SNEHA SUDHA KOMATH
Professor, School of Life Sciences
Jawaharlal Nehru University
New Delhi -110067, India.
Off. Phone : +91-11-26704502
E-mail : sskomath@mail.jnu.ac.in; sskomath@yahoo.com
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RESEARCH AREA
RESEARCH AREA
My lab focuses on understanding the molecular details of glycosylphosphatidylinositol (GPI) biosynthesis in the human pathogenic fungus, Candida albicans. The GPI is a complex glycolipid present ubiquitously present in eukaryotes. An elaborate pathway of roughly 10-12 steps works sequentially to produce a precursor GPI in the endoplasmic reticulum and attach it to the C-terminal ends of proteins that carry the appropriate GPI attachment signal sequence. A variety of proteins may be held by means of this anchor to the extracellular leaflet of the plasma membrane (and/ or cell wall). They may range from enzymes, enzyme inhibitors, signal receptors, proteins required for nutrient uptake and complement regulators, to hydrolytic enzymes, host-recognition factors, adhesins, virulence factors, and proteins that coat the surface of pathogens to evade host immune response. The GPI biosynthetic pathway is essential to the viability and functioning of the organism in lower eukaryotes, while in higher eukaryotes it is critical at certain stages of organismal development, such as in embryogenesis, but not at others. Despite an overall conservation of its core structure, the GPI anchor is embellished with organism-specific, developmental stage-specific, or cell/ tissue-specific modifications that customize the glycolipid as per the specific requirements of the cell to which they belong. In some instances, these differences are achieved by altering the order of key biosynthetic steps. In other cases, they involve subtle differences in the active site geometry of specific enzymes, and in yet others they are the outcome of a completely different set of regulatory mechanisms. Thus, despite the underlying structural conservation, differences abound, and the possibility of using GPIs and GPI biosynthetic steps as vaccines and drug targets in eukaryotic pathogens continues to generate much interest.
AWARDS/ FELLOWSHIPS/ RECOGNITIONS
Awards/ Honours
SERB-POWER Fellowship, 2021
Distinguished Alumnus Lecture (2019), School of Chemistry, University of Hyderabad
National Women Bioscientists’ Award, 2010
UGC-Junior Research Fellowship (JRF)/ Senior Research Fellowship (SRF)
Gold Medalist in Chemistry (M.Sc. Univ. of Hyderabad, 1991)
Ranked all-India 4th in AISSE (1984)
Membership of Academic Bodies/ Societies
Life member, Indian Biophysical Society
Life member, Fluorescence Society
Executive member, Protein Society
TEACHING
TEACHING
LS102A: Mathematics for Biologists
LS405A: Chemistry of Macromolecules
LS562: Biophysical Chemistry- Methods and applications
LS601A: Research Methodology-I (Physicochemical principles in the context of Biology)
LAB MEMBERS
LAB MEMBERS
CURRENT MEMBERS
Shailja Shefali
Thesis Title: Study of CaGpi8, the caspase-like subunit of the GPI transamidase (GPIT) complex from Candida albicans, and its functional characterization
Monika Bharati
Thesis title: Functional characterization of Gpi3, the catalytic subunit, of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) and its interaction with other subunits in Candida albicans.
Yatin Kumar
Thesis title: To study the cross talk of glycosylphosphatidylinostol (GPI) biosynthesis pathway with ergosterol biosynthesis pathway in Candida albicans.
Simran Sharma
Thesis Title: Studying the activity of Candida albicans histone acetyltransferase, Rtt109.
Isaac Cherian
Thesis Title: Characterization of glycosylphosphatidylinositol transamidase in Candida albicans.
Harshita Saini
Thesis Title: An analysis of the interaction between GPI biosynthesis and Ras signalling in Candida albicans.
Neha Thakran
Thesis title (tentative)- Characterization of mammalian and Giardia lamblia N-acetylglucosaminylphosphatidylinositol de-N-acetylase
Smriti Singh
LAB ALUMNI
MSc DiSSERtATION Students
MSc DiSSERtATION Students
PUBLICATIONS
PUBLICATIONS
Komath SS*. To each its own: Mechanisms of cross-talk between GPI biosynthesis and cAMP-PKA signaling in Candida albicans versus Saccharomyces cerevisiae. J Biol Chem. 2024 Jul;300(7):107444. doi: 10.1016/j.jbc.2024.107444. Epub 2024 Jun 4. PMID: 38838772; PMCID: PMC11294708.
