A5054341927- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Innovation and Socioeconomic Development
- Virus-based gene therapy research
- Prion Diseases and Protein Misfolding
- Advanced biosensing and bioanalysis techniques
- Metabolomics and Mass Spectrometry Studies
- HIV Research and Treatment
- Advanced Proteomics Techniques and Applications
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Nerve injury and regeneration
- Cytomegalovirus and herpesvirus research
- Gut microbiota and health
- Neurological disorders and treatments
- Neurological diseases and metabolism
Harvard University
2024-2025
Mass General Brigham
2024-2025
Beth Israel Deaconess Medical Center
2024-2025
McGovern Institute for Brain Research
2021-2025
Massachusetts Institute of Technology
2021-2025
Brigham and Women's Hospital
2024-2025
Discovery Centre
2023
University of Toronto
2019-2023
University of Ottawa
2020
Occupational Cancer Research Centre
2019
The type III-E CRISPR-Cas7-11 effector binds a CRISPR RNA (crRNA) and the putative protease Csx29 catalyzes crRNA-guided cleavage. We report cryo-electron microscopy structures of Cas7-11-crRNA-Csx29 complex with without target (tgRNA), demonstrate that tgRNA binding induces conformational changes in Csx29. Biochemical experiments revealed tgRNA-dependent cleavage accessory protein Csx30 by Reconstitution system bacteria showed yields toxic fragments cause growth arrest, which is regulated...
RNA editing offers the opportunity to introduce either stable or transient modifications nucleic acid sequence without permanent off-target effects, but installation of arbitrary edits into transcriptome is currently infeasible. Here, we describe Programmable Editing & Cleavage for Insertion, Substitution, and Erasure (PRECISE), a versatile method writing length existing pre-mRNAs via 5' 3' trans-splicing. In trans-splicing, an exogenous template introduced compete with endogenous pre-mRNA,...
Abstract Unique strains of α-synuclein aggregates have been postulated to underlie the spectrum clinical and pathological presentations seen across synucleinopathies. Whereas multiple system atrophy (MSA) is associated with a predominance oligodendroglial inclusions, in Parkinson’s disease (PD) preferentially accumulate neurons. The G51D mutation SNCA gene encoding causes an aggressive, early-onset form PD that exhibits neuropathological traits reminiscent both MSA. To assess strain...
Abstract Programmable and multiplexed genome integration of large, diverse DNA cargo independent repair remains an unsolved challenge editing. Current gene approaches require double-strand breaks that evoke damage responses rely on pathways are inactive in terminally differentiated cells. Furthermore, CRISPR-based bypass double stranded breaks, such as Prime editing, limited to modification or insertion short sequences. We present Addition via Site-specific Targeting Elements, PASTE, which...
Abstract The type III-E Cas7-11 effector nuclease forms a complex with CRISPR RNA (crRNA) and the putative caspase-like protease Csx29, catalyzes crRNA-guided target cleavage, has been used for targeting in eukaryotic cells. Here, we report cryo-electron microscopy structures of Cas7-11–crRNA–Csx29 without RNA, demonstrate that binding induces conformational change Csx29 results activation. Biochemical analysis confirmed Cas7-11-bound cleaves Csx30 RNA-dependent manner. Reconstitution system...
Changes in microbiome composition and function have been linked to human health diseases. Metaproteomics provides invaluable functional information on the state of a microbiome. However, lower-abundance bacteria complex microbiomes are difficult observe by metaproteomics. In this study, stepwise differential lysis protocols were developed for stool separate different microbial species increase depth metaproteomic measurements. We achieved Gram-positive (G+) Gram-negative (G–) bacteria,...