A5090032932- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- RNA regulation and disease
- Insect symbiosis and bacterial influences
- Gut microbiota and health
- Circadian rhythm and melatonin
- Tryptophan and brain disorders
- RNA Interference and Gene Delivery
- Evolution and Genetic Dynamics
- Animal Genetics and Reproduction
- Transgenic Plants and Applications
- Viral Infections and Immunology Research
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Neuroendocrine regulation and behavior
- Advanced biosensing and bioanalysis techniques
- Plant Virus Research Studies
- Acute Myeloid Leukemia Research
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Birth, Development, and Health
- Genetic Neurodegenerative Diseases
- Genomics and Phylogenetic Studies
Harvard University
2011-2024
Boston Children's Hospital
2019-2024
Harvard Affiliated Emergency Medicine Residency
2024
Boston University
2023
Massachusetts Institute of Technology
2023
Massachusetts General Hospital
2008-2020
Stanford University
2012
Stanford Medicine
2012
Harvard University Press
2009
Hubrecht Institute for Developmental Biology and Stem Cell Research
2001-2003
Double-stranded RNAs can suppress expression of homologous genes through an evolutionarily conserved process named RNA interference (RNAi) or post-transcriptional gene silencing (PTGS). One mechanism underlying is degradation target mRNAs by RNP complex, which contains ∼22 nt siRNAs as guides to substrate selection. A bidentate nuclease called Dicer has been implicated the protein responsible for siRNA production. Here we characterize Caenorhabditis elegans ortholog ( K12H4.8 ; dcr-1 ) in...
Tc1/ mariner elements are able to transpose in species other than the host from which they were isolated. As potential vectors for insertional mutagenesis and transgenesis of mouse, these cut-and-paste transposons tested their ability mouse germ line. First, levels activity several mammalian cells compared; reconstructed fish transposon Sleeping Beauty (SB) was found be an order magnitude more efficient transposons. SB then introduced into line as a two-component system: one transgene...
Argonaute-associated siRNAs and Piwi-associated piRNAs have overlapping roles in silencing mobile genetic elements animals. In Caenorhabditis elegans , mutator ( mut ) class genes mediate siRNA-guided repression of transposons as well exogenous RNAi, but their endogenous RNA pathways are not well-understood. To characterize the small RNAs dependent on genes, populations from a null allele mut-16 regulatory mg461 that disables only somatic RNAi were subjected to deep sequencing. Additionally,...
Small RNAs—including piRNAs, miRNAs, and endogenous siRNAs—bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, aberrant RNAs. To assess the requirements for siRNA formation activity in Caenorhabditis elegans, we developed a GFP-based sensor 22G siR-1, one of set abundant siRNAs processed from precursor mapping X chromosome, X-cluster. Silencing is also dependent on partially complementary, unlinked 26G siR-O7 siRNA. We show acts trans initiate The...
The use of mutant mice plays a pivotal role in determining the function genes, and recently reported germ line transposition Sleeping Beauty (SB) transposon would provide novel system to facilitate this approach. In study, we characterized SB mouse assessed its potential for generating mice. Transposition sites not only were clustered within 3 Mb near donor site but also widely distributed outside cluster, indicating that can be utilized both region-specific genome-wide mutagenesis....
The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. majority genes found thus far be associated with primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers remain discovered.
Endogenous small interfering RNAs (siRNAs) are a class of naturally occuring regulatory found in fungi, plants, and animals. Some endogenous siRNAs required to silence transposons or function chromosome segregation; however, the specific roles most unclear. The helicase gene eri-6/7 was identified nematode Caenorhabditis elegans by enhanced response exogenous double-stranded (dsRNAs) null mutant. encodes homologous RNA factors Armitage Drosophila, SDE3 Arabidopsis, Mov10 humans. Here we show...
Endogenous retroviruses and long terminal repeat (LTR) retrotransposons are mobile genetic elements that closely related to retroviruses. Desilenced endogenous associated with human autoimmune disorders neurodegenerative diseases. Caenorhabditis elegans spp. contain LTR and, as described here, numerous integrated viral genes including envelope part of retrotransposons. We found both silenced by ADARs [adenosine deaminases acting on double-stranded RNA (dsRNA)] together the interference...
Gene segments from other organisms, such as viruses, are detected foreign and targeted for silencing by RNAi pathways. A deep-sequencing map of the small RNA response to repeated transgenes introduced Caenorhabditis elegans revealed that specific siRNAs. Silencing gene depends on an antiviral involves changes in active silent chromatin modifications altered levels antisense Distinct Argonaute proteins target genes or protection against silencing. We used a transgene genome-wide screen...