Sethi SC, Bharati M, Kumar Y, Yadav U, Saini H, Alam P, Komath SS*. The ER-Resident Ras Inhibitor 1 (Eri1) of Candida albicans Inhibits Hyphal Morphogenesis via the Ras-Independent cAMP-PKA Pathway. ACS Infect Dis. 2024 Aug 9. doi: 10.1021/acsinfecdis.4c00175. Epub ahead of print. PMID: 39119676.
Naithani S, Komath SS, Nonomura A, Govindjee G. Plant lectins and their many roles: Carbohydrate-binding and beyond. J Plant Physiol. 2021 Nov;266:153531. doi: 10.1016/j.jplph.2021.153531. Epub 2021 Sep 21. PMID: 34601337.
Lupo V, Won S, Frasquet M, Schnitzler MS, Komath SS, Pascual-Pascual SI, Espinós C, Svaren J, Sevilla T. 2020. Bi-allelic mutations in EGR2 cause autosomal recessive demyelinating neuropathy by disrupting the EGR2-NAB complex. Eur J Neurol. 2020 27(12):2662-2667. doi: 10.1111/ene.14512.
Nonomura AM, Shevela D, Komath SS, Biel KY, Govindjee G. (2020) The carbon reactions of photosynthesis: role of lectins and glycoregulation. Photosynthetica 58(5): 1090-1097. DOI: 10.32615/ps.2020.064
Sah SK, Shefali S, Yadav A, Som P, Komath SS*. 2020. The caspase-like Gpi8 subunit of Candida albicans GPI transamidase is a metal-dependent endopeptidase. Biochem Biophys Res Commun. 23 April 2020, 525(1):61-66.
Chandraker A, Komath SS*. 2020. Expression, purification, and characterization of N-acetylglucosaminylphosphatidylinositol de-N-acetylase (ScGpi12), the enzyme that catalyses the second step of GPI biosynthesis in S. cerevisiae. Yeast. 2020 Jan;37(1):63-72. doi: 10.1002/yea.3457. Epub 2019 Dec 29.
Parveen S, Singh, S and Komath SS*. 2019. Saccharomyces cerevisiae Ras2 restores filamentation but cannot activate the first step of GPI anchor biosynthesis in Candida albicans. Biochem. Biophys. Res. Commun. 517(4):755-761. doi: 10.1016/j.bbrc.2019.07.128.
Jain P, Garai P, Sethi SC, Naqvi N, Yadav B, Kumar P, Singh SL, Yadav U, Bhatnagar S, Rahul, Puri N, Muthuswami R, Komath SS*. 2019. Modulation of azole sensitivity and filamentation by Gpi15, encoding a subunit of the first GPI biosynthetic enzyme, in Candida albicans. Sci Rep. 2019 Jun 11;9(1):8508. doi: 10.1038/s41598-019-44919-4.
Jain P, Sethi SC, Pratyusha VA, Garai P, Naqvi N, Singh S, Pawar K, Puri N, Komath SS*. 2018. Ras signaling activates glycosylphosphatidylinositol anchor biosynthesis via the GPI-N-acetylglucosaminyl transferase (GPI-GnT) in Candida albicans. J Biol Chem. 293(31), 12222-12238. 10.1074/jbc.RA117.001225
Pratyusha VA, Victoria GS, Khan MF, Haokip DT, Yadav B, Pal N, Sethi SC, Jain P, Singh SL, Sen S, Komath SS*. 2018. Ras hyperactivation versus overexpression: Lessons from Ras dynamics in Candida albicans. Sci. Rep. 2018 Mar 27;8(1):5248. doi: 10.1038/s41598-018-23187-8.
Yadav U, Rai T, Sethi SC, Chandraker A, Khan M, Komath SS*. 2018. Characterizing N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12), the enzyme that catalyzes the second step of GPI biosynthesis in Candida albicans. FEMS Yeast Res. 18(7), foy067.
Komath SS*, Singh SL, Pratyusha VA, Sah SK. 2018. Generating anchors only to lose them: The unusual story of glycosylphosphatidylinositol anchor biosynthesis and remodeling in yeast and fungi. IUBMB Life. 70(5):355-383. doi: 10.1002/iub.1734. Critical Review.
Soni S, Jain BP, Gupta R, Sudhakar D, Kar K, Komath SS*, Goswami S.* 2018. Biophysical Characterization of SG2NA Variants and their Interaction with DJ-1 and Calmodulin in vitro. Cell Biochem. Biophys. 76(4):451-461.
