- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Fungal and yeast genetics research
- Genomics and Phylogenetic Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Gene Regulatory Network Analysis
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Genetic Neurodegenerative Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
Institute for Systems Biology
2022-2024
The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual chromosomes assembled. Here, we describe the consolidation of multiple using advanced endoreduplication intercrossing tRNA expression cassettes to generate strain 6.5 chromosomes. 3D chromosome organization and transcript isoform profiles were evaluated Hi-C long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or...
Abstract The loss of the tail is among most notable anatomical changes to have occurred along evolutionary lineage leading humans and ‘anthropomorphous apes’ 1–3 , with a proposed role in contributing human bipedalism 4–6 . Yet, genetic mechanism that facilitated tail-loss evolution hominoids remains unknown. Here we present evidence an individual insertion Alu element genome hominoid ancestor may contributed evolution. We demonstrate this element—inserted into intron TBXT gene 7–9 —pairs...
We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was for attachment to another synthetic due concerns surrounding potential instability karyotype imbalance now attached synIII, yielding first yeast fusion chromosome. Additional chromosomes were constructed study nuclear function. ChrIII-I chrIX-III-I have twisted structures, depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special...
Use of synthetic genomics to design and build 'big' DNA has revolutionized our ability answer fundamental biological questions by employing a bottom-up approach. Saccharomyces cerevisiae, or budding yeast, become the major platform assemble large constructs thanks its powerful homologous recombination machinery availability well-established molecular biology techniques. However, introducing designer variations episomal assemblies with high efficiency fidelity remains challenging. Here we...
Abstract The Sc2.0 project is building a eukaryotic synthetic genome from scratch, incorporating thousands of designer features. A major milestone has been achieved with the assembly all individual chromosomes. Here, we describe consolidation multiple chromosomes using endoreduplication intercross to generate strain 6.5 Genome-wide chromosome conformation capture and long-read direct RNA sequencing were performed on this evaluate effects modifications, such as loxPsym site insertion, tRNA...
SUMMARY As part of the Synthetic Yeast 2.0 (Sc2.0) project, we designed and synthesized synthetic chromosome I. The total length synI is ∼21.4% shorter than wild-type I, smallest in Saccharomyces cerevisiae . SynI was for attachment to another due concerns potential instability karyotype imbalance. We used a variation previously developed, robust CRISPR-Cas9 method fuse I other arms varying length: chrIXR (84kb), chrIIIR (202kb) chrIVR (1Mb). All fusion strains grew like so decided attach...
Abstract Expression of Sox2 in mouse embryonic stem cells (mESCs) depends on a distal regulatory cluster DNase I hypersensitive sites (DHSs), but their individual contributions and degree independence remain mystery. Here, we comprehensively analyze the architecture at its endogenous locus using Big-IN to scarlessly integrate DNA payloads ranging up 143 kb. We analyzed 83 incorporating deletions, rearrangements, inversions affecting single or multiple DHSs, as well surgical alterations...
Abstract Use of synthetic genomics to design and build “big” DNA has revolutionized our ability answer fundamental biological questions by employing a bottom-up approach. S. cerevisiae , or budding yeast, become the major platform assemble large constructs thanks its powerful homologous recombination machinery availability well-established molecular biology techniques. However, efficiently precisely introducing designer variations episomal assemblies remains challenging. Here, we describe...