Ph. D., Jacobs University Bremen, Germany
- Assistant Professor: July 2021 – till date, Dept of Biotechnology, Indian Institute of Technology, Chennai, Tamil Nadu, India.
- Program Scientist: Dec 2018 – June 2021, Rajiv Gandhi Center for Biotechnology (RGCB), Trivandrum, Kerala, India.
- DST-INSPIRE faculty: Dec 2013 – Nov 2018, Rajiv Gandhi Center for Biotechnology (RGCB), Trivandrum, Kerala, India.
- Post doctoral fellow: Dec 2011 – Nov 2013, Institute of Biochemistry, Stuttgart University, Stuttgart, Germany.
- Junior Research fellow: Dec 2005 – June 2008, Department of Biochemistry, Indian Institute of Science (IISc), Bangalore, India.
Awards and Fellowships
- Young Scientist Medal (2019), from Indian Society for Parasitology, JNU, New Delhi.
- Kerala State Young Scientist award (2019), KSCSTE, Govt of Kerala.
- SERB Early Career award (2016), Department of Science & Technology, Govt of India.
- DBT – IYBA award (2015), Department of Biotechnology, Govt of India.
- DST-INSPIRE faculty award (Aug 2013), 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.
Research interest: Molecular Epigenetics & Plasmodium Biology
Epigenetic mechanisms of malaria parasite-host cell interactions
Research work in our laboratory is focused on Infection Biology; we aim to study the host-pathogen interactions through exploring the various Epigenetic signals of human malaria-causing pathogen and host. The obligate intracellular pathogens utilize the host factors for its growth and to establish chronic infections. Thus, it is highly essential to understand the molecular regulators of pathogens and the host cells that are involved in these processes and further it will be exploited to design better treatment strategies against infectious diseases. Using various Biochemical and Cell biology tools and genetic knockout strategies, we aim to study these processes in two important human pathogens viz Plasmodium spp. and Toxoplasma spp. We reported functions tRNA-specific methyltransferase from P. falciparum (BBA-Gene Regulatory Mechanisms, 2017) and characterized m6A RNA methyl-specific reader protein from P. falciparum (Epigenetics & Chromatin, 2020). Further, we have identified a novel epigenetic mechanism that controls the exported family surface proteins and virulence mechanisms in the malaria parasite that mediate the development of severe forms of cerebral malaria in humans (J Biol Chem, 2021); (ChemBioChem, 2018). Overall, our lab aims to understand the host-pathogen interactions for better drug and vaccine design against infectious diseases such as Malaria and Toxoplasmosis.
- Project 1: Epigenetic control of virulence proteins expression in Plasmodium spp.
The P. falciparum expresses and exports highly variable proteins on the surface of infected RBC for cytoadherence. The parasite changes its variable protein in response to host immunity. The variable proteins are encoded by multigene family (~60 genes), and located at the subtelomeric regions across all 14 chromosomes. It expresses one var gene at the time of infection and maintains the remaining 59 var genes in suppressed state. The gene suppressor mechanism is achieved through clustering of var genes to nuclear periphery. It has been shown that H3K36me3 is highly enriched in repressor clusters, however the mechanisms in which the H3K36me3 methyl mark is propagated, and forms suppressor var gene clusters to nuclear periphery is unknown. We have identified PHD domain that binds strongly to methyl mark and allosterically stimulates the enzyme activity to propagate H3K36me3 methyl marks and clusters var genes into nuclear periphery. Our preliminary study has identified novel mechanisms of var genes expression in Plasmodium spp (Figure 1) and detailed study on this line would pave way for better vaccine designs against malaria.
- Project 2: Molecular basis of Exportome regulation in Plasmodium spp to remodel the iRBCs
We have identified epigenetic methyl marks at unconventional sites on core histones of P. falciparum. Interestingly, all these methylations sites are located at the core histone on lateral surface of the nucleosome and reside very proximal to DNA contact point on histones. We characterized H3K64me3 mark and found it highly dynamic on the chromatin, enriched in ring, trophozoite stages and reduced in multinucleated schizont stage. This is first evidence show the dynamic deposition of the histone methylation marks in various developmental stages of P. falciparum. We have done a detailed characterization of H3K64me3 mark and have identified that the PfSET4 and PfSET5 enzymes of P. falciparum specifically methylate at H3K64. The global ChIP sequencing analysis has revealed that stage-specific dynamic distribution of H3K64me3 regulates the exportome family proteins in Plasmodium spp. This is first molecular evidence that shows the direct role of epigenetic players in stage specific gene expressions (J Biol Chem, 2021).
