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Research Topics in Life Sciences

Human diseases

The Center has initiated a pilot study on the genetic loci for breast cancer in the South Indian population, particularly to assess the incidence of mutated genes . This pilot study is expected to generate preliminary data for broader research on causes and mechanisms of breast cancer. A compendium of resource material on breast cancer will soon be available at this site.

Intercellular communication

Intercellular coupling i.e. coupling of intracellular biochemical pathways plays an important role in syncyctial coordination. The long term objective is a quantitative understanding of the role of intercellular gap junction communication in tissue function. Sub aims are (1) To measure the intrinsic permeability of a variety of fluorescent probes across homo- and hetero- oligomeric gap junction (GJ) channels in transfected cells. (2) To build artificial double-bilayer systems, incorporate whole GJ channels, and study their properties in controllable external conditions.

a)    Permeation of macromolecules through gap junction channels. We will explore the dependence of permeability on channel composition.  Absolute rates will be determined by simultaneous electrical (patch-clamp) and fluorescent measurements. Transfer rates of probes will delimit the bounds on the permeation rates of messenger molecules with similar size and charge.

b)    Forming lipid bilayers, incorporating whole GJ channels: In collaboration with Dr. S. Tripathi (TIFR, Bombay), we have (i) incorporated GJ hemichannels (half a GJ channel) in a single bilayer, mimicking previous work (ii) tried various methods to form artificial double bilayers, including multiple patch pipette membranes picked from bilayer “bubbles” and multiple “tip dips”, with some success already (unpublished results). We will next attempt to incorporate intact GJ channels in double bilayers.

Single molecule research

  1. DNA translocation across nanopore: Study of single molecule DNA has remained focus of interest in recent years. Progress made in the method of analyzing sequence information from ssDNA translocation across membrane pores has attracted interest of many researchers. We are interested in the study of DNA translocation across a -hemolysin channel. We will be exploring the combination of single molecule manipulation and detection methods along with single channel patch-clamp recording, to study DNA translocation along the nanopore and develop more sensitive methods to extract sequence information.
  2. Genetic Circuits: Knowledge of spatio-temporal information of protein molecule invivo is precious to biologist. We are interested in the simulation of heat-shock response of a bacterial network and extract spatio-temporal pattern of gene expression products (mRNAs and proteins). Fluorescence based experiments will be devised to capture real-time dynamics of mRNA and protein synthesis in single cells hosting signal-response networks. To this end, sensitive fluorescence microscopy and fluorescence correlation spectroscopy will be developed.

Development of biosensors

Molecules spontaneously organize on metal surfaces forming monolayers.  Surface modification can enable molecular recognition (chemical sensing). One possible approach towards the development of bio-sensors is by using the modified metal surfaces and engineering (functionalizing) the monolayer for effective interaction with the target molecules by using the inherent selectivity of biomolecules such as enzymes and antibodies. The interaction of the monolayer with the target molecule can be monitored by fluorescence, or changes in electrical conductivity or refractive index.

a.)    Adsorption of Lipases on nanoparticles (gold, silver) for enhancing their catalytical properties This will be studied by Raman spectroscopy. The lipase enzyme as well as the enzyme complexed with inhibitor will be adsorbed on a nanosurface. The function  of these molecules will be followed spectroscopically.
b.)    Quantum dots in monolayers: Immobilization of quantum dots on atomically flat surfaces (eg.. mica) and on near atomically flat surfaces (eg., silicon wafers) to study the interplay between molecules and the surfaces of nanoparticles. Additionally these surfaces are tailored to produce monolayers of desired functionality. Such modifications of the functionality might lead to changes of optical properties of quantum dots.