Amardeep Kaur

Research Associate

401 Terry Ave N
206-732-2102

Amardeep Kaur is a Research Associate in the Baliga Lab. Over her 22 years in scientific research, she has participated in various projects, including sequencing portions of Chromosome 15 as part of the Human Genome Sequencing Consortium.  She has also used various experimental techniques (i.e., genetic knockout mutants, microarray studies, growth assays) along with various software tools to elucidate gene regulatory networks of halophilic archaea Halobacterium salinarum (Kaur et al, 2006, 2010). Amardeep worked collaboratively to study adaptive prediction behavior of Saccharomyces cerevisiae where novel associations between two different environmental factors were investigated. 

Currently, Amardeep’s research projects involve experiments to discover new methods to repress antibiotic resistance using E. coli and to understand the complexity of tuberculosis and its infectious agent, Mycobacterium tuberculosis (Mtb). There is an urgent need to better understand the phenotypic heterogeneity of Mtb to identify new antitubercular drug targets. She works in the BSL-3 lab to generate various gene knockdown strains using CRISPR interference (CRISPRi) to identify vulnerabilities in Mtb that may be exploited as potential drug targets. She is involved in determining minimum inhibitory concentrations and performing kill curve experiments with antibiotic-treated CRISPRi-mediated knockdown strains to determine their susceptibility to various drugs. Additionally, she has been using high-throughput Biolog phenotype microarrays (with Omnilog instrument) to analyze the metabolic capabilities of the CRISPRi-mediated knockdown strains. Amardeep also helps in projects to investigate the transcriptional response of Mtb in response to different environmental conditions using RNA-seq and Path-seq.

Amardeep carries out regular lab duties such as ordering lab’s consumable supplies, keeping track of NGS reagents, and organizing Mtb strains in BSL3 laboratory freezers, etc.

