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SCHOOL OF NATURAL SCIENCES
NATURAL SCIENCES
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Faculty
Department of Life Sciences
Shailja Singh
Visiting Professor (Honorary),
Department of Life Sciences,
School of Natural Sciences
Email:
Education Details
Ph.D in Biomedical sciences, Ambedkar Centre for Biomedical Sciences, Univesity of Delhi, Delhi.
Masters in Biotechnology, GGD central University, Bilaspur.
Bachelors in Biology, GGD College, GGD Central University, Bilaspur.

Professional Experience:
2010-2012 - Principal Investigator, Innovative Young Biotechnology Award, Department of Biotechnology, India.
2003-2010 - Post-Doctoral Fellow, International Centre for Genetic Engineering and Biotechnology, India
  • Live cell imaging of invading Plasmodium falciparum merozoite at National Institute of Health, USA
  • Malaria experimental Genetics, Wellcome Trust Genome Campus Hinxton, Cambridge, UK
  • Imaging parasite infection Institute Pasteur, Paris, France
  • Experiments on sexual stage of malaria Parasite, Imperial College of London, UK
Currently Held Grants

Role of calcium signaling in egress of Plasmodium falciparum merozoites from host erythrocytes. Innovative Young Biotechnologist Grant, Department of Biotechnology, Govt of India. 2010-13: As Principal Investigator

Molecular machinery involved in apical organelle discharge in Plasmodium falciparum merozoites during host cell invasion. Indo-Swiss Bilateral Grant from Department of Science & Technology, Govt of India. 2012-14: As Co-Investigator

Understanding Critical Events in Biology of Blood Stage of Malaria Parasite. Department of Biotechnology, Govt of India. 2011-16: As Co-Investigator

Research Interests:
  • Parasitic infections: Molecular Mechanisms of Host Pathogen Interactions
  • Molecular signal and signaling machinery involved in invasion and egress of malaria parasites
My research focuses on understanding of the molecular signal and machinery involved in egress Plasmodium falciparum merozoites from host erythrocytes, involving multidisciplinary approach such as live cell imaging, molecular biology, cell biology and protein chemistry. P. falciparum causes the most virulent form of malaria in humans leading to tremendous morbidity and mortality. All the clinical symptoms of malaria are attributed to the blood stage of the parasite life cycle. To complete its life cycle in blood stage, P. falciparum merozoites invade erythrocytes, replicate, and then exit by a process known as egress. The egress of P. falciparum merozoites from the host erythrocytes is an essential yet poorly understood process. Live video microscopy has played a special role in studies on egress and invasion. Real-time light microscopic visualization of in vitro blood-stage egress in live parasites has been performed in the simian parasite Plasmodium knowlesi and in P. falciparum. In both cases it was observed that egress is a rapid event following by a quick degradation of parasitophorus and host cell plasma membrane. A cascade of proteolytic events plays a major role in degradation of membranes leading to egress of merozoites. However, the signals that regulate the temporal activation and/or secretion of proteases upon maturation of merozoites in intra-erythrocytic schizonts remain unclear. We have demonstrated for the first time a role of intracellular Ca2+ in regulation of egress of P. falciparum merozoites from schizonts. A sharp rise in intracellular Ca2+ just before egress, observed by time-lapse video microscopy, suggested a role for intracellular Ca2+ in this process. Chelation of intracellular free Ca2+ with chelators such as BAPTA-AM or inhibition of Ca2+ release with phospholipase C (PLC) inhibitors blocks merozoite egress. Interestingly, chelation of intracellular Ca2+ in schizonts was found to block the discharge of a key protease PfSUB1 (subtilisin like protease1) from apical organelle exonemes of P. falciparum merozoites to parasitophorous vacuole (PV). This leads to inhibition of processing of PfSERA5 (serine repeat antigen5); block in parasitophorous vacuolar membrane (PVM) rupture and merozoite egress. A complete understanding of the steps regulating egress of P. falciparum merozoites may provide novel targets for development of drugs that block egress and limit parasite growth. We are now studying the role of perforin like proteins in release of egress of P. falciparum merozoites.

Recent Publications:
* Corresponding Author

Shailja Singh and C.E. Chitnis (2016) Molecular signaling involved in entry and exit of malaria parasites from host erythrocytes. Cold Spring Harb Perspect Biol

S. Pati, S. Muthuraju, R. Ab. Hadi, T. J. Huat, S. Singh, M. Maletic-Savatic, J. M. Abdullah, and H. Jaafar (2016). Neurogenic Plasticity of Mesenchyme Stem Cell, an Alluring Cellular Replacement for Traumatic Brain Injury, Current Stem Cell Research & Therapy. Vol. 11, No. 15.

