Dr. Natarajan Ganesan

"Sequence Profiling Tools": In bioinformatics, this refers to all those software tools (web-based/downloadable) that provide a brief overview on all related information about an input sequence. The advent of post-genomics era has given rise to a range of web based tools and software to handle the deluge of biological information. A simple web-search returns any number of such services and software tools ranging from the popular public domains e.g. NCBI, ExPASy, Ensembl, PDB etc., to private research group sites, e.g. eF-site, Dipole moment server, SuperPose, REBASE. However, most of these remain obscure/under-explored to a bench-top molecular biologist who most often would like to quickly know which record in the BLAST report is useful for further analysis (given that the first few hits are already known) OR like to have a guess at what would a newly found ORF look like after translation. In other words, the user often needs an interface that acts like a Propaedia or a gateway, giving him a brief overview about his sequence (DNA/RNA/protein) while still allowing advanced operations without having to leave the browser session. Sites like Entrez provide this kind of facility for text related searches in biomedical field. Related link: http://bioinformatics.georgetown.edu/Sequerome.htm

"Biopolymer-based Drug Delivery Systems": One of the crucial aspects of anti-cancer platinum(II) drug design is controlling the release of the active Pt2+ species before binding to its target sites. Extending the theory of slow leaving side groups further, assume a bunch of Pt2+ to be coupled to a polymer consisting of multiple COO- sites. Poly(β-L-malate)(PMLA)is a polyanionic polyester, isolated from the plasmodia of Physarum polycephalum. PMLA consists of repeating units of L-malate (a common metabolite), joined by β-ester linkages. Since its discovery, this bio-resorbable polymer has aroused interest primarily for its biomedical applications, especially as drug delivery systems. As a result of its structure, PMLA is a reservoir of carboxylate groups, protruding from the polyester chain, and providing liganding groups similarly as CBDCA in carboplatin. A polymer-Pt complex has been synthesized by coupling polymalate to the diaqua Pt2+ species of cisplatin. The DNA binding properties of this complex show interesting results, suggesting unconventional DNA binding mechanisms and cytotoxic activities by PMLA-Pt(II) that are dictated by the polyanionic structure of PMLA.

"Carcinogen Adduct Dosimetry and Cancer Risk Assessment": Quantification of low levels of irreversible DNA damage (carcinogen-DNA adducts) is important in selectively identifying individuals as high risk cancer subjects. As a prototype, we have demonstrated the feasibility of a new assay for the detection of 4-aminobiphenyl-DNA adducts in human samples and plan to validate the same by proving its utility in carrying out epidemiological studies. The novelty of this assay is based on a modified 14C postlabelling method using the enzyme N-acetyltransferase (NAT) (E.C.-2.3.1.5) with labeled acetyl-CoA as the 14C donor. For very low levels of adduction, the samples would be subjected to an additional purification step involving immuno-affinity chromatography. The acetylated product will be detected and quantified using accelerator mass spectrometry (in collaboration with Turteltaub KW, CA). Following the documented sensitivity of AMS procedure, we expect a thousand-fold increase in adduct detection sensitivity over the existing procedures.

"Biosensors": The early stages of the body’s physiological response to either health or environmental trauma can be a useful diagnostic measure for the early detection of stress and a method for determining the appropriate "first response". Recent advances in micro-fabrication technologies allows the creation of novel chip-scale devices capable of non-intrusive, real time sensing of biomedical conditions. The development of the Transdermal Microsystem by the GAEL Labs, promises to be a major advance in this direction, providing a technology for transdermal sampling of molecules that do not normally diffuse across the skin. The device is a micro-fluidic sampling system coupled with a thermal ablation micro-device enabling sampling of the body analyte at the Stratum Corneum (SC)/Viable Epidermis (VE) interface through extraction of interstitial fluid. The detection of the bioanalyte is limited by its molecular weight, which normally is the limit set by blood-IF barrier (~ 60 Kd). The bioanalytes could vary from monitoring of glucose, lactate to smoking products like nicotine, cotinine etc. Assay of smoking related products gains importance in carrying out field trials, population studies to perform cancer risk assessment in relation to smoking. In some rare diseased conditions antibodies leak into the interstitial fluid (dengue viral infections) cases. The Biochip can be suitably modified for applications proteomics electrochemical DNA biosensors.

1. Development of wireless electrochemical ELISA kits for field-based studies - Protocols have been developed to immobilize antibodies to gold electrodes in a way that it possible to microfabricate and convert multi-well plates(e.g. 96 well)into electrochemical devices. With the help handheld read-out device it should be possible to obtain current readings (as opposed to bulky, albiet powerful, optical devices). Modifications can be also made to convert this into wireless transmitting devices to field based studies. Applications include clinical products for civilian/defense purposes.

2. Drug delivery systems using bioresorbable polymers - Certain slime molds have been found to produce a rare biopolymer out of ß-poly-L-malate, a natural metabolite. The physical and chemical properties of this polymer has been demonstrated to be useful as drug-delivery systems for platinum based anti-cancer drugs - Applications in Pharmaceuticals