1. | Title | Unusual DNA Structures |
Sponsored by | All India Council of Technical Education, GOI, New Delhi | |
Period | 1995 - cont. | |
Principal Investigator | Dr. Ritu Barthwal | |
Brief Description | The flexibility in DNA in unusual bent DNA structures due to binding with ligands has been investigated. The binding of anticancerous drugs daunomycin and adriamycin to d-CGATCG and dTGATCA, primarily by 1D and 2D NMR techniques is studied to get the details of helix geometry, overlap of base pairs, deoxyribose sugar conformation, glycosidic bond rotation, intermolecular interactions from torsional angle constraints and interproton distance analysis. The COSY and NOESY spectral simulations are done. Molecular modeling and energy minimised conformation of drug-DNA complex is determined to understand the molecular basis of drug action with an aim to do computer aided drug designing. |
2. | Title | Nucleic acid Interactions with specific oligopeptides and drugs |
Sponsored by | Department of Science and Technology (DST), GOI, New Delhi | |
Period | Oct.88 - Oct.92 | |
Principal Investigator | Dr. Ritu Barthwal | |
Brief Description | We have investigated the interaction of hexapeptide Lys-Pro-TyrSer-Leu-Asn comprising of residues 24-29 of the protein encoded by gene 5 of bacteriophage fd with single stranded deoxypentadenylate d(A)5 and duplex d-(GACTCGTC)2 containing a bulge loop in the centre by 2D NMR techniques. Chemical shift changes in the hexapeptide-DNA complexes at varying peptide to Nucleic Acid (P/N) ratios and temperature indicate involvement of Tyr, Leu, Asn residues in the complex. Tyr is in proximity of bases and gets partially stacked. Lys protons participate electrostatic interactions. 2D COSY and NOESY spectra show that change only marginally to accommodate the binding to hexapeptide. Specific intermolecular NOEs show proximity of Leu and Asn protons. Results indicate a geometry of complex that is close to the x-ray structure. The structure of daunomycin and its complex with d-CpG is investigated by 2D-NMR. The J couplings and NOEs involving 5H, 8axH, 8eqH, 5'CH3, 4'H, 1'H, 2'eqH protons change. Distances 7H- 8axH, 7H-8eqH,5'H-8axH, 5'H-8eqH, 1'H-2'axH change significantly. Major S-conformer of sugar has P- 153 degree and 135 degree for C and G residues respectively. The glycosidic bon rotation values are centered around -120 degree and -90 degree for C and G residues, respectively in complex. The existence of specific geometry compared with x- ray crystal structure, available in literature, reflects on anti cancerous action. The theoretical energy calculations on stacking interactions of actinomycin and daunomycin between different base pair systems have been done. The minimum energy of -34.67 Kcal/mole is seen for the triplet d-(GpCpT)2 base pair-daunomycin system. Unwinding angle of DNA to accommodate daunomycin and actinomycin vary in the range -6 to -16 degree. Overlap geometries of drug chromophore within base pairs have been obtained. These are compared with experimental results available. |
3. | Title | Biomolecular Interactions: A NMR, theoretical and other spectroscopic investigation of interaction of nucleic acids with oligopeptides and drugs. |
Sponsored by | Department of Science and Technology (DST), GOI, New Delhi | |
Period | April 84 - March 88 | |
Principal Investigator | Dr. Ritu Barthwal | |
Brief Description | We have investigated the interactions of Trp,
Tyr, Phe containing tri- and tetrapeptide (Lys-Tyr-Lys, Lys-Trp-Gly-Lys
OtBu, Lys-PheLys, etc.) with oligo- and poly- nucleotides d-CpG, Poly A,
Poly U, Poly C, d-CGCG, d-GpC, d-GCGC as model compounds for protein nucleic
acid interactions by 1D and 2D NMR techniques. The Keq and no. of molecules
binding per phosphate of DNA were obtained from scatchard plot using absorbance/fluorescence
spectroscopic methods. Using standard classical potentials, we had investigated
the energetics of interactions by energy calculations in terms of electrostatic,
polarization, dispersion and repulsion energy. Results indicates a preference
for binding of bases with aromatic amino acid in the order His > Trp
