A5076810349- Functional Brain Connectivity Studies
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- Olfactory and Sensory Function Studies
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Tryptophan and brain disorders
- CRISPR and Genetic Engineering
- Biochemical Analysis and Sensing Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Schizophrenia research and treatment
- Computational Drug Discovery Methods
- Stress Responses and Cortisol
- Chromosomal and Genetic Variations
- Plant-Microbe Interactions and Immunity
- Genomics and Chromatin Dynamics
- Microbial Metabolic Engineering and Bioproduction
- Neuroendocrine regulation and behavior
- Catalysis and Oxidation Reactions
- Viral Infectious Diseases and Gene Expression in Insects
- Lanthanide and Transition Metal Complexes
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Protein Structure and Dynamics
Johns Hopkins University
2016-2025
Johns Hopkins Medicine
2017-2025
Chinese Academy of Medical Sciences & Peking Union Medical College
2022-2025
Beijing Institute of Technology
2007-2025
Peking Union Medical College Hospital
2025
Jiangsu Institute of Parasitic Diseases
2025
Jiangnan University
2025
Zhejiang University
2024
Guilin University of Technology
2024
UNSW Sydney
2019-2024
We describe complete design of a synthetic eukaryotic genome, Sc2.0, highly modified Saccharomyces cerevisiae genome reduced in size by nearly 8%, with 1.1 megabases the deleted, inserted, or altered. Sc2.0 chromosome was implemented BioStudio, an open-source framework developed for design, which coordinates modifications from nucleotide to scales and enforces version control systematically track edits. To achieve synthesis, individual chromosomes built Consortium teams around world will be...
Designer Chromosome One of the ultimate aims synthetic biology is to build designer organisms from ground up. Rapid advances in DNA synthesis has allowed assembly complete bacterial genomes. Eukaryotic organisms, with their generally much larger and more complex genomes, present an additional challenge biologists. Annaluru et al. (p. 55 , published online 27 March) designed a eukaryotic chromosome based on yeast III. The chromosome, shorn destabilizing transfer RNA genes transposons, ∼14%...
INTRODUCTION The Saccharomyces cerevisiae 2.0 project (Sc2.0) aims to modify the yeast genome with a series of densely spaced designer changes. Both synthetic chromosome arm (synIXR) and entirely (synIII) function high fitness in yeast. For synthesis projects, precise engineering physical sequence match specified design is important for systematic evaluation underlying principles. Yeast can maintain nuclear chromosomes as rings, occurring by chance at repeated sequences, although cyclized...
INTRODUCTION Design and construction of an extensively modified yeast genome is a direct means to interrogate the integrity, comprehensiveness, accuracy knowledge amassed by community date. The international synthetic project (Sc2.0) aims build entirely designer, Saccharomyces cerevisiae genome. designed increase stability genetic flexibility while maintaining cell fitness near that wild type. A major challenge for synthesis lies in identifying eliminating fitness-reducing sequence variants...
INTRODUCTION It has long been an interesting question whether a living cell can be constructed from scratch in the lab, goal that may not realized anytime soon. Nonetheless, with advances DNA synthesis technology, complete genetic material of organism now synthesized chemically. Hitherto, genomes several organisms including viruses, phages, and bacteria have designed constructed. These synthetic are able to direct all normal biological functions, capable self-replication production...
We describe design, rapid assembly, and characterization of synthetic yeast Sc2.0 chromosome VI (synVI). A mitochondrial defect in the synVI strain mapped to synonymous coding changes within PRE4 (YFR050C), encoding an essential proteasome subunit; reduced Pre4 protein accumulation by half. Completing specifies consolidation 16 chromosomes into a single strain. investigated phenotypic, transcriptional, proteomewide consequences poly-synthetic strains. Another "bug" was discovered through...
A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines data from many institutions worldwide. However, introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether batch adjustment method, ComBat, can further reduce site-related...