Agarwal S, Sharma V, Phulera S, Abdin MZ, Ayana R, Singh S* (2015). Structural insights into a key carotenogenesis related enzyme phytoene synthase of P. falciparum: a novel drug target for malaria. Syst Synth Biol. Dec;9(Suppl 1):27-37. Doi 10.1007/s11693-015-9168-8. Epub 2015 Apr 9.PMID: 26702306

Bathula C, Singh S, Sen S (2015). Diversity oriented synthesis for novel anti-malarials. Syst Synth Biol. Dec;9(Suppl 1):55. doi: 10.1007/s11693-015-9175-9. Epub Jul 18.PMID: 26705261

Gupta S, Singh D, Singh S* (2015). In silico characterization of Plasmodium falciparum purinergic receptor: a novel chemotherapeutic target.Syst Synth Biol. Dec;9(Suppl 1):11-6. doi: 10.1007/s11693-015-9165-y. Apr 9.PMID: 26702303

Garg S, Agarwal S, Dabral S, Kumar N, Sehrawat S, Singh S* (2015). Visualization and quantification of Plasmodium falciparum intraerythrocytic merozoites Syst Synth Biol. Dec; 9 (Suppl 1): 23-6. doi: 10.1007/s11693-015-9167-9.

Garg S, Sharma V, Ramu D, Singh S*.In silico analysis of calcium binding pocket of perforin like protein 1: insights into the regulation of pore formation.. Syst Synth Biol. 2 Dec;9(Suppl 1):17-21. doi: 10.1007/s11693-015-9166-x. Epub 2015 Apr 8.PMID:26702304

C. Bathula, P. Dangi, S. Hati, R. Agarwal, A. Singh, P. Munshi, S. Singh and S. Sen (2015). Synthesis of natural product inspired spiro and fused scaffolds based on ring distortion and construction strategy. New Journal of Chemistry. Sep 39, 9281-9292; DOI: 10.1039/C5NJ01858G

Alam MM, Solyakov L, Bottrill AR, Flueck C, Siddiqui FA, Singh S, Mistry S, Viskaduraki M, Lee K, Hopp CS, Chitnis CE, Doerig C, Moon RW, Green JL, Holder AA, Baker DA, Tobin AB (2015). Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nat. Commun. Jul 7;6:7285. doi: 10.1038/ncomms8285. PMID 26149123

Kaderi Kibria KM, Rawat K, Klinger CM, Datta G, Panchal M, Singh S, Iyer GR, Kaur I, Sharma V, Dacks JB, Mohmmed A, Malhotra P (2015). A role for adaptor protein complex 1 in protein targeting to rhoptry organelles in Plasmodium falciparum. Biochim Biophys Acta. Mar;1854(3):699-710. doi: 10.1016/j.bbamcr.2014.12.030. Epub 2015 Jan 5 PMID:25573429

Prabhu G, Agarwal S, Sharma V, Madurkar SM, Munshi P, Singh S*, Sen S (2015). A natural product based DOS library of hybrid systems. Eur J Med Chem. Mar 14;95:41-48. doi: 10.1016/j.ejmech.2015.03.023. PMID:25794788

Hati S, Madurkar SM, Bathula C, Thulluri C, Agarwal R, Siddiqui FA, Dangi P, Adepally U, Singh A, Singh S*, Sen S (2015). Design, synthesis and biological evaluation of small molecules as potent glycosidase inhibitors and antimalarials. Eur J Med Chem. Jul 15;100:188-96. doi: 10.1016/j.ejmech.2015.04.059. Epub 2015 Apr 30.PMID: 26087029

Krishnan R, Kumar V, Ananth V, Singh S, Nair AS, Dhar PK (2015). Computational identification of novel microRNAs and their targets in the malarial vector, Anopheles stephensi. Syst Synth Biol. Jun;9(1-2):11-7. doi: 10.1007/s11693-014-9159-1. Epub 2015 Feb 21.PMID: 25972985

Raj N, Helen A, Manoj N, Harish G, Thomas V, Singh S, Sehrawat S, Seth S, Nair AS, Grover A, Dhar PK (2015). In silico study of peptide inhibitors against BACE 1. Syst Synth Biol. DOI 10.1007/s11693-015-9169-7

Dawn A, Singh S*, More KR, Siddiqui FA, Pachikara N, Ramdani G, Langsley G, Chitnis CE (2014). The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes. PLoS Pathog. Dec 18;10(12):e1004520. doi: 10.1371/journal.ppat.1004520. eCollection 2014 Dec PMID:25522250

Sharma V, Agarwal S, Madurkar SM, Datta G, Dangi P, Dandugudumula R, Sen S, Singh S* (2014). Diversity-oriented synthesis and activity evaluation of substituted bicyclic lactams as anti-malarial against Plasmodium falciparum. Malaria J. Nov 28;13:467. doi: 10.1186/1475-2875-13-467.

