Circadian regulation refers to daily, 24-hour oscillations in biological functions and is a universal, evolutionarily conserved feature from bacteria to humans. Proper circadian regulation is important for human health, as chronic disruption of circadian regulation due to jetlag or night shift work is associated with multiple defects in metabolism, innate immunity, and sleep. These defects include susceptibility to infection, inflammation, obesity, and diabetes. Many diseases also cause loss of circadian regulation, including bacterial infection and many neurological diseases, such as autism and Parkinson?s disease. Despite the profound effects of circadian regulation on human health and physiology, it remains unclear how loss of circadian regulation contributes to the progression of these diseases. That is, a major gap in the field is the identification of specific circadian- regulated pathways that contribute to the pathogenesis of different diseases. My lab uses genetically tractable model organisms (fruit flies and mice) to investigate how disruption of circadian-regulated functions and behaviors contribute to the pathogenesis of bacterial infection and neurological disease models. This proposal focuses on investigating: 1) the role of metabolism in survival of bacterial infection; 2) the role of phagocytic innate immune cells in neurological defects associated with models of Fragile X syndrome, a human disease that causes both circadian dysregulation and autism; and 3) the role of sleep in defense against oxidative stress and the Drosophila model of Parkinson?s disease, which causes circadian dysregulation and sleep loss. These studies of circadian-regulated processes in the context of diseases that lead to circadian dysregulation will help to elucidate the cellular and molecular mechanisms underlying these diseases and identify new potential therapeutic targets

Public Health Relevance

Circadian rhythms are composed of daily, evolutionarily conserved, 24-hour oscillations in biological functions. While many different disease states cause disruption of circadian regulation (including bacterial infection, autism, breast cancer, schizophrenia, epilepsy, bipolar disorder, Parkinson?s, Alzheimer?s and Huntington?s diseases, and even aging alone), a major gap in the field is the identification of specific circadian-regulated pathways that contribute to the pathogenesis of different diseases. My lab uses genetically tractable model organisms (fruit flies and mice) to investigate how the disruption of circadian-regulated functions and behaviors contribute to the pathogenesis of bacterial infection and neurological disease models; these studies will help to elucidate the cellular and molecular mechanisms underlying these diseases and identify new potential therapeutic targets

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM127049-03
Application #
9921430
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Falcon-Morales, Edgardo
Project Start
2018-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Genetics
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Hill, Vanessa M; O'Connor, Reed M; Shirasu-Hiza, Mimi (2018) Tired and stressed: Examining the need for sleep. Eur J Neurosci :