Scientist Profile

Krishnasastry Musti, Ph.D.

Email

mvks@nccs.res.in

Research Areas

Pathogenesis and Cellular Response, Macromolecular Structure and Function, Cell Organization and Function

 

Experience

Scientist  'G'

 

Research

My group focuses on the evolution of cooperation and establishment of disease by bacterial populations using basic biology, game theory, network cooperations, especially weak links and their ability to stablize and bring robustness in establishment of disease.

The organisms in focus are Mycobacterium tuberculosis, Helicobacter pylori and leptospiral species. The key questions are how cooperation evolves in these organisms and understanding the costs invovled in establishment of diseases. How they they generate public good and how it gets utilized?

  • Evolution of Cooperation - How 'cooperation' evolves, 'public good' is generated and mechanisms behind it?
  • Generation and Utility of IgA - The selection, generation and utility of IgA using Malaria infection as a model.
  • Membrane Damage and Repair - The mechanisms behind sensing membrane damage and repair mechansism orchestrated by bacterial pathogens

Illustration of Prisoners Dilema

How does 'defection' aka 'non-cooperation' arises?

"Cheaters always win" in evolution. In the absence of selection, 'cheating' aka 'defection' fluorishes. Why cheating wins is because there is always a 'cost' associated with every act of 'cooperation' and those who do not wish to incur the 'cost', in the absence of selection, 'defection' aka 'non-cooperatio' is favoured evolutionarily! Importantly, defection is very important in pathogenesis.. Surprising, isn't it!

Intelligent pathogens such as tuberculosis and helicobacter paly the game of evolution very well! In fact, exceedingly well. A population that cheats or 'defects' coexist with the population that 'cooperates'. Nature's naked truth is cooperators enjoy the company of cooperators while defectos (non-cooperators reap the benefit of sacrifices made by cooperators...Difficult to follow.. Those who dont pay taxes enjoy the same road as the person who paid all taxes. In the absence of selection (punishment in case of taxes) defection favours.. Right..Who cooperates in case of bacteria? How do they do it? Why does it cooperate? What is the ultimate goal? Who is the beneficiary?

We use game theory, evolutionary biology to design experiments and experimental vaccines.

These are the aspects we address in our laboratory. Challenging?....hmmm.....Those interested in challenging the dogma can join us on one condition... He/She must be a 'cooperator' becuase 'defection' (not putting enough effort) may not get the degree!       

Utility of IgA in preventing Cerebral Pathology and Lung Inflammation

Who decides the type of 'iso-type', Antigen or B-cells?

We all know upon immunization the system genertes either an IgG or IgA or IgE or something else. How this decision is made ie. the type of 'iso-type' to be elicited? We have found unique system to generate IgA isotype and its utility in experimental system using Malaria is being studied. How does the IgA memory evolves? Whether or not structural features important in this process? If yes, how? Is there utility to IgA? The figure on the left shows the utility of Malaria specific IgA in controlling lung inflammation and cerebral pathology in mice when Malaria specific IgA is induced. Can we apply this concept to other bacterial diseases? We think so. Possibilities are many.

Ready to take the challenge?.

Illustration of Membrane Damage, sensing and Recovery

How mammalian cells sense 'damage' and respond?

How plasma membrane repairs itself after damage by bacterial toxin attack? How proteins like bacterial toxins or other proteins interact with mammalian cell membrane caveolae or lipid rafts?  This goal revolves around understanding the dynamics of caveolae in mammalian cells.

Our laboratory is currently pursuing answers to these paradigms viz:

How does the membrane damage is sensed?
How damage control is initiated?
How can we define damage?
How this knowledge is applicable to other infectious systems?

The key aspect is to understand how the 'phosphorylation state' of a kinase is sensed and translated to 'mechanical movement of a vesicle'

For any work, Dar ke aage, jeet hi !

Selected Publications

Chakraborty S, Srivastava A, Jha MK, Nair A, Pandey SP, Srivastava N, Kumari S, Singh S, Krishnasastry MV, Saha B (2015) Inhibition of CD40-Induced N-Ras Activation Reduces Leishmania major Infection., J. Immunol., 194: 3852-3860.

