San Diego, California, United States
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What's in a biologist's bag when traveling for a conference👇👇 #sciencehumor #biologyfun #lablife #academia #academiclife Image from KAMacGillivray
What's in a biologist's bag when traveling for a conference👇👇 #sciencehumor #biologyfun #lablife #academia #academiclife Image from KAMacGillivray
Liked by Bianca Ynez Ruiz Smith
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Swimming microrobots made out of algae can deliver a payload of cancer-fighting drugs directly to metastatic tumors in the lungs, according to a new…
Swimming microrobots made out of algae can deliver a payload of cancer-fighting drugs directly to metastatic tumors in the lungs, according to a new…
Liked by Bianca Ynez Ruiz Smith
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Incredibly honored by this! EMBO is a truly outstanding organization and I look forward to contributing to it.
Incredibly honored by this! EMBO is a truly outstanding organization and I look forward to contributing to it.
Liked by Bianca Ynez Ruiz Smith
Experience & Education
Publications
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Proteome-wide identification of amino acid substitutions deleterious for protein function
bioRxiv
DNA sequencing has led to the discovery of millions of mutations that change the encoded protein sequences, but the impact of nearly all of these mutations on protein function is unknown. We addressed this scarcity of functional data by developing Miro, a proteomic technology that uses mistranslation to introduce amino acid substitutions and biochemical assays to quantify functional differences of thousands of protein variants by mass spectrometry. We apply this technology to the proteome of…
DNA sequencing has led to the discovery of millions of mutations that change the encoded protein sequences, but the impact of nearly all of these mutations on protein function is unknown. We addressed this scarcity of functional data by developing Miro, a proteomic technology that uses mistranslation to introduce amino acid substitutions and biochemical assays to quantify functional differences of thousands of protein variants by mass spectrometry. We apply this technology to the proteome of yeast to reveal amino acid substitutions that impact protein structure, ligand binding, protein-protein interactions, protein post-translational modifications, and protein thermal stability. Adapting Miro to human cells will provide a means to efficiently accelerate our mechanistic interpretation of genomic mutations to predict disease risk.
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Modulating Mistranslation Potential of tRNA-Ser in Saccharomyces cerevisiae
Genetics
Transfer RNAs (tRNAs) read the genetic code, translating nucleic acid sequence into protein. For tRNASer the anticodon does not specify its aminoacylation. For this reason, mutations in the tRNASer anticodon can result in amino acid substitutions, a process called mistranslation. Previously, we found that tRNASer with a proline anticodon was lethal to cells. However, by incorporating secondary mutations into the tRNA, mistranslation was dampened to a nonlethal level. The goal of this work was…
Transfer RNAs (tRNAs) read the genetic code, translating nucleic acid sequence into protein. For tRNASer the anticodon does not specify its aminoacylation. For this reason, mutations in the tRNASer anticodon can result in amino acid substitutions, a process called mistranslation. Previously, we found that tRNASer with a proline anticodon was lethal to cells. However, by incorporating secondary mutations into the tRNA, mistranslation was dampened to a nonlethal level. The goal of this work was to identify second-site substitutions in tRNASer that modulate mistranslation to different levels. Targeted changes to putative identity elements led to total loss of tRNA function or significantly impaired cell growth. However, through genetic selection, we identified 22 substitutions that allow nontoxic mistranslation. These secondary mutations are primarily in single-stranded regions or substitute G:U base pairs for Watson-Crick pairs. Many of the variants are more toxic at low temperature and upon impairing the rapid tRNA decay pathway. We suggest that the majority of the secondary mutations affect the stability of the tRNA in cells. The temperature sensitivity of the tRNAs allows conditional mistranslation. Proteomic analysis demonstrated that tRNASer variants mistranslate to different extents with diminished growth correlating with increased mistranslation. When combined with a secondary mutation, other anticodon substitutions allow serine mistranslation at additional nonserine codons. These mistranslating tRNAs have applications in synthetic biology, by creating "statistical proteins," which may display a wider range of activities or substrate specificities than the homogenous form.
