- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Southeast Asian Sociopolitical Studies
- Evolution and Genetic Dynamics
- Animal Genetics and Reproduction
- Biofuel production and bioconversion
- Archaeology and Natural History
- Fungal and yeast genetics research
- Chromosomal and Genetic Variations
- Reproductive Biology and Fertility
- RNA and protein synthesis mechanisms
- Erythrocyte Function and Pathophysiology
- DNA Repair Mechanisms
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Bacterial Genetics and Biotechnology
- Sperm and Testicular Function
- Cystic Fibrosis Research Advances
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Protist diversity and phylogeny
- Historical and Cultural Archaeology Studies
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- Cancer therapeutics and mechanisms
- American Environmental and Regional History
National Institute of Diabetes and Digestive and Kidney Diseases
2015-2024
National Institutes of Health
2015-2024
University of Applied Sciences Kufstein
2020
Dankook University
2020
Innsbruck Medical University
2020
Universität Innsbruck
2020
Philadelphia VA Medical Center
2019
University of Pennsylvania
2019
Nanjing University of Chinese Medicine
2012
Ministry of Education
2012
Abstract Homology-directed repair (HDR) of double-strand DNA breaks is a promising method for genome editing, but thought to be less efficient than error-prone nonhomologous end joining in most cell types. We have investigated HDR induced by CRISPR-associated protein 9 (Cas9) Caenorhabditis elegans. find that very robust the C. elegans germline. Linear templates with short (∼30–60 bases) homology arms support integration base and gene-sized edits high efficiency, bypassing need selection....
Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome by using deep and diverse high-throughput data. Since transcriptional activity that been evolutionarily conserved likely to have an advantageous function, we performed large-scale interspecific comparisons increase confidence in predicted annotations. To support comparative genomics, filled divergence gaps Drosophila phylogeny generating draft...
Two signals activate meiosis in yeast: starvation and expression of the a1 alpha 2 products mating-type locus. Prior studies suggest that these stimulate an activator meiosis, IME1 (inducer meiosis) product. We have cloned a gene, IME2, with properties similar to those IME1: both genes are required for RNAs induced meiotic cells. Elevated dosage or IME2 stimulates recombination pathway without starvation; thus, IME may be part switch activates meiosis. was found expression, multicopy plasmid...
Small regulatory RNAs are key regulators of gene expression. One class small RNAs, termed the endogenous interfering (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism RNAi RNAi). A complex proteins composed ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo processes in Caenorhabditis elegans. We conducted a genetic screen identify additional components machinery. Our recovered alleles eri-9, which encodes novel...
Abstract Given their copy number differences and unique modes of inheritance, the evolved gene content expression sex chromosomes is unusual. In many organisms X Y are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. addition to current chromosomes, Drosophila has small gene-poor X-chromosome relic (4 th ) that re-acquired autosomal status. Here we use single cell RNA-Seq on fly larvae demonstrate pair 4 specifically primary based...
In the yeast Saccharomyces cerevisiae, meiosis and spore formation require induction of sporulation-specific genes. Two genes are thought to activate sporulation program: IME1 IME2 (inducer meiosis). Both induced upon entry into meiosis, is required for expression. We report here that essential expression four contrast, not absolutely genes, but contributes their rapid induction. Expression from a heterologous promoter permits these meiotic recombination, in absence IME1. propose products...
Abstract Background Gene dosage change is a mild perturbation that valuable tool for pathway reconstruction in Drosophila . While it often assumed reducing gene dose by half leads to two-fold less expression, there partial autosomal compensation , which may be mediated feedback or buffering expression networks. Results We profiled engineered flies where was reduced from two one. of most one-dose genes reduced, the gene-specific responses were heterogeneous. Expression two-dose are...
Two signals are required for meiosis and spore formation in the yeast Saccharomyces cerevisiae: starvation MAT products a1 alpha 2, which determine a/alpha cell type. These lead to increased expression of IME1 (inducer meiosis) gene, is sporulation sporulation-specific gene expression. We report here sequence consequences from GAL1 promoter. The deduced product a 360-amino-acid protein with tyrosine-rich C-terminal region. Expression PGAL1-IME1 vegetative cells led moderate accumulation four...
Abstract Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells wide range organisms. However, genome-wide off-target effects introduced by editors mammalian genome have been examined only one study. Here, we investigated fidelity cytosine editor 4 (BE4) and adenine (ABE) mouse embryos using unbiased whole-genome sequencing family-based trio cohort. The same sgRNA was used for BE4 ABE. We demonstrate that BE4-edited mice carry an...
Poly-ubiquitination of target proteins typically marks them for destruction via the proteasome and provides an essential mechanism dynamic control protein levels. The E1 ubiquitin-activating enzyme lies at apex ubiquitination cascade, its activity is necessary all subsequent steps in reaction. We have isolated a temperature-sensitive mutation Caenorhabditis elegans uba-1 gene, which encodes sole this organism. Manipulation UBA-1 different developmental stages reveals variety functions...
The production of multiple transcript isoforms from one gene is a major source transcriptome complexity. RNA-Seq experiments, in which transcripts are converted to cDNA and sequenced, allow the resolution quantification alternative isoforms. However, methods analyze splicing underdeveloped errors resulting incorrect calls occur every experiment. We used data develop sequencing aligner error models. By applying these models known input simulations, we found that result false alignment minor...
ObjectivesThe objective of this study was to perform a quantitative analysis the structural and functional alterations in intervertebral disc during vivo degeneration, using emerging tools that enable rigorous assessment from microscale macroscale, as well correlate these outcomes with noninvasive, clinically relevant imaging parameters.DesignDegeneration induced rabbit model by puncturing annulus fibrosus (AF) 16-gauge needle. 2, 4, 8, 12 weeks following puncture, degenerative changes discs...
IME1 is required in yeast for meiosis and expression of IME2 other early meiotic genes. a 360-amino acid polypeptide with central C-terminal tyrosine-rich regions. We report here that fusion protein composed the lexA DNA-binding domain activates transcription vivo reporter gene containing upstream binding sites. Activation by shares several features natural activity: both are dependent on RIM11 product; impaired same ime1 missense mutations; restored intragenic suppressors. The region...
The sperm/oocyte decision in the hermaphrodite germline of Caenorhabditis elegans provides a powerful model for characterization stem cell fate specification and differentiation. sex determination program that governs gamete has been well studied, but direct mediators cell-type-specific transcription are largely unknown. We report identification spe-44 as critical regulator sperm gene expression. Deletion causes sperm-specific defects cytokinesis, cycle progression, organelle assembly...
Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage with motifs bind are regulated by STAT5. Moreover, it clear whether genome-wide STAT5 modulated its concentration. To clarify these issues we established growth hormone (GH) stimulation wild-type (WT) mouse embryonic fibroblasts (MEFs) MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation, 23 827 111 939 sites were detected...
Topoisomerase II alleviates DNA entanglements that are generated during mitotic replication, transcription, and sister chromatid separation. In contrast to mitosis, meiosis has two rounds of chromosome segregation following one round replication. II, chromatids segregate from each other, similar mitosis. Meiosis I, on the other hand, segregates homologs, which requires pairing, synapsis, recombination. The exact role topoisomerase plays is unknown. a screen reexamining Caenorhabditis elegans...
Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily of secreted molecules. BMPs play essential roles in multiple developmental and homeostatic processes metazoans. Malfunction BMP pathway can cause a variety diseases humans, including cancer, skeletal disorders cardiovascular diseases. Identification factors that ensure proper spatiotemporal control signaling is critical for understanding how this regulated. We have used unique sensitive genetic...