Kumar A, Deore S, Lotke A, Bankar T, Parab P and Krishnasastry MV (2015) KIX domain specific Immunoglobulin A can protect from adverse Lung and Cerebral pathology induced by Plasmodium berghei ANKA, Biochem. Biophys. Res. Commun., 464: 943-948. PMID: 26188504 DOI: 10.1016/j.bbrc.2015.07.07

Kumar S, Mittal E, Deore S, Kumar A, Rahman A and Krishnasastry MV (2015) Mycobacterial tlyA gene product is localized to cell-wall without signal sequence., Front. Cell. Infect. Microbiol., 0: 0. DOI: 10.3389/fcimb.2015.00060

Bandyopadhyay S, Chandel HS, Singh S, Roy S, Krishnasastry MV, Saha B. (2015) Counteractive functions are encrypted in the residues of CD154, Hum. Immunol., S0198-8859(15)0: S0198-8859(15)0. PMID: 26429321 DOI: 10.1016/j.humimm.2015.09.

Mittal E, Kumar S, Rahman A, Krishnasastry MV (2014) Modulation of phagolysosome maturation by bacterial tlyA gene product., J. Biosci., 39: 821-834. PMID: 25431411

Rahman A and Krishnasastry MV (2014) Hemolytic activity of mycobacterial TlyA (Rv1694) is independent of its rRNA methylation activity., Curr. Sci., 106: 725-729..

Khan TH, Srivastava N, Srivastava A, Sareen A, Mathur RK, Chande AG, Musti KV, Roy S, Mukhopadhyaya R, Saha B (2014) SHP-1 plays a crucial role in CD40 signaling reciprocity., J. Immunol., 193: 3644-3653.

Reza MJ, Kamble A, Ahmad M, Krishnasastry MV and Sahu A. (2013) Dissection of functional sites in herpesvirus saimiri complement control protein homolog, J. Virol., 87: 282-295. PMID: 23077301

Naiyer MM,Saha S, Hemke V,Roy S,Singh S,Musti KV, Saha B (2013) Identification and characterization of a human IL-10 receptor antagonist, Hum. Immunol., 74: 28-31. PMID: 23000375

Naiyer MM, Saha S, Hemke V, Roy S, Singh S, Musti KV, Saha B (2013) Identification and characterization of a human IL-10 receptor antagonist., Hum. Immunol., 74: 28-31. PMID: 23000375

Wakankar MS, Krishnasastry MV, Jaokar TM, Patel KA, Gaikwad SM (2013) Solution and in silico studies on the recombinant lectin from Cicer arietinum seeds., Int. J. Biol. Macromol., 56: 149-55. DOI: 10.1016/j.ijbiomac.2013.0

Khan S,Alonso L,Roduit C,Bandyopadhyay S,Singh S,Saha S,Tacchini-Cottier F,Roy S,Dietler G,Kasas S,Das P,Krishnasastry MV,Saha B, (2012) Differential peptide binding to CD40 evokes counteractive responses, Hum. Immunol, 73: 465-469. PMID: 22406255

Srivastava SS and Krishnasastry MV. (2012) Cell membrane repair pathway involves sensing of dynamics of caveolae and caspase-1., Adv. Exp. Med. Biol., 749: 117-129. PMID: 22695842

Rahman A,Srivastava SS,Sneh A,Ahmed N,Krishnasastry MV (2010) Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium tuberculosis: a non-conventional hemolysin and a ribosomal RNA methyl transferase, BMC Biochem., 11: 35-. PMID: 20854656

Ahmed N, Pany S, Rahman A,Srivastava SS,Sneh A,Krishnasastry MV. (2010) Modulation of PP2A activity by Jacalin: is it through caveolae and ER chaperones?, Glycoconj. J., 27: 723-734. PMID: 19823931

Srivastava SS,Pany S,Sneh A,Ahmed N,Rahman A,Musti KV, (2009) Membrane bound monomer of Staphylococcal alpha-hemolysin induces caspase activation and apoptotic cell death despite initiation of membrane repair pathway, PLoS One, 4: e6293-. PMID: 19621082

Ahmed N,Dasari S,Srivastava SS,Sneh A,Ahmad A,Islam KM,Krishnasastry MV, (2008) Taxol and 10-deacetylbaccatinIII induce distinct changes in the dynamics of caveolae, FEBS Lett, 582: 3595-3600. PMID: 18817775

Pany S,Krishnasastry MV, (2007) Aromatic residues of Caveolin-1 binding motif of alpha-hemolysin are essential for membrane penetration, Biochem Biophys Res Commun, 363: 197-202. PMID: 17850762

Ansary, AA, Kumar, SA, Krishnasastry, MV, Abyaneh, MK, Kulkarni, SK, Ahmad, A, Khan, MI. (2007) CdS quantum dots: Enzyme mediated in vitro synthesis, characterization and conjugation with plant lectins., J. Biomed. Nanotech., 3: 406-413. DOI: 10.1166/jbn.2007.045