Singh SL and Komath SS*. 2017. Fluorescently Labelled Aerolysin (FLAER) Labelling of Candida albicans Cells. Bio-protocol 7(11): e2303. DOI: 10.21769/BioProtoc.2303.
Singh SL, Rai RC, Sah SK, Komath SS*. 2016. The catalytic subunit of the first mannosyltransferase in the GPI biosynthetic pathway affects growth, cell wall integrity and hyphal morphogenesis in Candida albicans. 2016. Yeast. Aug;33(8):365-83. doi: 10.1002/yea.3179.
Gupta M, Mazumder M, Dhatchinamoorthy K, Nongkhlaw M, Haokip DT, Gourinath S, Komath SS, Muthuswami R. 2015. Ligand-induced conformation changes drive ATP hydrolysis and function in SMARCAL1. FEBS J. 282(19):3841-59. doi: 10.1111/febs.13382.
Shah AH, Rawal MK, Dhamgaye S, Komath SS, Saxena AK, and Prasad R. 2015. Mutational Analysis of Intracellular Loops Identify Cross Talk with Nucleotide Binding Domains of Yeast ABC Transporter Cdr1p. Sci. Rep. 5:11211. doi: 10.1038/srep11211.
Pawar K, Yadav A, Prasher P, Mishra S, Singh B, Singh P and Komath SS*. 2015. Identification of an indole-triazole-amino acid conjugate as highly effective antifungal agent. Journal Article Med. Chem. Commun. Online Manuscript doi: 10.1039/C5MD00156K.
Ahmad MF, Mann PG and Komath SS*. 2015. A Signal with a Difference: The role of GPI anchor signal sequence in dictating conformation and function of the Als5 adhesin in Candida albicans. Adv. Exp. Med. Biol. 842:147-163. doi: 10.1007/978-3-319-11280-0_10. (Invited article)
Anshuman, Singh SL, Yadav B and Komath SS*. 2014. Saccharomyces cerevisiae Gpi2, an accessory subunit of the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, selectively complements some of the functions of its homolog in Candida albicans. Glycoconj. J. 31(6-7):497-507. doi: 10.1007/s10719-014-9536-8. (Invited article)
Yadav B, Bhatnagar S, Ahmad MF, Jain P, Pratyusha VA, Kumar P, Komath SS*. 2014. First step of glycosylphosphatidylinositol (GPI) biosynthesis cross-talks with ergosterol biosynthesis and Ras signaling in Candida albicans. J Biol Chem. 289(6):3365-82. doi: 10.1074/jbc.M113.528802. Epub 2013 Dec 19.
Pooja, Parasher P, Singh P, Panwar K, Vikramdeo KS, Mondal N, Komath SS*. 2014. Synthesis of amino acid appended indoles: Appreciable anti-fungal activity and inhibition of ergosterol biosynthesis as their probable mode of action. Eur. J. Med. Chem. 80: 325-339.
Ashraf M, Sreejith P, Yadav U and Komath SS*. 2013 Catalysis by N-acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase (PIG-L) from Entamoeba histolytica: New roles for conserved residues. J. Biol. Chem. 288:7590-7595. doi: 10.1074/jbc.M112.427245. Epub 2013 Jan 22.
Rawal MK, Khan MF, Kapoor K, Goyal N, Sen S, Saxena AK, Lynn AM, Tyndall JDA, Monk BC, Cannon RC, Komath SS, and Prasad R. 2013. Insight into PDR ABC pump drug transport through mutagenesis of Cdr1p transmembrane domains. J. Biol. Chem. 288(34):24480-93. doi: 10.1074/jbc.M113.488353. Epub 2013 Jul 3.
Victoria GS, Yadav B, Hauhnar L, Jain P, Bhatnagar S and Komath SS*. 2012. Mutual Co-Regulation Between GPI-N-acetylglucosaminyl Transferase and Ergosterol Biosynthesis in Candida albicans. Biochem. J. 443(3):619-25.
Ahmad MF, Yadav B, Kumar P, Puri A, Mazumder M, Ali A, Samudrala G, Muthuswami R, and Komath SS*. 2012. The GPI anchor signal sequence dictates the folding and functionality of the ALS5 adhesin from Candida albicans. PLoS One 7(4):e35305.
Dutta P, Tanti GK, Sharma S, Goswami SK, Komath SS, Mayo MW, Hockensmith JW, Muthuswami R. 2012. Global Epigenetic Changes Induced by SWI2/SNF2 Inhibitors Characterize Neomycin-Resistant Mammalian Cells. PLoS One 7(11):e49822.
