The faculty is carrying out research work on chronic inflammatory disorders, immunomodulation, new drug development, micronutrients, dietary mutagens, isolation and characterization of soil bacteria antagonistic to plant pathogens, bio-control, and proteins and enzymes. Biochemical mechanisms underlying the cirrhosis of the liver and rheumatoid arthritis are being studied in order to identify sites for therapeutic intervention. The department is augmenting its ongoing research in disease biochemistry particularly with reference to the signal transduction pathways using cell lines and animal model, development of molecular diagnostic methods to detect and identify the pathogenic fungi and immunomodulation. Immunomodulation has wider implications in medicine. The faculty is working on the immune responses to various medicinal herbs and other material, and intends to pursue this in order to assess the importance of immunomodulation in insulin resistance syndrome to find out ways to alleviate the response using finely characterized biomolecules. Work on the isolation and characterization of dietary mutagens is also going on. Biosensors, functional proteomics, stem cell research and regeneration are other areas, which the department would like to promote. 

The Department of Biochemistry at JH has been actively involved in working with agencies such as the ICMR in implementing its program. This department has been a member of the task force constituted by the ICMR on micronutrients for a UNICEF funded study on the estimation of the level of vitamin A in children in Assam and Rajasthan. The Department would like to continue similar studies of national importance and work to implement the programmes of the Government of India.

Thrust areas

Currently the research in the Department is focused on: 

i.        Chronic inflammatory disorders and immunomodulation

ii.      Genotoxicity of Food, Antioxidant Mechanism of Dietary Polyphenols

iii.    Micronutrients

iv.    Bio-control 

Future plans

In the coming five years, the Department proposes to work on: 

i.       Signal transduction in relation to chronic inflammatory disorders

ii.      Molecular Diagnostics

iii.    Nanobiosensors 

A glimpse of the proposed research activities:

1.      Chronic inflammatory disorders:

Chronic inflammatory disorders, which include liver fibrosis/cirrhosis, rheumatoid arthritis and diabetes, are serious health problems, where modulation of signal transduction pathways has been reported. For example, liver fibrosis, which is effectively an uncontrolled wound healing response characterized by the accumulation of the extracellular matrix rich in fibrillar collagens (predominantly collagen I and III), involves NF-κB, which has been reported to modulate the signal transduction pathway in inflammatory conditions. Fibrosis demonstrates a beautiful interplay between the epithelial, inflammatory, myofibroblast and the extracellular matrix components, leading to progressive scar formation. The extracellular matrix components are secreted by the myofibroblast-like activated hepatic stellate cells (aHSC), which trans-differentiate from the HSC, the vitamin A storing cell residing in the Disse space. Selective killing of aHSC by apoptotic inducing substances has been reported to reverse fibrosis. We propose to work on some novel peptides and therapeutic agents for their ability to induce apoptosis/modulate the signal transduction pathway in aHSC. The effect will be studied in vitro on selected parameters such as the NF-κB (determined by confocal analysis with antibodies recognizing p65-phosphoSer536, a marker for active NF-κB) in cultured rat and human HSC and apoptosis assays (Caspase 3 activity). Selectivity for HSC will be determined by assessing the relative loss of HSC (αSMA+) versus hepatocytes and liver macrophages in mixed co-cultures. 

The impact of the development of a therapy for liver fibrosis would be profound. Liver disease is amongst the major causes of mortality across the world and rates of death are expected to increase by 4-fold in the next decade. Deaths attributed to chronic liver disease are increasing India due to injuries caused by alcohol consumption, metabolic diseases and viral infections (hepatitis B and C). Transplantation, which is the only effective therapeutic option for end-stage disease is a major financial burden on the health care system and many patients die waiting for a matched donor organ. 

Further, the protocols standardized would be useful to study and understand other chronic complications such as rheumatoid arthritis, Insulin Resistance Syndrome (IRS) and diabetes to understand the role of novel therapeutic compounds (including those of herbal origin). 

2.      Molecular Biology:

The discovery that cooked food can be mutagenic has led to efforts for isolating mutagenic compounds from food. Cancer is a worldwide problem and has to be understood intricately as far as human health is concerned. Nutrition plays an important role in the development of several cancers such as prostate, colon, liver and breast. Approximately twenty four different types of food mutagens have been identified till date. 

Dietary polyphenols are important constituents of plant derived human diet and a number of these are considered to possess chemopreventive and therapeutic properties against cancer. Studies on chemopreventive potential of  polyphenols such as epigallocatechin-3-gallate (EGCG) genistein (soy isoflavone) sulphorafane (isothiocyanate) and other well recognized naturally occurring antioxidants assume significance as they are constituents of human diet. Therefore the mechanism of action of these and other such compounds would be explored for therapeutic targets and drug design. In the next five years, we propose to: (i) develop the technique for Solid Phase Extraction, and identification/characterization/detection of meat mutagens (ex: Imidazoquinolines; 2-Amino, 3, 8 dimethylimidazo (4, 5-f quinoxaline); 2-Amino, 1 methyl 6 phenylimidazo (4, 5-b) pyridine; Aminoimidazoazaarenes) using HPLC and MS, (ii) Establish the genotoxicity of candidate mutagens in HepG2 and LNCaP using Comet assay (to visualize DNA damage), Fluorescence In Situ Hybridisation (to visualize localized DNA damage), Sister Chromatid Exchange Frequency (to evaluate single strand breaks in DNA), and DNA adduct formation (to demonstrate DNA damage), and (iii) to understand the mechanism of action and evualting the antimutagenic potential of the single and combined polyphenols in Prostate/Hepatic Carcinoma Cell Lines PC3, LNCaP or DU145/HepG2. 

Further, we also propose to establish infrastructure for molecular diagnostics, which is the fastest-growing segment of the in vitro diagnostics industry. Efforts will be made to develop highly sensitive DNA based diagnostic laboratory methods (based on molecular probes and primers for diagnosis of targeted genes/mutations) for detection of pathogens and mutations.  

3.      Nanosensors:

UGC, in 2008, sanctioned a new program of study (MSc) in Bioelectronics and Instrumentation to the Department of Biochemistry. We have identified development of nanosensors as diagnostic tools as the thrust area of the Department. 

Biosensor devices having nanoscale dimensions are capable to probe minute amount of analyte in very brief period of time. We intends to evaluate the the applications of nanostructures of silicon and other materials in sensors for infectious diseases.  

Carbon nanotubes, gold quantum dots and porous silicon (PS) form excellent material for sensing applications. Particularly, PS, due to its large internal surface, is capable of adsorbing an enormous amount of different compounds. The average porous size can be easily adjusted to allow the penetration of molecular compounds with different sizes. The PS substrate can be used for sensing applications because it can readily be integrated with silicon technology. We propose to investigate the PS for the development of DNA biosensors based on nucleic acid recognition processes for testing infectious diseases.  

This proposed work could lead to the development of technology which can further be implemented to produce sensitive multiplexed assays for clinical diagnostics of genetic and infectious disease.