THE ROLE OF ACTIVE AND ACTIVE-SITE ALKYLATED HUMAN O6-METHYLGUANINE-DNA METHYTRANSFERASE (MGMT AND R-MGMT) IN DNA REPAIR AND BIOMONITORING

Ph.DDOCTOR OF PHILOSOPH

O.sup.6 -Methylguanine-DNA-methyltransferase (MGMT) specific antibodies

US5817514Granted Paten

METHODS OF ASSAYING DNA-REPAIRING ENZYMES AND THEIR ALKYLATED DERIVATIVES

EP0739419A1Published Applicatio

06-METHYLGUANINE-DNA-METHYLTRANSFERASE (MGMT) SPECIFIC ANTIBODIES

WO1994012660A1Published Applicatio

Fabrication and characterization of 3D bioprinted triple-layered human alveolar lung models

The global prevalence of respiratory diseases caused by infectious pathogens has resulted in an increased demand for realistic in-vitro alveolar lung models to serve as suitable disease models. This demand has resulted in the fabrication of numerous two-dimensional (2D) and three-dimensional (3D) in-vitro alveolar lung models. The ability to fabricate these 3D in-vitro alveolar lung models in an automated manner with high repeatability and reliability is important for potential scalable production. In this study, we reported the fabrication of human triple-layered alveolar lung models comprising of human lung epithelial cells, human endothelial cells, and human lung fibroblasts using the drop-on-demand (DOD) 3D bioprinting technique. The polyvinylpyrrolidone-based bio-inks and the use of a 300 mm nozzle diameter improved the repeatability of the bioprinting process by achieving consistent cell output over time using different human alveolar lung cells. The 3D bioprinted human triple-layered alveolar lung models were able to maintain cell viability with relative similar proliferation profile over time as compared to non-printed cells. This DOD 3D bioprinting platform offers an attractive tool for highly repeatable and scalable fabrication of 3D in-vitro human alveolar lung models.Published versio

Optofluidic Detection for Virus Infection Monitoring using Effective Refractive Index

International audienc

Implication of Localization of Human DNA Repair Enzyme O(6)-Methylguanine-DNA Methyltransferase at Active Transcription Sites in Transcription-Repair Coupling of the Mutagenic O(6)-Methylguanine Lesion

DNA lesions that halt RNA polymerase during transcription are preferentially repaired by the nucleotide excision repair pathway. This transcription-coupled repair is initiated by the arrested RNA polymerase at the DNA lesion. However, the mutagenic O(6)-methylguanine (6MG) lesion which is bypassed by RNA polymerase is also preferentially repaired at the transcriptionally active DNA. We report here a plausible explanation for this observation: the human 6MG repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) is present as speckles concentrated at active transcription sites (as revealed by polyclonal antibodies specific for its N and C termini). Upon treatment of cells with low dosages of N-methylnitrosourea, which produces 6MG lesions in the DNA, these speckles rapidly disappear, accompanied by the formation of active-site methylated MGMT (the repair product of 6MG by MGMT). The ability of MGMT to target itself to active transcription sites, thus providing an effective means of repairing 6MG lesions, possibly at transcriptionally active DNA, indicates its crucial role in human cancer and chemotherapy by alkylating agents