BME Lecture Series (ZOOM): Tim Downing, UC Irvine
Seminar via Zoom: https://uci.zoom.us/j/95095953124
Synthetic Genome Regulation for Cell and Tissue Engineering
Abstract: The Downing Lab recently developed a new sequencing method (Repli-Bisulfite Sequencing) that enables analysis of DNA methylation within newly replicated strands of DNA over time. Using this method, we discovered that much of the methylation heterogeneity observed within HUES64 human embryonic stem cells (hESCs) is temporal in nature and associated with DNA replication. Here, we employ bioinformatic analyses to explore how properties of post-replication DNA methylation dynamics relate to well-established features of the genome and the broader chromatin landscape. Our findings reveal that unique patterns of methylome replication associate with distal regulatory regions throughout the genome, enrich for cytosine residues dynamically methylated across cell types, and coincide with the location of stem cell-specific transcription factor binding and chromatin architectures. We also find correlations between sub-cell cycle kinetics in DNA methylation and the divergence of bulk methylation patterns observed during multiple cell generations and natural aging. Taken together, our studies suggest that (epi)genome replication may act as an important source of (temporal) regulatory variation in hESCs while, simultaneously, conferring susceptibility to epigenetic drift throughout the human lifespan. The Downing Lab is also interested in understanding how the chemical and biophysical microenvironment influences adult cell behavior and phenotype through epigenetic gene regulatory mechanisms. We hope to use this information in the design of next-generation biomaterials. The second part of this presentation will describe how focal adhesions and cell-mediated forces contribute to inefficiencies observed during the acquisition of stemness from somatic cell states.
Bio: Tim Downing has been on the faculty at UC Irvine since 2016 and holds a primary appointment in the Department of Biomedical Engineering. He also holds a courtesy appointment in the Department of Microbiology & Molecular Genetics. The Downing Lab focuses on understanding gene regulation during tissue development, regeneration and disease progression. Building on this information, the lab also aims to develop molecular tools and biomaterials to synthetically regulate the epigenome for better control over cell fate and behavior. Downing is a 2019 NIH (DP2) New Innovator Award recipient and a 2020 recipient of the “Rising Star” Award from the Cellular and Molecular Bioengineering (CMBE) Special Interest Group within the Biomedical Engineering Society (BMES).