Nongkhlaw M., Gupta M., Komath S. S. and Muthuswami R. 2012. Motifs Q and I are required for ATP hydrolysis but not for ATP binding in SWI2/SNF2 proteins. Biochemistry 51(18):3711-22.
Ashraf M, Yadav B, Sreejith, Kumar KS, Vats D, Muthuswami R and Komath SS*. 2011. The N-Acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase from Entamoeba histolytica: Metal alters catalytic rates but not substrate affinity. J. Biol. Chem. 286: 2543-2549. doi:10.1074/jbc.c110.178343
Singh P, Verma P, Yadav B, Komath SS*. 2011. Synthesis and evaluation of indole-based new scaffolds for antimicrobial activities-Identification of promising candidates. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3367-72.
Victoria GS, Kumar P and Komath SS*. 2010. The Candida albicans homolog of PIG-P: Gene dosage and role in growth and filamentation. Microbiology. 156, 3041-3051.
Singh P, Kaur J, Yadav B and Komath SS*. 2010. Targeting efflux pumps—In vitro investigations with acridone derivatives and identification of a lead molecule for MDR modulation. Bioorg. Med. Chem. 18:4212–4223.
Pandey, G., Fatma, T., Cowsik, S. M. and Komath SS.* 2009. Specific interaction of jacalin with phycocyanin, a fluorescent phycobiliprotein. J. Photochem. Photobiol. B. Biol. 97(2):87-93.
Pandey, G., Fatma, T and Komath SS.* 2009. Specific interaction of the legume lectins, concanavalin A and peanut agglutinin, with phycocyanin. Photochem. Photobiol. 85(5):1126-33.
Singh P, Kaur J, Yadav B and Komath SS*. 2009. Design, synthesis and evaluation of acridone derivatives using Candida albicans- Search for MDR modulators led to identification of an anti-candidiasis agent. Bioorg. Med. Chem. 17(11):3973-9. Epub 2009 Apr 18.
Nongkhlaw M, Jha DK, Hockensmith, JW, Komath SS* and Muthuswami R.* 2009. Elucidating the mechanism of DNA-dependent ATP hydrolysis mediated by DNA-dependent ATPase A, a member of the SWI2/SNF2 protein family. Nucleic Acid Research 37(10):3332-41. Epub 2009 Mar 26.
Oswal N, Sahni NS, Bhattacharya A, Komath SS*, Muthuswami R.* 2008. Unique motifs identify PIG-A proteins from glycosyltransferases of the GT4 family. BMC Evol Biol. Jun 4;8:168.
Rai V, Gaur M, Kumar A, Shukla S, Komath SS *, Prasad R.* 2008. A novel catalytic mechanism for ATP hydrolysis employed by the N-terminal nucleotide-binding domain of Cdr1p, a multidrug ABC transporter of Candida albicans. Biochim Biophys Acta. (Biomembranes) 1778(10):2143-53.
Rai V, Gaur M, Shukla S, Shukla S, Ambudkar SV, Komath SS and Prasad R. 2006. Conserved Asp327 of Walker B motif in the N-terminal Nucleotide Binding Domain (NBD-1) of Cdr1p of Candida albicans has acquired a new role in ATP hydrolysis. Biochemistry. 45(49):14726-39.
Komath SS*, Kavitha M, Swamy MJ.* 2006. Beyond carbohydrate binding: New directions in plant lectin research. Org Biomol Chem. 4(6):973-88. Most downloaded paper of the month.
Prasad R, Gaur NA, Gaur M and Komath SS. 2005. Efflux Pumps in Drug Resistance of Candida. Infect Disord Drug Targets. 6(2):69-83.
Saini P, Prasad T., Gaur NA, Shukla S., Jha S, Komath SS., Khan LA, Haq QMR and Rajendra Prasad. 2005. Alanine scanning of transmembrane helix 11 of Cdr1p ABC antifungal efflux pump of Candida albicans: identification of amino acid residues critical for drug efflux. J Antimicrob Chemother. 56:77-86.
Rai V, Shukla S, Jha S, Komath SS* and Prasad R.* 2005 Functional characterization of N-terminal nucleotide binding domain (NBD-1) of a major ABC drug transporter Cdr1p of Candida albicans: Uncommon but conserved Trp326 of Walker B is important for ATP binding. Biochemistry. 44: 6650-6661.
