A5080162380- Protein Structure and Dynamics
- Genomics, phytochemicals, and oxidative stress
- Computational Drug Discovery Methods
- RNA Research and Splicing
- Microbial Natural Products and Biosynthesis
- Glutathione Transferases and Polymorphisms
- DNA and Nucleic Acid Chemistry
- Advanced Electron Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Genetics, Bioinformatics, and Biomedical Research
- Metal complexes synthesis and properties
- Tryptophan and brain disorders
- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Electron Spin Resonance Studies
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Protein purification and stability
SIB Swiss Institute of Bioinformatics
2022-2024
École Polytechnique Fédérale de Lausanne
2018-2024
Cornell University
2018
University at Buffalo, State University of New York
2015
Abstract Physical interactions between proteins are essential for most biological processes governing life 1 . However, the molecular determinants of such have been challenging to understand, even as genomic, proteomic and structural data increase. This knowledge gap has a major obstacle comprehensive understanding cellular protein–protein interaction networks de novo design protein binders that crucial synthetic biology translational applications 2–9 Here we use geometric deep-learning...
De novo protein design explores uncharted sequence and structure space to generate novel proteins not sampled by evolution. A main challenge in de involves crafting "designable" structural templates guide the searches toward adopting target structures. We present a convolutional variational autoencoder that learns patterns of structure, dubbed Genesis. coupled Genesis with trRosetta sequences for set folds found is capable reconstructing native-like distance angle distributions five native...
Studying electrophile signaling is marred by difficulties in parsing changes pathway flux attributable to on-target, vis-à-vis off-target, modifications. By combining bolus dosing, knockdown, and Z-REX—a tool investigating on-target/on-pathway signaling, we document that labeling of one zebrafish-Keap1-paralog (zKeap1b) stimulates Nrf2- driven antioxidant response (AR) (like the human-ortholog). Conversely, zKeap1a a dominant-negative regulator electrophile-promoted Nrf2-signaling, itself...
T-REX (targetable reactive electrophiles and oxidants) enables electrophile targeting in living systems with high spatiotemporal precision at single-protein-target resolution. allows functional consequences of individual signaling events to be directly linked on-target modifications. is accomplished by expressing a HaloTagged protein interest (POI) introducing Halo-targetable bioinert photocaged precursor electrophilic signal (RES). Light exposure releases the unfettered RES on demand,...
The key mRNA-binding proteins HuR and AUF1 are reported stress sensors in mammals. Intrigued by recent reports of sensitivity these to the electrophilic lipid prostaglandin A2 other redox signals, we here examined their sensing abilities a prototypical redox-linked lipid-derived electrophile, 4-hydroxynonenal (HNE). Leveraging our T-REX electrophile delivery platform, found that only HuR, not AUF1, is kinetically-privileged sensor HNE HEK293T cells, functions through specific cysteine, C13....
Abstract Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such have been challenging to understand, even as genomic, proteomic, and structural data grows. This knowledge gap has a major obstacle comprehensive understanding cellular protein-protein interaction (PPI) networks de novo design protein binders that crucial synthetic biology translational applications. We exploit geometric deep learning...
DNA sequences that undergo large changes in secondary structure upon binding of small molecules are the basis for molecular switches. Here we report a Zn2+ complex promotes conversion fully complementary double helix into hairpins. The conformational switch is promoted by an isolated or free ZnCl2 and macrocyclic ligand. selective over biologically relevant transition-metal ions including Cu2+ Fe2+. dual ligand/DNA approach may improve selectivity metal-ion-sensing applications.
Abstract De novo protein design aims to explore uncharted sequence-and structure areas generate novel proteins that have not been sampled by evolution. One of the main challenges in de involves crafting “designable” structural templates can guide sequence search towards adopting target structures. Here, we present an approach learn patterns based on a convolutional variational autoencoder, dubbed Genesis. We coupled Genesis with trRosetta sequences for set folds and found is capable...
De novo protein design aims to explore uncharted sequence- and structure areas generate novel proteins that have not been sampled by evolution. One of the main challenges in de involves crafting “designable” structural templates can guide sequence search towards adopting target structures. Here, we present an approach learn patterns based on a convolutional variational autoencoder, dubbed Genesis. We coupled Genesis with trRosetta sequences for set folds found is capable reconstructing...
Abstract The key mRNA-binding proteins HuR and AUF1 are reported stress sensors in mammals. Intrigued by recent reports of sensitivity these to the electrophilic lipid prostaglandin A2 other redox signals, we here examined their sensing abilities a prototypical redox-linked lipid-derived electrophile, 4-hydroxynonenal (HNE). Leveraging our T-REX electrophile delivery platform, found that only HuR, not AUF1, is kinetically-privileged sensor HNE HEK293T cells, functions through specific...
Abstract Studying electrophile signaling is marred by difficulties in parsing changes pathway flux attributable to on-target, vis-à-vis off-target, modifications. By combining bolus dosing, knockdown, and Z-REX—a tool investigating on-target/on-pathway signaling, we document that labeling of one zebrafish-Keap1-paralog (zKeap1b) stimulates Nrf2-driven antioxidant response (AR) (like the human-ortholog). Conversely, zKeap1a a dominant-negative regulator electrophile-promoted Nrf2-signaling,...