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Alumni

Arumugam Rajavelu, PhD

DST-INSPIRE faculty

+91-471-2529598

arajavelu@rgcb.res.in

Arumugam-Rajavelu
Arumugam-Rajavelu

Arumugam Rajavelu, PhD

DST-INSPIRE faculty

+91-471-2529598

arajavelu@rgcb.res.in

  • Profile

    • Ph.D Biochemistry (2008 - 2011), Jacobs University Bremen, Germany
    • M.Sc Microbiology (Faculty of Medicine) (2002 - 2005), Dr. ALM PGIBMS Taramani campus, University of Madras, Chennai, India
    • B.Sc Microbiology (1999 - 2002), Periyar University, Salem, India
    • Dec 2013 - Till date, DST-INSPIRE Faculty at Rajiv Gandhi Center for Biotechnology (RGCB), Trivandrum, Kerala, India
    • Post doctoral fellow (Dec 2011 - Nov 2013), Laboratory of Prof. Albert Jeltsch, Stuttgart University, Stuttgart, Germany
    • Junior Research fellow (Dec 2005 - June 2008), Laboratory of Prof G. Padmanaban and Prof P.N. Rangarajan, Department of Biochemistry, Indian Institute of Science (IISc), Bangalore, India
    • Trainee Scientist (July 2005 - Nov 2005), Jubilant Biosys, Bangalore, India
    • DBT - Innovative Young Biotechnologist Award (IYBA) 2014, from Department of Biotechnology, Govt of India.
    • DST-INSPIRE faculty award (Aug 2013) from Department of Science and Technology, Govt of India
    • Postdoctoral Fellowship from Stuttgart University, funded by German Research Foundation (DFG), Stuttgart, Germany
    • PhD Fellowship funded by German Research Foundation (DFG), Germany (July 2008 - Sep 2011). PhD awarded with Special Distinction
    • DBT JRF fellowship from Indian Institute of Science (IISc), funded by Dept of Biotechnology, Govt of India

     

    Funding agencies

    1. Department of Science & Technology (DST), Govt of India, India

    Journals

    1. Oncogene
    2. BMC Biochemistry
    3. Chemosphere
    4. European Journal of Clinical Investigation
    5. JoVE
    6. Microbiology and Immunology
  • Research

    Malaria is an infectious disease caused by apicomplexan parasite, till date five Plasmodium species P. falciparum, P. vivax, P. Malariae, P. ovale and P. knowlesi have been identified which infects humans. Among the five species, the P. falciparum causes the most severe form of malaria. The female anopheles mosquito injects 20-100 sporozoites to human dermis to initiate the infection, these sporozoites reaches to liver via blood stream. In liver the parasites replicate and release the merozoites into blood stream, which further infects RBC and continues as asexual intraerythrocytic developmental cycle (IDC). The asexual growth of parasite consist different stages, including rings, trophozoites and schizonts, the mature schizonts ruptures the RBC and releases upto 30 merozoites that can invade into new RBCs and continue as asexual life cycle. The clinical manifestations of malarial disease occur during the IDC cycle of P. falciparum, which includes the severe form of cerebral malaria. The recent evidences indicates that P. falciparum under goes massive changes in “transcriptional activity´´ during IDC cycle, which suggested the role of epigenetic players at different stages of parasite development.

    Research work in my laboratory focuses on malarial biology and malarial epigenetics. We work on the tight regulation of chromatin in malarial parasite during its development in RBC and identification of modifications on the RNA in the parasites. We are also interested in understand the epigenetic protein’s role in differential gene expression in parasites, which eventually pave way to identify the new drug targets in the deadliest malarial parasites.

    Functional role of RNA modifications in Plasmodium falciparum (DST-INSPIRE funded)

    Modifications of RNA control the protein synthesis in mammals as well as protozoan parasites. We are interested to study the role of RNA modifications in malarial parasite's growth and its development. Using biochemical and molecular approach, we will find out the possible modifications present in the RNA of P. falciparum and its role in protein synthesis at different stages of malarial parasites.

