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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 |
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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.
Das,S and Lohia, A. (2002) De-linking of S phase and
cytokinesis in the protozoan parasite Entamoeba histolytica-Cell.
Microbiol. 4, 55-60.
2.
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.
3.
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.
4.
Mukherjee C., Clark CG and Lohia A (2008) Entamoeba
shows reversible variation in ploidy under different growth
conditions and between life cycle phases PLoS NTD
2(8):e281.
5.
Mukherjee C, Majumder S, Lohia A.(2009) Inter-Cellular
Variation in DNA Content of Entamoeba histolytica Originates from
Temporal and Spatial Uncoupling of
Cytokinesis from the Nuclear Cycle. PLoS Negl Trop Dis.3(4):e409.
Full list of publications(reverse
chronological order )
Projects
a)
Regulation of phagocytosis, cell division and motility in
Entamoeba histolytica: DBT 2010-2012
b)
Identifying proteins that determine the function of novel
kinesins from Entamoeba histolytica DST, SERC
2010-2013
Awards
Contact
anuradha@boseinst.ernet.in
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