The Center for Molecular Integrative Neuroresilience is supported by three Research Cores that are critical for the successful execution of individual research projects. The Administrative/Statistical Core A provides oversight and coordination, in addition to biostatistical and educational training support, for the Center’s activities. The Biosynthetic Component of Core B generates biosynthetic polyphenol botanical metabolites to support all in vitro bioactivity and mechanistic studies of the research projects.
Additionally, the Bioanalytical Component of Core B monitors the bioavailability of polyphenols in genetically modified/gnotobiotic mice carrying select commensal microbes to explore the role of the microbiome in polyphenol bioavailability and eventually, efficacy of treatment conducted by the Research Project. The Bioanalytical Component of Core B will provide critical support by monitoring the bioavailability of specific bioactive polyphenols following treatments. The Behavioral and Electrophysiology Core C will operate by providing behavioral phenotyping and electrophysiological support for all the studies proposed in the research projects, which are fundamental aspects for assessment of efficacy following polyphenol treatments in the experimental animals being tested.
Administrative - Biostatistics/Data Management - Supporting Core A
The purpose of the Administrative-Biostatistics/Data Management Supporting Core A is to coordinate and integrate all activities of the studies in the Botanical Supplement Dietary Research Center (BSDRC) application. This is particularly important for the success of the BDSRC studies because all the research projects and Cores are heavily interdependent, including data sharing across multiple projects, and the future direction of one project is in part contingent on the results of another.
This Core, led by Giulio Maria Pasinetti, MD, PhD, and managed by Susan Gursahai, provides a forum for communication, including a framework for formal, structured interactions between the BDSRC investigators; interactions between participating institutions; management of contractual agreements; and allocation of funds. To achieve the administrative goals, Core A, through the Administrative Tier I Plan component:
- Manages an Internal Steering Committee, whose main goal is to promote integration and coordination among the research projects and Cores of the BDSRC studies.
- Implements a plan to govern research projects and Cores leadership through an Internal Steering Committee.
- Establishes an External Advisory Board, designed to provide oversight and assist the PD/PI and Co-PD/PI in scientific and administrative decisions, as well as with other issues involving financial regulatory oversight.
To facilitate the success of these operations and other management goals of Core A, the Administrative Tier I Plan component will operate through three Work Groups: The Administrative Work Group, the Study Coordination Work Group, and the Outreach Work Group. In addition, Core A includes a Biostatistics/Data Management Tier II Plan component, which operates through two Work Groups: the Biostatistics Work Group and the Data Management Work Group, whose main goals are to facilitate data analysis, storage, and scientific communication.
Bioavailability and Biosynthetic - Scientific Core B
The purpose of Core B, led by Rick Dixon, PhD, and James Simon, PhD, is to directly support the overall goals of the Center to clarify mechanisms that dietary polyphenol botanical supplements may use to promote cognition and psychological resiliency. The Core achieves this goal by providing authentication and quality control of all materials used by individual projects; supporting in vivo bioavailability experiments through profiling of polyphenol metabolites in target tissues; and providing mg levels of key polyphenol metabolites through targeted synthetic and bio-synthetic schemes for mechanistic testing by individual projects. To streamline this effort, Core B is divided into two components--Bioanalytical and Biosynthesis. This structure evolved from the previous Mount Sinai School of Medicine Center of Excellence in Complementary and Alternative Medicine, which investigated grape polyphenols in prevention of Alzheimer’s disease. Both University of North Texas and Rutgers provided key functions in the biosynthesis and bioavailability core. The proven complementary nature of individual investigators within Core B creates a strong synergistic team to support individual projects and collaborative efforts focused on achieving center objectives.
Biobehavioral - Scientific Core C
Core C, led by Jun Wang, PhD, and Ming-Hu Han, PhD, supports the overall goals of the BDSRC by facilitating preclinical behavioral testing and electrophysiology studies. The overall goals of the BDSRC are to define the molecular and cellular mechanisms by which bioactive botanicals may beneficially promote psychological resilience in the context of social defeat, preserve cognitive function in the context of sleep deprivation, and to develop probiotic supplements that optimize the utilization of these specific botanicals, with the final goal to develop bioactive botanicals with defined mechanisms of action for immediate application in humans.
Core C is divided into Behavioral Phenotyping and Electrophysiology components. Dr. Wang directs the Behavioral Phenotyping component and provides all the behavior testing proposed in the BDSRC. The Electrophysiology component, directed by Dr. Han provides critical information concerning how these compounds affect brain synaptic function in nucleus accumbens (NAc) (Research Project 1) and hippocampal formation (Research Project 2).
Core C will also provide toxicology analysis for safety profiles of the tested phenolic compounds. The activity of Core C will be based on the specific goals of individual projects, with the overall objective of correlating the biological effects of phenolic compounds with synaptic activity as well as behavioral phenotypes. Dr. Russo, leader of Project 1, will provide his expertise in mechanisms of neuropsychiatric disorders, such as depression and anxiety.