Protein nanomaterial design is an emerging discipline with applications in medicine and beyond. A long-standing design approach uses genetic fusion to join protein homo-oligomer subunits via α-helical linkers to form more complex symmetric assemblies, but this method is hampered by linker flexibility and a dearth of geometric solutions. Here, we describe a general computational method for rigidly fusing homo-oligomer and…
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My lab studies how the early vertebrate embryo forms using zebrafish as a model system. While it has been known for a very long time that the vertebrate embryo forms progressively from the head to the tail, one of the key recent discoveries is that most of the vertebrate body comes from a unique bipotent progenitor that can produce either neurons or muscle cells, depending on the signals that the progenitor cell receives.
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We present a live-attenuated RNA hybrid vaccine technology which uses an RNA vaccine delivery vehicle to deliver in vitro-transcribed full-length live-attenuated viral genomes to the site of vaccination. This technology allows ready manufacturing in a cell-free environment, regardless of viral attenuation level, and promises to avoid many safety and manufacturing challenges of traditional live-attenuated vaccines. We demonstrate this technology through…
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Our team at the Allen Institute for Brain Science studies cell type diversity in the mouse and human brains. To understand the function of the brain and how its dysfunction leads to brain diseases, an essential first step is to obtain a “parts list” of the brain, i.e. to uncover the vast range of neuronal and nonneuronal cell types and their properties and then try to understand how they work together.
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Our laboratory studies the process of mRNA translation in normal cell physiology and disease. We are particularly interested in understanding how the protein and RNA components of the translation machinery interface to enable gene-specific translation. Our central hypothesis is that deregulation of translationally regulated gene networks can initiate and drive disease phenotypes such as tumorigenesis and cancer progression.
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Prostate cancer (PC) is driven by androgen receptor (AR) activity, a master regulator of prostate development and homeostasis. Frontline therapies for metastatic PC deprive the AR of the activating ligands testosterone (T) and dihydrotestosterone (DHT) by limiting their biosynthesis or blocking AR binding. Notably, AR signaling is dichotomous, inducing growth at lower activity levels, while suppressing growth at higher levels.…
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The authors are developing adeno-associated viruses (AAVs) and transgenic tools to target and perturb a diverse array of brain cell types in mouse and beyond. They leverage single cell epigenomics and transcriptomic data to identify marker genes and regulatory elements that label discrete neuronal populations and utilize an array of molecular approaches to create new genetic tools.
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Functional assessment of disease-associated sequence variation at non-coding regulatory elements is complicated by their high degree of context sensitivity to both the local chromatin and nuclear environments. Allelic profiling of DNA accessibility across individuals has shown that only a select minority of sequence variation affects transcription factor (TF) occupancy, yet low sequence diversity in human populations means that no experimental…
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Structural Basis for Broad Coronavirus Neutralization

Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and…
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