    Tight regulation of chromatin in human malarial parasites

    The major portion of P. falciparum's genes exists as euchromatin when compared to higher order eukaryotes. The malarial parasite's chromatin is tightly regulated in order to achieve the optimal expression of genes at different stages of parasites during IDC cycle. Here we are interested to study the role of post translational modifications on the histone proteins and its role in var gene expression and chromatin dynamics during IDC cycle of parasites.

    Extramural Funding

    1. Department of Science & Technology, Govt of India, India
    2. Department of Biotechnology, Govt of India, India
    3. Kerala State Science & Technology, Govt of Kerala, Kerala, India

    Intramural Funding

    1. Rajiv Gandhi Centre for Biotechnology (RGCB), TVM, Kerala
  • Publications

      From RGCB :

    1. Govindaraju G, Jabeena C, Sethumadhavan D, Rajaram N, Rajavelu A* (2017). DNA methyltransferase homologue DNMT2 in Plasmodium falciparum specifically methylates endogenous aspartic acid tRNA. Biochim Biophys Acta - Gene Regulatory Mechanisms. S1874-9399(17)30206-7
    2. Verma M, Chandar R, Chakrapani B, Coumar MS, Govindaraju G, Rajavelu A, Chavali S, Dhayalan A (2017). PRMT7 interacts with ASS1 and citrullinemia mutations disrupt the Interaction. J Mol Biol. 429 (15): 2278 - 2289.
    3. Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC* (2016). Genetic and epigenetic mechanisms in the development of arteriovenous malformations in the brain. Clinical Epigenetics. 8 (1), 78. *Corresponding author.
    4. From Post-Doctoral work :

    5. Deplus R#, Blanchon L#, Rajavelu A#, Boukaba H# et al (2014). Regulation of DNA methylation patterns by CK2 mediated phosphorylation of Dnmt3a. Cell Reports. 8 (3); 743-753. #Shared first authors.
    6. Emperle M, Rajavelu A, Reinhardt R, Jurkowska R, Jeltsch A (2014). Cooperative DNA binding and protein/DNA fiber formation increases the activity of the Dnmt3a DNA methyltransferase. J Biol Chem. 289 (43), 29602-29613.
    7. Bashtrykov P, Rajavelu A, Hackner B, Ragozin S, Carell T, Jeltsch A (2014). Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain. ChemBioChem. 9(3), 743-8.
    8. Rilova E, Erdmann A, Gros C, Masson V, Aussagues, Cassabois VP, Rajavelu A, et al (2014). Design, Synthesis and Biological Evaluation of 4‐Amino‐N‐(4‐aminophenyl) benzamide Analogues of Quinoline‐Based SGI‐1027 as Inhibitors of DNA Methylation. ChemMedChem. 9 (3), 590-601.
    9. S Asgatay, C Champion, G Marloie, T Drujon, C Senamaud-Beaufort, Ceccaldi A, Erdmann A, Rajavelu A et al (2014). Synthesis and Evaluation of Analogues of N-Phthaloyl-L-tryptophan (RG108) as Inhibitors of DNA Methyltransferase 1. J Med Chem. 57 (2), 421-434.
    10. Ceccaldi A*, Rajavelu A*, Ragozin S, Senamaud-Beaufirt C, Bashtrykov P, Testa N, Dali-Ali H, Maulay-Bailly C, Amand S, Guianvarc’h D, Jeltsch A, Arimondo PB (2013). Identification of Novel Inhibitors of DNA methylation by Screening of a Chemical Library. ACS Chemical Biology. 8 (3); 543-8.
    11. From PhD work :

