Dr. Boyan Bonev

Keywords: epigenetics, brain development, single-cell genomics, CRISPR, cerebral organoids

Research methods: The long-term objective of my lab is to decode the epigenetic mechanisms of cell fate decisions in the mammalian brain using single-cell multiomics, lineage tracing and high-throughput perturbations. To accomplish this, we develop novel experimental and computational methods to integrate multiple epigenetic modalities at the single-cell level, analyse genome-wide CRISPR perturbations in vivo and interpret massively parallel reporter assays to understand the function of non-coding genetic variants in neurodevelopmental disorders. Our research is highly interdisciplinary and combines computational biology, single cell –omics, and CRISPR-based techniques in vivo and using human cerebral organoids.

Brief research description: The long-term objective of my lab is to decode the epigenetic mechanisms of cell fate decisions in the mammalian brain. Our major focus is on the the cerebral cortex, which is the region of the brain responsible for cognitive function, sensory perception and consciousness. It contains an unparalleled variety of neuron subtypes, which are generated in a precise temporal sequence from neural progenitors. Many important players in cortical development have been identified, but the precise contribution and the functional importance of the epigenome to lineage specification, developmental plasticity and disease in vivo remain unclear. My lab studies how cellular identity in the cortex is established by the complex interplay between transcriptional regulators, cis-regulatory elements and the chromatin landscape, taking place within the physical constraints imposed by 3D nuclear architecture. There is increasing evidence that chromatin remodellers and epigenetic regulation is essential for determining fate choices in the cortex many genetic mutations associated with neurodevelopmental disorders are located in the non-coding regions of the genome. However, the precise regulatory landscape, the molecular mechanisms and the functional importance of the epigenome in cortical development remain unclear.

Current GSN students: Laura Grünberg

Selected publications:

1. Noack F., Vangelisti S., Raffl G., Carido M., Diwakar J., Chong F. & Bonev B Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler Nature Neuroscience (2022) 25, 154-167. doi: 10.1038/s41593-021-01002-4

2. Aboelnour E. & Bonev B Decoding the organization, dynamics and function of the 4D Genome Developmental Cell (2021) 56(11), 1562-1573 doi: 10.1016/j.devcel.2021.04.023

3. Boxer LD., Renthal W., Greben AW., Whitwam T., Silberfeld A., Stroud H., Li E., Yang MG., Kinde B, Griffith EC., Bonev B. & Greenberg ME. MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes Molecular Cell (2020) 77, 294-309 doi: 10.1016/j.molcel.2019.10.032

4. Bonev B.#, Cohen N., Szabo Q., Fritsch L., Papadopoulos G., Lubling Y., Xu X., Lv X., Hugnot JP, Tanay A. & Cavalli G#. Multiscale 3D genome rewiring during mouse neural development. Cell (2017) 171, 557.e1–557.e24. # Co-Corresponding Author doi: 10.1016/j.cell.2017.09.043

5. Bonev B., Stanley P. & Papalopulu, N. microRNA-9 modulates Hes1 ultradian oscillations by forming a negative feedback loop. Cell Reports (2012) 2(1): 10-18. doi: 10.1016/j.celrep.2012.05.017