THESIS DEFENSE — PUBLIC SEMINAR: ABCB1 AS A NOVEL INSIGHT FOR THE UNIQUENESS OF BATS

Start Date & Time: 
Thursday, 1 February, 2018 - 10:00
End Date & Time: 
Thursday, 1 February, 2018 - 11:00
Venue: 

Training Room 3D, Level 3 Duke-NUS

Speaker: 
Speaker Details: 

JAVIER YU PENG KOH
IBM PhD PROGRAM (INTAKE 2013)

Synopsis: 

Bats are the only mammals to have attained true flight. In addition, they possess the unique characteristics of long lifespan, being reservoir for numerous deadly viruses and low tumorigenesis rate. For decades, bat biologists have hypothesized theories to how bats have acquired such characteristics. These include hibernation, free radical theory and DNA damage theory of aging. However, these theorieslackedmechanistic evidences to support their claim. Our recent comparative genome analysis of two different bat species, Pteropus alecto and Myotis davidii, suggested that bats have an improved DNA damage resistance, possibly via an evolutionary positively selected DNA damage response pathway. Unexpectedly, treatment of γ-irradiation to human, mouse and bat cells demonstrated no significant differences in their γH2AX response. Instead, bat cells exhibited exceptional resilience to DNA damage induced by genotoxic agents in comparison to the other mammals. Using doxorubicin, we found that the mechanism of DNA damage resistance in bat cells was due to the intrinsic ability of drug efflux via ABC transporters. We also identified ABCB1 as the sole ABC transporter responsible. Inhibition of the transporter using chemical inhibitors or short-interfering RNAs restores doxorubicin effect on γH2AX in bat cells, and significantly increased their sensitivity to doxorubicin-induced DNA damage and cell death. Moreover, we were able to show that the drug efflux ability is present in multiple different bat species and different tissues of Pteropus alecto. Together, our findings indicate that bats possess a broad and unique ABCB1 expression to protect from DNA damage.

Thesis Advisor: A/Prof. Koji Itahana