Anuradha Lohia
Professor, Biochemistry
PhD: IICB/Calcutta University/ 1986

Research interest

Cell cycle of Entamoeba histolytica:

Fidelity and stability of the genome are crucial for the propagation of any species and therefore must be maintained during proliferation of the organism. The eukaryotic cell cycle follows strict control mechanisms that ensure faithful duplication and segregation of the genome. The progression of the Entamoeba histolytica cell division cycle shows important differences with this paradigm. Heterogeneity of genome content is commonly observed in axenic cultures of E.histolytica. Cells with multiple nuclei and nuclei
 

with heterogeneous genome contents suggest that regulatory mechanisms that ensure alternation of DNA synthesis and mitosis in typical eukaryotes are absent in this organism. Thus, several endo-reduplicative cycles of DNA synthesis occur without mitosis in E.histolytica. Our data also shows that, unlike other organisms that switch to a fixed number of endo-reduplicative cycles under special circumstances, E.histolytica does not execute a precise number of endo-reduplicative cycles. We show that irregularity in endo-reduplication and genome-partitioning events lead to heterogeneity in the genome content of E.histolytica trophozoites in their proliferative phase. Proliferating cells, in general, ensure the constancy of their genome by various mechanisms during each cycle. In this context, E.histolytica is exceptional, because it can tolerate variations in its genome content. In order to understand the molecular mechanisms that are responsible for this phenotype, my lab is using the following approaches.

Analysis of the genome sequence showed absence of sequence homologs of several eukaryotic cell cycle regulatory proteins. Therefore, we have undertaken to identify the cell cycle gene networks transcriptional analysis on high throughput microarray chips. We developed a method of gene ‘knock-down’ by targeted dsRNA expression to study the function of specific genes. Using this method, we are studying 6 kinesin genes from amoeba, of which 4 are N-terminal kinesins. ‘Knock-down’ transformants of the N-terminal kinesins suggest that 2 of these genes play an important role in regulating genome content and microtubular spindle assembly. In another project, we are studying the role of Eh Rho1, a homolog of Hs RhoA, in regulating cell division. Eh Diaphanous and Formin homology proteins have been characterized as substrates of activated Eh Rho1 and their ‘knock-down’ transformants are being analysied for their role in regulating actin polymerization mediated cytokinesis. Functional analysis of Eh CDKs and cyclins show important differences in their temporal activity during the amoeba cell cycle compared to the eukaryotic cell cycle. Our lab is also studying epigenetic mechanisms that regulate gene expression in E.histolytica and structural elements like S/MAR sequences that maybe involved in these processes. Our studies form the basis for enquiring if variations in genome content affect the pathogenicity of E.histolytica.  [details]

Important publications

  1. Gangopadhyay, S.S., Ray, S.S., Sinha, P. and Lohia, A. (1997) Unusual Genome organisation in Entamoeba histolytica leads to two overlapping transcripts. Mol. Bioch. Parasitol.89, 73-83.

  2.  Gangopadhyay, S.S., Ray, S.S., Kennady, K., Pande, G. and Lohia, A. (1997) Heterogeneity of DNA content in axenically growing Entamoeba histolytica HM1:IMSS clone A. Mol. Biochem. Parasitol. 90, 9-20.

  3. Ganguly, A and Lohia,  A (2001) The cell cycle of Entamoeba invadens during vegetative growth and differentiation.Mol. Biochem. Parasitol. 112, 277-285.

  4. Das,S and Lohia, A. (2002) De-linking of S phase and cytokinesis in the       protozoan parasite Entamoeba histolytica-Cell. Microbiol. 4, 55-60.

  5.  Kaur, GK and Lohia, A (2004) .-Inhibition of gene expression with double strand RNA interference in Entamoeba histolytica-Biochem. Biophys. Res. Comm.320, 1118-1122.

  6.  Das, S., Mukherjee, C., Sinha, P. and Lohia, A. (2005) Constitutive association of MCM 2-3-5 proteins with chromatin in Entamoeba histolytica-Cell. Microbiol. 7, 259-267.

  7.  Banerjee, S., Fisher, O., Lohia, A. and Ankri, S.(2005)-Entamoeba histolytica DNA methyltransferase (Ehmeth) is a nuclear matrix protein that binds EhMRS2, a DNA that includes a scaffold /matrix attachment region (S/MAR).-Mol. Biochem. Parasitol. 139, 91-97.

  8. Loftus B, Anderson I, Davies R, Alsmark UC, Samuelson J, Amedeo P, Roncaglia P, Berriman M, Hirt RP, Mann BJ, Nozaki T, Suh B, Pop M, Duchene M, Ackers J, Tannich E, Leippe M, Hofer M, Bruchhaus I, Willhoeft U, Bhattacharya A, Chillingworth T, Churcher C, Hance Z, Harris B, Harris D, Jagels K, Moule S, Mungall K, Ormond D, Squares R, Whitehead S, Quail MA, Rabbinowitsch E, Norbertczak H, Price C, Wang Z, Guillen N, Gilchrist C, Stroup SE, Bhattacharya S, Lohia A, Foster PG, Sicheritz-Ponten T, Weber C, Singh U, Mukherjee C, El-Sayed NM, Petri WA Jr, Clark CG, Embley TM, Barrell B, Fraser CM, Hall N.-(2005)The genome of the protist parasite Entamoeba histolytica-Nature  433, 865-868.

  9. Lohia A (2006)  Leishmania proteins can correct defects due to human mitochondrial mutations.J Biosci. 31:507-8.

Full list of publications(reverse chronological order )

Projects

  •   Replication control in E.histolytica. FIRCA, NIH, USA 2005-2008.

  •   Development of a lead compound from Oxalis corniculata. DBT, 2005-2008.

  •   A genomic and proteomic analysis of nuclear matrix components to identify their role in regulation of gene expression in the human pathogen Entamoeba histolytica. DST, Indo-Israeli collaborative project. 2006-2008.

  •   Identifying cell cycle gene networks in E.histolytica, FIRCA, NIH, USA 2006-2009.

Awards

  • Elected Fellow Indian Academy of Sciences, 2006.

  • Stree Shakti Science Sanman, 2005.

  • Zee network Astitva award (2005).

  • DBT National award for Young Woman Bioscientist (2001).

  • Elected member of GRC (1998).

  • Rockefeller Foundation Biotechnology Career Fellowship (1992-1994)

  • Outstanding Young Person (Science) Junior Chamber of Commerce (1992)

  • Fogarty Special Fellowship (1991).



Contact


anuradha@boseinst.ernet.in