Faculty Profile

Dr. G. Mukhopadhyay, Professor

 

Dr. Mukhopadhyay received his PhD from Jadavpur University (Indian Institute of Chemical Biology), Calcutta and did his postdoctoral study in the laboratory of Biochemistry, National Cancer Institute, NIH, USA.

 

Research Interests:

 

Major focus of the laboratory is on the study of bacterial protein secretion system. The laboratory is also studying regulation of gene expression in pathogenic fungus as collaborative project.

 

Helicobacter pylori type IV secretion system:

 

Helicobacter pylori are the major cause of chronic gastritis and play an important role in the pathogenesis of peptic ulcer, gastric adeno carcinoma and gastric lymphoma. Although half of the world’s population carries the highly diverse bacteria Helicobacter pylori, the clinical sequel develop in only a fraction of colonized individuals and most likely depend on differentially represented bacterial determinants and host characteristics.

 

Type IV secretion systems (TFSS) play an important role for the virulence of a number of pathogenic bacteria including H. pylori. TFSS are ancestrally related to the bacterial conjugation system and are thought to be versatile transporters of proteins and/or nucleic acids (effectors molecules) across the bacterial membrane to the extra cellular space or into eukaryotic target cells. Basic aims of this work are to understand the biogenesis and adaptation of TFSS to pathogen-host interactions using variety of biochemical, cell biological and molecular biological methods. In the long run the study may help to identify new target(s) for anti bacterial treatments and use of the system as transporter of foreign molecule(s).

 

Regulation of gene expression:

 

In ‘collaboration’ with Prof. Rajendra Prasad, SLS we are studying regulation of CDRI gene (coding for drug efflux pump) expression in pathogenic fungus Candida albicans.

 

Number of students awarded Ph. D.: 12
Number of students submitted Ph. D. Thesis: 02
Number of Ph. D. students currently enrolled: 03

 

Ongoing Project:

 

Mutational analysis of a multidrug ABC transporter to dissect mechanism of drug efflux, DBT, 2012-14.

 

Selected Publications:

 

 

 

 

Dr. Chinmay K. Mukhopadhyay, Professor

 

Dr. Mukhopadhyay did his doctoral studies in Biochemistry at the Department of Biochemistry from Calcutta University and received the postdoctoral training in the Department of Cell Biology, Cleveland Clinic Foundation, USA. He joined the ‘Special Centre for Molecular Medicine’ in 2001.

 

Research Interests:

 

Iron is essential micronutrient for all the organisms because of its ability to function as a protein bound red-ox element. Defective regulation of iron homeostasis genes lead to either, iron excess and related tissue injuries due to iron-stimulated oxidative damage or iron deficiency disorders. Alterations of iron pool are implicated in hepatic injury related cancers, neurodegenerative diseases, ageing, and microbial infections. Dr. Mukhopadhyay’s research interest is to understand the role of iron in metabolic disorders like insulin resistance related disorders, Neurodegenerative diseases like Parkinson disease and Alzheimer disease as well as in survival and growth of protozoan parasite leishmania donovani within macrophages that might be helpful for designing therapeutic interventions to combat these diseases. In short, the laboratory are interested in the following areas-

 

A.      Cross talk between iron and oxygen (reactive oxygen species and hypoxia) in metabolic disorders.
B.      Iron homeostasis in glia and neuron: implications in neurodegenerative diseases.
C.      Role of iron in the growth of Leishmania donovani and in interaction with host macrophages.

 

Selected Publications

 

 

Research:  projects in Dr. Mukhopadhyay’s laboratory are sponsored by CSIR, DBT (2) and US-India BRCP-R21.

 

Collaboration

 

 

Number of students awarded/submitted Ph. D.: 10
Number of Ph. D. students currently enrolled: 07

 

 

Dr. Rakesh K. Tyagi, Professor

 

Prof. R. K. Tyagi carried out his doctoral studies in biochemistry at Jawaharlal Nehru University, New Delhi. He pursued his research work in the area of ‘Molecular Endocrinology’ as a Feinberg Research Fellow at the Weizmann Institute of Science, Israel and later as INSERM international fellow in France. Prior to joining the ‘Special Centre for Molecular Medicine’ in April 2001 he was working in an NIH sponsored research scheme at the University of Texas Health Science Centre, USA. He has two international patents to his credit. He was elected to the National Academy Sciences, India during the year 2010.

