Antimalarial drug targets and drugs targeting dolichol metabolic pathway of Plasmodium falciparum.

Because of mutation and natural selection, development of drug resistance to the existing antimalarial is the major problem in malaria treatment. This problem has created an urgent need of novel antimalarial drug targets as well as lead compounds. The important characteristic of malaria is that it shows the phenomenon of balanced polymorphisms. Several traits have been selected in response to disease pressure. Therefore such factors must be explored to understand the pathogenesis of malaria infection in human host. Apicoplast, hub of metabolism is present in Plasmodium falciparum (causative agent of falciparum malaria) having similarities with plant plastid. Among several pathways in apicoplast, Dolichol metabolic pathway is one of the most important pathway and has been known to play role in parasite survival in the human host. In P.falciparum, a phosphorylated derivative of Dolichol participates in biosynthesis of glycoproteins. Several proteins of this pathway play role in post translational modifications of proteins involved in the signal transduction pathways, regulation of DNA replication and cell cycle. This pathway can be used as antimalarial drug target. This report has explored progress towards the study of proteins and inhibitors of Dolichol metabolic pathway. For more comprehensive analysis, the host genetic factors and drug-protein interaction have been covered.

Distribution of MGEs and their insertion sites in the Macaca mulatta genome.

Mobile genetic elements (MGEs) are fragments of DNA that can move around within the genome through retrotransposition. These are responsible for various important events such as gene inactivation, transduction, regulation of gene expression and genome expansion. The present work involves the identification and study of the distribution of Alu and L1 retrotransposons in the genome of Macaca mulatta, an extensively used organism in biomedical studies. We also make comparisons with MGE distributions in other primate genomes and study the physicochemical properties of the local DNA structure around the transposon insertion site using ELAN. The present work also includes computational testing of the pre-insertion loci in order to detect unique features based on DNA structure, thermodynamic considerations and protein interaction measures. Although there is significant sequence divergence between the elements of M. mulatta and H. sapiens, their genome wide distribution is very similar; comparing the distribution of L1's in all available X chromosome sequences suggests a common mechanism behind the spread of MGE's in primate genomes.