Sahasrabuddhe, A,A. Ahmed, N. Krishnasastry, M.V. (2006) Stress-induced phosphorylation of caveolin-1 and p38, and down-regulation of EGFr and ERK by the dietary lectin jacalin in two human carcinoma cell lines., Cell Stress Chaperon., 11: 135-147. PMID: 16817319

Sahasrabuddhe AA,Gaikwad SM,Krishnasastry MV,Khan MI, (2004) Studies on recombinant single chain Jacalin lectin reveal reduced affinity for saccharides despite normal folding like native Jacalin, Protein Sci, 13: 3264-3273. PMID: 15557267

Vijayvargia R,Kaur S,Krishnasastry MV, (2004) alpha-Hemolysin-induced dephosphorylation of EGF receptor of A431 cells is carried out by rPTPsigma, Biochem Biophys Res Commun, 325: 344-352. PMID: 15522239

Vijayvargia R,Suresh CG,Krishnasastry MV, (2004) Functional form of Caveolin-1 is necessary for the assembly of alpha-hemolysin, Biochem Biophys Res Commun, 324: 1130-1136. PMID: 15485672

Vijayvargia R,Kaur S,Sangha N,Sahasrabuddhe AA,Surolia I,Shouche Y,Krishnasastry MV, (2004) Assembly of alpha-hemolysin on A431 cells leads to clustering of Caveolin-1, Biochem Biophys Res Commun, 324: 1124-1129. PMID: 15485671

Pany S,Vijayvargia R,Krishnasastry MV, (2004) Caveolin-1 binding motif of alpha-hemolysin: its role in stability and pore formation, Biochem. Biophys. Res. Commun., 322: 29-36. PMID: 15313169

Kapoor. M., Reddy, C.C., Krishnasastry, M.V., Surolia, N., Surolia, A. (2004) Slow-tight binding inhibition of enoyl-acyl carrier protein reductase from Plasmodium falciparum by triclosan., Biochem. J., 381: 719-724. PMID: 15086316

Vandana S,Navneet S,Surinder K,Krishnasastry MV, (2003) Modulation of EGF receptor autophosphorylation by alpha-hemolysin of Staphylococcus aureus via protein tyrosine phosphatase, FEBS Lett, 535: 71-76. PMID: 12560081

Matsui, E., Krishnasastry, M.V., Abe, J., Matsui, I. K. and Harata, K. (2002) Molecular structure and novel DNA binding sites located in loops of flap endonuclease-1., J.Biol.Chem, 277: 37840-37847. PMID: 12147694

Bachhawat, K., Thomas, C. J., Amutha, B., Krishnasastry, M. V., Khan, M. I., Surolia, A. (2001) On the stringent requirement of mannosyl substitution in mannooligo-saccharides for the recognition by garlic (Allium sativum) lectin: A surface plasmon resonance study., J.Biol.Chem, 276: 5541-5546. PMID: 11076955

Zheng R, Matsui E, Shen Y, Musti KV, Feng Y, Darnis S, KawarabayasiY, Kikuchi H, Harata K, Matsui I. (2001) The novel function of a shortregion K253xRxxxD259 conserved in the exonuclease domain of hyperthermostable DNA polymerase I from Pyrococcus horikoshii., Extremophiles, 5: 111-117. PMID: 11354454

Shen, Y., Krishinasastry, M. V., Hiramoto, M., Kikuchi, H., Kawarabayashi, Y., and Matsui, I. (2001) Invariant Asp1122 and Asp1124 are essential residues for polymerization catalysis of family D DNA polymerase from Pyrococcus horikoshii, J.Biol.Chem, 276: 27376-27383. PMID: 11319225

Sangha, N., Surinder, K., Vandana, S. and Krishnasastry, M.V. (1999) Importance of carboxy terminus in the folding and function of a-hemolysin of Staphylococcus aureus., J.Biol.Chem, 274: 9193-9199. PMID: 10092591

Vandana, S., Manoj, R. and Krishnasastry, M.V. (1997) The Role of the amino terminus in the kinetics and assembly of a-hemolysin of Staphylococcus aureus., J.Biol.Chem, 272: 24858-24863. PMID: 9312085

Krishnasastry, M., Walker, B., Braha, O., and Bayley, H. (1995) Surface labeling of key residues during the assembly of the transmembrane pore formed by staphylococcal a-hemolysin., FEBS Lett, 356: 66-71. PMID: 7988723

Walker, B.J., Kasianowicz, J. Krishnasastry, M., and Bayley, H. (1994) A pore-forming protein with a metal-actuated switch., Protein Engg., 7: 655-662. PMID: 8073035

