Biomedical subjects

Wei Ding

Publications and source records attributed to Wei Ding.

3 recordsLinked to original sources

PubMed2026

Repeat region engineering of Cas13a crRNA enables conformational gating-based autocatalytic CRISPR biosensing.

CrRNA engineering has emerged as a pivotal strategy for extending CRISPR-Cas13a biosensing. However, structural modulation of the direct repeat (DR) region remains exceptionally challenging due to its intricate architecture and the high energetic barrier of the Cas13a-crRNA interface, which is conventionally viewed as a rigid and immutable scaffold. Here, we demonstrate that the DR region is instead a programmable topological element with unexpected structural plasticity. By systematically engineering the DR through sequence insertion and structural splitting, we identified multiple DR variants that retain robust catalytic activity. Crucially, this topological reconfiguration enables Cas13a activity to be precisely gated by unmodified nucleic acid blockers, a level of regulation unattainable with the wild-type crRNA. Building on this flexible modulation, we developed Dre-CRISPR, a DR-engineered platform that couples target-triggered DR restoration to a self-reinforcing autocatalytic loop. This self-amplifying system provides a 2 × 106-fold sensitivity enhancement over nonamplified systems. Furthermore, the Dre-CRISPR platform extends the diagnostic scope of Cas13a to a broader spectrum of analytes, ranging from microRNAs to enzymatic activities and heavy metal ions. Our findings redefine the crRNA scaffold as a versatile signaling node and provide a generalizable framework for developing high-sensitivity, self-amplifying CRISPR biosensors through topology-driven guide RNA engineering.

CRISPR-Associated Proteins↗

PubMed2026

DPM2 promotes melanoma progression and serves as a prognostic factor.

Recently, dolichol phosphate mannose synthase (DPMS) has emerged as a promising new target for treatment in various cancers. Nonetheless, DPM2, a crucial element of the DPMS family, remains unexplored in melanoma research. This study aims to explore the predictive significance and biological role of DPM2, utilizing extensive databases and functional tests conducted in vitro. We conducted an in-depth examination of the DPM2 expression feature within The Cancer Genome Atlas database. Group differences were evaluated using Student's t-test, one-way analysis of variance, and long-rank test, while survival distributions were estimated using the Kaplan-Meier method. Functional experiments were conducted in multiple melanoma cell lines to evaluate the effects of altered DPM2 expression. Our research indicated a direct correlation between the expression levels of DPM2 and the severity of melanoma. In addition, an elevated level of DPM2 expression was significantly linked to unfavorable prognoses. Suppression of DPM2 inhibits the proliferation, migration, and invasion of melanoma cells and induces their apoptosis. These findings suggest that DPM2 plays a pivotal role in melanoma progression and may serve as an independent prognostic biomarker for the disease.

DPM2↗

PubMed2026

Unlocking the unexplored AMPSphere in marine rare species.

BACKGROUND: Antimicrobial peptides (AMPs) have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Natural microbial communities are considered as the priority targets for next-generation AMP bioprospecting initiatives. While progress has been made in characterizing AMPs from the dominant microbial taxa in natural ecosystems, current research largely overlooks the biosynthetic potential of rare species. Given their distinct evolutionary pressures, rare species likely produce AMPs with novel structures and unconventional mechanisms of action. RESULTS: In this study, enrichment cultivation of a marine biofilm was conducted in 138 carbon source- and oxygen level-based conditions, followed by metagenomic sequencing using both Illumina and Nanopore platforms. Analysis of 435 high-quality genomes derived from the metagenomes suggests that these bacterial strains are significantly underrepresented (< 0.01%) in global marine biofilm communities. Through multi-model prediction, we identified 3,054,472 candidate AMPs from the genomes, including 1048 high-confidence ones, thereby significantly expanding the previously known AMPSphere. Furthermore, AMPs derived from the rare bacterial species exhibit unique sequence characteristics, structural diversity, remarkable stability under diverse pH conditions and pepsin exposure, and strong therapeutic potential in animal models, reflecting their specialized adaptive and defensive strategies developed within ecological systems. CONCLUSIONS: The features of the underexplored AMPs from low-abundance bacteria in marine biofilms provide valuable resources and theoretical foundations for the development of highly effective antimicrobial agents. Video Abstract.

Biofilms↗