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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Harvard University
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Cheng, Yu-Shan; Sacchettini, James C (2016) Structural Insights into Mycobacterium tuberculosis Rv2671 Protein as a Dihydrofolate Reductase Functional Analogue Contributing to para-Aminosalicylic Acid Resistance. Biochemistry 55:1107-19
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