Walker, B.J., Krishnasastry, M.V., and Bayley, H. (1993) Functional complementation of staphylococcal a-hemolysin fragments. Overlaps, nicks, and gaps in the glycine-rich loop., J.Biol.Chem, 268: 5285-5292. PMID: 8444902

Walker, B.J., Krishnasastry, M.V., Zorn, L., Kasianowicz, J., and Bayley, H. (1992) Functional expression of the a-hemolysin of Staphylococcus aureus in intact Escherichia coli and in cell lysates. Deletion of five C-terminal amino acids selectively impairs hemolytic activity., J. Biol. Chem., 267: 10902-10909. PMID: 1587866

Krishnasastry, M.V., Robertson, D.E., Mohyniham, J.A. and Roberts, M. F. (1992) Enzymatic degradation of cyclic 2,3-diphosphoglycerate to 2,3-diphosphoglycerate in Methanobacterium thermoautotrophicum., Biochemistry, 31: 2926-2935. PMID: 1550819

Walker, B.J. and Krishnasastry, M.V. Zorn, L., and Bayley, H. (1992) Assembly of the oligomeric membrane pore formed by staphylococcal a-hemolysin examined by truncation mutagenesis., J. Biol. Chem., 267: 21782-21786. PMID: 1400487

Mahanta SK,Sastry MV,Surolia A, (1990) Topography of the combining region of a Thomsen-Friedenreich-antigen-specific lectin jacalin (Artocarpus integrifolia agglutinin). A thermodynamic and circular-dichroism spectroscopic study, Biochem J, 265: 831-840. PMID: 2306217

Krishnasastry, M. V., Swamy, M.J. and Surolia, A. (1989) Analysis of dynamics and mechanism of ligand binding to Artocarpus integrifolia agglutinin. A 13C and 19F NMR study., J.Biol.Chem, 263: 14826-14833. PMID: 3170566

Khan. MI, Swamy, MJ, Krishnasastry, MV, Sajjan, SU, Patanjali, SR, Swarnalata, GV, Banerjee, P and Surolia, A (1988) Saccharide binding to three Gal/GalNAc specific lectins: Fluorescence, spectroscopic and stopped-flow kinetic studies, Glycoconj J, 5: 75-84. DOI: 10.1007/BF01048333

Krishnasastry, M. V., Banerjee, P., Patanjali, S. R., Swamy, M.J., Swarnalata, G.V. and Surolia, A. (1986) Analysis of saccharide binding to Artocarpus integrifolia lectin reveals specific recognition of T-antigen (beta D-Gal(1->3)D-GalNAc)., J.Biol.Chem, 261: 11726-11733. PMID: 3745164

Krishnasastry, M. V. and Surolia, A. (1986) Intrinsic fluorescence studies on saccharide binding to Artocarpus integrifolia lectin., Biosci. Reports, 6: 853-860. PMID: 3828488

Khan, M. I., Krishnasastry, M.V. and Surolia, A. (1986) Thermodynamic and kinetic analysis of carbohydrate binding to the basic lectin from winged bean (Psophocarpus tetragonolobus)., J.Biol.Chem, 261: 3013-3019. PMID: 3753974

Swamy, M.J., Krishnasastry, M.V., Khan, M.I. and Surolia, A. (1986) Thermodynamic and kinetic studies on saccharide binding to soya-bean agglutinin., Biochem. J., 234: 515-522. PMID: 3755041

Swamy, M.J., Krishnasastry, M.V. and Surolia, A. (1985) Prediction and comparison of the secondary structure of legume lectins, J. Biosci., 9: 203-212. DOI: 10.1007/BF02702696

Krishnasastry, M.V., Narasimhulu, P.L. and Sen, K.D. (1984) Empirical static quadrupole polarizability for some closed shell free atoms and ions, J. Chem. Phys., 80: 584-585. DOI: 10.1063/1.446402

 

 

Technical

Anil Lotke, Technican 

 

Research

Anil Kumar, Senior Research Fellow, worked on the utility of IgA in Malaria infection model.

Santosh Kumar, Senior Research Fellow, discovered the cooperator noise in mycobacterial species.

Ekansh Mittal, Senior Research Fellow, Provided the evidences of survival mechanism of mycobacterial noise.

Shika Nag, Senior Research Fellow, worked on the mechanism of damage by mycobacterial noise.

Sapna Deore, Senior Research Fellow, worked on the Malaria specific IgA and its ability to inhibit merozoite invasion.

Raj Kumar Gaur, Junior Research Fellow, working on the evolution of bet-hedging strategies of mycobacteria.

 

Our work Philosophy

If you find something very difficult to do,
give it to a lazy person...

...he will find an easy way do it

Only one person per lab allowed
(I am already here)


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