A5053867071- RNA regulation and disease
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- SARS-CoV-2 and COVID-19 Research
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- SARS-CoV-2 detection and testing
- Molecular Communication and Nanonetworks
- Genomics and Chromatin Dynamics
- Viral Infections and Vectors
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Ovarian cancer diagnosis and treatment
- Advancements in Semiconductor Devices and Circuit Design
- Nanowire Synthesis and Applications
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
- Advanced Biosensing Techniques and Applications
- Vector-Borne Animal Diseases
- Insect and Pesticide Research
- Advanced biosensing and bioanalysis techniques
Howard Hughes Medical Institute
2020-2022
University of California, San Francisco
2019-2022
University of Cambridge
2018
The Gurdon Institute
2018
University of Chicago
2013
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the cell receptor angiotensin-converting enzyme (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt ACE2. Cryo-electron microscopy (cryo-EM) revealed one nanobody, Nb6, binds in fully inactive conformation with binding domains locked into their inaccessible down state, incapable...
An essential step for understanding the transcriptional circuits that control development and physiology is global identification characterization of regulatory elements. Here, we present first map elements across ageing an animal, identifying 42,245 accessible in at least one Caenorhabditis elegans stage. Based on nuclear transcription profiles, define 15,714 protein-coding promoters 19,231 putative enhancers, find both types element can drive orientation-independent transcription....
The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in to various conditions. Phosphorylated (eIF2-P) inhibits eIF2’s nucleotide exchange eIF2B, a twofold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly vitro vivo. In absence eIF2B’s α-subunit, ISR induced because unassembled tetramer subcomplexes accumulate cells. Upon addition small-molecule inhibitor ISRIB, tetramers assemble...
ABSTRACT Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. gains entry into host cells via interaction between its Spike protein the cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this confers potent neutralization viral entry, providing avenue for vaccine design therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt ACE2. By screening...
Abstract Viral infection triggers activation of the integrated stress response (ISR). In to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates translation initiation factor eIF2, converting it from a initiator into potent inhibitor and this restricts synthesis proteins. Phosphorylated eIF2 (eIF2-P) inhibits by binding eIF2’s dedicated, heterodecameric nucleotide exchange eIF2B conformationally inactivating it. We show that NSs Sandfly Fever Sicilian virus...
Summary R ibosome-associated Q uality C ontrol (RQC) pathways protect cells from toxicity caused by incomplete protein products resulting translation of damaged or problematic mRNAs. Extensive work in yeast has identified highly conserved mechanisms that lead to the degradation faulty mRNA and partially synthesized polypeptide. Here, we used CRISPR-Cas9-based screening search for additional RQC strategies mammals. We found failed leads specific silencing initiation on message. This negative...
In eukaryotic cells, stressors reprogram the cellular proteome by activating integrated stress response (ISR). its canonical form, stress-sensing kinases phosphorylate translation initiation factor eIF2 (eIF2-P), which ultimately leads to reduced levels of ternary complex required for mRNA translation. Previously we showed that translational control is primarily exerted through a conformational switch in eIF2’s nucleotide exchange factor, eIF2B, shifts from active A-State conformation...
The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in to various conditions. Phosphorylated (eIF2-P) inhibits eIF2's nucleotide exchange eIF2B, a two-fold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly vitro vivo. In absence eIF2B's α-subunit, ISR induced because unassembled tetramer subcomplexes accumulate cells. Upon addition small-molecule inhibitor ISRIB, tetramers assemble...
Abstract An essential step for understanding the transcriptional circuits that control development and physiology is global identification characterization of regulatory elements. Here we present first map elements across ageing an animal, identifying 42,245 accessible in at least one C. elegans stage. Based on nuclear transcription profiles, define 15,714 protein-coding promoters 19,231 putative enhancers, find both types element can drive orientation-independent transcription....
Abstract The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in to various conditions. Phosphorylated (eIF2-P) inhibits eIF2’s nucleotide exchange eIF2B, a two-fold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly vitro vivo. In absence eIF2B’s α-subunit, ISR induced because unassembled tetramer subcomplexes accumulate cells. Upon addition small-molecule inhibitor ISRIB, tetramers...
Abstract Viral infection triggers activation of the integrated stress response (ISR). In to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates translation initiation factor eIF2, converting it from a initiator into potent inhibitor and this restricts synthesis proteins. Phosphorylated eIF2 (eIF2-P) inhibits by binding eIF2’s dedicated, heterodecameric nucleotide exchange eIF2B conformationally inactivating it. We show that NSs Sandfly Fever Sicilian virus...
Abstract In eukaryotic cells, stressors reprogram the cellular proteome by activating integrated stress response (ISR). its canonical form, stress-sensing kinases phosphorylate translation initiation factor eIF2 (eIF2-P), which ultimately leads to reduced levels of ternary complex required for mRNA translation. Translational control is primarily exerted through a conformational switch in eIF2’s nucleotide exchange factor, eIF2B, shifts from active A-State conformation inhibited I-State upon...
Abstract Introduction: Metastatic ovarian cancer remains an urgent clinical problem. The homing and invasion of cells into the omentum, preferred site metastasis, is a rate-limiting step in disease progression. We have recently shown that immune cell-containing structures known as milky spots are required for colonization omental adipose. Experiments were designed using well-established models experimental metastasis assays to answer following questions: Does cell localization depend upon...