Director
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Prof. Dr. Asit Baran Mandal Director |
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CSIR NETWORK PROGRAM – 11TH FIVE YEAR PLAN Inputs provided by: Prof. Asit Baran Mandal, Director, CLRI |
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Title and significance of the project |
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Development of various nanomaterials and their interaction with biomolecules: Application in medicine and biology |
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Nanooxides, nano composites, etc have important potential applications in several
areas of industry, medicine, biology, pharmaceuticals, etc. With decreasing size,
the oxides of metal ions are conferred with unique properties, which are relevant
to medicine, for example, superparamagnetism. Hydrophilic nanoparticle carriers
have important potential applications for the administration of therapeutic molecules.
Most of the recently developed hydrophobic-hydrophilic carriers require the use
of organic solvents for their preparation and have a limited protein-loading capacity.
The assembly of nanoparticles or the use of nanocomposites for drug delivery or
in treatment of cancerous cells is gaining importance.
Molecular self assembly-the spontaneous formation of molecules into covalently bonded well defined stable structures is very important concept in biological systems like adhesion and in the functions of elastomeric proteins. Potential applications include hinged co-ordination networks and switchable molecular units. Such materials responsive to biologically relevant stimuli form the basis of many research problems in materials science and biomolecular chemistry. In this regard, large biopolymers such as crosslinked elastin-based networks with inverse temperature volume transitions due to the ordering of hydrophobic ordered regions within the cross-linked network on heating seem to be excellent candidates. A preliminary analysis of such transitions shows that these Elastic molecules must store energy (go to a higher energy state) when the elongating force is applied, and the energy must be released on return to the equilibrium resting structure. However, the concept of resiliency and elasticity associated with these materials is poorly understood and any design of new biomaterials based on these properties require a thorough understanding of the structure –function relationship of such biomacromolecules and in designing new biomaterials. Research at CLRI has led to the understanding of Programmed cell death, or apoptosis, which is essential for the elimination of unwanted cells in the body. Failures can lead to the build up of these cells, viz. the uncontrolled replication of tumor cells. Some cancer therapies induce apoptosis. Therefore, monitoring apoptosis would be useful to test the efficacy of apoptotic drugs. The changes occur in the phospholipid composition of the cell membrane during apoptosis. Phosphatidylserine translocates from the inner surface of the lipid bilayer that comprises the cell membrane, to the outer surface, i.e., endo to exo migration. It has been seen that the phosphate moiety is susceptible to chelation by Zn compounds. The attachment of metal oxide nano particles to apoptotic cells would enable to detect and quantify apoptosis in vivo by magnetic resonance imaging and cyclotron. The attachment of metal oxides nano particles to Zn chelators to the surfaces, in a cell-free non-biological assay, the phosphate binding ligand, could be pulled out of an aqueous phase and moved into an organic phase by phosphatidylserine. Gold nano particles may also be used for this purpose and its colour change due to phosphorylation and aggregation may also be accomplished. Nano technological approach in testing potential inhibitors of kinase activity and the utility of cyclotron may also be explored in skin biology. Furthermore, collagen nano-tubes and its interaction with various enzymes will be studied in detail by using various experimental and theoretical techniques. 1.Name of the Lab & Scientist(s) assigned to the Project (You can include scientists from other laboratories if the Project is networked with other institutes) Central Leather Research Institute Dr Asit Baran Mandal, Sc H, Director CLRI: Coordinator from CLRI; Dr Mary Babu, Sc F, Dr PK Sehgal, Sc F, Dr BSR Reddy, Sc F, Dr Balachandran Unni Nair, Sc F; Dr A Rajaram, Sc F, Dr Aruna Dhathathreyan, Sc EII; Dr Rama Rajaram, Sc EII, Dr J Raghava Rao, Sc EII; Dr M Kanthimathi, Sc EII; Dr T Narasimhaswamy, Sc EI; Dr V Subramanian, Sc EI, Dr S Jaisankar, Sc EI, Dr M Sugunalakshmi, Sc EI, Dr KJ Sreeram, Sc C; Dr A Gnanamani, Sc B, Mrs N Nishad Fathima, Sc B. 2.Scientific & Technical Description of the Project: a.Objectives: i.To synthesize nano metal oxides exploiting biomolecules as templates ii.Preparation of nanocomposite polymers for delivery of drugs iii.Delivery of mononuclear stem cells from umbilical cord using nanocomposites iv.Understanding self-organizational ability of elastin based polypeptides towards general design of self-assembling biomaterials v.Application of cyclotron and magnetic resonance for nanobiotechnology Work Plan: (i) Selection of protein (DNA, Collagen, enzymes etc) and polysaccharide based templates (Chitosan, alginate, etc); (ii) optimization of preparation strategies like pH, temperature, etc based on nature of template – metal ion interaction and stability of resulting complexes; (iii) optimization of process conditions for converting the complexes into metal oxide through careful removal of templates; (iv) characterization of metal oxides through XRD, TEM/SEM, XPS, etc; (v) application studies including magnetization, coloring, etc; (vi) synthesis of poly(ethylene oxide)-Poly(L-Lactic acid)/Poly (b-benzyl-L-aspartate), PEG coated nanospheres; Poly(lactide-co-glycolide)-[(propylene oxide)-poly(ethylene oxide)]; (vii) Development of nanocomposite polymers for use in medical devices, delivery of stem cells etc. (viii) modeling of interfacial layer properties in amino acids, peptides and proteins; (ix) tuning viscosity of aminoacids, peptides, supramolecular assemblies of proteins; (x) understanding structure-function relationship in elastomeric proteins using 2-D models at interface so as to understand properties of resilency and elasticity, (xi) use of cyclotron and magnetic resonance to understand apoptic processes, subsequent to the interaction of nanooxides to cell surface and thus conformational behavior. b.Benefits expected from the project: Development of nano oxides, nanocomposite polymers, nanoparticles, etc with improved properties such as superparamagnetism, color etc for controlled drug delivery technology. Enable the delivery of stem cells, drugs, etc through the aid of nanocomposites. Enable the understanding of the elastic mechanism of unique extracellular matrix proteins and enable repair of elastic tissues in ageing and disease. c.Applications in medical/agricultural/pharmaceutical/other areas: a. For sustained delivery of drugs including anticancer agents, magnetic and catalytic applications, gas sensors, pigments, magnetic storage devices, magneto optical devices etc. b. Prepare nanocomposites for delivery of stem cells and drugs. c. Create organized molecular assemblies forming functional interfaces. d. Study the relevance of nanooxide adsorbed cell surfaces in controlling apoptic processes using cyclotron and magnetic resonance imaging. 3.Deliverables/Outcome at the completion of the project from the task/s assigned to Laboratory Nano oxides of metals in the size range of less than 10 nm developed through the spatial separation of metal centres by biomolecules. Nanocomposites for stem cell and drug delivery and creation of organized molecular assemblies Study of changes in apoptic processes on adsorption of metal oxides to cell surfaces through cyclotron and magnetic resonance. |
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Financial Resource Deployment (Rs in Lakhs)
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Equipments sought under the project are a.Powder XRD along with ICDD software: Rs 70 lakhs b.Ellipsometer: Rs 35 lakhs c.Atomic force microscope: Rs 50 lakhs d.Flow cytometer: Rs 65 lakhs e.DSC: Rs 15 lakhs f.Other small equipments: Rs 5 lakhs |
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