P. N. Rangarajan
Our laboratory is investigating transcription factors and the 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 in P. pastoris. We have observed that Methionine Synthase, a key enzyme involved in methionine biosynthesis is localized in the nucleus of P. pastoris, whereas, 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 collaborations 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 the 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 candidate (DINARAB).