Kenoth R, Komath SS and Swamy MJ. 2003. Physicochemical and saccharide-binding studies on the galactose-specific seed lectin from Trichosanthes cucumerina. Arch. Biochem. Biophys. 413(1):131-138.
Manoj N, Jeyaprakash AA, Pratap JV, Komath SS, Kenoth R, Swamy MJ, Vijayan M. 2001. Crystallization and preliminary X-ray studies of snake gourd lectin: homology with type II ribosome-inactivating proteins. Acta Crystallogr. D Biol. Crystallogr. 57:912-9144.
Komath SS, Kenoth R. Swamy MJ. 2001. Thermodynamic analysis of saccharide binding to snake gourd (Trichosanthes anguina) seed lectin. Fluorescence and absorption spectroscopic studies. Eur J Biochem. 268:111-119.
Komath SS, Bhanu K, Maiya BG and Swamy MJ. 2000. Binding of porphyrins to jacalin [jack fruit (Artocarpus integrifolia) agglutinin]. Absorption and fluorescence spectroscopic investigations. Biosci. Rep. 20:265-276.
Komath SS, Kenoth R, Giribabu L, Maiya BG and Swamy MJ. 2000. Fluorescence and absorption spectroscopic studies on the interaction of porphyrins with snake gourd (Trichosanthes anguina) seed lectin. J. Photochem. Photobiol. (B. Biology) 55:49-55.
Chaudhary A, Vasudha S, Rajagopal K, Komath SS, Garg N, Yadav M, Mande SC and Sahni G. 1999. Function of the central domain of streptokinase in substrate plasminogen docking and processing as revealed by site-directed mutagenesis. Protein Science, 8:2791-2805.
Padma P, Komath SS, Nadimpalli SK and Swamy MJ. 1999. Purification in high yield and characterization of a new galactose-specific lectin from the seeds of Trichosanthes cucumerina. Phytochemistry, 50: 363-371.
Komath SS and Swamy MJ. 1998. Fluorescence quenching, time resolved fluorescence and chemical modification studies on the tryptophan residues of snake gourd (Trichosanthes anguina) seed lectin. J. Photochem. Photobiol.(B. Biology) 50:108-118.
Padma P, Komath SS, Swamy MJ. 1998. Fluorescence quenching and time-resolved fluorescence studies on the Momordica charantia (bitter gourd) seed lectin. Biochem. Mol. Biol. Int. 45(5), 911-920.
Komath SS, Nadimpalli SK. and Swamy M J. 1998. Identification of histidine residues in the sugar binding site of snake gourd (Trichosanthes anguina) seed lectin. Biochem. Mol. Biol. Int. 44(1):107-16.
Komath SS and Swamy MJ. 1998. Further characterisation of the saccharide specificity of snake gourd (Trichosanthes anguina) seed lectin. Current Science, 75(6): 608-611.
Bhanu K, Komath SS and Swamy MJ. 1997. Interaction of porphyrins with concanavalin A and pea lectin. Current Science. 73(7):598-602.
Ramakrishnan M, Komath SS, Sheeba V and Swamy MJ. 1997. Differential scanning calorimetric studies on the thermotropic phase transitions of dry and hydrated forms of N-acylethanolamines of even chainlengths. Biochim. Biophys. Acta. 1329(2):302-10.
Komath SS, Nadimpalli SK and Swamy MJ. 1996. Purification in high yield and characterisation of the galactose-specific lectin from the seeds of snake gourd (Trichosanthes anguina). Biochem. Mol. Biol. Int. 39(2):243-252.
Vijayadamodar GV, Komath SS, Roy S and Bagchi B. 1994. Dielectric relaxation in dipolar solid rotator phases. Phase Transitions. 50:21-45.
Roy S, Komath SS and Bagchi B. 1993. Molecular theory of ultrafast solvation in liquid acetonitrile. J. Chem. Phys. 99(4):3139-3058.
Komath SS and Bagchi B. 1993. Solvation dynamics in a Brownian dipolar lattice. Comparison between computer simulation and various molecular theories of solvation dynamics. J. Chem. Phys. 98(11):8987-8993.
Roy S, Komath SS and Bagchi B. 1993. Dielectric friction and solvation dynamics: novel results on relaxation in dipolar liquids. Proc. Indian Acad. Sci. (Chem. Sci.). 105(1): 79-85.
Chattopadhyay A, Komath SS and Raman B. 1992. Aggregation of lasalocid A in membranes: a fluorescence study. Biochim. Biophys. Acta. 1104:147-150.
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