insights into the potential therapeutic treatment in anxiety in patients with SCZ.

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