Agarwal S, Sharma V, Kaul T, Abdin MZ, Singh S* (2014). Cytotoxic effect of carotenoid phytonutrient lycopene on P. falciparum infected erythrocytes. Mol Biochem Parasitol. Sep 27;197(1-2):15-20. doi: 10.1016/j.molbiopara.

Shidhi PR, Suravajhala P, Nayeema A, Nair AS, Singh S, Dhar PK (2014). Making novel proteins from pseudogenes. Bioinformatics. Sep 17. pii: btu615.

Wirth CC, Glushakova S, Scheuermayer M, Repnik U, Garg S, Schaack D, Kachman MM, Weißbach T, Zimmerberg J, Dandekar T, Griffiths G, Chitnis CE, Singh S, Fischer R, Pradel G (2014). Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes. Cell Microbiol. doi: 10.1111/cmi.12288.

Sharma M, Dhiman C, Dangi P, Singh S* (2014). Designing synthetic drugs against Plasmodium falciparum: a computational study of histone-lysine N methyltransferase (PfHKMT). Syst Synth Biol. Jun;8(2):155-60. doi:10.1007/s11693-014-9144-8. Epub 2014 Apr 8

Panchal M, Rawat K, Kumar G, Kibria KM, Singh S, Kalamuddin M, Mohmmed A, Malhotra P, Tuteja R (2014). Plasmodium falciparum signal recognition particle components and anti-parasitic effect of ivermectin in blocking nucleo-cytoplasmic shuttling of SRP. Cell Death Dis. 5:e994. doi: 10.1038/cddis.2013.521

Garg S, Agarwal S, Kumar S, Yazdani SS, Chitnis CE, Singh S* (2013). Calcium-dependent permeabilization of erythrocytes by a perforin-like protein during egress of malaria parasites. Nat. Commun. 4:1736. doi: 10.1038/ncomms2725. PMID: 23591903.

Agarwal S, Singh MK, Garg S, Chitnis CE, Singh S* (2013). Ca(2+)-mediated exocytosis of subtilisin-like protease 1: a key step in egress of Plasmodium falciparum merozoites. Cell Microbiol. 15(6):910-21. doi: 10.1111/cmi.12086. PMID: 23217145.

Singh S, More KR and Chitnis CE (2013). Role of calcineurin and actin dynamics in regulated secretion of microneme proteins in Plasmodium falciparum merozoites during erythrocyte invasion. Cell Microbiol. Aug 5. doi: 10.1111/cmi.12177. PMID: 23910910.

Singh S and Chitnis CE (2013). Flow cytometry based methods for measurement of cytosolic calcium and surface protein expression in Plasmodium falciparum merozoites. Methods Mol Biol. 923:281-90. PMID: 22990785.

Hans N, Singh S, Pandey AK, Reddy KS, Gaur D and Chauhan VS (2013). Identification and charecterization of a novel Plasmodium falciparum adhesin involved in erythrocyte invasion. PLoS One. Sep 13;8(9):e74790. doi: 10.1371/journal.pone.0074790. PMID: 24058628.

Imam M, Singh S, Kaushik NK, Chauhan VS (2013). Plasmodium falciparum Merozoite Surface Protein 3: oligomerization, self-assembly and heme complex formation. J Biol Chem. Dec 19. PMID:24362023.

Hans N, Singh S, Jain S K and Chauhan V S (2013). Identification of novel rhoptry neck protein of Plasmodium falciparum. Mol Biochem Parasitol. 2013 Mar 13;188 (1):34-39. doi: PMID: 23499754.

Siddiqui FA, Dhawan S, Singh S, Singh B, Gupta P, Pandey A, Mohmmed A, Gaur D, Chitnis CE (2013). A thrombospondin structural repeat containing rhoptry protein from Plasmodium falciparum mediates erythrocyte invasion. Cell Microbiol. Feb 6. doi: 10.1111/cmi.12118 PMID: 2338792.

Bansal A, Singh S, More KR, Hans D, Nangalia K, Yogavel M, Sharma A, Chitnis CE (2013). Characterization of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) and its role in microneme secretion during erythrocyte invasion. J Biol Chem. Jan 18;288(3):1590-602. doi: 10.1074/jbc.M112.411934. Epub 2012 Nov 30. PMID: 23204525.

