A5056217079- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Fuel Cells and Related Materials
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Transgenic Plants and Applications
- Toxin Mechanisms and Immunotoxins
- Lipid Membrane Structure and Behavior
- Cancer-related gene regulation
- Advanced biosensing and bioanalysis techniques
- HVDC Systems and Fault Protection
- Plant Molecular Biology Research
- Animal Virus Infections Studies
- Peptidase Inhibition and Analysis
- Molecular Biology Techniques and Applications
- Respiratory viral infections research
- Plant-Microbe Interactions and Immunity
- Sirtuins and Resveratrol in Medicine
- Viral Infectious Diseases and Gene Expression in Insects
- Studies on Chitinases and Chitosanases
- RNA regulation and disease
- RNA Interference and Gene Delivery
- Nematode management and characterization studies
University of Michigan
2019-2025
Eli Lilly (United States)
2023-2025
The University of Texas at Austin
2024
University of Cambridge
2011-2020
University of Edinburgh
2019
University of Illinois Urbana-Champaign
2017
Urbana University
2017
Eastern Kentucky University
2010
Orion Genomics (United States)
2004
Members of the family Coronaviridae have largest genomes all RNA viruses, typically in region 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East (MERS-CoV), are medical importance, with high mortality rates and, case SARS-CoV, significant pandemic potential. Other Porcine epidemic diarrhea virus Avian coronavirus, important livestock pathogens. Ribosome profiling is a technique which exploits capacity translating...
Chemical modifications of RNAs have long been established as key modulators nonprotein-coding RNA structure and function in cells. There is a growing appreciation that messenger (mRNA) sequences responsible for directing protein synthesis can also be posttranscriptionally modified. The enzymatic incorporation mRNA has many potential outcomes, including changing stability, recruitment, translation. We tested how one the most common present coding regions, pseudouridine (Ψ), impacts using...
Sorghum bicolor is a close relative of maize and staple crop in Africa much the developing world because its superior tolerance arid growth conditions. We have generated sequence from hypomethylated portion sorghum genome by applying methylation filtration (MF) technology. The evidence suggests that 96% genes been tagged, with an average coverage 65% across their length. Remarkably, this level gene discovery was accomplished after generating raw less than 300 megabases 735-megabase genome....
Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe modified protocol software package designed to benefit more broadly the community terms simplicity utility. The protocol, applicable diverse organisms, including organelles, based largely on previously published methodologies, but uses duplex-specific nuclease (DSN) as convenient, species-independent way reduce rRNA contamination....
Abstract Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct proportion translating ribosomes to shift nt and continue in the new reading frame. Such normally occurs at set ratio utilized expression many viral genes number cellular genes. An open question whether proteins might function as trans -acting switches turn on or off response conditions. Here we show that model RNA virus, encephalomyocarditis -activated by...
Post-transcriptional modifications to messenger RNAs (mRNAs) have the potential alter biological function of this important class biomolecules. The study mRNA is a rapidly emerging field, and full complement chemical in mRNAs not yet established. We sought identify quantify present yeast using an ultra-high performance liquid chromatography tandem mass spectrometry method detect 40 nucleoside variations parallel. observe six modified nucleosides with high confidence highly purified samples...
While the centrality of posttranscriptional modifications to RNA biology has long been acknowledged, function vast majority modified sites remains be discovered. Illustrative this, there is not yet a discrete biological role assigned for one most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (m
Four new mRNA modifications were detected in S. cerevisiae by integrating an improved LC-MS/MS approach with enhanced purification and validation process. Codons containing these further identified to impede translation.
Single-stranded guide RNAs (sgRNAs) are important therapeutic modalities that facilitate selective genome editing by the CRISPR/Cas9 system. While these synthesized through solid phase oligonucleotide synthesis similar to small interfering RNA (siRNAs) and antisense (ASOs) therapeutics, their sequence length complex secondary tertiary structure hinder analytical characterization. The resulting current sgRNA methodologies have limited chromatographic selectivity near FLP MS compatibility....
Nanodiscs have become a popular membrane mimetic system offering well-defined bilayer environment to stabilize proteins for in vitro analyses using range of analytical methods; however, lipid compositions common their deployment are simplistic and often fail model native complexity. Furthermore, there has been general lack rigorous biophysical characterization nanodiscs comprising more than one lipid. To address these challenges, we coupled nanodisc formation purification workflow with...
