Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.
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2014-04
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Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.
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Janbon, G, KL Ormerod, D Paulet, EJ Byrnes, V Yadav, G Chatterjee, N Mullapudi, C Hon, et al. (2014). Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLoS Genet, 10(4). p. e1004261. 10.1371/journal.pgen.1004261 Retrieved from https://hdl.handle.net/10161/8468.
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Vikas Yadav
Jennifer Lodge
Jennifer Lodge, Ph.D., a professor of molecular genetics and microbiology, is Duke’s vice president for Research & Innovation.
As the university’s chief research and innovation officer, Lodge leads oversight of Duke’s $1.2 billion annual research portfolio, including grants administration, ethical practices and commercialization. Lodge works with campus and medical center research staff, faculty and trainees, and is a key figure in Duke’s connection with external partners.
Before coming to Duke in January 2022, Lodge served as vice chancellor for research and senior associate dean for research for the School of Medicine at Washington University in St. Louis (WUSTL). There, she was responsible for WUSTL’s research development, ethics, education, compliance and research administration systems, and earned a reputation for encouraging innovation and entrepreneurship.
Lodge’s own research is on the human pathogenic fungus Cryptococcus neoformans. Her lab has been funded continuously by NIH for more than two decades, with as many as three prestigious R01 grants at one time. Her lab in the Duke University School of Medicine continues to explore the biochemical processes by which this fungus builds its cell walls. Such knowledge could lead to new antifungal therapies and vaccines.
Lodge is a fellow of the American Academy of Microbiology, the American Association for the Advancement of Science (AAAS) and the National Academy of Inventors. She is also the former chair of the Group on Research at the American Association of Medical Colleges (AAMC).
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