- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Selenium in Biological Systems
- Trace Elements in Health
- Metalloenzymes and iron-sulfur proteins
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Glycosylation and Glycoproteins Research
- Redox biology and oxidative stress
- Axon Guidance and Neuronal Signaling
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Protein purification and stability
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- Electrocatalysts for Energy Conversion
- Advanced battery technologies research
- Porphyrin Metabolism and Disorders
- Hydrogen Storage and Materials
- Chemical Synthesis and Analysis
- Angiogenesis and VEGF in Cancer
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Protein Tyrosine Phosphatases
University of Georgia
2023-2024
Yale University
2019-2023
Whitney Museum of American Art
2021-2022
University of Manitoba
2014-2019
The identification of four-stranded G-quadruplexes (G4s) has highlighted the fact that DNA additional spatial organisations at its disposal other than double-stranded helices. Recently, it became clear formation G4s is not limited to traditional G3+NL1G3+NL2G3+NL3G3+ sequence motif. Instead, G3 triplets can be interrupted by deoxythymidylate (DNA) or uridylate (RNA) where base forms a bulge loops out from G-quadruplex core. Here, we report first high-resolution X-ray structure unique...
Hydrogenases catalyze hydrogen/proton interconversion that is normally electrochemically reversible (having minimal overpotential requirement), a special property otherwise almost exclusive to platinum metals. The mechanism of [NiFe]-hydrogenases includes long-range proton-coupled electron-transfer process involving specific Ni-coordinated cysteine and the carboxylate nearby glutamate. A variant in which this has been exchanged for selenocysteine displays two distinct changes...
Unique chemical and physical properties are introduced by inserting selenocysteine (Sec) at specific sites within proteins. Recombinant facile production of eukaryotic selenoproteins would benefit from a yeast expression system; however, the selenoprotein biosynthetic pathway was lost in evolution kingdom Fungi as it diverged its relatives. Based on our previous development efficient bacteria, we designed novel Sec biosynthesis Saccharomyces cerevisiae using Aeromonas salmonicida translation...
Abstract Protein translation is orchestrated through tRNA aminoacylation and ribosomal elongation. Among the highly conserved structure of tRNAs, they have distinguishing features which promote interaction with their cognate aminoacyl synthetase (aaRS). These key are referred to as identity elements. In our study, we investigated tRNA:aaRS pair that installs 22nd amino acid, pyrrolysine (tRNAPyl:PylRS). Pyrrolysyl-tRNA synthetases (PylRSs) naturally encoded in some archaeal bacterial genomes...
Transfer RNAs have been extensively explored as the molecules that translate genetic code into proteins. At this interface of genetics and biochemistry, tRNAs direct efficiency every major step translation by interacting with a multitude binding partners. However, due to variability tRNA sequences abundance diverse post-transcriptional modifications, guidebook linking specific translational outcomes has yet be elucidated. Here, we review substantial efforts collectively uncovered engineering...
Significance Substitution of cysteine by selenocysteine is held responsible for the increased performance many enzymes: The higher activity [NiFeSe]-hydrogenases compared with their [NiFe] counterparts often attributed to Sec replacement one active-site ligand. Replacing each four residues in an O 2 -tolerant [NiFe]-hydrogenase shows that this substitution alone does not overcome inability evolve H a characteristic group 1d hydrogenases. A nonbridging lying on direct path between Ni and...
Amino acid availability is a key factor that can be controlled to optimize the productivity of fed-batch cultures. To study amino limitation effects, serum-free chemically defined basal medium was formulated exclude acids became depleted in batch culture. The effect limiting glutamine, asparagine, and cysteine on cell growth, metabolism, antibody productivity, product glycosylation investigated three Chinese hamster ovary (CHO) lines (CHO-DXB11, CHO-K1SV, CHO-S). Cysteine detrimental both...
Abstract Selenoproteins contain the 21st amino acid, selenocysteine. Selenocysteine is only acid that synthesized on its cognate tRNA, and it inserted at specific recoded UGA stop codons via a complex translation system. Although highly similar to cysteine, selenocysteine has unique properties, including stronger nucleophilic ability lower reduction potential. Efforts site‐specifically incorporate create recombinant selenoproteins involve UAG codon expression of necessary machinery. This...
Abstract Ribosomes are remarkable in their malleability to accept diverse aminoacyl-tRNA substrates from both the same organism and other organisms or domains of life. This is a critical feature ribosome that allows use orthogonal translation systems for genetic code expansion. Optimization these generally involves focusing on compatibility tRNA, synthetase, non-canonical amino acid with each other. As we expand diversity tRNAs used include structures, question arises as tRNA suitability...
Post-translational modifications (PTMs) can occur on almost all amino acids in eukaryotes as a key mechanism for regulating protein function. The ability to study the role of these various biological processes requires techniques modify proteins site-specifically. One strategy this is genetic code expansion (GCE) bacteria. low frequency post-translational bacteria makes it preferred host whether presence modification influences protein’s Genetic employs orthogonal translation systems...
The production of recombinant proteins for functional and biophysical studies, especially in the field structural determination, still represents a challenge as high quality quantities are needed to adequately perform experiments. This is part solved by optimizing protein constructs expression conditions maximize yields regular flask systems. Still, work flow effort can be substantial with no guarantee obtain improvements. study presents combination workflows that used dramatically increase...
The presence of selenocysteine in a protein confers many unique properties that make the production recombinant selenoproteins desirable. Targeted incorporation Sec into choice is possible by exploiting elongation factor Tu-dependent reassignment UAG codons, strategy has been continuously improved variety means. Improving selenoprotein yield directed evolution requires selection and screening markers are titratable, have high dynamic range, enable high-throughput screening, can discriminate...