Abstract

The goal of this Sequencing Core is to provide sequencing and analysis services to 3 of the Scientific Projects for a Center for Excellence in Translational Research that focuses on innovative diagnostics for childhood and drug resistant tuberculosis. The core will support the projects by using Next-Generation Sequencing to discover novel biomarkers of drug resistant in well-characterized clinical strains, to characterize mycobacterial DNA fragment that may be present in the urine of patients with active disease and to profile pools of constructed mutants that have undergone in vitro and in vivo selection under drug ? pressure. We will leverage our extensive previous experience in microbial whole genome sequencing and a range of custom analysis tools to ensure the technical success ofthe projects. The results of these studies will be used to lay the framework for development of a rapid and inexpensive diagnostic test that can detect the genetic signature of Mycobacteria tuberculosis and its drug resistant mutants.

Public Health Relevance

Next-generation sequencing technologies enable major advances in the discovery of new biomarkers of drug resistance and the sensitive detection of microbial infection in humans. This project makes use of these innovations to further the development of a rapid diagnostic designed to hasten the diagnosis and appropriate treatment of adults and children with drug sensitive and resistant TB.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI109755-04
Application #
9232987
Study Section
Special Emphasis Panel (ZAI1-LR-M)
Project Start
Project End
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
4
Fiscal Year
2017
Total Cost
$403,458
Indirect Cost

  Institution

Name
Harvard Medical School
Department
Type
Domestic Higher Education
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Gong, Lingyan; Ouyang, Wei; Li, Zirui et al. (2018) Direct numerical simulation of continuous lithium extraction from high Mg2+/Li+ ratio brines using microfluidic channels with ion concentration polarization. J Memb Sci 556:34-41
Hicks, Nathan D; Yang, Jian; Zhang, Xiaobing et al. (2018) Clinically prevalent mutations in Mycobacterium tuberculosis alter propionate metabolism and mediate multidrug tolerance. Nat Microbiol 3:1032-1042
Linger, Yvonne; Knickerbocker, Christopher; Sipes, David et al. (2018) Genotyping Multidrug-Resistant Mycobacterium tuberculosis from Primary Sputum and Decontaminated Sediment with an Integrated Microfluidic Amplification Microarray Test. J Clin Microbiol 56:
Sakatos, Alexandra; Babunovic, Gregory H; Chase, Michael R et al. (2018) Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria. Sci Adv 4:eaao1478
Thakore, Nitu; Norville, Ryan; Franke, Molly et al. (2018) Automated TruTip nucleic acid extraction and purification from raw sputum. PLoS One 13:e0199869
Thakore, Nitu; Garber, Steve; Bueno, Arial et al. (2018) A bench-top automated workstation for nucleic acid isolation from clinical sample types. J Microbiol Methods 148:174-180
Gong, Lingyan; Ouyang, Wei; Li, Zirui et al. (2017) Force fields of charged particles in micro-nanofluidic preconcentration systems. AIP Adv 7:125020
Yadon, Adam N; Maharaj, Kashmeel; Adamson, John H et al. (2017) A comprehensive characterization of PncA polymorphisms that confer resistance to pyrazinamide. Nat Commun 8:588
Calderón, R I; Velásquez, G E; Becerra, M C et al. (2017) Prevalence of pyrazinamide resistance and Wayne assay performance analysis in a tuberculosis cohort in Lima, Peru. Int J Tuberc Lung Dis 21:894-901
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

Showing the most recent 10 out of 19 publications