 

Research Interests:

 

Nuclear hormone receptors in health and disease

 

The Nuclear Receptor family is a large group of ligand-activated transcription factors with 48 members presently identified in the human genome. Members of this family of receptors are involved in regulation of numerous physiological and patho-physiological processes and have great potential as targets for the treatment of diseases such as cancer, diabetes, coronary heart disease and asthma. Nuclear Receptors (NRs), that include steroid hormone receptors, are intra-cellular transcription factors that regulate gene expression in response to their cognate ligands. They function either as homodimers or as heterodimers with retnoid X receptor (RXR). NRs are attractive targets for drug discovery because their activities can be modulated and have proved to be ‘drug-responsive’. However, some newly discovered members of this family of receptors remain incompletely understood, both in terms of physiological role and activating ligands. In brief, nuclear receptors represent enormous potential for drug discovery and are continuously being examined to unravel the mysteries underlying their mechanisms of actions. Towards better understanding of the functional significance of these hormone receptors some of the comprehensive research projects have been initiated in our laboratory. Presently, the role of androgen receptor mediated signaling in prostate cancer progression and the role of Pregnane & Xenobiotic Receptor in metabolism and clearance of endogenous metabolites and xenobiotics (including prescription drugs) is under investigation.

 

Selected Publications

 

 

Research: projects sponsored by ICMR, CSIR, DST & UGC.

 

Number of students awarded/submitted Ph. D.: 09
Number of Ph. D. students currently enrolled: 06

 

Dr. Suman Kumar Dhar, Professor

 

Dr. Suman Kumar Dhar did his Ph. D. in molecular parasitology from Jawaharlal Nehru University, New Delhi. During his graduate school he studied the replication and maintenance of ribosomal DNA circle in the protozoan parasite Entamoeba histolytica, which causes amebiasis in humans. Later during his post-doctoral tenure he studied the initiation of mammalian DNA replication at the Brigham and Women’s Hospital, Harvard Medical School, Boston, USA. Here he identified the human origin recognition complex subunit six (ORC6). He also showed for the first time that human ORC is essential for viral DNA replication (Epstein Barr virus and human papilloma virus) and geminin, a replication inhibitor could block specifically the viral DNA replication without affecting mammalian DNA replication. He has obtained an international and US patent based on his research findings. 

 

Research interests:

 

DNA replication initiation in the pathogenic bacteria Helicobacter pylori

 

Helicobacter pylori is a gram-negative, spiral-shaped pathogenic bacterium which causes peptic ulcer diseases and chronic gastritis. WHO has recognized H. pylori as a primary risk factor for the development of intestinal type gastric adenocarcinoma. The genome sequences of two unrelated isolates H. pylori 26695 and J99 have been reported recently. There is no vaccine available in the market at present and prevalence of antibiotic resistant strains is on the rise. Experimental data to understand the basic biology of the bacteria concerning the chromosomal DNA replication of H. pylori are scarce. The genomic analysis revealed few interesting data, in particular in the initiation of replication. An origin of DNA replication is not very evident from the genomic analysis. The dnaC gene, which codes for DnaC protein delivering the DnaB helicase to prep riming complex is absent. Likewise HolB gene, a subunit of core DNA polymerase enzyme was also not found from the sequence analysis. These findings suggest that H. pylori DNA replication may have some unique features. Replication proteins are good targets for therapy. Compounds blocking the replication initiation process could be very useful in this regard. Presently we are studying the initiation of chromosomal DNA replication in H. pylori.

 

Cell cycle regulation and DNA synthesis in Plasmodium falciparum

 

Malaria continues to be a major health problem globally. The situation is becoming alarming due to the lack of an effective vaccine and increasing incidence of antimalarial drug resistance. There is an urgent need to understand the fundamental biology and biochemical processes at the different stages of the parasite. This will help to identify new targets for the development of novel drugs and vaccines. One aspect of parasite metabolism, which could be useful in this regard, is DNA replication. DNA replication takes place at five distinct points in the parasite life cycle. DNA replication initiation, the rate determining step in DNA replication has not been characterized in P. falciparum. In Saccharomyces cerevisiae, six protein origin recognition complex (ORC) binds to specific DNA sequences near origin of replication and recruit other factors like Cdc6, Cdt1 and Mcm2-7 and form the pre-Replication complex (preRC) facilitating replication initiation. P. falciparum genomic database searches revealed the presence of ORC1, ORC5, Cdc6 and MCM homologs. Our goal is to understand the mechanism of chromosomal DNA replication initiation by biochemical and genetic analysis of these proteins at different points during erythrocytic stage of the parasite life cycle. The role of replication initiation proteins in apicoplast DNA replication will also be explored. Using protein-protein interaction we are trying to identify and characterize other members of the preRC which might reveal features unique to the parasite DNA replication machinery. Investigation of the components involved in chromosomal and plastid DNA replication initiation and identification of chromosomal DNA replication origin may lead to the identification of new potential drug targets for malaria therapy.

 

Research: projects in Dr. Dhar’s laboratory are sponsored by European Union (FP7, MALSIG), Swarnajayanti Fellowship (DST, India), National Biosciences Award (Department of Biotechnology, India) and Centre of Excellence in Parasitology (Department of Biotechnology, India).