RNA viruses are a major human health threat. The life cycles of many highly pathogenic like influenza A virus (IAV) and Lassa depends on host mRNA, because viral polymerases cleave 5′-m7G-capped transcripts to prime mRNA synthesis ("cap-snatching"). We hypothesized that start codons within cap-snatched could generate chimeric human-viral mRNAs with coding potential. report the existence this mechanism gene origination, which we named "start-snatching." Depending reading frame,...
siRNA therapeutics provide a selective and powerful approach to reduce the expression of disease-causing genes. For regulatory approval, these modalities require sequence confirmation which is typically achieved by intact tandem mass spectrometry sequencing. However, this process produces highly complex spectra are difficult interpret results in less than full coverage. We sought develop bottom-up sequencing platform ease data analysis Analogous proteomics, requires chemical or enzymatic...
Among RNAs, transfer RNAs (tRNAs) contain the widest variety of abundant posttranscriptional chemical modifications. These modifications are crucial for tRNAs to participate in protein synthesis, promoting proper tRNA structure and aminoacylation, facilitating anticodon:codon recognition, ensuring reading frame maintenance ribosome. While were long thought be stoichiometric, it is becoming increasingly apparent that these can change dynamically response cellular environment. The ability...
Abstract Transfer RNAs (tRNAs) contain dozens of chemical modifications. These modifications are critical for maintaining tRNA tertiary structure and optimizing protein synthesis. Here we advance the use Nanopore direct RNA-sequencing (DRS) to investigate synergy between that known stabilize structure. We sequenced 42 cytosolic isoacceptors from wild-type yeast five tRNA-modifying enzyme knockout mutants. data permitted comprehensive analysis three neighboring conserved in T-loops:...
Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we repurpose the type III-A CRISPR complex from Thermus thermophilus (TtCsm) programmable capture and concentration specific RNAs mixtures. The target bound TtCsm generates two cyclic oligoadenylates (i.e., cA
A microfluidic platform for Nanodisc formation and membrane protein incorporation will enable studies of interactions at model interfaces.
ABSTRACT While the centrality of post-transcriptional modifications to RNA biology has long been acknowledged, function vast majority modified sites remains be discovered. Illustrative this, there is not yet a discrete biological role assigned for one most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (m 5 U54). Here, we uncover contributions m U54 both tRNA maturation and protein synthesis. Our mass spectrometry analyses demonstrate that cells lacking enzyme...
Monoclonal antibody therapy has an important role to play as a post-exposure prophylactic and therapeutic for the treatment of viral infections, including emerging infections. For example, several patients present Ebola virus outbreak in West Africa were treated with ZMapp, cocktail three monoclonal antibodies which are expressed Nicotiana benthamiana.The majority clinical use mammalian cell lines offer native folding glycosylation antibody. expression vegetal systems offers advantages over...
Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we make two major advances that simultaneously limit sample handling and significantly enhance the sensitivity SARS-CoV-2 RNA directly from patient samples. First, repurpose type III-A CRISPR complex Thermus thermophilus (TtCsm) programmable capture concentration specific RNAs mixtures. The target bound TtCsm primarily generates cyclic oligoadenylates (i.e., cA3 cA4) allosterically...
Chemical modifications to protein encoding messenger RNA (mRNA) can modulate their localization, translation and stability within cells. Over 15 different types of mRNA have been identified by sequencing liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) technologies. While LC-MS/MS is arguably the most essential tool available for studying analogous post-translational modifications, high-throughput discovery quantitative characterization has hampered difficulty obtaining...
Flaviviruses are a family of RNA viruses that commonly found in arthropods and can be transmitted to both animal human hosts. A large portion these flaviviruses pathogens, infecting up 400 million people each year. These include Yellow Fever, Dengue, West Nile, Zika, Powassan viruses. Transfer between hosts, combined with the high error rate RNA-dependent polymerases virus, drive increased rates mutation potentially increase viral pathogenicity. Current evidence indicates genomes modified...
Abstract Segmented negative-strand RNA viruses (sNSVs) include the influenza viruses, bunyaviruses, and other major pathogens of humans, animals plants. The genomes these are extremely short. In response to this severe genetic constraint, sNSVs use a variety strategies maximise their coding potential. Because eukaryotic hosts parasitized by can regulate gene expression through low levels translation initiation upstream canonical open reading frames (ORFs), we asked whether could expand own...