A5035765666- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- RNA Research and Splicing
- Virus-based gene therapy research
- Parasites and Host Interactions
- RNA regulation and disease
- Bacterial Genetics and Biotechnology
- Force Microscopy Techniques and Applications
- Trace Elements in Health
- Retinal Development and Disorders
- Mosquito-borne diseases and control
- Machine Learning in Bioinformatics
- interferon and immune responses
- Fluid Dynamics and Mixing
- Endoplasmic Reticulum Stress and Disease
- Microbial Inactivation Methods
- Advanced Electron Microscopy Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Cytokine Signaling Pathways and Interactions
- Animal Genetics and Reproduction
New York Consortium in Evolutionary Primatology
2025
Stanford University
2020-2024
Google (United Kingdom)
2024
DeepMind (United Kingdom)
2024
Northern Illinois University
2024
University of Cambridge
2012-2022
University of Maryland, College Park
2016-2022
Abstract The introduction of AlphaFold 2 1 has spurred a revolution in modelling the structure proteins and their interactions, enabling huge range applications protein design 2–6 . Here we describe our 3 model with substantially updated diffusion-based architecture that is capable predicting joint complexes including proteins, nucleic acids, small molecules, ions modified residues. new demonstrates improved accuracy over many previous specialized tools: far greater for protein–ligand...
Abstract More than three billion years of evolution have produced an image biology encoded into the space natural proteins. Here we show that language models trained on tokens generated by can act as evolutionary simulators to generate functional proteins are far away from known We present ESM3, a frontier multimodal generative model reasons over sequence, structure, and function ESM3 follow complex prompts combining its modalities is highly responsive biological alignment. prompted...
More than three billion years of evolution have produced an image biology encoded into the space natural proteins. Here we show that language models trained at scale on evolutionary data can generate functional proteins are far away from known We present ESM3, a frontier multimodal generative model reasons over sequence, structure, and function ESM3 follow complex prompts combining its modalities is highly responsive to alignment improve fidelity. prompted fluorescent Among generations...
West Nile virus (WNV) is a prototypical emerging for which no effective therapeutics currently exist. WNV uses programmed −1 ribosomal frameshifting (−1 PRF) to synthesize the NS1′ protein, C terminally extended version of its non-structural protein 1, expression enhances neuro-invasiveness and viral RNA abundance. Here, frameshift signals derived from four strains were investigated better understand PRF in this quasispecies. Sequences previously predicted promote strongly activity, but was...
The alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern (EEEV), and western (WEEV) are arthropod-borne positive-strand RNA viruses that capable of causing acute fatal in many mammals, including humans. VEEV was weaponized during the Cold War is recognized as a select agent. Currently, there no FDA-approved vaccines or therapeutics for these viruses. spread other members this family due to climate change-mediated vector range expansion underscores need research aimed at...
Abstract Background POLG , located on nuclear chromosome 15, encodes the DNA polymerase γ(Pol γ). Pol γ is responsible for replication and repair of mitochondrial (mtDNA). only found in mitochondria most animal cells. Mutations are common single-gene cause diseases have been mapped over coding region ORF. Results Using PhyloCSF to survey alternative reading frames, we a conserved signature an frame exons 2 3 herein referred as ORF-Y that arose de novo placental mammals. synplot2 program,...
Abstract Leishmania virulence and disease development critically depends on the ability of promastigotes to infect, differentiate into amastigote forms replicate inside mammalian host macrophages. Understanding changes associated with differentiation in axenic culture conditions is a key identifying factors. Here we compared efficiency conventional pH–temperature-dependent shift method induce recently identified trigger for mediated by mitochondrial reactive oxygen species (ROS). Using two...
Cryogenic electron microscopy (cryo-EM) has emerged as a viable structural tool for molecular therapeutics development against human diseases. However, it remains challenge to determine structures of proteins that are flexible and smaller than 30 kDa. The 11 kDa KIX domain CREB-binding protein (CBP), potential therapeutic target acute myeloid leukemia other cancers, is which defied structure-based inhibitor design. Here, we develop an experimental approach overcome the size limitation by...
The AAA
The research article describing the discovery of ribosomal frameshifting in bacterial CopA gene also reported occurrence expression human ortholog ATP7B based on assays using dual luciferase reporters. An examination publicly available ribosome profiling data and phylogenetic analysis proposed site cast doubt validity this claim prompted us to reexamine evidence. We observed similar apparent efficiencies as original authors same type vector that synthesizes both luciferases a single...
Summary SNARE proteins drive membrane fusion as their core domains zipper into a parallel four-helix bundle 1,2 . After fusion, these bundles are disassembled by the AAA+ protein Sec18/NSF and its adaptor Sec17/ α-SNAP 3,4 to make them available for subsequent rounds of fusion. often flanked C-terminal transmembrane or N-terminal 5 Previous structures NSF–α-SNAP–SNARE complex revealed domain threaded through D1 ATPase ring 6 , posing topological constraint would prevent complete substrate...
Most synapses in the brain transmit information by presynaptic release of vesicular glutamate, driving postsynaptic depolarization through AMPA-type glutamate receptors (AMPARs). The nanometer-scale topography synaptic AMPARs regulates response amplitude controlling number activated vesicle fusion. mechanisms AMPAR and their interactions with scaffolding proteins are unclear, as is spatial relationship between vesicles. Here, we used cryo-electron tomography to map molecular visualize
The lifecycle of Leishmania, the causative agent leishmaniasis, alternates between promastigote and amastigote stages inside insect vertebrate hosts, respectively. While pathogenic symptoms leishmaniasis can vary widely, from benign cutaneous lesions to highly fatal visceral disease forms depending on infective species, all Leishmania species reside host macrophages during stage their lifecycle. infectivity is therefore directly related its ability invade, survive replicate within...
Activation of the unfolded protein response (UPR) in eukaryotic cells represents an evolutionarily conserved to physiological stress. Here, we report that mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable inducing UPR sarcoma cells. However, this effect appears be distinct from classical role for these drugs as inhibitors. Instead, detected compounds associated with ribosomes isolated treated Specifically, treatment resulted protection chemical...
During the decoding of a subset mRNAs proportion ribosomes productively shift to -1 reading frame at specific, slippage-prone site. While great majority occurrences Programmed Ribosomal Frameshifting (-1 PRF) involve viruses, other mobile elements or retroelements, dramatic instance utilized human cellular frameshifting in non-retroelement derived mRNA has been reported. The for which was claimed due stimulatory pseudoknot is that encodes immune functioning C-C chemokine receptor 5 (CCR5),...
Genetic screens are valuable for identifying novel genes involved in the regulation of developmental processes. To identify associated with cell growth