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A study led by Indian-origin researcher Sangeeta Bhatia from the Massachusetts Institute of Technology (MIT) examined the impact of circadian rhythms on drug metabolism. 

Published in Science Advances, the research sheds light on how administering drugs at different times of the day could significantly alter their effectiveness.

Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, collaborated with her team to explore the intricate relationship between circadian rhythms and liver function. 

Employing miniature livers engineered from human donor cells, the researchers discovered that numerous genes involved in drug metabolism are under circadian control. These fluctuations influence the availability of drugs in the body and their breakdown efficiency. For instance, enzymes responsible for metabolizing drugs like Tylenol exhibit heightened activity at specific times of the day.

"This study unveils a crucial aspect of drug metabolism that has largely remained unexplored. Our findings emphasize the need for tailored dosing schedules to maximize therapeutic benefits while minimizing adverse effects," highlights Bhatia, the senior author of the study.

Furthermore, the research exposes how the liver's susceptibility to infections, such as malaria, fluctuates throughout the circadian cycle. Variations in inflammatory responses at different times of the day influence the liver's ability to combat pathogens.

"Our findings suggest that infections may exploit the liver's weakened defense mechanisms during certain periods, underscoring the importance of timing in disease susceptibility," explains Bhatia.

The implications of this research extend beyond drug metabolism, as it provides a platform to explore infections that are notoriously challenging to replicate in laboratory settings. By leveraging circadian variations, researchers can enhance infection rates in engineered liver cultures, facilitating drug screening for diseases like malaria.

Funding for the research was provided by various institutions, including the MIT International Science and Technology Initiatives MIT-France program and grants from the U.S. National Cancer Institute and the French National Research Agency.