Singh S and Chitnis CE (2012). Signaling mechanism involved in apical organelle discharge during invasion of apicomplexan parasites. Microbes and Infection. 10: 820–824. PMID: 22634343.

Ahmad M, Singh S, Afrin F, Tuteja R (2012). Novel RuvB nuclear ATPase is specific to intraerythrocytic mitosis during schizogony of Plasmodium falciparum. Mol Biochem Parasitol. 185: 58-65. PMID: 22705314.

Tarique M, Satsangi AT, Ahmad M, Singh S and Tuteja R (2012). Plasmodium falciparum MLH is schizont stage specific endonuclease. Mol Biochem Parasitol. 181: 153-61. PMID: 22079692

Sahar T, Reddy KS, Bharadwaj M, Pandey AK, Singh S, Chitnis CE and Gaur D (2011). Plasmodium falciparum Reticulocyte Binding-Like Homologue Protein 2 (PfRH2) Is a Key Adhesive Molecule Involved in Erythrocyte Invasion. PLoS ONE. 6(2): e17102. doi:10.1371. PMID: 21386888.

Srivastava A, Singh S, Dhawan S, Alam M, Mohmmed A and Chitnis CE (2010). Localization of apical sushi protein in Plasmodium falciparum merozoites. Mol Biochem Parasitol. 174: 66-69. PMID: 20540969.

Singh S, Alam M, Pal-Bhowmick I, Brzostowski, Chitnis CE (2010). Distinct external signals trigger sequential release of apical organelles during erythrocyte invasion by malaria parasites. PLoS Pathogens. 6:e1000746 PMID: 20140184.

Singh S, Alam M and Chitnis CE. Molecular Interaction in Red Cell Invasion by Malaria Parasites (2010). Emerging Frontiers in Immuno genomics of Infectious Diseases. Pp.39-43.

Pattnaik P, Shakri AR, Singh S, Goel S, Mukherjee P and Chitnis CE (2007). Immunogenicity of a recombinant malaria vaccine based on receptor binding domain of Plasmodium falciparum EBA175. Vaccine. 25: 806-13. PMID: 20140184.

Singh S, Mayor A, Bir N, Sawhney R, Pattnaik P, Singh SK, Sharma A and Chitnis CE (2005). Receptor-binding domains lie in central regions of Duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites. Blood. 105: 2557-2563. PMID: 1534559. (Shailja Singh and AM, NB, RS have contributed equally to this work as first author as mentioned in the Journal, so represented as one of the first authors)

Singh S, Dwarakanath BS, Mathew TL (2005). Role of topoisomerases in cytotoxicity induced by DNA ligand Hoechst-33342 and UV-C in a glioma cell line. Indian J Exp Biol. 43: 313-23. PMID: 15875714.

Singh S, Dwarakanath BS, Mathew TL (2004). DNA ligand Hoechst-33342 enhances UV induced cytotoxicity in human glioma cell lines. J Photochem Photobiol B. 77: 45-54. PMID:15542361.

Bharara R, Singh S, Pattnaik P, Chitnis CE, Sharma A (2004). Structural analogs of sialic acid interfere with the binding of erythrocyte binding antigen-175 to glycophorin A, an interaction crucial for erythrocyte invasion by Plasmodium falciparum. Mol Biochem Parasitol. 138: 123-9. PMID: 5500923.

Gurudutta G, Babbar AK, Singh Shailja, Pati S and Sharma RK (2001). Evaluation of potential tracer ability of 99mTc labeled acetylated LDL for Scintigraphy of LDL scavenger receptor sites of macrophage origin. Nuclear Medicine and Biology. 28: 235-241. PMID: 11323232.

National & International Recognition:
Recipient of Innovative Young Biotechnology Award, Department of Biotechnology, Government of India.
2002 Best paper presentation, International Conference on Radiation Damage and its Modification, New Delhi, India
2001 Travel award, Humboldt-Kolleg, a symposium on Genetics and human health, Manipal, India

Major Presentations, Conferences and Workshops:
Shailja Singh and Chetan E. Chitnis. Calcium-dependent protein phosphatase (Calcineurin) is an essential regulator of micronemal exocytosis in Plasmodium falciparum merozoites. Istituto Superiore di Sanità, Rome, Italy on 22-23 Nov, 2011