- Project 3: Understanding the mechanisms of artemisinin drug resistant P. falciparum
The artemisinin drug resistant P. falciparum is emerging problem to the tropical countries. Recent reports identified that the parasite harbors mutations in ubiquitin ligase adaptor Kelch13 protein in propeller domain. We hypothesized that K13 protein mutations could bring the differential proteome of metabolic pathways associated proteins in P. falciparum to exert the resistant to artemisinin. The preliminary data from our lab identified that selective “gain and loss” of proteins in artemisinin resistant parasites. The MALDI analyses have identified three important proteins that are associated with metabolic activity shows differential expression in artemisinin resistant P. falciparum. Further characterization of these proteins would identify the mechanisms of drug resistance and will find path for drug discovery against resistant malaria parasite.
Selected research publications
- Jabeena CA, Govindaraju G, Devadathan VS, Soundararajan G, Jaleel A, Dhakshmi S, Rajavelu A*. Dynamic association of the H3K64 trimethylation mark on the genes encoding exported proteins in Plasmodium falciparum. J Biol Chem. 2021 Apr 8;296:100614. *Corresponding author.
- Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC*. Aberrant regulation of retinoic acid signaling genes in cerebral Arterio Venous Malformation nidus and neighbouring astrocytes. Journal of Neuroinflammation. 2021, Mar 1; 18(1): 61. *Corresponding authors.
- Govindaraju G, Varma RSK, Jabeena CA, Devadathan VS, Chavali S, Rajavelu A*. N6-Adenosine methylation, a regulatory mark on mRNA is recognized by YTH domain protein in human malaria parasite falciparum. Epigenetics & Chromatin, 2020, 13 (1), 33. *Corresponding author.
- Mahesh A, Khan MI, Govindaraju G, Verma M, Awasthi S, Chavali PL, Chavali S, Rajavelu A*, Dhayalan A*. SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis. BBA – Molecular Cell Research. 2020 Feb;1867(2):118611. *Corresponding authors.
- Jabeena CA, Rajavelu A*. Epigenetic players of chromatin structure regulation in Plasmodium falciparum. ChemBioChem. 2019 , 15, 20(10). *Corresponding author.
- Awasthi S, Verma M, Mahes A, Khan MI, Govindaraju G, Rajavelu A, Chaval PL, Chavali S, Dhayalan A. DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA. Nucl Acid Res. 2018, Mar 30. 46(12):6304-6317.
- Rajavelu A, Lungu C, Emperle M, Dukatz M, Bröhm A, Broche J, Hanelt I, Parsa E, Schiffers S, Karnik R, Meissner A, Carell T, Rathert P, Jurkowska RZ, Jeltsch A. Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2. Nucl Acid Res. 2018 Sep 28; 46 (17):9044-9056.
- Emperle M, Rajavelu A, Kunert S, Arimondo PB, Reinhardt R, Jurkowska RZ, Jeltsch A. The DNMT3A R882H mutant displays altered flanking sequence preferences. Nucl Acid Res. 2018 Apr 6;46(6):3130-3139.
- Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC*. Gene expression analysis of nidus of cerebral arteriovenous malformations reveals vascular structures with deficient differentiation. Plos One, 2018, 13; 13 (6). *Corresponding authors.
- Govindaraju G, Jabeena CA, Sethumadhavan DV, Rajaram N, Rajavelu A*. DNA methyltransferase homologue TRDMT1 in Plasmodium falciparum specifically methylates endogenous aspartic acid tRNA. BBA – Gene Regulatory Mechanisms. 2017 Oct; 1860(10): 1047-1057. *Corresponding author.
- Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC*. Genetic and Epigenetic mechanisms in the development of arteriovenous malformation in the brain. Clinical Epigenetics. 2016, 8 (1), 78. *Corresponding authors.
- Verma M, Chandar R, Chakrapani B, Coumar MS, Govindaraju G, Rajavelu R, Chavali S, Dhayalan A. PRMT7 interacts with ASS1 and citrullinemia mutations disrupt the Interaction. J Mol Biol. 2017, 429 (15): 2278 – 2289.