INTRODUCTION Although much effort has been devoted to studying yeast in the past few decades, our understanding of this model organism is still limited. Rapidly developing DNA synthesis techniques have made a “build-to-understand” approach feasible reengineer on genome scale. Here, we report completion 770-kilobase synthetic chromosome II (synII). SynII was characterized using extensive Trans-Omics tests. Despite considerable sequence alterations, synII virtually indistinguishable from wild...
Drugs against multiple targets may overcome the many limitations of single and achieve a more effective safer control disease. Numerous high-throughput experiments have been performed in this emerging field. However, systematic identification drug their best intervention requires knowledge underlying disease network calls for innovative computational methods that exploit structure dynamics. Here, we develop robust algorithm finding target optimal (MTOI) solutions network. MTOI identifies...
Synthetic chromosome rearrangement and modification by loxP -mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic arm synIXR (43 sites) then used a computational pipeline infer or unscramble the sequence of recombinations that created observed genomes. Deep sequencing 64 strains revealed 156 deletions, 89 inversions, 94 duplications, 55 additional complex rearrangements; several...
Although the design of synthetic yeast genome Sc2.0 is highly conservative with respect to gene content, deletion several classes repeated sequences and introduction thousands designer changes may affect organization potentially alter cellular functions. We report here Hi-C-determined three-dimensional (3D) conformations chromosomes. The absence repeats leads a smoother contact pattern more precisely tractable chromosome conformations, large-scale genomic globally unaffected by presence...
SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution) is a genome restructuring technique that can be used in synthetic genomes such as of Sc2.0, the yeast genome, which contains hundreds to thousands strategically positioned loxPsym sites. has been induce rearrangements strains harboring one or more chromosomes, well plasmid DNA vitro vivo. Here we describe collection heterozygous diploid produced mating haploid semisynthetic Sc2.0 native parental...
Abstract Despite the known benefits of data‐driven approaches, lack approaches for identifying functional neuroimaging patterns that capture both individual variations and inter‐subject correspondence limits clinical utility rsfMRI its application to single‐subject analyses. Here, using data from over 100k individuals across private public datasets, we identify replicable multi‐spatial‐scale canonical intrinsic connectivity network (ICN) templates via use multi‐model‐order independent...
A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This reaction afforded two kinds different products by substrate control. detailed investigation the mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, aryl was crucial intermediate. method employed 4-DPAIPN as photocatalyst i-Pr2NEt sacrificial donor leading to metal-free conditions.
Multitarget drugs have been to be found effective in controlling complex diseases. However, how design multitarget presents a great challenge. We developed computer-assisted strategy screen for inhibitors using combination of molecular docking and common pharmacophore matching. This was successfully applied dual-target against both the human leukotriene A4 hydrolase (LTA4H-h) nonpancreatic secretory phospholipase A2 (hnps-PLA2). Three compounds screened from chemical database MDL Available...
Drug molecules not only interact with specific targets, but also alter the state and function of associated biological network. How to design drugs evaluate their functions at systems level becomes a key issue in highly efficient low-side-effect drug design. The arachidonic acid metabolic network is that produces inflammatory mediators, which several enzymes, including cyclooxygenase-2 (COX-2), have been used as targets for anti-inflammatory drugs. However, neither century-old nonsteriodal...
Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL a redesigned synthetic Saccharomyces cerevisiae chromosome XV, synXV. We designed and built synXV to harbor strategically inserted features, modified elements, synonymously recoded genes throughout the chromosome. Based on chromosome, developed method enable chrDBTL: CRISPR-Cas9-mediated mitotic recombination endoreduplication...
Psychosis (including symptoms of delusions, hallucinations, and disorganized conduct/speech) is a main feature schizophrenia frequently present in other major psychiatric illnesses. Studies individuals with first-episode (FEP) early psychosis (EP) have the potential to interpret aberrant connectivity associated during period minimal influence from medication confounds. The current study uses data-driven whole-brain approach examine patterns functional network (FNC) multi-site dataset...