Swati Garg, Shalini Agrawal, Chetan Chitnis, Shams Yazdani, Shailja Singh*. Blood stage Perforin like protein 1 and its functional significance in egress of Plasmodium falciparum merozoites. BioWorld 2012, Kusuma School of Biological Sciences, 10-12 December 2012, IIT- New Delhi, India

Shailja Singh and Chetan E. Chitnis. Role of Calcium-dependent protein phosphatase in micronemal discharge in Plasmodium falciparum merozoites. Recent development in malaria research 1-3 Dec, 2010

Shailja Singh and Chetan E. Chitnis. Molecular machinery involved in apical organelle discharge during erythrocyte invasion by malaria parasite. Instituto de Medicina Molecular, Lisbon, Portugal, 4-6 Nov, 2010

Shailja Singh and Chetan E. Chitnis. Sequential release of apical organelle during erythrocyte invasion by malaria parasite. BioMalPar at the EMBL Advanced Training Centre, Heidelberg, Germany, 3-5 May 2010.

Shailja Singh. Imaging calcium signalling and apical organelle discharge in P. falciparum merozoites. Confocal Microscopy Workshop in collaboration with ICGEB INDIA, 23-25 Nov 2009

Shailja Singh and Chetan E. Chitnis. Calcium signaling involved in Invasion of P. falciparum merozoites. BioMalPar II Kick Off Meeting. Wolfson Medical Building at the University of Glasgow, University of Glasgow, Glasgow, Scotland. 11-13 Nov 2009

Shailja Singh and Chetan E. Chitnis. Distinct external signal trigger sequential release of apical organelle during erythrocyte invasion by malaria parasite. Gordon Research Conferences 6-12 Sep 2009, Oxford, London

Shailja Singh, G.U. Gurudutta, B.S. Dwarkanath and T.L. Mathew. Effects of DNA ligand Hoechst-33342 on the fidelity of DNA repair of restriction enzyme induced double strand breaks. International Conference on Radiation Damage and its Modification, Institute of Nuclear Medicine and Allied Sciences, Delhi, INDIA, 12–15 Nov, 2002.

Shailja Singh, G.U. Gurudutta and B.S. Dwarakanath, A novel method for studying DNA repair fidelity in mammalian cells. 4th Annual Symposium on Frontiers in Biomedical Research, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, INDIA, 11 -12 Apr, 2002.

Shailja Singh, B.S. Dwarakanath and T.L. Mathew, Topoisomerases are involved in synergistic cell killing by DNA ligand Hoechst and UV-C. Annual Symposium in Biomedical Sciences, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, INDIA, 11-12 Apr, 2002.

Shailja Singh, B.S. Dwarakanath, N.K. Chaudhury, and T.L. Mathew. Role of Topoisomerases in Synergistic Cell Killing by DNA Ligand Hoechst –333342 and UV-C. International Conference on Emerging Trends in Cancer Research. Jawaharlal Nehru University, New Delhi, INDIA, 14–16 Mar, 2002.

Shailja Singh, B.S. Dwarakanath, J.S. Adhikari, Sudhir Chandana and T.L. Mathew. Inhibition of UV-induced DNA repair by the minor groove binding DNA ligand Hoechst-333342 in human tumor cell lines.XXV All India Cell Biology Conference, Indian Institute of Science. Bangalore, INDIA, 1 –3 Nov, 2001

Shailja Singh. DNA ligand Hoechst-33342 inhibits repair of UV induced DNA damage in human tumor cell lines. 1st Annual Symposium in Biomedical Sciences, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, INDIA, 13-14 Apr, 2001.

Shailja Singh, B.S. Dwarakanath, T. Lazer Mathew and Vinay Jain. DNA Ligand Hoechst-33342 enhances UV induced cytotoxicity in human tumor cell lines. International conference on Radiation-Biology, Trivandrum, INDIA, 17–23 Feb, 2000.

Executive Summary:

Dr. Shailja Singh gained her PhD from the University of Delhi in the area of Biomedical Sciences. Following this she joined the laboratory of Dr. Chetan Chitnis, International Centre for Genetic Engineering and Biotechnology as postdoctoral Fellow. In 2010, she got innovative Young Biotechnology Award from Department of Biotechnology, Govt of India, to conduct her independent research on molecular signal and machinery involved in egress of Plasmodium falciparum merozoites from host erythrocytes. Shailja’s work has been published in reputed, high-impact international journals and to further her interests she now intend to investigate the molecular intricacies mediating host pathogen interplay in Plasmodium falciparum pathogenesis. The outcomes of the research may provide novel therapeutic targets for the development of anti malarial drugs and save the life of millions around the globe and help in reducing malaria burden in human population.

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