    12. Rajavelu A, Jurkowska R, Fritz J, Jeltsch A (2012). Function and disruption of DNA Methyltransferase 3a cooperative DNA binding and nucleoprotein filament formation. Nucleic Acid Res, 40(2): 569-80.
    13. Jurkowska R*, Rajavelu A* Anspach N, Urbanke C, Jankevicius G, Ragozin S, Nellen W, Jeltsch A (2011). Oligomerization and Binding of the Dnmt3a DNA Methyltransferase to Parallel DNA Molecules: Heterochromatic localization and role of Dnmt3L. J Biol Chem. 286 (27); 24200-7. *shared first authors.
    14. Siddique AN*, Nunna S*, Rajavelu A, Zhang Y, Jurkowska RZ, Reinhardt R, Rots MG, Jurkowski T & Jeltsch A. Targeted methylation and gene silencing of VEGF-A in human cells by using a Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity. J Mol Biol. 425(3), 479-91 * shared first authors.
    15. Rajavelu A, Tulyasheva Z, Jaiswal R, Jeltsch A*, Kuhnert N* (2011). The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols. BMC Biochem. 12; 16.
    16. Halby L, Sénamaud-Beaufort C, Ajjan S, Ceccaldi A, Drujon T, Rajavelu A, Champion C, Jurkowska R, Lequin O, Nelson WG, Jeltsch A, Guy A, Guianvarc’h D, Ferroud C and Arimondo PB (2012). Rapid synthesis of new DNMT inhibitors derivatives of Procainamide. ChemBioChem, 13(1): 157-65.
    17. Ceccaldi A, Rajavelu A, Champion C, Rampon C, Jurkowska R, Jankevicius G, Sénamaud-Beaufort C, Ponger L, Gagey N, Dali Ali H, Tost J, Vriz S, Ros S,Dauzonne D, Jeltsch A, Guianvarc'h D, Arimondo PB (2011). C5-DNA methyltransferase Inhibitors: From Screening to Effects on Zebrafish Embryo Development. Chembiochem. 14; 12 (9); 1337-45.
    18. Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, Jeltsch A (2010). The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem. 285(34); 26114-20.
    19. Zhang Y, Jurkowska R, Soeroes S, Rajavelu A, Dhayalan A, Bock I, Rathert P, Brandt O, Reinhardt R, Fischle W, Jeltsch A (2010). Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res. 38(13); 4246-53.
    20. From JRF work :

    21. Nagaraj VA, Arumugam R, Prasad D, Rangarajan PN, Padmanaban G (2010). Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion. Mol Biochem Parasitol. 174(1):44-52.
    22. Nagaraj VA, Prasad D, Arumugam R, Rangarajan PN, Padmanaban G (2010). Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol. Parasitol Int. 59(2):121-7
    23. Nagaraj VA, Arumugam R, Chandra NR, Prasad D, Rangarajan PN, Padmanaban G (2009). Localisation of Plasmodium falciparum uroporphyrinogen III decarboxylase of the heme-biosynthetic pathway in the apicoplast and characterization of its catalytic properties. Int J Parasitol. 39(5):559-68.
    24. Nagaraj VA,Arumugam R , Gopalakrishnan B, Jyothsna YS, Rangarajan PN, Padmanaban G (2008). Unique properties of Plasmodium falciparum porphobilinogen deaminase. J Biol Chem. 283(1): 437-44.
    SI. No Title Author's Name Publisher Year of publication
    1 Part V: Cell Function and Metabolism
    The Inhibition of the Mammalian DNA Methyltransferase 3a (Dnmt3a) by Dietary Black Tea and Coffee Polyphenols
    Arumugam Rajavelu, Zumrad Tulyasheva, Rakesh Jaiswal, Albert Jeltsch, and Nikolai Kuhnert Nutritional Biochemistry Apple Academic Press (AAP 2015
  • Team


    V.S. Devadathan ,PhD Student, CSIR-UGC fellow

    Human malarial parasite under goes for tight gene regulation during its development in RBCs and liver stages, it is unknown how the various chromatin modifiers are involved to regulate this process. We apply various biochemical and cell biology techniques to address the functions of chromatin modifiers in parasite gene regualtion process.

