Articles by Katelyn A. Walzer in JoVE
طرق بالتحقيق في الدور التنظيمي للالرنا الصغيرة وخاص بالريبوسوم إشغال Gregory LaMonte*1,2, Katelyn A. Walzer*1,2, Joshua Lacsina3, Christopher Nicchitta3, Jen-Tsan Chi1,2 1Department of Molecular Genetics and Microbiology, Duke University School of Medicine, 2Center for Genomic and Computational Biology, Duke University School of Medicine, 3Department of Cell Biology, Duke University School of Medicine
Other articles by Katelyn A. Walzer on PubMed
A Single Chromosome Unexpectedly Links Highly Divergent Isolates of Toxoplasma Gondii MBio. 2012 | Pubmed ID: 22215568 Toxoplasma gondii is an obligate intracellular parasite that can cause disease in all warm-blooded animals studied to date, including humans. Over a billion people have been infected with this parasite worldwide. In Europe and North America, Toxoplasma has a clonal population structure, where only three lineages are highly dominant (strain types I, II, and III). Khan et al. [mBio 2(6): e00228-11, 2011] have carried out phylogenetic analyses on a large number of diverse strains from outside of these lineages and found evidence for a significant split between the clonal North American/European lineages and those in South America. In contrast to most of the genome, nearly all North American/European strains sampled, and the majority of South American strains sampled, harbored at least portions of a monomorphic chromosome Ia (Ia*). In contrast to previous models, these data suggest that the monomorphic haplotype originated in South America and migrated to the North. These authors propose that South American haplotype 12 was a precursor to modern-day type II, while South American haplotypes 6 and 9 crossed with haplotype 12 to give rise to the type I and III lineages, respectively. However, the findings reported by Khan et al. complicate the origin of chromosome Ia, since there are members of haplotypes 9 and 12 with nearly complete versions of Ia* and members of haplotypes 6 and 12 with over 50% of Ia*. This unexpected finding raises exciting new questions about how an entire common chromosome can be found within strains that are highly divergent at most other genomic loci.
Hammondia Hammondi, an Avirulent Relative of Toxoplasma Gondii, Has Functional Orthologs of Known T. Gondii Virulence Genes Proceedings of the National Academy of Sciences of the United States of America. Apr, 2013 | Pubmed ID: 23589877 Toxoplasma gondii is a ubiquitous protozoan parasite capable of infecting all warm-blooded animals, including humans. Its closest extant relative, Hammondia hammondi, has never been found to infect humans and, in contrast to T. gondii, is highly attenuated in mice. To better understand the genetic bases for these phenotypic differences, we sequenced the genome of a H. hammondi isolate (HhCatGer041) and found the genomic synteny between H. hammondi and T. gondii to be >95%. We used this genome to determine the H. hammondi primary sequence of two major T. gondii mouse virulence genes, TgROP5 and TgROP18. When we expressed these genes in T. gondii, we found that H. hammondi orthologs of TgROP5 and TgROP18 were functional. Similar to T. gondii, the HhROP5 locus is expanded, and two distinct HhROP5 paralogs increased the virulence of a T. gondii TgROP5 knockout strain. We also identified a 107 base pair promoter region, absent only in type III TgROP18, which is necessary for TgROP18 expression. This result indicates that the ROP18 promoter was active in the most recent common ancestor of these two species and that it was subsequently inactivated in progenitors of the type III lineage. Overall, these data suggest that the virulence differences between these species are not solely due to the functionality of these key virulence factors. This study provides evidence that other mechanisms, such as differences in gene expression or the lack of currently uncharacterized virulence factors, may underlie the phenotypic differences between these species.
Hammondia Hammondi Harbors Functional Orthologs of the Host-modulating Effectors GRA15 and ROP16 but is Distinguished from Toxoplasma Gondii by a Unique Transcriptional Profile Eukaryotic Cell. Dec, 2014 | Pubmed ID: 25280815 Toxoplasma gondii and its nearest extant relative, Hammondia hammondi, are phenotypically distinct despite their remarkable similarity in gene content, synteny, and functionality. To begin to identify genetic differences that might drive distinct infection phenotypes of T. gondii and H. hammondi, in the present study we (i) determined whether two known host-interacting proteins, dense granule protein 15 (GRA15) and rhoptry protein 16 (ROP16), were functionally conserved in H. hammondi and (ii) performed the first comparative transcriptional analysis of H. hammondi and T. gondii sporulated oocysts. We found that GRA15 and ROP16 from H. hammondi (HhGRA15 and HhROP16) modulate the host NF-κB and STAT6 pathways, respectively, when expressed heterologously in T. gondii. We also found the transcriptomes of H. hammondi and T. gondii to be highly distinct. Consistent with the spontaneous conversion of H. hammondi tachyzoites into bradyzoites both in vitro and in vivo, H. hammondi high-abundance transcripts are enriched for genes that are of greater abundance in T. gondii bradyzoites. We also identified genes that are of high transcript abundance in H. hammondi but are poorly expressed in multiple T. gondii life stages, suggesting that these genes are uniquely expressed in H. hammondi. Taken together, these data confirm the functional conservation of known T. gondii virulence effectors in H. hammondi and point to transcriptional differences as a potential source of the phenotypic differences between these species.