A5035457281- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Animal Genetics and Reproduction
- Molecular Biology Techniques and Applications
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Gene expression and cancer classification
- Machine Learning in Materials Science
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Chromosomal and Genetic Variations
- Plant Virus Research Studies
- Computational Drug Discovery Methods
- Epigenetics and DNA Methylation
University of California, Berkeley
2022-2024
Stanford University
2020-2023
Harvard University
2017-2020
Center for Systems Biology
2017
Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate factor (TF)-DNA affinities apparent on-rates by about 70-fold directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. maximize the number of weakly preferred microstates near target sites, thereby increasing density, well predicted statistical mechanics....
Abstract Current approaches for inserting autonomous transgenes into the genome, such as CRISPR–Cas9 or virus-based strategies, have limitations including low efficiency and high risk of untargeted genome mutagenesis. Here, we describe precise RNA-mediated insertion (PRINT), an approach site-specifically primed reverse transcription that directs transgene synthesis directly at a multicopy safe-harbor locus. PRINT uses delivery two in vitro transcribed RNAs: messenger RNA encoding avian R2...
The ability to rewrite large stretches of genomic DNA enables the creation new organisms with customized functions. However, few methods currently exist for accumulating such widespread changes in a single organism. In this study, we demonstrate rapid approach rewriting bacterial genomes modified synthetic DNA. We recode 200 kb Salmonella typhimurium LT2 genome through process term SIRCAS (stepwise integration rolling circle amplified segments), towards constructing an attenuated and...
R2 non-long terminal repeat (non-LTR) retrotransposons are among the most extensively distributed mobile genetic elements in multicellular eukaryotes and show promise for applications transgene supplementation of human genome. They insert new gene copies into a conserved site 28S ribosomal DNA with exquisite specificity. clades defined by number zinc fingers (ZFs) at N terminus retrotransposon-encoded protein, postulated to additively confer Here, we illuminate general principles recognition...
R2 non-long terminal repeat retrotransposons insert site-specifically into ribosomal RNA genes (rDNA) in a broad range of multicellular eukaryotes. R2-encoded proteins can be leveraged to mediate transgene insertion at 28S rDNA loci cultured human cells. This strategy,
Abstract Short tandem repeats (STRs) are enriched in eukaryotic cis -regulatory elements and their polymorphisms alter gene expression, yet how they regulate transcription remains unknown. We find that STRs can modulate factor (TF)-DNA affinities on rates by up to 70-fold directly binding TF DNA-binding domains, with energetic impacts approaching or exceeding mutations consensus sites. maximize the number of weakly preferred microstates near target sites, thereby increasing density motifs...
Abstract Transcription factors (TF) are proteins that bind DNA in a sequence-specific manner to regulate gene transcription. Despite their unique intrinsic sequence preferences, vivo genomic occupancy profiles of TFs differ across cellular contexts. Hence, deciphering the determinants TF binding, both and context-specific, is essential understand regulation impact regulatory, non-coding genetic variation. Biophysical models trained on vitro binding assays can estimate affinity landscapes...
Single-cell Hi-C (scHi-C) allows the study of cell-to-cell variability in chromatin structure and dynamics. However, high level noise inherent current scHi-C protocols necessitates careful assessment data quality before biological conclusions can be drawn. Here, we present GiniQC, which quantifies unevenness distribution inter-chromosomal reads contact matrix to measure noise. Our examples show utility GiniQC assessing as a complement existing control measures. We also demonstrate how help...
Gene expression is regulated primarily by transcription factors (TFs) that bind specific regulatory DNA sequences within the genome, thereby recruiting or repressing transcriptional machinery to activate repress transcription, respectively. However, despite decades of research, we remain largely unable predict TF binding and/or downstream gene from sequence alone. Here, leverage a microfluidic platform yield quantitative, high‐throughput measurements TF‐DNA affinities and dissociation rates...
Genome recoding will provide a deeper understanding of genetics and transform biotechnology. We bypass the reliance previous genome methods on site-specific enzymes demonstrate rapid recombineering based strategy for writing genomes by Stepwise Integration Rolling Circle Amplified Segments (SIRCAS). installed largest number codon substitutions in single organism yet published, creating strain Salmonella typhimurium with 1557 leucine changes across 200 kb genome.