> Tyr > Phe. For nucleic acid base pairs, the stacking energy is
maximum for guanine and GC base pair, respectively. On intercalation within
different sequences of base pairs, the stability of complexes with Tyr
and Phe decreases in the order :
CG AT AT CG CG AT TA GC The overlap geometries for the minimum energy conformations were obtained which are in accord with experimental results. The unwinding angle on intercalation varies in the range 0 to -40 degree and energy of interaction is in the range -16 to -29 Kcal/mole. The NMR results indicate that binding of Tyr containing peptide is preferential and decreases in the order d-GCGC > d-CGCG > d-CCGG > d-GpC > d-CpG. Apparently the 5'd- GpC3' site is preferred for amino acid. The interaction for various amino acid residues decreases in the order Trp > Tyr > His as predicted theoretically. The deoxynucleotide conformation remains practically unchanged on interactions; it being 01' endo sugar pucker, anti or high anti glycosidic bond rotation and a right handed B-DNA geometry. Observed intermolecular NOEs exhibit proximity of peptide protons to nucleic acid suggesting the existence of specific geometry of peptide-nucleic acid complex in each case. |
4. | Title | Molecular changes in structural and enzymatic proteins of cell wall subjected to saline stress. |
Sponsored by | UPCST, Lucknow | |
Period | 1996 - Contd | |
Principal Investigator | Dr. G.S.Randhawa & Dr. R. Prasad | |
Brief Description | Salinity is one of the major problems which affects crop production. Mechanism(s) that impart tolerance to plants are still unresolved. In this project investigations are being carried out to identify and characterise the proteins induced in response to salinity. Cell Wall and soluble fractions of the seedlings of peanut grown under experimental conditions were prepared and their protein profiles determined by SDS PAGE. Attempts are being made to characterise the saline induced or supressed proteins in the cell wall fraction by various methods. |
5. | Title | Molecular cloning, genomic localization and characterization of nitrogen fixation (fix) genes of Rhizobium meliloti |
Sponsored by | Department of Science & Technology (DST), GOI, New Delhi | |
Period | June 90 - Dec. 93 | |
Principal Investigator | Dr. G.S.Randhawa | |
Brief Description | The aim of the project was to understand the molecular genetics of Rhizobium - legume symbiosis. Several mutants of R.meliloti defective in nitrogen fixation were isolated. These mutants were used to take out Rhizobium DNA fragments carrying nitrogen-fixing genes. This knowledge will be helpful in the Rhizobium strain improvement programmes. |
6. | Title | Steroid 16 alpha hydroxylase - Immunochemical characterization and development of a molecular probe. |
Sponsored by | University Grant Commission, New Delhi | |
Period | Nov.93 - Nov. 96 | |
Principal Investigator | Dr. R.P.Singh & Dr. Ben M.J.Pereira | |
Brief Description | The 16-alpha-hydroxylase enzyme in microbes is of potential significance for the production of steroids of medicinal significance particularly the anti inflammatory and antirheumatic agents. In the present ongoing project, we have aimed to identify the microbial strains with significant ability of 16 alphahydroxylation. The enzyme responsible for this reaction will be isolated and characterised. A detailed analysis is currently underway to identify the microbial strain with the 16-alpha hydroxylase activity. The microbial strain with significantly higher activity for this enzyme will be used for isolation of this enzyme and subsequently the regulatory elements affecting the enzyme activity will be identified to maximise the enzyme activity. |
7. | Title | Microbial biosynthesis of therapeutic steroids especially for combating stress in armed forces personnel. |
Sponsored by | Defence Research Development Organisation (DRDO), New Delhi | |
Period | Dec.92 - Dec. 94 | |
Principal Investigator | Dr. R.P.Singh & Dr. Ben. M.J.Pereira | |
