Only a subset of individuals with an alcohol-use disorder develop clinically significant organ damage (~10- 30%) but it is not known what factors predispose individuals to develop clinically significant organ pathology? There is compelling evidence to support the hypothesis that disruption of circadian homeostasis (e.g., shift work, social jet lag) is a plausible susceptibility factor for vulnerability to alcohol-induced pathologies. Interest in the study of circadian rhythms is growing; however, an obstacle to study the interactions between circadian rhythms and alcohol-induced organ damage has been the lack of a combined circadian rhythm and alcohol expertise that is required to conduct these studies as well as the high cost associated with establishing the infrastructure necessary to perform circadian research. The objective of this R24 Alcohol Research Resource Program is to overcome these obstacles by providing the necessary infrastructure, support, and expertise that will allow both alcohol researchers in the United States and internationally to incorporate the study of circadian rhythms into their existing research programs. In order to achieve this objective we propose the following Specific Aims:
Aim 1. Provide the essential resources to conduct novel, innovative studies involving alcohol and circadian rhythms. The proposed infrastructure, expertise and personnel in our R24 Program will allow alcohol researchers to investigate innovative hypotheses by conducting studies in our facility. At the conclusion of each study, investigators will be provided with biospecimens from their study to evaluate study-specific outcomes.
Aim 2. To provide biospecimens from alcohol-fed, circadian disrupted mice and circadian disrupted humans consuming alcohol. Our R24 Alcohol Research Resource Program will provide biospecimens (from our biorepository) to alcohol researchers to investigate hypotheses using standardized experimental manipulations and assessments. The biospecimens will be from studies that have already been conducted and those that are available for request including both human and mouse specimens.
Aim 3. Provide consultation and analytic tools for circadian rhythm research. Our R24 Alcohol Research Resource Program will be a resource for the alcohol research community by providing consultation and training in circadian rhythms research (Aim 3a) and by conducting circadian-specific analyses of data collected in other laboratories (Aim 3b). The resources of this NIAAA R24 Alcohol Research Resource Program will facilitate scientific rigor and reproducibility across labs in alcohol and circadian rhythm experimentation. These efforts are expected to lead to a significantly greater understanding of the overlapping or dissimilar disease mechanisms in each organ which should lead to identification of novel targets and interventions to prevent and treat alcohol-induced organ damage.
