A5027603950- Advanced Electron Microscopy Techniques and Applications
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Advanced NMR Techniques and Applications
- Enzyme Structure and Function
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
- Electron and X-Ray Spectroscopy Techniques
- Machine Learning in Bioinformatics
- Geophysical and Geoelectrical Methods
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Phylogenetic Studies
- Advanced X-ray Imaging Techniques
- Bacterial Genetics and Biotechnology
- Cell Image Analysis Techniques
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Geomagnetism and Paleomagnetism Studies
- Genetics and Neurodevelopmental Disorders
Massachusetts Institute of Technology
2021-2025
Swarthmore College
2016-2021
Rapid structural analysis of purified proteins and their complexes has become increasingly common thanks to key methodological advances in cryo-electron microscopy (cryo-EM) associated data processing software packages. In contrast, analogous cells via tomography (cryo-ET) remains challenging due critical technical bottlenecks, including low-throughput sample preparation imaging, laborious methods. Here, we describe a rapid situ cryo-ET workflow that results the routine determination sub-nm...
ABSTRACT Cryo-electron tomography (cryo-ET) allows one to observe macromolecular complexes in their native, spatially contextualized environment. Tools visualize such at nanometer resolution via iterative alignment and averaging are well-developed but rely on assumptions of structural homogeneity among the under consideration. Recently developed downstream analysis tools allow for some assessment diversity have limited capacity represent highly heterogeneous macromolecules, including those...
Abstract The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into periplasm of E. coli . How this bacterial homologous assemblies in eukaryotic organelles recruit, extract, degrade membrane-embedded substrates is unclear. Following overproduction protein components, recent cryo-EM structures showed symmetric cages surrounding manner proposed inhibit degradation substrates. Here, we present native complexes, which...
Throughout the history of electron microscopy, ribosomes have served as an ideal subject for imaging and technological development, which in turn has driven our understanding ribosomal biology. Here, we provide a historical perspective at intersection microscopy technology development ribosome biology reflect on how this technique shed light each stage life cycle dynamic macromolecular machine. With emphasis prokaryotic systems, specifically describe pairing cryo-EM with thoughtful...
ABSTRACT FtsH, a AAA protease, associates with HflK/C subunits to form megadalton complex that spans the inner membrane and extends into periplasm of E. coli . How this homologous assemblies in eukaryotic organelles recruit, extract, degrade membrane-embedded substrates is unclear. Following overproduction protein components, recent cryo-EM structures reveal symmetric cages surrounding FtsH manner proposed inhibit degradation substrates. Here, we present native complexes which instead forms...
ABSTRACT Rapid structural analysis of purified proteins and their complexes has become increasingly common thanks to key methodological advances in cryo-electron microscopy (cryo-EM) associated data processing software packages. In contrast, analogous cells via tomography (cryo-ET) remains challenging due critical technical bottlenecks, including low-throughput sample preparation imaging, laborious methods. Here, we describe the development a rapid situ cryo-ET workflow that results routine...
The G-quadruplex (GQ) is a well-studied non-canonical DNA structure formed by G-rich sequences found at telomeres and gene promoters. Biological studies suggest that GQs may play roles in regulating expression, replication, repair. Small molecule ligands were shown to alter GQ stability thereby serve as novel therapies, particularly against cancer. In this work, we investigate the interaction of sequence, 5’-GGGTTGGGTTGGGTTGGG-3’ (T1), with water-soluble porphyrin, N- methyl mesoporphyrin IX...
Cryogenic electron microscopy (cryo-EM) has the potential to capture snapshots of proteins in motion and generate hypotheses linking conformational states biological function. This been increasingly realized by advent machine learning models that allow 100s-1,000s 3D density maps be generated from a single dataset. How identify distinct structural within these volume ensembles quantify their relative occupancies remain open questions. Here, we present an approach inferring variable regions...
ABSTRACT CryoDRGN is a machine learning system for heterogeneous cryo-EM reconstruction of proteins and protein complexes from single particle data. Central to this approach deep generative model density maps, which we empirically find effectively models both discrete continuous forms structural variability. Once trained, cryoDRGN capable generating an arbitrary number 3D thus interpreting the resulting ensemble challenge. Here, showcase interactive automated processing approaches analyzing...
Throughout the history of electron microscopy, ribosomes have served as an ideal subject for imaging and technological development, which in turn has driven our understanding ribosomal biology. Here, we provide a historical perspective at intersection microscopy technology development ribosome biology reflect on how this technique shed light each stage life cycle dynamic macromolecular machine. With emphasis prokaryotic systems, specifically describe pairing cryo-EM with clever experimental...
Proteins and their complexes routinely change conformation composition when performing essential cellular functions.The range of heterogeneity accessible to a given protein between its synthesis degradation defines structural landscape, key goal biology is determine this full ensemble structures.Here, we present tomoDRGN, machine learning based tool designed resolve ensembles highly heterogeneous structures in native environments, as imaged by cryo-ET.
Non-canonical DNA structures, notably G-quadruplexes and i-motifs, draw significant attention because biological evidence suggests that they play crucial roles in a variety of disease-related processes.G-quadruplex is composed planar guanine tetrads which are engaged efficient - stacking further stabilized by monovalent central cation (e.g.K + or Na ).Sequences with G-quadruplex forming potential present telomeres oncogene promoters, according to bioinformatics studies.I-motifs...