Research Groups
Mammalian Biology: Malaria
Research Interests and Description
Staff Research Scientist: Renu Tuteja, PhD
Group Leader: Virander Chauhan
Research Interests
Malaria parasite, parasite biology, nucleic acid metabolism, translation, protein translocation, unwinding.
Description of Research
To understand the basic biology of the malaria parasite we are working on the enzymes (helicases) involved in nucleic acid metabolic pathways. Helicases catalyze the unwinding of duplex nucleic acids in an ATP-dependent manner. We have reported that these are feasible, novel drug targets for malaria control, and the genome wide analysis of helicases from Plasmodium falciparum and their comparison with the human host. This analysis revealed the presence of some parasite specific helicases. We have reported the purification and detailed characterization of a novel helicase from P. falciparum and our results indicate that helicase PfD66 is a homologue of Dbp5 and DDX19 from yeast and human, respectively. The biochemical characterization shows that it contains DNA and RNA unwinding, nucleic acid dependent ATPase and RNA binding activities. It is interesting to note that this enzyme can unwind DNA duplexes in both the 5’ to 3’ and 3’ to 5’directions. Using truncated derivatives, we have shown that the Q motif is essentially required for all of its activities.
The characterization of a novel helicase (PfH69) from P. falciparum has suggested that, besides the conserved domains, the N-terminal is also essential for all the enzyme activities. Through bioinformatics analysis we have shown the existence of the parasite specific UvrD helicase in the P. falciparum genome and that this enzyme is not present in the human host. This helicase is a component of mismatch repair (MMR) complex. We have identified and functionally characterized the main components of the eIF4F complex, i.e. eIF4E, eIF4A and eIF4G and PABP from P. falciparum, and have reported that PfeIF4A and PfeIF4E are co-localized and predominantly localized in the cytoplasm. The parasite cultures treated with co-addition of PfeIF4A and PfeIF4E double stranded RNA showed ~67% growth inhibition suggesting that inhibition of two components of the same pathway is more effective for inhibiting the proliferation of the malaria parasite P. falciparum. These observations suggest that PfeIF4A and PfeIF4E are critical for parasite growth and survival. We also work on the characterization of components of protein translocation pathways from P. falciparum. Studies on the characterization of the catalytic subunit of signal peptidase complex (SPC) PfSP21 show that it is modulated by phosphorylation. PfSP21 dsRNA specifically inhibits the growth of P. falciparum in culture due to the decrease in the amount of endogenous PfSP21 protein. These findings suggest that PfSP21 is essential for the growth and survival of the parasite.
Recent Publications
Mehta, J., Tuteja, R. 2011. A novel dual Dbp5/DDX19 homologue from Plasmodium falciparum requires Q motif for activity. Mol Biochem Parasitol 176, 58-63 PubMed link
Umate, P., Tuteja, N., Tuteja, R. 2011. Genome-wide comprehensive analysis of human helicases. Commun Integr Biol 4, 118-37 PubMed link
Tuteja, R. 2010. Genome wide identification of Plasmodium falciparum helicases: a comparison with human host. Cell Cycle 9, 104-120 PubMed link
Zhang, M., Fennell, C., Ranford-Cartwright, L., Sakthivel, R., Gueirard, P., Meister, S., Caspi, A., Doerig, C., Nussenzweig, R.S., Tuteja, R., Sullivan, W.J. Jr., Roos, D.S., Fontoura, B.M.A., Ménard, R., Winzeler, E.A., Nussenzweig V. 2010. The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. J Exp Med 207, 1465-1474 PubMed link
Tuteja, R. 2010. A method to inhibit the growth of Plasmodium falciparum by double-stranded RNA-mediated gene silencing of helicases. Methods Mol Biol 587, 389-400 PubMed link
Prakash, K., Tuteja, R. 2010. A novel DEAD box helicase Has1p from Plasmodium falciparum: N-terminal is essential for activity. Parasitol Int 59, 271-277 PubMed link
