Diurnal Plasticity of Primate Genome across Multiple Tissues of the Central Nervous System and Peripheral Organs
Abstract
Human behavior, physiology, and metabolism change profoundly between day and night. These changes organize activity-sleep, hunger, caloric intake, digestion, insulin action, metabolism, toxic product breakdown, excretion events to the right times of the day. Shift-work as well as the modern lifestyle of staying awake late into the night repeatedly disrupts these coordinated orchestration of body s function. Continued lifestyle disruption adversely affects the fine control of organs functions and consequently leads to chronic diseases including metabolic diseases. Metabolic diseases are also trigger for inflammation, arthritis, depression, overuse of psychotropic drugs, sleep disorders, and reduced longevity. Conversely, several chronic diseases also show circadian disruptions. However, there is very little insight on how thousands of genes in different brain regions and body organs fine tune various metabolic activities during day and night. As a first step to understand this complex time-dependent orchestration of metabolism, the proposal will test which genes are activated and repressed at what time of the day in more than three dozen tissue types of a non-human primate. Although mice and insects have been used in the past to find time-dependent gene activities, the amount of data from these animals is not comprehensive and their physiology and metabolism are very different from that of humans. Therefore, the proposal will make use of a tissue bank of frozen organs and brain section collected at different times of the day. Samples will be processed by modern sequencing technology to measure the activity extent of thousands of genes in different organs. Statistical analyses will identify the genes that show daily cycle and what time they reach their peak activities. Genes with similar peak activities will be examined for their potential function in metabolism and communication between organs. The knowledge will illuminate which aspects of metabolism are tied to day-night cycle. This knowledge will explain at the molecular level how unusual lifestyle affects our clock and metabolism. The data will also raise the possibility that certain drugs used to treat diabetes and metabolic diseases can be more effective if they are given at specific time of the day. In summary, the experiments will, for the first time, comprehensively test the time of effective function of thousands of genes in multiple organs, and the knowledge gained will have profound immediate and future impact on understanding the mechanism of metabolic disease and its effective treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510169
Entities
People
- Satchidananda Panda
Organizations
- Salk Institute for Biological Studies
- United States Army