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The Circadian Cycle in NIAMS-Relevant Tissues

NIAMS Extramural Scientific Planning Retreat 2013 April 4, 2013 Session 2: The Circadian Cycle in NIAMS-Relevant Tissues. The Circadian Cycle in NIAMS-Relevant Tissues. Goal:

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The Circadian Cycle in NIAMS-Relevant Tissues

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  1. NIAMS Extramural Scientific Planning Retreat 2013April 4, 2013Session 2: The Circadian Cycle in NIAMS-Relevant Tissues

  2. The Circadian Cycle in NIAMS-Relevant Tissues • Goal: • Inform NIAMS staff about this emerging area of investigation and explore research opportunities relevant to diseases and tissues within the mission of NIAMS • Guest Speakers: • Dr. Fred Turek, Northwestern University • Dr. Karyn Esser, University of Kentucky

  3. The Circadian Cycle in NIAMS-Relevant Tissues—Discussion Questions • What role do clock mechanisms play in regulating complex biological processes? • How does this basic process influence and/or cause disease? • What are the high priority basic research questions? • What are the current opportunities for translating knowledge of basic mechanisms into new therapies and/or more effective treatment regimens? • What is the best formula for building multidisciplinary teams to promote integration of knowledge and to explore new experimental modalities?

  4. The Circadian Cycle—History of Circadian Publications

  5. The Circadian Cycle—History of Circadian Publications Diabetes Cancer Cardiovascular Disease (CVD) Provided for comparison Number of Publications Identified in Web of Science Search, Keyword = Circadian

  6. The Circadian Cycle—Examples of NIAMS Grants for this Discussion For more information about these and other grants, see http://projectreporter.nih.gov

  7. The Circadian Cycle—All Cells Have Clocks • Central Clock • Suprachiasmatic nucleus (SCN) • Entrained by light • Peripheral Clocks • Time setting (entrainment) done through neurohumoral factors • Time of feeding and time of activity can set peripheral clocks, independent of light Molecular clocks can be reset by exposure to external stimuli: split time of light vs. time of feeding or vs. time of activity can disrupt clock synchrony in system, leading to “social jetlag”

  8. The Circadian Cycle—Molecular Clock’s Non-Timekeeping Function • Clock controlled genes (CCGs) • Very few (e.g., Dbp) are common across tissues • Most are unique to each tissue and include genes that contribute to cell physiology

  9. The Circadian Cycle—Rheumatoid Arthritis Diurnal Pattern of Rheumatoid Arthritis Symptoms Corresponds to Rhythms of Circulating Cytokines, Particularly IL-6 Sierakowski and Cutolo. Scand J Rheumatol. 2011. 40 Suppl 125:1.

  10. The Circadian Cycle—Rheumatoid Arthritis Integration of Molecular, Endocrine, and Immunological Circadian Patterns may Enable Optimization of Timing for Rheumatoid Arthritis Treatment Cutolo. Curr Opin Rheumatol. 2012. 24(3): 312.

  11. The Circadian Cycle in NIAMS-Relevant Tissues—Opportunities • Explore availability of NIH Common Fund support • Utilize existing resources to look at circadian rhythms in conjunction with disease research • Some databases include tissues from adrenal glands, suprachiasmatic nucleus (SCN), muscle, heart, and liver • Include sleep/wake cycles in clinical trials • However, including sleep data does not necessarily encompass everything relevant to circadian rhythms • Generate datasets to query for circadian gene expression • Study injury repair at different times of day • Raise NIAMS researcher communities’ awareness of the effects of circadian rhythms on relevant tissues • Consider novel strategies to support teams of investigators with experience in NIAMS-relevant tissues and circadian rhythm research

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