Circadian Rhythms and the Circadian Organization of Living ...
NIAMS Extramural Scientific Planning Retreat 2013 April 4, 2013 Session 2: The Circadian Cycle in...
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Transcript of NIAMS Extramural Scientific Planning Retreat 2013 April 4, 2013 Session 2: The Circadian Cycle in...
NIAMS Extramural Scientific Planning Retreat 2013April 4, 2013
Session 2: The Circadian Cycle in NIAMS-Relevant Tissues
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
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?
The Circadian Cycle—History of Circadian Publications
The Circadian Cycle—History of Circadian Publications
DiabetesCancer
CardiovascularDisease (CVD)
Provided for comparison
Number of Publications Identified in Web of Science Search, Keyword = Circadian
The Circadian Cycle—Examples of NIAMS Grants for this Discussion
Grant Number Program Area Principal Investigator Grant Title Relevance to Retreat Session
R01 AR046122 Arthritis and Rheumatic Diseases
Lin Chang Neuroendocrine Alterations in Fibromyalgia and IBS
Medium
R01 AR056666 Extracellular Matrix Biology
Andrzej T. Slominski Role of Exogenous Melatonin in Skin Biology Low
R01 AR055246 Muscle Biology and Diseases
Karyn Ann Esser Circadian Rhythms and Skeletal Muscle High
R03 AR05641 Muscle Biology and Diseases
John Joseph McCarthy Circadian Regulation of MyoD1 Transcription High
R01 AR056439 Skin Biology and Diseases Bogi Andersen Control of Hair Follicle Cycling Medium
R01 AR042177 Skin Biology and Diseases Cheng-Ming Chuong Development and Regeneration of Skin Appendages
Medium
F32 AR059471 Skin Biology and Diseases Yang Sui Brooks Role of RORa in Epidermal Differentiation Control
Low
T32 AR007465 Skin Biology and Diseases Sarah E. Millar Dermatology Research Training Grant Low
R01 AR045433 Bone Biology and Diseases Clifford J. Rosen Genetics of IGF1 and Bone Density: the role of Nocturnin
High
R21 AR055633 Bone Biology and Diseases Clifford J. Rosen Seasonal Bone Loss in Mice High
K01 AR062132 Skin Biology and Diseases Jun Dai Growth/Differentiation Control of Keratinocytes by ROR Alpha
Low
For more information about these and other grants, see http://projectreporter.nih.gov
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”
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
The Circadian Cycle—Rheumatoid ArthritisDiurnal 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.
The Circadian Cycle—Rheumatoid ArthritisIntegration of Molecular, Endocrine, and Immunological
Circadian Patterns may Enable Optimization of Timing for Rheumatoid Arthritis Treatment
Cutolo. Curr Opin Rheumatol. 2012. 24(3): 312.
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