RNAi pathways detect and silence foreign nucleic acids such as viruses well endogenous genes in many species. The phylogenetic profile across eukaryotes of proteins that mediate key steps is correlated with the profiles multiple mRNA splicing intron number, suggesting may surveil to divergent or absent introns viruses. Here we examine role Caenorhabditis elegans . We found viable null mutations U1 U2 small nuclear ribonucleic protein (snRNP)-specific factor cause defects RNAi. U1A ortholog...
Abstract In a genome-wide analysis of the active transposons in Caenorhabditis elegans we determined localization and sequence all copies each six transposon families. Most most transposons, Tc1 Tc3, are intact but individually have unique sequence, because patterns single-nucleotide polymorphisms. The 32 elements is invariant C. strain N2, which has no germline transposition. However, at same loci strains with transposition, can acquire elsewhere N2 genome or chimeric derived from two...
Since the discovery of transposable elements (TEs) in maize 1940s by Barbara McClintock have been described as junk, selfish with no benefit to host, and more recently major determinants genome structure evolution. TEs are DNA sequences that capable moving new sites making additional copies themselves while doing so. To limit propagation TEs, host silencing mechanisms directed at transposon-encoded genes required for mobilization. The mutagenic properties potential form affect gene...
The microbiota is a key determinant of the physiology and immunity animal hosts. factors governing transmissibility viruses between susceptible hosts are incompletely understood. Bacteria serve as food for Caenorhabditis elegans represent an integral part natural environment C. elegans. We determined effects bacteria isolated with from its on transmission Orsay virus in using quantitative host susceptibility assays. observed that Ochrobactrum species promoted transmission, whereas...
Background:The strong familiality of living to extreme ages suggests that human longevity is genetically regulated.The majority genes found thus far be associated with primarily function in lipoprotein metabolism and insulin/ IGF-1 signaling.There are likely many more genetic modifiers remain discovered.Methodology/Principal Findings: Here, we first show 18 single nucleotide polymorphisms (SNPs) the RNA editing ADARB1 ADARB2 old age a U.S. based study centenarians, New England Centenarian...
Since the discovery of transposable elements (TEs) in Maize 1940s by Barbara McClintock [1] have been described as junk, selfish with no benefit to host, and more recently major determinants genome structure evolution. TEs are DNA sequences that capable moving new sites make additional copies while doing so. To limit propagation TEs, host silencing mechanisms directed at transposon-encoded genes required for mobilization. The mutagenic properties potential form affect gene expression,...
The microbiota is a key determinant of the physiology and immunity animal hosts. factors governing transmissibility viruses between susceptible hosts are incompletely understood. Bacteria serve as food for Caenorhabditis elegans represent an integral part natural environment C. . We determined effects bacteria isolated with from its on transmission Orsay virus in using quantitative host susceptibility assays. observed that Ochrobactrum species promoted transmission, whereas Pseudomonas...
The microbiota is a key determinant of the physiology and antiviral immunity animal hosts. factors governing transmissibility viruses between susceptible hosts are incompletely understood. Bacteria serve as food for Caenorhabditis elegans represent an integral part natural environment C. elegans. We determined effects bacteria isolated with from its on transmission Orsay virus in using quantitative host susceptibility assays. observed that Ochrobactrum species promoted transmission, whereas...
ABSTRACT Endogenous retroviruses and LTR retrotransposons are mobile genetic elements that closely related to retroviruses. Desilenced endogenous associated with human autoimmune disorders neurodegenerative diseases. C. elegans Caenorhabdites contain and, as described here, numerous integrated viral genes including envelope part of retrotransposons. We found both silenced by ADARs ( a denosine d eaminases cting on ouble-stranded RNA (dsRNA)) together the RNAi factor ERI-6/7, homolog Mov10...
ABSTRACT Streptomyces ramocissimus , the producer of elongation factor Tu (EF-Tu)-targeted antibiotic kirromycin, contains three divergent tuf -like genes, with tuf1 encoding regular kirromycin-sensitive EF-Tu1; functions tuf2 and tuf3 are unknown. Analysis gene organization in nine producers kirromycin-type antibiotics revealed that they all contain homologues sometimes but was found S. only. The -flanking regions were sequenced, two -surrounding open reading frames shown to be oriented...