(July 2000 - present)
Office: Essex Hall 277-2
Phone: 253-3000 ext 3550
Toxoplasma gondii: It has been estimated that approximately one-third of North Americans are infected by Toxoplasma gondii, a pathogenic member of the phylum Apicomplexa. In Canada, the outbreak of T. gondii infection was reported to be associated with the contaminated municipal water supply in British Columbia in 1995.
T. gondii is an obligatory intracellular parasite of mammals and birds. Human infection often occurs by ingestion of contaminated food or undercooked meat containing tissue cysts. Neonate or acute infections in pregnant women can give rise to blindness, mental retardation and hydrocephaly in children. In healthy adults, the infections are usually asymptomatic because an immune response or an antibiotic treatment quickly eliminates the parasites. However, some parasites can escape the immune response and chemotherapy by differentiating and residing within a cyst structure that will remain in the brain and other organs during the lifetime of the infected host.
Being capable of infecting and replicating within virtually any nucleated cell, T. gondii is an excellent model for the study of intracellular parasitism. Our research program aims to better understand the molecular mechanism(s) critical to T. gondii infection. Currently we focus on post-transcriptional regulation processes during the life cycle of T. gondii, which includes its ability to differentiate between tachyzoites (TZ) and bradyzoites (BZ) allowing it to evade the host immune response.
- To study the translational reprograming during the parasite’s life cycle, we monitor protein markers (i.e. TgHoDI and TgPABPC) and mRNAs during the formation of mRNPs (messenger ribonucleoprotein complexes) and mRNP aggregates.
To probe the RNA-protein interaction, an RNA-protein tethering assay is the method of choice in which the protein of interest (i.e. TgHoDI) is directed to a reporter mRNA by the strong interaction between the bacteriophage MS2’s RNA (MS2L) and its coat protein (MS2CP).
We are currently investigating the significance of mRNP granules in mRNA maintenance and the parasite infection.
- To investigate the role of non-coding RNAs in regulating parasite’s life cycle, we examine the mechanism(s) controlling the expression of natural antisense RNA (NAT) arisen from the locus encoding of ubiquitin-like protease (TgUlp1). As the first enzyme of the sumoylation pathway, TgUlp1 protease activity is shown to be regulated at the transcription and/or post-transcription levels. Using promoter assays carried out under Tz and Bz growth conditions, we showed that both TgUlp1 mRNA and NAT are temporally regulated during differentiation. Created by CRISPR-Cas9 genome editing method, transgenic TgDicer-KO strain lacking the RNase III activity exhibits a drastically different TgUlp1 NAT expression from that of its parental line and has altered growth phenotype. It is strongly suggesting that Dicer is responsible for the processing of TgUlp1 NAT and the direct involvement of RNA interference pathway in NAT functions.