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Conditional accumulation of toxic tRNAs to cause amino acid misincorporation
Nucleic Acids Research
To develop a system for conditional amino acid misincorporation, we engineered tRNAs in the yeast Saccharomyces cerevisiae to be substrates of the rapid tRNA decay (RTD) pathway, such that they accumulate when RTD is turned off. We used this system to test the effects on growth of a library of tRNASer variants with all possible anticodons, and show that many are lethal when RTD is inhibited and the tRNA accumulates. Using mass spectrometry, we measured serine misincorporation in yeast…
To develop a system for conditional amino acid misincorporation, we engineered tRNAs in the yeast Saccharomyces cerevisiae to be substrates of the rapid tRNA decay (RTD) pathway, such that they accumulate when RTD is turned off. We used this system to test the effects on growth of a library of tRNASer variants with all possible anticodons, and show that many are lethal when RTD is inhibited and the tRNA accumulates. Using mass spectrometry, we measured serine misincorporation in yeast containing each of six tRNA variants, and for five of them identified hundreds of peptides with serine substitutions at the targeted amino acid sites. Unexpectedly, we found that there is not a simple correlation between toxicity and the level of serine misincorporation; in particular, high levels of serine misincorporation can occur at cysteine residues without obvious growth defects. We also showed that toxic tRNAs can be used as a tool to identify sequence variants that reduce tRNA function. Finally, we generalized this method to another tRNA species, and generated conditionally toxic tRNATyr variants in a similar manner. This method should facilitate the study of tRNA biology and provide a tool to probe the effects of amino acid misincorporation on cellular physiology.
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Spectral Library Searching To Identify Cross-Linked Peptides
Journal of Proteome Research
Methods harnessing protein cross-linking and mass spectrometry (XL-MS) offer high-throughput means to identify protein-protein interactions (PPIs) and structural interfaces of protein complexes. Yet, specialized data dependent methods and search algorithms are often required to confidently assign peptide identifications to spectra. To improve the efficiency of matching high confidence spectra we developed a spectral library based approach to search cross-linked peptide data derived from Protein…
Methods harnessing protein cross-linking and mass spectrometry (XL-MS) offer high-throughput means to identify protein-protein interactions (PPIs) and structural interfaces of protein complexes. Yet, specialized data dependent methods and search algorithms are often required to confidently assign peptide identifications to spectra. To improve the efficiency of matching high confidence spectra we developed a spectral library based approach to search cross-linked peptide data derived from Protein Interaction Reporter (PIR) methods using the spectral library search algorithm, SpectraST. Spectral library matching of cross-linked peptide data from query spectra increased the absolute number of confident peptide relationships matched to spectra, and thereby number of protein-protein interactions identified. By matching library spectra from bona fide, previously established PIR-cross-linked peptide relationships, spectral library searching reduces the need for continued, complex mass spectrometric methods to identify peptide relationships, increases coverage of relationship identifications and improves the accessibility of XL-MS technologies.
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Honors & Awards
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NSF GRFP Scholarship
National Science Foundation Graduate Research Fellowship (NSF GRF) Program
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MHRT Program Scholarship
National Institute on Minority Health and Health Disparities, National Institutes of Health - Minority Health and Health Disparities Research Training (MHRT) Program (T37)
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Genome Sciences Summer Research For Undergraduates Scholarship
Department of Genome Sciences at the University of Washington
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SACNAS National Conference Travel Scholarship
Society for Advancement of Chicanos and Native Americans in Science (SACNAS)
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Air Force Aid Society: General Henry H. Arnold Education Grant
Air Force Aid Society
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MARC Program Scholarship
National Institute of General Medical Sciences, National Institutes of Health - Maximizing Access to Research Careers (MARC) Awards (T34)
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LSAMP Academic Year Scholarship
Louis Stokes Alliance for Minority Participation in Research (LSAMP) Program
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Twilight Technology, Inc. Technology Student Scholarship
Twilight Technology
Languages
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English
Native or bilingual proficiency
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Spanish
Limited working proficiency
More activity by Bianca Ynez Ruiz
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Two papers in Nature describe a new genome editing technique that enables the insertion, inversion and deletion of long DNA sequences at…
Two papers in Nature describe a new genome editing technique that enables the insertion, inversion and deletion of long DNA sequences at…
Liked by Bianca Ynez Ruiz Smith
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The Hispanics and LatinX in Mass Spectrometry networking session at the #ASMS2024 Conference was a huge success! It was incredible to meet so many…
The Hispanics and LatinX in Mass Spectrometry networking session at the #ASMS2024 Conference was a huge success! It was incredible to meet so many…
Liked by Bianca Ynez Ruiz Smith
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Brand new preprint up on Biorxiv. "Development of highly multiplex targeted proteomics assays in biofluids using the Stellar mass spectrometer" For…
Brand new preprint up on Biorxiv. "Development of highly multiplex targeted proteomics assays in biofluids using the Stellar mass spectrometer" For…
Liked by Bianca Ynez Ruiz Smith
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