Publications

4882752 Kaur 1 chicago-fullnote-bibliography 50 default year 1 1 410 https://baliga.systemsbiology.net/wp-content/plugins/zotpress/
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Peterson, Eliza J. R., Aaron N. Brooks, David J. Reiss, Amardeep Kaur, Julie Do, Min Pan, Wei-Ju Wu, et al. “MtrA Modulates Mycobacterium Tuberculosis Cell Division in Host Microenvironments to Mediate Intrinsic Resistance and Drug Tolerance.” Cell Reports 42, no. 8 (August 29, 2023): 112875. https://doi.org/10.1016/j.celrep.2023.112875. Cite
Arrieta-Ortiz, Mario L., Min Pan, Amardeep Kaur, Evan Pepper-Tunick, Vivek Srinivas, Ananya Dash, Selva Rupa Christinal Immanuel, Aaron N. Brooks, Tyson R. Shepherd, and Nitin S. Baliga. “Disrupting the ArcA Regulatory Network Amplifies the Fitness Cost of Tetracycline Resistance in Escherichia Coli.” MSystems 8, no. 1 (February 23, 2023): e0090422. https://doi.org/10.1128/msystems.00904-22. Cite
Patra, Biranchi, Yoshiko Kon, Gitanjali Yadav, Anthony W. Sevold, Jesse P. Frumkin, Ravishankar R. Vallabhajosyula, Arend Hintze, et al. “A Genome Wide Dosage Suppressor Network Reveals Genomic Robustness.” Nucleic Acids Research 45, no. 1 (January 9, 2017): 255–70. https://doi.org/10.1093/nar/gkw1148. Cite
Robinson, Courtney K., Kim Webb, Amardeep Kaur, Pawel Jaruga, Miral Dizdaroglu, Nitin S. Baliga, Allen Place, and Jocelyne Diruggiero. “A Major Role for Nonenzymatic Antioxidant Processes in the Radioresistance of Halobacterium Salinarum.” Journal of Bacteriology 193, no. 7 (April 2011): 1653–62. https://doi.org/10.1128/JB.01310-10. Cite
Bonneau, Richard, Marc T. Facciotti, David J. Reiss, Amy K. Schmid, Min Pan, Amardeep Kaur, Vesteinn Thorsson, et al. “A Predictive Model for Transcriptional Control of Physiology in a Free Living Cell.” Cell 131, no. 7 (December 28, 2007): 1354–65. https://doi.org/10.1016/j.cell.2007.10.053. Cite
Brooks, Aaron N., David J. Reiss, Antoine Allard, Wei-Ju Wu, Diego M. Salvanha, Christopher L. Plaisier, Sriram Chandrasekaran, Min Pan, Amardeep Kaur, and Nitin S. Baliga. “A System-Level Model for the Microbial Regulatory Genome.” Molecular Systems Biology 10 (2014): 740. Cite
Kaur, Amardeep, Min Pan, Megan Meislin, Marc T. Facciotti, Raafat El-Gewely, and Nitin S. Baliga. “A Systems View of Haloarchaeal Strategies to Withstand Stress from Transition Metals.” Genome Research 16, no. 7 (July 2006): 841–54. https://doi.org/10.1101/gr.5189606. Cite
Lopez Garcia de Lomana, Adrian, Amardeep Kaur, Serdar Turkarslan, Karlyn Beer, Fred Mast, Jennifer Smith, John Aitchison, and Nitin Baliga. “Adaptive Prediction Emerges Over Short Evolutionary Time Scales.” Genome Biology and Evolution in press (June 2017). Cite
Whitehead, Kenia, Adrienne Kish, Min Pan, Amardeep Kaur, David J. Reiss, Nichole King, Laura Hohmann, Jocelyne DiRuggiero, and Nitin S. Baliga. “An Integrated Systems Approach for Understanding Cellular Responses to Gamma Radiation.” Molecular Systems Biology 2 (2006): 47. https://doi.org/10.1038/msb4100091. Cite
Kaur, Amardeep, Phu T. Van, Courtney R. Busch, Courtney K. Robinson, Min Pan, Wyming Lee Pang, David J. Reiss, Jocelyne DiRuggiero, and Nitin S. Baliga. “Coordination of Frontline Defense Mechanisms under Severe Oxidative Stress.” Molecular Systems Biology 6 (July 2010): 393. https://doi.org/10.1038/msb.2010.50. Cite
Plaisier, Christopher L., Fang-Yin Lo, Justin Ashworth, Aaron N. Brooks, Karlyn D. Beer, Amardeep Kaur, Min Pan, David J. Reiss, Marc T. Facciotti, and Nitin S. Baliga. “Evolution of Context Dependent Regulation by Expansion of Feast/Famine Regulatory Proteins.” BMC Systems Biology 8 (2014): 122. https://doi.org/10.1186/s12918-014-0122-2. Cite
Facciotti, Marc T., David J. Reiss, Min Pan, Amardeep Kaur, Madhavi Vuthoori, Richard Bonneau, Paul Shannon, et al. “General Transcription Factor Specified Global Gene Regulation in Archaea.” Proceedings of the National Academy of Sciences of the United States of America 104, no. 11 (March 13, 2007): 4630–35. https://doi.org/10.1073/pnas.0611663104. Cite
Van, Phu T., Amy K. Schmid, Nichole L. King, Amardeep Kaur, Min Pan, Kenia Whitehead, Tie Koide, et al. “Halobacterium Salinarum NRC-1 PeptideAtlas: Toward Strategies for Targeted Proteomics and Improved Proteome Coverage.” Journal of Proteome Research 7, no. 9 (September 2008): 3755–64. https://doi.org/10.1021/pr800031f. Cite
Abidi, Abrar A., Eliza J. R. Peterson, Mario L. Arrieta-Ortiz, Boris Aguilar, James T. Yurkovich, Amardeep Kaur, Min Pan, Vivek Srinivas, Ilya Shmulevich, and Nitin S. Baliga. “Intricate Genetic Programs Controlling Dormancy in Mycobacterium Tuberculosis.” BioRxiv, July 22, 2019, 709378. https://doi.org/10.1101/709378. Cite
Facciotti, Marc T., Wyming L. Pang, Fang-yin Lo, Kenia Whitehead, Tie Koide, Ken-ichi Masumura, Min Pan, et al. “Large Scale Physiological Readjustment during Growth Enables Rapid, Comprehensive and Inexpensive Systems Analysis.” BMC Systems Biology 4 (2010): 64. https://doi.org/10.1186/1752-0509-4-64. Cite
Pang, W. Lee, Amardeep Kaur, Alexander V. Ratushny, Aleksandar Cvetkovic, Sunil Kumar, Min Pan, Adam P. Arkin, John D. Aitchison, Michael W. W. Adams, and Nitin S. Baliga. “Metallochaperones Regulate Intracellular Copper Levels.” PLoS Computational Biology 9, no. 1 (2013): e1002880. https://doi.org/10.1371/journal.pcbi.1002880. Cite
Srinivas, Vivek, Mario L. Arrieta-Ortiz, Amardeep Kaur, Eliza J. R. Peterson, and Nitin S. Baliga. “PerSort Facilitates Characterization and Elimination of Persister Subpopulation in Mycobacteria.” Edited by Charles Langelier. MSystems 5, no. 6 (December 1, 2020): e01127-20, /msystems/5/6/mSys.01127-20.atom. https://doi.org/10.1128/mSystems.01127-20. Cite
Schmid, Amy K., David J. Reiss, Amardeep Kaur, Min Pan, Nichole King, Phu T. Van, Laura Hohmann, Daniel B. Martin, and Nitin S. Baliga. “The Anatomy of Microbial Cell State Transitions in Response to Oxygen.” Genome Research 17, no. 10 (October 2007): 1399–1413. https://doi.org/10.1101/gr.6728007. Cite