    Devadathan
    Devadathan

    V.S. Devadathan ,PhD Student, CSIR-UGC fellow

    Human malarial parasite under goes for tight gene regulation during its development in RBCs and liver stages, it is unknown how the various chromatin modifiers are involved to regulate this process. We apply various biochemical and cell biology techniques to address the functions of chromatin modifiers in parasite gene regualtion process.

    Jabeena, PhD Student, CSIR-UGC fellow

    Plasmodium falciparum is the most deadly human malarial parasite estimated to cause 207 million infections and about 627,000 deaths occur annually. Recently, there have been a tremendous increase in the neglected tropical diseases which mainly affects the under developed nations, importantly the drug resistant malarial parasites are increasing. The P. falciparum develops in two different hosts to complete its life cycle and the genes are tightly regulated and differentially expressed in its definitive as well as the intermediate host. The covalent epigenetic modifications of histone tails contributes to the dynamics of nucleosomes and transcriptional activation and repression. I am focusing on the unique post translational modifications of Plasmodium falciparum which are involved in the differential expression of virulence genes. We will apply various biochemical and cell biology techniques to identify the epigenetic network of P. falciparum and which will help us to identify the new drug targets in malarial parasite.

    Jabeena
    Jabeena

    Jabeena, PhD Student, CSIR-UGC fellow

    Plasmodium falciparum is the most deadly human malarial parasite estimated to cause 207 million infections and about 627,000 deaths occur annually. Recently, there have been a tremendous increase in the neglected tropical diseases which mainly affects the under developed nations, importantly the drug resistant malarial parasites are increasing. The P. falciparum develops in two different hosts to complete its life cycle and the genes are tightly regulated and differentially expressed in its definitive as well as the intermediate host. The covalent epigenetic modifications of histone tails contributes to the dynamics of nucleosomes and transcriptional activation and repression. I am focusing on the unique post translational modifications of Plasmodium falciparum which are involved in the differential expression of virulence genes. We will apply various biochemical and cell biology techniques to identify the epigenetic network of P. falciparum and which will help us to identify the new drug targets in malarial parasite.

    G. Gayathri, Junior Researh Fellow

    The human malarial parasite Plasmodium falciparum has the complex life cycle, which causes the severe form of malaria including cerebral malaria. The epigenetic modification of nucleic acids (DNA and RNA) particularly C5 methylation in eukaryotes controls the developmental process of organisms. It has been proposed that the chemical modifications of P. falciparum genome might play an important role in parasite development, pathogenesis and diseases development. To understand the malarial parasite’s pathogenesis process, it is quite important to study the signaling network of various chemical modifications in RNA and DNA of protozoan parasites, particularly in human malarial parasite Plasmodium falciparum . Currently we are interested to identify the various chemical modifications in genome of the Plasmodium parasites and find out its role in the signaling process which might be essential for the parasite development and pathogenesis. Identification of specific epigenetic readout pathway in human malarial parasite would serve as an alternative drug target which will help to develop specific anti-malarial drug.

    Gayathri Photo
    Gayathri Photo

    G. Gayathri, Junior Researh Fellow

    The human malarial parasite Plasmodium falciparum has the complex life cycle, which causes the severe form of malaria including cerebral malaria. The epigenetic modification of nucleic acids (DNA and RNA) particularly C5 methylation in eukaryotes controls the developmental process of organisms. It has been proposed that the chemical modifications of P. falciparum genome might play an important role in parasite development, pathogenesis and diseases development. To understand the malarial parasite’s pathogenesis process, it is quite important to study the signaling network of various chemical modifications in RNA and DNA of protozoan parasites, particularly in human malarial parasite Plasmodium falciparum . Currently we are interested to identify the various chemical modifications in genome of the Plasmodium parasites and find out its role in the signaling process which might be essential for the parasite development and pathogenesis. Identification of specific epigenetic readout pathway in human malarial parasite would serve as an alternative drug target which will help to develop specific anti-malarial drug.

  • Alumni