A5087804253- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Fungal and yeast genetics research
- Fungal Infections and Studies
- Bioinformatics and Genomic Networks
- Bacteriophages and microbial interactions
- Antifungal resistance and susceptibility
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Gut microbiota and health
- Gene Regulatory Network Analysis
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Steroid Chemistry and Biochemistry
- 14-3-3 protein interactions
- Antibiotic Resistance in Bacteria
- Microbial Natural Products and Biosynthesis
- Immune Cell Function and Interaction
- Biomedical Text Mining and Ontologies
- Renal and related cancers
- RNA regulation and disease
- Plant-Microbe Interactions and Immunity
- Single-cell and spatial transcriptomics
- Enterobacteriaceae and Cronobacter Research
Massachusetts Institute of Technology
2020-2022
University of California, San Francisco
2015-2021
Howard Hughes Medical Institute
2021
University of California System
2017
Protein-protein interaction specificity is often encoded at the primary sequence level. However, contributions of individual residues to are usually poorly understood and obscured by mutational robustness, degeneracy, epistasis. Using bacterial toxin-antitoxin systems as a model, we screened combinatorially complete library antitoxin variants three key positions against two toxins. This enabled us measure effect substitutions on in hundreds genetic backgrounds. These distributions allow...
Abstract Type II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a nuclease (747 amino acids in length) multiple functional states, revealing stepwise process DNA targeting involving conformational switch REC2 domain insertion. Our provide insights into intricately folded guide RNA which acts as structural...
The rewiring of gene regulatory networks can generate phenotypic novelty. It remains an open question, however, how the large number connections needed to form a novel network arise over evolutionary time. Here, we address this question using controlled by fungal transcription regulator Ndt80. This conserved protein has undergone dramatic switch in function—from ancestral role regulating sporulation derived biofilm formation. function corresponded large-scale genes regulated However,...
We examine how a complex transcription network composed of seven 'master' regulators and hundreds target genes evolved over span approximately 70 million years. The controls biofilm formation in several Candida species, group fungi that are present humans both as constituents the microbiota opportunistic pathogens. Using variety approaches, we observed two major types changes have occurred since four extant species examined last shared common ancestor. Master regulator 'substitutions'...
Gene duplication is crucial to generating novel signaling pathways during evolution. However, it remains unclear how the redundant proteins produced by gene ultimately acquire new interaction specificities establish insulated paralogous pathways. Here, we used ancestral sequence reconstruction resurrect and characterize a bacterial two-component system that duplicated in α-proteobacteria. We determined of existed before immediately after this event then identified key mutations responsible...
Toxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins reverse inhibition. Although Escherichia coli encodes 11 with known or putative endoribonuclease activity, the targets of most these remain poorly characterized. Using a new RNA sequencing (RNA-seq) pipeline enables mapping quantification cleavage single-nucleotide resolution, we characterized specificities 9 from E. coli. We found use low-information...
Type I toxin-antitoxin (TA) systems typically consist of a protein toxin that imbeds in the inner membrane where it can oligomerize and form pores change permeability, an RNA antitoxin interacts directly with mRNA to inhibit its translation. In Escherichia coli, symE/symR is annotated as type TA system non-canonical toxin. SymE was initially suggested be endoribonuclease, but has predicted structural similarity DNA binding proteins. To better understand function, we used RNA-seq examine...
Abstract The type II-A CRISPR effector SpCas9 has gained widespread popularity as an efficient and programmable genome editing tool. However, much remains to be known about novel compact variants that may overcome some limitations of current systems 1,2 . Recently, alternative CRISPR-Cas with highly nucleases capable in mammalian cells have been discovered through metagenomic analysis uncultivated microbes, including Cas9d (a II-D effector) 3 Here, we report the cryo-EM structures a nuclease...
Abstract Gene duplication is crucial to generating novel signaling pathways during evolution. However, it remains unclear how the redundant proteins produced by gene ultimately acquire new interaction specificities establish insulated paralogous pathways. Here, we used ancestral sequence reconstruction resurrect and characterize a bacterial two-component system that duplicated in α-proteobacteria. We determined of existed before immediately after this event then identified key mutations...
ABSTRACT We examine how a complex transcription network composed of seven “master” regulators and hundreds target genes evolved over span approximately 70 million years. The controls biofilm formation in several Candida species, group fungi that are present humans both as constituents the microbiota opportunistic pathogens. ability to form biofilms is crucial for microbial colonization different host niches, particularly when an implanted medical device present. examined compared underlying...
Abstract Toxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins reverse inhibition. Although Escherichia coli encodes 11 with known or putative endoribonuclease activity, the target of most these remain poorly characterized. Using a new RNA-seq pipeline enables mapping quantification RNA cleavage single-nucleotide resolution, we characterize targets specificities 9 from E. . We find use low-information motifs...