A5056661054- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Methane Hydrates and Related Phenomena
- Advanced biosensing and bioanalysis techniques
- Seismic Waves and Analysis
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- Seismology and Earthquake Studies
- Biochemical and Molecular Research
- Earthquake Detection and Analysis
- RNA modifications and cancer
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Protein Structure and Dynamics
- Genetics, Bioinformatics, and Biomedical Research
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- DNA and Biological Computing
- Amino Acid Enzymes and Metabolism
- Chemical Synthesis and Analysis
Fred Hutch Cancer Center
2015-2024
Seattle University
2001-2024
North Seattle College
2006-2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2008-2023
Cancer Research Center
1992-2020
University of Washington
2000-2013
New England Biolabs (United States)
2011
Washington University in St. Louis
2010
Bellevue College
2002
Brookhaven National Laboratory
1998
Wrapped DNA TAL effectors are proteins that bacterial pathogens inject into plant cells bind to host activate expression of genes. The DNA-binding domain is composed tandem repeats within which a repeat-variable diresidue sequence confers nucleotide specificity. Deng et al. (p. 720 , published online 5 January) report the structure effector dHax3, containing 11.5 repeats, in DNA-free and DNA-bound states, Mak 716 PthXo1 effector, 22 bound its target. Together, structures reveal...
The crystal structure of an unmodified hammerhead RNA in the absence divalent metal ions has been solved, and it was shown that this ribozyme can cleave itself when are added. This biologically active fold is same as found previously for two modified ribozymes. Addition cations at low pH makes possible to capture uncleaved metal-bound form. A conformational intermediate, having additional Mg(II) bound cleavage-site phosphate, captured by freeze-trapping prior cleavage. most significant...
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action naturally occurring distorters prevalence co-evolving suppressors hampered their use for control. Here we generate synthetic distortion system by exploiting specificity homing endonuclease I-PpoI, which is able selectively cleave ribosomal gene sequences malaria vector Anopheles gambiae are located...
Abstract Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents research applications, each existing platform has significant limitations in one or more of three key properties necessary therapeutic application: efficiency cleavage at the desired target site, specificity (i.e. rate ‘off-target’ sites), and efficient/facile means delivery cells. Here, we describe development a...
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used create cytoreagents are complex expensive. Consequently, we develop targeted mRNA nanocarriers that simply mixed with reprogram them via transient expression. Here, describe three examples establish approach is simple generalizable. First, demonstrate delivering encoding a genome-editing agent can efficiently knock-out selected genes in...
Homing endonucleases are highly specific DNA cleaving enzymes that encoded within genomes of all forms microbial life including phage and eukaryotic organelles. These proteins drive the mobility persistence their own reading frames. The genes encode homing often embedded self-splicing elements such as group I introns, II introns inteins. This combination molecular functions is mutually advantageous: endonuclease activity allows surrounding inteins to act invasive elements, while splicing...
A renewed interest in the Laue diffraction technique has been brought about by development of new, more intense and brilliant synchrotron sources along with their insertion devices such as wigglers undulators, prospect using these to study structural dynamics time-resolved crystallography. Theoretical studies during past decade have identified unique features polychromatic geometry greatly improved our understanding method. This led innovative approaches data processing its software...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe 2.1 .ANG. resolution structure of iron superoxide dismutase from Pseudomonas ovalisBarry L. Stoddard, P. Lynne Howell, Dagmar Ringe, and Gregory A. PetskoCite this: Biochemistry 1990, 29, 38, 8885–8893Publication Date (Print):September 25, 1990Publication History Published online1 May 2002Published inissue 25 September 1990https://pubs.acs.org/doi/10.1021/bi00490a002https://doi.org/10.1021/bi00490a002research-articleACS PublicationsRequest...
Homing endonucleases stimulate gene conversion by generating site-specific DNA double-strand breaks that are repaired homologous recombination. These enzymes potentially valuable tools for targeted correction and genome engineering. We have engineered a variant of the I-AniI homing endonuclease nicks its cognate target site. This contains mutation basic residue essential proton transfer solvent activation in one active The cleavage mechanism, DNA-binding affinity, substrate specificity...
Homing endonucleases mobilize their own genes by generating double-strand breaks at individual target sites within potential host DNA. Because of high specificity, these proteins are used for “genome editing” in higher eukaryotes. However, alteration homing endonuclease specificity is quite challenging. Here we describe the identification and phylogenetic analysis over 200 naturally occurring LAGLIDADG (LHEs). Biochemical structural characterization from one clade tree demonstrates strong...
Site-specific homing endonucleases are capable of inducing gene conversion via homologous recombination. Reprogramming their cleavage specificities allows the targeting specific biological sites for correction or conversion. We used computational protein design to alter specificity I-MsoI three contiguous base pair substitutions, resulting in an endonuclease whose activity and its new site rival that wild-type original site. Concerted all simultaneous substitutions was more successful than a...
Inteins are genetic elements, inserted in-frame into protein-coding genes, whose products catalyze their removal from the protein precursor via a protein-splicing reaction. Intein domains can be split two fragments and still ligate flanks by trans-protein-splicing A bioinformatic analysis of environmental metagenomic data revealed 26 different loci with novel genomic arrangement. In each locus, conserved enzyme coding region is broken in intein, free-standing endonuclease gene between. Eight...