| 58 | 2024 Annual Report Dr. Gonen Nitzan The Mina & Everard Goodman Faculty of Life Sciences The Mammalian Sex Determination Lab Research Areas • 3D genome organisation • CRISPR genome editing • Stem cell biology • Developing in vitro systems to model the gonads 1. Studying the Role of the NonCoding Genome During Sex Determination Abstract A main research interest of our lab is to understand, at the molecular level, how sex is determined during embryonic development, i.e., how an embryo develops into either male or female. In mammals, sex determination is genetically driven, with XY individuals developing as males and XX individuals developing as females. However, if the process of sex determination is impaired, patients appear as XY females or XX males (sex reverse). These are all classified as patients with Disorders of Sex Development (DSD), with a prevalence of 1: 2,500-4,000 newborns. In the lab, we use the mouse as a model system and are interested in understanding the regulation of the key transcription factors controlling gonad formation and how these interact with each other. We also study the role of the non-coding genome in mediating the process of sex determination and DSD pathologies. We employ cutting-edge techniques to address these questions, including CRISPR/Cas9 genome editing, transgenic mice production, advanced sequencing techniques as well as microscopy and molecular biology. 2. Developing an In Vitro Model to Study the Gonads Abstract To develop an in vitro system that allows us to model the mammalian gonads, we use mouse Embryonic Stem Cells (ESC) and develop differentiation protocols towards the gonadal cell type of the gonads. In addition, we use similar protocols with Human ESC and induced Pluripotent Stem Cells to model DSD patients in vitro. Furthermore, we perform tissue engineering to model the testis and the spermatogenesis process using these stem cell-derived somatic cells and germ cells in a 3D culture system. We recently developed neonatal testis organoids that highly resemble the mouse testis in terms of structure and transcriptomics. Publications 2023 and 2024 • Meshi Ridnik, Elisheva Abberbock, Veronica Alipov, Shelly Ziv Lhermann, Shoham Kaufman, Maor Lubman, Francis Poulat, Nitzan Gonen. “Two Redundant Transcription Factor Binding Sites in a Single Enhancer are Essential for Mammalian Sex Determination.” Nucleic Acids Research, 2024. • Aviya Stopel, Cheli Lev, Stav Dahari, Or Adibi, Leah Armon, Nitzan Gonen. “Towards a “Testis in a Dish”: Generation of Mouse Testicular Organoids that Recapitulate Testis Structure and Expression Profiles.” International Journal of Biological Sciences, 2024. • Michael Klutstein, Nitzan Gonen. “Epigenetic Aging of Mammalian Gametes.” Molecular Reproduction and Development, 2023. Prof. Goobes Gil Department of Chemistry Biomaterials and Advanced Materials Analytical Design Research Areas • Solid-state NMR spectroscopy • Structural biology of proteins in humans and other organisms • Development of tools for molecular structure and binding characterization of proteins bound to the surfaces of solid substrates • Study of advanced nanomaterials for use in contemporary batteries • Preparation of biomaterials inspired by natural enzymes for efficient degradation of cellulose and production of alternative chemical fuels Abstract The Goobes group’s main thrust is to design new biomaterials and advanced materials based on fundamental atomic/nanoscale understanding of materials and underlying physical principles governing their formation and traits. The team employs new synthetic and biomimetic concepts to construct energy-related advanced materials for use in batteries and future energy storage applications and separately biocompatible green biomaterials for use in biology and medicine. Inspired by biology, we develop approaches to mitigate the challenges of carbon fixation. Osteopontin regulates bone structure from disordered layers of bone mineral apatite. Asparagine binds crystal surfaces as part of protein activity.
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