Keynote Speakers

Abstract: Background: Recent large-scale genomic and transcriptomic analyses uncovered previously unknown magnitudes of transcriptional correlation and overlap (71%) in individuals suffering from schizophrenia (SCZ) and bipolar disorder (BD). This suggests a shared SCZ/BD spectrum, but leaves the causes for the widely divergent sex-specific manifestations of these clinical pathologies largely unclear. While current research advances enable unprecedented insight into the functional genomic context of a multitude of diseases, RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena.

Results: To overcome these limitations, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male- and female-originated cell lines, and connectomics of transcription factor and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. Applying our pipeline enabled disentangling the differences between affected men and women and identified the disease-affected systems of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs.

Conclusions: Bioinformatically supported high-throughput techniques such as short RNA sequencing can bridge the gap between traditional molecular interaction studies and purely bioinformatics-based prediction paradigms. Using this approach, we identified the miRNA families mir-10 and mir-199 at the center of the cholinergic/neurokine interface. Highlighting the linkage via microRNAs and the differences between the sexes in the complex network of cortical cholinergic neurons supports the hypothesis of sexually dimorphic upstream RNA controllers of mental functioning.

Biography: Hermona Soreq was trained at The Hebrew University, Tel Aviv University, The Weizmann Institute of Science and the Rockeffeler University, NYC. She joined the faculty of The Hebrew University in 1986, where she holds a University Slesinger Chair in Molecular Neuroscience and is a founding member of the Edmond and Lily Safra Center for Brain Science. Soreq’s studies the mechanisms controlling acetylcholine functioning; she uses molecular biology and genomics to explore cholinergic signaling, with a recent focus on its short and long non-coding RNA regulators, including microRNAs. Her work spans both basic and biomedical studies on cholinergic signaling in health and disease, particularly on anxiety-related topics and she is the elected President of the International Organization of Cholinergic Mechanisms. Soreq served as the elected Dean of the Faculty of Science (2005-2008), authored hundreds of publications, including 56 published in Science, Nature, PNAS, Neuron and other high-impact journals and has been the recipient of co-recipient of significant funding from US, European and Israeli National and private foundations including an Advanced ERC Award and an Israeli I-Core Center of Excellence on mass trauma. She is a member of The Hebrew University’s Board of Governors and scientific advisory boards for national and international bodies with major interests in life sciences. Her honors include Honorary PhDs from the Universities of Stockholm (1996), Ben-Gurion University (2007), and Erlangen (2008), Teva Founders’ Award (2006), The Lise Meitner Alexander von Humboldt Award, Germany (2009), a Miller Fellowship at US UC Berkeley (2009), a Berlin NeuroCure visiting fellowship (2015-2021), a Rappaport prize for bio-medical research (2015), an International Psychoneuroimmunology Award (2016), the ILANIT-Katzir Prize for outstanding research achievements in the Life Sciences (2017) and a FEBS keynote lecture award (2020). She also contributes to the Neuro-Cure Center, Berlin, the Immunosensation Center, Bonn and the International Advisory Boards of the UK-Israel Council and BGU’s Center of Biotechnology.