Biology subjects

Lu, X. M.

Publications and source records attributed to Lu, X. M..

3 recordsLinked to original sources

bioRxiv2022

Deciphering the non-coding code of pathogenicity and sexual differentiation in the human malaria parasite.

The complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. However, this cascade of transcripts is unlikely to be regulated by the limited number of identified parasite-specific transcription factors. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified and shown to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs in P. falciparum we explored the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identified a total of 1,768 lncRNAs, of which 58% were identified as novel lncRNAs in P. falciparum. The subcellular localization and stage-specific expression of several putative lncRNAs were validated using RNA fluorescence in situ hybridization (RNA-FISH). Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs was explored using Chromatin Isolation by RNA Purification (ChIRP). ChIRP-seq of candidate lncRNAs revealed that lncRNA occupancy sites within the parasite genome are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis, erythrocyte remodeling, and regulation of sexual differentiation. We further validated the function of one specific lncRNA (lncRNA-ch14) using the CRISPR-Cas9 genome editing tool. Genomic and phenotypic analysis of the {bigtriangleup}lncRNA-ch14 line demonstrated the importance of this lncRNA in sexual differentiation and sexual reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation. These findings also open new avenues for targeted approaches towards therapeutic strategies against the deadly malaria parasite.

microbiology↗

bioRxiv2022

Decoding The Nuclear Genome of The Human Pathogen Babesia duncani Shed Light on its Virulence, Drug Susceptibility and Evolution among Apicomplexa

Babesia species are tick-transmitted apicomplexan pathogens and the causative agents of babesiosis, a malaria-like disease of major medical and veterinary importance. Of the different species of Babesia reported so far, Babesia duncani causes severe to lethal infection in patients. Despite the highly virulent nature of this parasite and the risk it may pose as an emerging pathogen, little is known about its biology, metabolic requirements, and pathogenesis. B. duncani is unique among apicomplexan parasites that infect red blood cells in that it can be continuously cultured in vitro in human erythrocytes but can also infect mice leading to fulminant babesiosis infection and death. Here we have taken advantage of the recent advances in the propagation of this parasite in vitro and in vivo to conduct detailed molecular, genomic and transcriptomic analyses and to gain insights into its biology. We report the assembly, 3D structure, and annotation of the nuclear genome of this parasite as well as its transcriptomic profile and an atlas of its metabolism during its intraerythrocytic life cycle. Detailed examination of the B. duncani genome and comparative genomic analyses identified new classes of candidate virulence factors, suitable antigens for diagnosis of active infection, and several attractive drug targets. Translational analyses and efficacy studies identified highly potent inhibitors of B. duncani thus enriching the pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.

microbiology↗

bioRxiv2019

Plasmodium condensin core subunits (SMC2/SMC4) mediate atypical mitosis and are essential for parasite proliferation and transmission

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and ChIP-seq analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and II complexes form at these stages. Knockdown of smc2 and smc4 gene expression revealed essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle.

cell biology↗