Central Project 1
Biomaterial Bank (BMB)
Prof. Dr. Dr. Petra Ina Pfefferle1, Prof. Dr. Harald Renz2 1University of Marburg, Institute of Laboratory Medicine and Pathobiochemistry – Molecular Diagnostics, Biomedical Research Centre (BMFZ) 2 University of Marburg, Institute of Laboratory Medicine and Pathobiochemistry – Molecular Diagnostics, Central Laboratory
As structured and quality-managed central service-platforms in joint projects biobanks serve as sustainable tools to provide biomaterials for the assessment of genetic and other molecular markers. As service platforms, BMB facilitate analysis of data and contribute to an improved etiological understanding of human disorders. Novel approaches in research of affective disorders indicate that interaction between heritable and early environmental factors might play a crucial role in the genesis of major depressive and bipolar disorders. In this context, epigenetically mediated gene-x-environment interactions modifying brain structures and function are discussed as basic mechanisms and organ-based preconditions, which pave the way to dys-regulated trajectories in human behaviour and mood. To ensure reliable assessments of epigenetic and other molecular diseaseassociated parameters in longitudinal studies such as MACS (WP1), qualitycontrolled storage conditions and validated analytical techniques for biomaterials are required. The applicants have a long-standing experience in clinical laboratory analyses, BMB and joint data management of samples from clinical and epidemiological studies. In (inter)national multi-centre studies the applicants have employed an efficient logistic network, which is based on a rapid sample transport- and quality-controlled assessment system. In addition, we have employed novel CHIP (chromatin precipitation) and multiplexed cytokine assays tailored for high-throughput analyses in large studies. Based on our expertise CP1 will contribute to the FOR consortium as follows: (i) Implementation of a BMB which collects samples from patients and controls of the MACS (WP1) as a service platform for all other WP. CP1 will include all quality-controlled steps from transport to storage and/or analyses of blood, urine, saliva, hair, stool, cerebrospinal fluid (CSF). For overarching statistical approaches and deep phenotyping, data assessed in CP1 will be transferred to the WP1 data bank. (ii) CP1 will contribute to epigenetic characterisation of candidate gene loci CACNA1C and NCAN by assessment of histone modifications at the promoter regions of these loci. Peripheral blood mononuclear cells (PBMC) obtained from healthy subjects of MACS (WP1) (+/- genetic risk and +/- environmental exposure) will be analyzed by chromatin precipitation (CHiP) assays. In a comprehensive statistical approach in cooperation with WP1, WP3, WP5 and WP6 chromatin modification will be analysed for associations with other epigenetic patterns and clinical and imaging markers of affective disorders. (iii) Based on previous findings from our FOR consortium we hypothesise that reduced hippocampal volume and amygdala hyper-responsiveness is associated with pro-inflammatory cytokine expression TNFα, IL-1β, Il-2 and IL-6 and an elevated risk for affective disorders. To proof this thesis proinflammatory cytokine patterns in PBMC obtained from n=600 randomly selected patients and controls from the MACS (WP1) will be assessed in CP1. To proof if systemic pro-inflammatory conditions are associated with clinical and imaging parameters of affective disorders we will assess cytokine signatures from MACS (WP1) randomly selected patients and controls (n=600). In a statistical approach obtained data will be analysed in cooperation with WP1 and WP6 for associations with clinical and imaging parameters of affective disorders.
Regarding biobanking, CP1 collaborates closely with the clinical research group KFO241 in Göttingen (Prof. Dr. Thomas Schulze).