The objective of this Core is to provide sequencing services to support the other projects in this Program Project in their efforts to determine the functions of proteins in the M. tuberculosis (Mtb) genome. We will take advantage of next-generation sequencing technology (aka """"""""deep-sequencing""""""""), which enables novel ways of probing gene functions. Three primary activities are envisioned to support the main projects. First, deep-sequencing will be used to analyze changes in gene essentiality in knockout and knock-down mutants via transposon mutagenesis. Second, deep-sequencing will be used to efficiently evaluate changes in gene expression in mutants (also known as RNA-Seq). Finally, deep-sequencing will be used for characterization of mutations in phenotypic and suppressor mutants as a way to associate genes with known processes and pathways. These sequencing services will be provided to support the three scientific projects, which will select and prioritize the strains of interest for sequencing. The resulting data will be supplied back to the other projects through a genome browser and other tools, and will be made available to the public as a resource to augment and enrich our understanding of the functions of ORFs in the M. tuberculosis genome.
M. tuberculosis the most prevalent human pathogen worldwide, and a better understanding of the biology of the organism through the functions of genes in the genome is needed for development of new therapies. The goal of this Core is to exploit next-generation DNA sequencing in several ways to provide insight on the functions of genes in the Mtb genome whose functions are currently unknown.
|Rego, E Hesper; Audette, Rebecca E; Rubin, Eric J (2017) Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity. Nature 546:153-157|
|Rock, Jeremy M; Hopkins, Forrest F; Chavez, Alejandro et al. (2017) Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform. Nat Microbiol 2:16274|
|DeJesus, Michael A; Gerrick, Elias R; Xu, Weizhen et al. (2017) Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. MBio 8:|
|Jansen, Robert S; Rhee, Kyu Y (2017) Emerging Approaches to Tuberculosis Drug Development: At Home in the Metabolome. Trends Pharmacol Sci 38:393-405|
|Kurthkoti, Krishna; Amin, Hamel; Marakalala, Mohlopheni J et al. (2017) The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas. MBio 8:|
|Mishra, Bibhuti B; Lovewell, Rustin R; Olive, Andrew J et al. (2017) Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol 2:17072|
|Guinn, Kristine M; Rubin, Eric J (2017) Tuberculosis: Just the FAQs. MBio 8:|
|Köster, Stefan; Upadhyay, Sandeep; Chandra, Pallavi et al. (2017) Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA. Proc Natl Acad Sci U S A 114:E8711-E8720|
|Botella, Helene; Vaubourgeix, Julien; Lee, Myung Hee et al. (2017) Mycobacterium tuberculosis protease MarP activates a peptidoglycan hydrolase during acid stress. EMBO J 36:536-548|
|Baric, Ralph S; Crosson, Sean; Damania, Blossom et al. (2016) Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio 7:|
Showing the most recent 10 out of 28 publications