 

Selected Publications:

 

 

Number of students awarded Ph. D.: 10 (including submission)
Number of Ph. D. students currently enrolled: 08

 

 

Dr. Saima Aijaz, Assistant Professor

 

Dr. Saima Aijaz received her Ph.D. from the Indian Institute of Science, Bangalore, India. During her doctoral studies, she worked on the molecular characterization of the inner capsid protein of Rotavirus with a view to develop a recombinant vaccine. She has carried out post doctoral work at the University of Bath, United Kingdom and at the University College London (UCL), United Kingdom. At UCL, she worked extensively on the functional characterization of epithelial tight junctions. Dr. Aijaz joined the Special Centre for Molecular Medicine in January, 2008.

 

Research Interest:

 

Regulation of Epithelial Tight Junctions

 

Epithelial cells protect and enclose all our organs and line the body cavities. These cells form layers with tightly packed cells that are joined to each other by intercellular adhesive complexes that consist of tight junctions (TJ), adherens junctions (AJ), desmosomes (D) and gap junctions (GJ). Tight junctions are the most apical component of the epithelial adhesion complex and are composed of a complex protein network that is linked to the cytoskeleton. Tight junctions seal the passage between adjacent cells regulating the passage of ions and solutes through this paracellular space and contribute to the maintenance of cell polarity by helping to maintain distinct apical and baso-lateral domains in the plasma membrane. New evidence shows that TJs also regulate cell proliferation and differentiation. Consequently, breakdown or leakage through the TJ causes various diseases ranging from allergies to bacterial and viral diseases and even cancer. The tight junction complex also serves as an initial point of contact for several pathogens which have devised sophisticated strategies to disrupt the tight junction in order to infect host cells. The main focus of my laboratory is to investigate the mechanisms that regulate (i) how tight junctions are assembled, (ii) how TJs are maintained and (iii) how TJs break-down in various disease contexts. We are using a variety of approaches to address these questions with the ultimate aim of identifying TJ-based therapeutic strategies against diseases that occur as a result of TJ break-down or due to leakage through TJs.

 

Research Funding: Research in the laboratory is funded by The Department of Biotechnology.

 

Selected Publications:

 

• Aijaz S, D'Atri F, Citi S, Balda MS, Matter K. (2005). Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Dev Cell. ; 8(5):777-786.
• Saima Aijaz, Steven Goodrick, Karl Matter and Maria Balda (2006): 'Tight Junctions' in Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, Pages 1868-1873; Springer.

 

Number of Ph. D. students currently enrolled: 04

 

 

Dr. Dipankar Ghosh, Assistant Professor

 

 Early host pathogen interactions

 

The mammalian epithelial barrier is frequently the first line of defense against environmental or infectious risks. Intricate array of ancient innate immune determinants augment this barrier, preventing pathogens against invasion and encouraging commensals to flourish. The process is remarkably complex; using only ~13 types of Toll Like Receptors (TLRs) the gut epithelium can discriminate between 10¹⁴ commensals and identify/attack even 10 pathogenic bacteria in minutes! We are interested in understanding these early events of host-microbe interactions.

 

Commensals and pathogens both form biofilms in early associations with the host. These biofilms are remarkably different from their planktonic counterparts including morphology, gene expression and “multicellular like” behavior.  Biofilm bacteria communicate between themselves using Quorum Sensing (QS) – a primordial cell-cell communication system mediated by small molecules. In pathogens QS controls numerous factors like virulence factors, drug resistance and others which make biofilms so dangerous on medical devices and so many other infections. Much less is known about commensal QS which possibly control host microbiome.  We investigate the relationships between these two ancient processes: biofilm QS and epithelial innate immunity! In a collaborative program with Dr. Venkat Panchagnula at National Chemical Laboratory, Pune, we have developed proprietary Laser Desorption Ionization Mass Spectrometry (LDI-MS) technology that allows high throughput untargeted metabolomics of biofilm QS. Using this technology in multi-institutional collaborations including, Prof. Rakesh Lodha in the All India Institute of Medical Sciences (AIIMS, Delhi); Prof. Giovanni Di Bonaventura in University of Cheiti-Pascara and Bambino Gesù Hospital (Italy); Prof. Miguel Cámara at the University of Nottingham and the National Biofilms Innovation Centre (United Kingdom) – we are investigating QS in multiple disease models. These include biofilms of Pseudomonas aeruginosa – a dreaded multiple drug resistant pathogen that leads to many acute infections like Ventilator Associated Pneumonia, Ocular Keratitis, wound infections, Irritable Bowel Syndrome and others.  We have shown that P. aeruginosa QS directly interfere with the human innate immunity through cross-kingdom signaling that can have far reaching consequence on biofilm based diseases and management. Using these tools we also investigate microbial contamination in food mechanisms of probiotics and analyses of next generation of functional foods. The laboratory enjoys government funding as well as grants from major domestic FMCG industry for its research.

 

 

     

 

 

 

Selected Publications: