- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- Enzyme Structure and Function
- Bacterial biofilms and quorum sensing
- Protist diversity and phylogeny
- Microtubule and mitosis dynamics
- Antibiotic Resistance in Bacteria
- Cellular Mechanics and Interactions
- Fungal and yeast genetics research
- Machine Learning in Bioinformatics
- Advanced Electron Microscopy Techniques and Applications
- Cellular transport and secretion
- Enzyme Production and Characterization
- Microbial Metabolic Engineering and Bioproduction
- Microbial Community Ecology and Physiology
- Legume Nitrogen Fixing Symbiosis
- Vibrio bacteria research studies
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- Advanced Fluorescence Microscopy Techniques
Harvard University
2016-2025
Marine Biological Laboratory
2007-2025
Harvard University Press
2012-2024
Center for Systems Biology
2011-2023
University of California, San Francisco
2001-2008
University of Wisconsin–Madison
2007
Genentech
2007
Washington State University
1998-2001
James S. McDonnell Foundation
1980
University of Strathclyde
1973
Intrinsic disorder refers to segments or whole proteins that fail self-fold into fixed 3D structure, with such sometimes existing in the native state. Here we report data on relationships among intrinsic disorder, sequence complexity as measured by Shannon's entropy, and amino acid composition. identified protein crystal structures, nuclear magnetic resonance, circular dichroism, prediction from sequence, all exhibit similar distributions are shifted lower values compared to, but...
Coordinating cell wall synthesis and division Most bacteria are protected by peptidoglycan walls, which must be remodeled to split the cell. Cell requires tubulin homolog FtsZ, a highly conserved cytoskeletal polymer that specifies future site of division. Bisson-Filho et al. Yang found dynamic treadmilling FtsZ filaments controls both location activity associated synthetic enzymes. This creates discrete sites circle around plane divide Science , this issue p. 739 744
Rod-shaped bacteria elongate by the action of cell wall synthesis complexes linked to underlying dynamic MreB filaments. To understand how movements these filaments relate synthesis, we characterized dynamics and elongation machinery using high-precision particle tracking in Bacillus subtilis. We found that moved circumferentially around cell, perpendicular its length, with nearby moving independently both directions. Inhibition various methods blocked movement MreB. Thus, uncoordinated,...
MreB is essential for rod shape in many bacteria. Membrane-associated filaments move around the circumference, helping to insert cell wall radial direction reinforce shape. To understand how oriented motion arises, we altered of Bacillus subtilis. isotropic round cells, and orientation restored when externally imposed. Stationary orient within protoplasts, purified tubulates liposomes vitro, orienting tubes. Together, this demonstrates orients along greatest principal membrane curvature, a...
Abstract Bacterial cell division requires recruitment of peptidoglycan (PG) synthases to the site by tubulin homologue, FtsZ. Septal PG promote septum growth. FtsZ treadmilling is proposed drive processive movement septal and constriction in some bacteria; however, precise mechanisms spatio-temporally regulating synthase activity are poorly understood. Here using single-molecule imaging proteins Gram-positive pathogen Staphylococcus aureus , we showed that complex FtsW/PBP1 its putative...
Dynamic instability-the switching of a two-state polymer between phases steady elongation and rapid shortening-is essential to the cellular function eukaryotic microtubules, especially during chromosome segregation. Since discovery dynamic instability 20 years ago, no other biological has been found exhibit this behavior. Using total internal reflection fluorescence microscopy resonance energy transfer, we observe that prokaryotic actin homolog ParM, whose assembly is required for...
Multiple unrelated polymer systems have evolved to partition DNA molecules between daughter cells at division. To better understand polymer-driven segregation, we reconstituted the three-component segregation system of R1 plasmid from purified components. We found that ParR/ parC complex can construct a simple bipolar spindle by binding ends ParM filaments, inhibiting dynamic instability, and acting as ratchet permitting incorporation new monomers riding on elongating filament ends. Under...
The peptidoglycan (PG) sacculus, a meshwork of polysaccharide strands cross-linked by short peptides, protects bacterial cells against osmotic lysis. To enlarge this covalently closed macromolecule, PG hydrolases must break peptide cross-links in the to allow insertion new glycan between existing ones. In rod-shaped bacterium Bacillus subtilis, cell wall elongation requires two redundant endopeptidases, CwlO and LytE. However, it is not known how these potentially autolytic enzymes are...
Cell elongation in rod-shaped bacteria is mediated by the Rod system, a conserved morphogenic complex that spatially controls cell wall assembly glycan polymerase RodA and crosslinking enzyme PBP2. Using Escherichia coli as model we identified PBP2 variant promotes system function when essential accessory components of machinery are inactivated. This hyperactivates synthesis vivo stimulates activity RodA-PBP2 complexes vitro. Cells with activated synthase also exhibited enhanced...
Fluorescent<sc>d</sc>-amino acids (FDAAs) enable efficient<italic>in situ</italic>labeling of peptidoglycan in diverse bacterial species.
The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue translocation (MALT1) paracaspase with structural similarity to caspases, which recruits TNF...
Abstract The FtsZ protein is a central component of the bacterial cell division machinery. It polymerizes at mid-cell and recruits more than 30 proteins to assemble into macromolecular complex direct wall constriction. polymers exhibit treadmilling dynamics, driving processive movement enzymes that synthesize septal peptidoglycan (sPG). Here, we combine theoretical modelling with single-molecule imaging live cells show FtsZ’s drives directional sPG via Brownian ratchet mechanism....
The widespread use of antibiotics has placed bacterial pathogens under intense pressure to evolve new survival mechanisms. Genomic analysis 51,229 Mycobacterium tuberculosis (Mtb)clinical isolates identified an essential transcriptional regulator, Rv1830, herein called resR for resilience as a frequent target positive (adaptive) selection. mutants do not show canonical drug resistance or tolerance but instead shorten the post-antibiotic effect, meaning that they enable Mtb resume growth...