Brief Description | With the identification and deveolpment of a variety of microorganisms, it has become possible to use these strains for the production of industrially significant chemicals, drugs, immunomodulators, animal feed vaccine, etc. Many of these microbial technology based processes have been already commercialised. This project was aimed towards identifying the suitable and efficient microbes for the production of steroids particularly the antistress factors. Out of a battery of microorganisms isolated from industrial waste, few had been found to be potent in the biotransformation of cholesterol to a number of metabolites. These metabolites are being currently assessed to define their chemical structure and therapeutic value. |
8. | Title | Biochemical investigation on the maturation of sperm in the epididymis |
Sponsored by | University Grant Commission | |
Period | Aug.87 - Aug. 91 | |
Principal Investigator | Dr. Ben. M.J.Pereira | |
Brief Description | This project attempts to find the molecular mechanisms underlying the maturation of sperm within the males using goat as the animal model. Post translational modifications in the sperm surface proteins have been detected during their transit through the epididymal duct which are suggested to be the basis for the control of fertility in males. |
9. | Title | Isolation of Tonoplast ATPase messenger RNA of mung bean |
Sponsored by | University Grant Commissions, New Delhi | |
Period | Nov.91 - Nov.93 | |
Principal Investigator | Dr. Vinay Sharma | |
Brief Description |
10. | Title | Biochemical studies on tonoplast; components and regulation of solute transport in higher plants Vacuoles. |
Sponsored by | Department of Science & Technology (DST), GOI, New Delhi | |
Period | April 87 - March 90 | |
Principal Investigator | Dr. Vinay Sharma | |
Brief Description | The plant vacuoles accumulate a variety of metabolities, many of which are of great commercial value. The regulating factor for the accumulation of these components should logically reside at the vacuolar membrane i.e., the tonoplast. We propose to characterize the tonoplast components and the associated enzymes in vacuoles of legunious plants. Such investigations are not only the key to better understanding of intracellular communication but may also prove to be beneficial to increase the crop productivity. |
11. | Title | Cell Surface and membrane glycoproteins : Biosynthesis, regulation and function. |
Sponsored by | Department of Science & Technology (DST), GOI, New Delhi | |
Period | April 92 - May 95 | |
Principal Investigator | Dr. C.B.Sharma | |
Brief Description | The project is directed to understand the role of cell surface glycoproteins in cell-cell interaction like host-pathogen interaction. This study is important from the biotechnological point of view since yeast cells in which this study is being done, unlike mammalian cells also carry out O-glycosylation. |
12. | Title | Cell Surface and membrane glycoproteins of higher plants; Their biosynthesis, reglation and processing. |
Sponsored by | Department of Science & Technology (DST), GOI, New Delhi | |
Period | April 84 - Oct. 88 | |
Principal Investigator | Dr. C.B.Sharma | |
Brief Description |
13. | Title | Isolation, purification and characterization of Enzymes of Dolichol Pathway in Plant seeds |
Sponsored by | Volkswagen Foundation, Germany | |
Period | June 82 - June 85 | |
Principal Investigator | Dr. C.B.Sharma | |
14. | Title | Centre for Bioconversion |
Sponsored by | Ministry of Human Research & Development, GOI, New Delhi | |
Period | Dr. C.B.Sharma & Dr. G.S.Randhawa | |
Principal Investigator | Reciprocal effects of few pesticides in aquatic system. | |
15. | Title | Reciprocal effects of few pesticides in aquatic system. |
Sponsored by | University Grant Commission, New Delhi | |
Period | March 87 - June 90 | |
Principal Investigator | Dr. V.P.Agarwal | |
16. | Title | Centre of Environmental Engineering |
Sponsored by | Ministry of Human Research & Development, GOI, New Delhi | |
Period | 1984 - 1995 | |
Principal Investigator | Dr. R.P.Mathur | |
Brief Description | The project involved creating infrastructure in the area of Environmental Engineering. The research component pertained to Environmental Management. |