Dr. B. M. Swamy

About Us

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All about Glycobiology

Glycobiology is an emerging field of science devoted to research on Glycans and understanding the biological functions of carbohydrates. Cell surface glycosylation on the membrane proteins and membrane lipids is a crucial event for the development and function of multicellular organisms such as adhesion and recognition.

Aberrant Glycosylation is reported during malignancy and the molecules which recognize such changes like Lectins or antibodies are useful tools in understanding cancer, which is a frontier area of research and is intensively investigated in many laboratories.

Research Interest

The major research interest of the Glycobiology group is focused on understanding the structure-function relationship of Lectins or carbohydrate binding proteins of fungal and plant origin and to explore their clinical and Agricultural applications.

   

Lectins with unique carbohydrate binding specificities are becoming important molecular tools for understanding the structure of cell surface Glycans, particularly altered glycosylations during patho-physiological conditions.

Emphasis

The main emphasis is especially on Lectins with unique sugar specificity which recognize tumor associated antigens such as TF, Tn, CA 125 and sialyl Lewis antigens as they can be used as diagnostic tools, therapeutic agents or as targeted drug delivery system.


Present status of Research in Glycobiology

  • Five lectins from pathogenic fungi; Sclerotium Rolfsii Lectin (SRL), Rhizoctonia Bataticola Lectin (RBL), Cephalosporium Lectin (CSL), Aspergillus Niger Lectin (ANL) and Purpureocillium Lilacinum Lectin are purified to homogeneity and characterized for their physicochemical properties.
  • Five plant lectins from Remusatia Vivipara, Dioscorea Bulbifera , Adenia Hondala, Butea Monosperma and Lantana Camara Lectin are purified to homogeneity and characterized for their physicochemical properties.
  • A sialic acid specific bacterial Lectin from Corynebacterium Amycolatum (CAL) has been purified and characterized.
  • 3-D structure of SRL was determined by X-ray crystallography at near atomic resolution of 1.1 Å. Complete amino acid sequence (141 residues) of SRL was determined by MALDI-TOF MS/MS independently apart from X–ray analysis.
  • SRL interacting membrane proteins containing O-GalNAc sites in HT29 cells were identified by Mass spectrometries which are implicated in cell survival, apoptosis and tumoroigenesis.
  • X ray crystal structure of RVL, a lectin from edible tuber Remusatia Vivipara is determined
  • A mannose binding Lectin from Dioscorea Bulbifera Bulbils has been purified, characterised and its biological significance reported.
  • Glycan array analysis confirms unique carbohydrate binding properties of SRL, RBL and CSL.
  • CSL has exquisite specificity towards α1-6 linkage of core Fucosylated Complex N linked cancer associated Glycans and has diagnostic potential.
  • SRL, RBL and CSL with their unique carbohydrate binding properties for TF, N-glycans of CA 125 and core fucosylated glycans respectively have potential applications in cancer detection and diagnosis.
  • SRL binds specifically to human colon cancer HT29 cells and brings about apoptosis involving both extrinsic and intrinsic pathways. Lectin suppresses tumour growth completely when tested in vivo.
  • SRL induces apoptosis involving both extrinsic and intrinsic pathways in ovarian cancer PA 1 cells and breast cancer MCF7 cells, where as shows marginal effect on normal mammary epithelial cells HMECs.
  • SRL is mitogenic to normal PBMCs where as it induces apoptosis in Leukemic Molt-4 cells.
  • The pharmacokinetics and bio-distribution of SRL in the mouse model using HT29 tumor xenograft-bearing nude mice demonstrated efficacy and non toxic nature of SRL.
  • Molecular mechanism of anticancer activity of SRL in HT29 cells has been demonstrated showing activation of multiple signaling pathways by SRL leading to apoptosis.
  • In vivo preclinical studies, demonstrates potential of SRL as anticancer agent when injected intra peritoneal both in mice bearing human colon HT29 and breast cancer MCF 7 xenografts.
  • DNA sequence of SRL with few changes successfully expressed in E coli, resulted in three recombinant lectins with remarkably different sugar binding properties compared to native with promising clinical applications.
  • RBL is a potent mitogen towards human PBMCs and is cytotoxic to human ovarian cancer PA-1 cells and induces apoptosis activating intrinsic pathway.
  • RBL has contrasting effects in human leukemia cells and normal CD3 and CD34 positive cells.
  • Both SRL and RBL have anti metastaic and anti angiogenic effects apart from apoptotic effect hence enhances their clinical potential as a drugs.
  • RVL, high mannose N-glycan binding lectin limits cell growth, motility and invasiveness of human breast cancer MDA-MB-468 and MCF-7 cells
  • CSL shows mitogenic effect on human PBMCs.
  • CSL induces strong cytotoxicity in gastrointestinal PANC-1 cells HepG2 and HT-29 cells by induction of apoptotic effect. CSL has both diagnostic and therapeutic potential that can be exploited for potential application in therapeutics and diagnosis.
  • CSL is being studied for its role in infection process causing mycotic keratitis in humans.
  • Initiated exploring application of RVL and DBL in HIV research as they have anti-HIV activity
  • DNA sequence of SRL was assembled chemically with few changes and successfully expressed in E coli, resulted in three recombinant lectins with remarkably different sugar binding properties compared to native with promising clinical applications.
  • Crystal structure of SRL recombinants determined and recombinants of SRL or variants SSR1 and SSR2 are characterized with respect to their fine sugar specificity.
  • Process of developing SRL recombinants as anticancer agents is in progress under DBT-BIRAC programme.
  • RBL has differential binding to human normal colon and cancer tissues.
  • RBL inhibits human colon cancer HT 29, SW480 and SW620 cell growth and induces apoptosis in SW620cells RBL has anti anti-metastasis and anti angiogenic effect.
  • Plant lectins are also studied for their other agricultural applications.
    The work is also focused to explore Lectins for insecticidal effects using both cutting and chewing as well sucking pests for developing pest resistant transgenic plants. Some of the salient features of the past and present work.
  • Sclerotium Rolfsii Lectin exerts insecticidal activity on Spodoptera Litura Larvae by binding to membrane proteins of midgut epithelial cells and triggering caspase-3-dependent apoptosis.
  • Sclerotium Rolfsii Lectin expressed in transgenic tobacco show protection against Spodoptera Litura and Myzus Persicae.
  • RVL, the Lectin from edible tuber Remusatia Vivipara shows potent nematicidal activity and the X ray crystal structure of RVL is being determined.
DNA sequence of SRL with few changes successfully expressed in E coli, resulted in three recombinant Lectins with remarkably different sugar binding properties compared to native with promising clinical applications. The technology is patented and Patent granted.
  • Both SRL and RBL are developmentally regulated Lectins play crucial role in the development and morphogenesis of the fungi by interaction with respective putative endogenous receptors.
  • CSL, a Lectin from human pathogen Cephalosporium isolated from corneal smears of a keratitis patient has been assigned its role in infection process causing mycotic keratitis. Physiological Role of CSL and AOL in causing mycotic keratitis are demonstrated. The mechanism of pathogenesis involves TLR2/4 followed by upregulation of proinflammatory cytokines IL6, IL8.

