Our laboratory is investigating regulation of carbon metabolism in the methylotrophic yeast, Pichia pastoris. Investigations thus far have led to the characterization of two zinc finger transcription factors, Mxr1p and ROP. Mxr1p is a transcriptional activator of genes of methanol utilization pathway while ROP is a transcriptional repressor. Interestingly, Mxr1p and ROP bind to similar promoter sequences and thus have the same DNA binding specificity. Recent studies indicate that Mxr1p regulates the expression of genes encoding enzymes involved in the metabolism of several non-fermentative carbon sources such as acetate, ethanol etc. We are also studying intracellular trafficking of proteins and in one study, we observed that Methionine Synthase, a key enzyme involved in methionine biosynthesis is localized in the nucleus of P. pastoris while it is cytosolic in other eukaryotic cells. Our long term goal is to understand the biology of P. pastoris such that the new knowledge generated can lead to novel biotechnological applications.
In the area of infectious diseases, our laboratory has been involved in the development of recombinant vaccines against Hepatitis B and rabies. We have also identified a number of genes whose expression is altered in mouse brain during infection by neurotropic viruses such as Japanese encephalitis virus (JEV) and rabies virus. Recently, one of the JEV-inducible genes was shown to encode a novel nuclear noncoding RNA named VINC/NEAT1/epsilon RNA which is essential for the formation of nuclear paraspeckles. Several other JEV-inducible host genes are being characterized.
Research collaboration with Prof. G. Padamanaban over the last decade has led to the identification and characterization of all the enzymes of the heme biosynthetic pathway of the malarial parasite. In addition, we demonstrated that curcumin, a component of turmeric, in combination with artemisinin can be a potent antimalarial.
Research collaborations with biotech industry
have led to the development of a recombinant Hepatitis B vaccine (BEVAC
and ELOVAC-B) as well a novel combination DNA Rabies vaccine
Vijay Kumar N. & Rangarajan P.N. (2012). The zinc finger proteins Mxr1p and repressor of phosphoenolpyruvate carboxykinase (ROP) have the same DNA binding specificity but regulate methanol metabolism antagonistically in Pichia pastoris. J. Biol. Chem. 287, 34465-34473.
Vijay Kumar N. & Rangarajan P.N. (2011). Catabolite repression of phosphoenolpyruvate carboxykinase by a zinc finger protein under biotin- and pyruvate carboxylase-deficient conditions in Pichia pastoris. Microbiology 157, 3361 - 3369.
Kranthi, B. V., Kumar, R., Vijay Kumar, N., Rao, D. N. and Rangarajan, P. N. (2009) Identification of key DNA elements involved in promoter recognition by Mxr1p, a master regulator of methanol utilization pathway in Pichia pastoris. Biochimica et Biophysica Acta 1789, 460-468.
Sreenivasa Murthy, U.M. & Rangarajan, P. N. (2010). Identification of protein interaction regions of VINC/NEAT1/Men epsilon RNA. FEBS Letters 584, 1531-1535
Vathsala, P. G., Dende, C., Nagaraj, V. A., Bhattacharya, D., Das, D., Rangarajan, P. N. and Padmanaban, G. (2012). Curcumin-arteether combination therapy of Plasmodium berghei-infected mice prevents recrudescence through immunomodulation. PLos One 7(1): e29442.
Arun Nagaraj, V., Arumugam, R., Gopalakrishnan, B., Jyothsna, Y., Rangarajan, P. N. and Padmanaban, G. (2008). Unique properties of Plasmodium falciparum porphobilinogen deaminase Journal of Biological Chemistry 283, 437-444.
Kranthi, B. V., Balasubramanian, N. & Rangarajan, P. N. (2006). Isolation of a single-stranded DNA-binding protein from the methylotrophic yeast, Pichia pastoris and its identification as zeta crystallin. Nucleic Acids Research 34, 4060-4068.
Saha, S., Murthy, S. & Rangarajan, P. N. (2006). Identification and characterization of a virus-inducible non-coding RNA in mouse brain. Journal of General Virology 87, 1991-1995.
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