Rajagopalan, Malini, Ph.D.

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Contact: malini.rajagopalan@uthct.edu

Education:
Ph.D, 1986, The University of Delhi, India

Research Interest:

Cell cycle of Mycobacterium tuberculosis.

Current Projects:

1. FtsZ and Cell division in Mycobacterium tuberculosis.
2. Regulation of cell cycle of Mycobacterium tuberculosis.

Lay Summary:
Infections with the opportunistic pathogens Mycobacterium tuberculosis (M. tb) and M. avium-intracellulare [MAC complex] represent some of the leading causes of increased morbidity and mortality in AIDS patients. Tuberculosis cases have been on steady rise globally, causing real concerns. These problems have been fueled by the emergence of tubercle bacilli that are resistant to one and/or more anti-tuberculosis drugs (MDR-TB). Thus the development of novel antimycobacterial drugs is much needed for the chemotherapy of tuberculosis especially MDR-TB. We have been studying the cell cycle of M. tb with the goal of identifying key players that can serve as potential drug targets. One such protein is FtsZ, a homolog of eukaryotic tubulins. Our current work is focused on characterization of activities of M. tb FtsZ using biochemical and genetic approaches.

Research Overview:
To understand the role of FtsZ in the cell division of M. tb, identify and characterize proteins that interact with FtsZ. These studies will also examine the role of FtsZ interacting proteins in M. tb cell division.

We are also concentrating on understanding factors that regulate the expression and function of M. tb FtsZ during growth in broth and in vivo.

Selected Papers and Abstracts:

• Yamamoto K, Moomey M, Rajagopalan M, Madiraju MV. 2008. Facilitation of dissociation reaction of nucleotides bound to Mycobacterium tuberculosis DnaA. J Biochem. ;143(6):759-64. 2008.
• Chen. Y, Anderson, D.E., Rajagopalan, M, and Erickson, H. 2007. Assembly dynamics of Mycobacterium tuberculosis FtsZ. Journal of Biological Chemistry. 282(38):27736-43.
• Chauhan, A., Lofton, A., Maloney, E., Fol, M, Madiraju, M.V. and Rajagopalan, M. (2006) Interference of Mycobacterium tuberculosis cell division by Rv2719c, a cell-wall hydrolase. Molecular Microbiology 62(1):132-47.
• Fol, M., Chauhan, A., Maloney, M., Moomey, M., Madiraju, M., Jagannath, C. and M. Rajagopalan. Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator. Molecular Microbiology 60(3): 643.
• Chauhan A, Madiraju VVS, Fol M, Lofton H, Maloney, E, Reynolds R and Rajagopalan M. (2006). Mycobacterium tuberculosis cells growing in macrophages are filamentous and deficient in FtsZ rings. J. Bacteriology 188(5):1856.
• Madiraju MVVS, Moomey M, Neuenschwander P, Muniruzzamaman S, Yamamoto K, Grimwade J and Rajagopalan M. (2006) The intrinsic ATPase activity of Mycobacterium tuberculosis DnaA promotes rapid oligomerization of DnaA on oriC. Molecular Microbiology 59(6):1876.
• Murty V. Madiraju and M. Rajagopalan (2005). DNA Replication and Cell division Chapter for a book on Mycobacterial Molecular Microbiology. Horizon Press.
• Rajagopalan M, Maloney E, Dziadek J, Poplawska M, Lofton H, Chauhan A, Madiraju MV. (2005) Genetic evidence that mycobacterial FtsZ and FtsW proteins interact, and colocalize. FEMS Microbiol Lett. 2005 Sep 1; 250(1):9-17.
• Rajagopalan M, Atkinson MA, Lofton H, Chauhan A, Madiraju MV.(2005) Mutations in the GTP-binding and synergy loop domains of Mycobacterium tuberculosis. BBRC. 2005 Jun 17; 331(4):1171-7.
• Dziadek, J.,Rutherford, S.A., Madiraju, M.V.V.S., Atkinson, M.A.L and Rajagopalan, M. (2003). Conditional expression of M. smegmatis ftsZ, an essential cell division gene. Microbiology 149: 1593-1603.
• Dziadek J, Rutherford SA, Madiraju M, Atkinson MAL, Rajagopalan, M. (2003). Conditional expression of Mycobacterium smegmatis ftsZ , an essential cell division gene. Microbiology 149:1593-1603.
• Greendyke R*, Rajagopalan M*, Parish T, Madiraju M. (2002) Conditinal expression of Mycobacterium smegmatis dnaA gene, an essential DNA replication gene. Microbiology 14:3887-3990. (* Equal contribution)
• Dziadek J, Rajagopalan M, Parish T, KurepinaK, Kreiswirth BN, Madiraju MVVS. (2002) Mutations in the CCGTTCACA DnaA-box of Mycobacterium tuberculosis ori Cthat abolish replication of ori C plasmids are tolerated on the chromosome. J. Bacteriol.184:3848-55.
• Yamamoto K, Rajagopalan M , Madiraju M. Phospholipids promote dissociation of ADP from the Mycobacterium avium DnaA protein. J Biochem ( Tokyo ) 2002 131(2): 219-24.
• Dziadek J, Madiraju M, Rutherford S, Atkinson, MAL, Rajagopalan M. (2002).Physiological consequences associated with the Mycobacterium tuberculosis FtsZ overproduction in mycobacterial hosts. Microbiology 148:961-971.
• Yamamoto K, Muniruzzaman S, Rajagopalan M. Madiraju MVVS. (2002). Modulation of Mycobacterium tuberculosis DnaA protein- adenine-nucleotide interactions by acidic phospholipids. Bicohem J. 363:305-311.