Crystal Structure of Sclerotium Rolfsii Lectin ( SRL) at 1.1 Å

SRL crystal structure image

Sclerotium Rolfsii Lectin Monomer: 17kDa

SRL crystal structure image

Sclerotium Rolfsii Lectin Dimer: 34kDa

RVL crystal

SRL crystal structure image

Crystal structure of RVL determined at 2.4Å Resolution

Localization of FITC-SRL in PA-1 cells

SRL crystal structure image

Localization of FITC-SRL in PA-1 cells

ROS induction by RBL in HT 29, SW480 and SW620 cells

SRL crystal structure image

Localization of FITC-SRL in PA-1 cells

Venn diagram of c-JUN : c-JUN is the common entity among all the time points.

SRL crystal structure image

Molecular mechanism of antitumor activity of Sclerotium Rolfsii Lectin by proteomic and genomic analysis

Antiangiogenic effect of SRL and RBL by CAM assay.

TBS/Disc

SRL crystal structure image

TBS/Disc

SRL 50μg/Disc

SRL crystal structure image

SRL 50μg/Disc

SRL 100μg/Disc

SRL crystal structure image

SRL 100μg/Disc

Control

SRL crystal structure image

Control

5μg RBL/Disc

SRL crystal structure image

5μg RBL/Disc

10μg RBL/Disc

SRL crystal structure image

10μg RBL/Disc

In-vivo Antitumor activity of S. rolfsii lectin (SRL)

HT29 xenograft models

SRL crystal structure image

Intra peritonial administration (Nude mice)

In vivo Efficacy studies of SRL on MCF-7 xenografts

SRL crystal structure image

SRL on MCF-7 xenografts

RVL exerts potent nematicidal and insecticidal activity

Spodoptera litura

SRL crystal structure image

Spodoptera Litura

RVL

SRL crystal structure image

RVL

RVL- Mucin Complex

SRL crystal structure image

RVL- Mucin Complex

CNT

SRL crystal structure image

CNT

RVL treated

SRL crystal structure image

RVL treated

CNT and RVL treated

SRL crystal structure image

CNT and RVL treated

CNT and RVL treated

SRL crystal structure image

CNT and RVL treated

CNT and RVL treated

SRL crystal structure image

CNT and RVL treated


Laboratory members

Ph.Ds Awarded Research Scholars (1995-2020)

  • 1. Dr. Ramachandra S. Naik
  • 2. Dr. H. M. Vamadevaiah
  • 3. Dr. Ganapathi V. Hegde
  • 4. Dr. Anuradha G. Bhat
  • 5. Dr. P. M. Sundaram
  • 6. Dr. C. Shubhada
  • 7. Dr. Avinash Kudva
  • 8. Dr. G. J. Sathisha
  • 9. Dr. Vishwanath B. Chachadi
  • 10. Dr. Nagaraja N. Nagre
  • 11. Dr. Ganapathi G. Bhat
  • 12. Dr. Sachin M. Eligar
  • 13. Dr. Mohammad Azharuddin Savanur
  • 14. Dr. Vishwanathreddy Hothpet
  • 15. Dr. Srikanth Barkeer
  • 16. Dr. Gulam Nabi Vanti
  • 17. Dr. Suhas Ballal
  • 18. Dr. Sindhura B. R
  • 19. Dr. Anupama S
  • 20. Dr. Prajna M. Hegde
  • 21. Dr. Mamta Sharma

Currently Working Research Scholars

  • 1. Mr. Shivakumar Belur (Thesis submitted)
  • 2. Mr. Narasimhappagari Jagadeesh (CSIR,SRF)
  • 3. Ms. Kavitha Y. Hiremath (Completed presubmission colloquim)
  • 4. Ms. Supreeth S. Kulkarni