DBT Programme Support on Neuroproteomics for Proteomic Investigation of Neurological Disorders with NIMHANS
Tuberculous meningitis is the severest form of extrapulmonary tuberculosis.  It has one of the highest mortality in spite of chemotherapy.  Tuberculosis is endemic in India and its prevalence is reported to be increasing in patients.  Early diagnosis and treatment of the disease is becoming difficult due to the lack of effective diagnostic methods.  Improved early diagnosis could potentially save the patients.  IOB in collaboration with NIMHANS has initiated genome wide profiling of tuberculous meningitis with a specific aim to understand the biology of disease and to identify potential biomarkers which could help in early diagnosis.  We will be validating the molecules identified using immunohistochemistry.  Proteomic approach is considered as the accelerated method for identification of potential biomarker for early diagnosis.  We also plan to carry out mass spectrometry based quantitative proteomics studies for discovery of a panel of diagnostic biomarkers for tuberculous meningitis.

Epilepsy is another common chronic neurological condition characterized by recurrent unprovoked seizures.  The molecular basis of epilepsy is ill understood.  Temporal lobe epilepsy is the commonest form of epilepsy but is also the most difficult to treat with most patients suffering from intractable seizures.  Knowledge of genes and pathways that are activated in this form of epilepsy has the potential to be used to classify patients into those that will respond to conventional drug therapy and those who will not.  In addition, such pathway information could be used to develop novel therapeutics.  Scientists at IOB are carrying out transcriptomic and proteomic profiling of brain tissue obtained during stereotactic craniotomy at NIMHANS to identify the molecules that are specific to epileptogenic foci.

CSIR grant : "Genomic and proteomic profiling of gallbladder cancer"
India has the highest incidence of gallbladder cancer in the world. It has one of the highest mortality rates of all cancers, which is largely due to lack of early detection of this devastating disease. Thus, there is an urgent need for discovering biomarkers for early detection of gallbladder cancer. We are carrying out genomewide expression profiling using DNA microarrays to identify genes that are upregulated in gallbladder cancers. We are also carrying out immunohistochemical labeling of tissue microarrays that we have prepared for validating potential candidates identified from these DNA microarray studies.  In addition, we will carry out proteomic profiling using quantitative and high resolution mass spectrometry.  This combined genomic and proteomic approach should lead to discovery of biomarkers that can be rapidly tested further in the large number of cases being diagnosed in India.

DBT multi-institutional coordinated research grant: “Establishment of National Database on Tuberculosis (TB)”
India accounts for about 30% of the global burden of tuberculosis - more than any other country in the world.  Though a combination of environmental and host genetic factors are important in the disease progression, recent studies have shown that genetic and proteomic diversity of mycobacteria also play a role in modifying the disease outcome. The availability of the complete genome sequence of the standard laboratory strain of M. tuberculosis, H37Rv, in addition to clinical isolates (e.g. CDC1551) will help investigations on genetic polymorphism and proteome diversity of this pathogen.  Genomes of several other mycobacteria are also currently being sequenced and available. We are developing a Proteomic and Host-Pathogen Interaction Database for tuberculosis, which will include both published data from the literature as well as unpublished data being generated by the Indian scientific community.  We have also developed a central website, which will facilitate integration of data that will emanate from ‘TBNET India’ program conceived by DBT and inform the international community about this bold bioinformatics initiative.  In order to keep the database up to date, we will facilitate the participation of investigators to contribute and review data by developing a Distributed Annotation System for tuberculosis - the model will be adopted from the recently developed Human Proteinpedia by our Institute.  Development of this web based portal for tuberculosis will enable investigation of clinical, therapeutic and diagnostic aspects of tuberculosis.  It will also serve as a binding force for the various arms of the ‘TBNET India’. 

DBT multi-institutional research grant: “Identification of genes involved in X-linked mental retardation”
X-linked mental retardation is a common child hood disorder.  The molecular mechanisms remain a mystery.  Identification of precise molecular mechanisms should lead to better classification, diagnosis, prevention and therapy.  It is anticipated that many more genes and mechanisms may play a role in X-linked mental retardation. Using a custom designed microarray for comparative genomic hybridization, scientists at IOB, NIMHANS and CHG are planning to identify genetic mechanisms and potential molecules that play a major role in the etiology of mental retardation.  The discovery of genes involved in mental retardation will be helpful in the diagnosis, classification and therapy of the disorder.

DBT research grant “Mouse Protein Reference Database”
The laboratory mouse has emerged as a popular model organism in biomedical research. The applicability of mouse model systems to human biology has led to its use in areas ranging from stem cell biology and genetics to cancers and neurodegenerative diseases. Over the last several decades, vast amounts of genetic, genomic and proteomic data derived from systematic experimentation in mice have become available. However, there is currently no repository for data pertaining to the mouse proteome, although there are several resources for mouse genomic data. IOB is developing a Mouse Protein Reference Database (MPRD) as a comprehensive repository of information pertaining to mouse proteins including domain architecture, protein functions, protein-protein interactions, post-translational modifications, enzyme-substrate relationships, sub-cellular localization and tissue expression.  It will also include a mouse knockout database as well as data on mouse models of human disease. MPRD should help the scientific community to integrate systems level data to better understand disease mechanisms.

DBT Young Investigator grant to a Faculty Scientist, Dr. Keshava Prasad: “A functional analysis of Protein Tyrosine Phosphatases in EGF Receptor signal transduction pathway using a novel Substrate Trapping Mutant strategy”
Crucial role of kinases in signaling cascades has been well investigated and documented.  Role of phosphatases in signaling is poorly understood because of the experimental difficulties in studying them. Dr. Keshava Prasad is investigating the role of tyrosine phosphatases involved with receptor kinases signaling pathways. The epidermal growth factor has been one area of interest for research at IOB where scientists are using a variety of functional approaches such as substrate trapping mutants, yeast two hybrid analysis and other cutting edge strategies to elucidate the critical role of these phosphatases in cell signaling.

ICMR Senior Research Fellow grant to a Research Scientist, Manoj Kashyap
Research Title: mRNA and genome copy number profiling of esophageal cancers
Esophageal cancer is the third leading cancer in males and fourth leading in females in India, but not much is known about the molecular etiology of the disease. Manoj and coworkers at IOB are using DNA microarray technology to obtain gene expression profiles of esophageal cancer tissues along with adjacent normal tissue. In addition, the copy number variations in these samples are determined using array based comparative genomic hybridization technique. Differentially expressed molecules are being validated using immunohistochemistry and tissue microarrays. These studies will provide candidate molecules for use as biomarkers for early detection of esophageal cancers.

CSIR Senior Research Fellow grant to a Research Scientist, Harrys Kishore
Research Title: “Functional analysis of protein tyrosine phosphatases in humans”
Kinases and phosphatases have an equal role to play in phosphorylation and dephosphorylation of proteins that are responsible for transmitting signals from an external stimulus to the final expression of required functional genes through a cascade of signaling molecules.  However, actions of phosphatases are less investigated as opposed to kinases. Harrys and coworkers at IOB are identifying substrates of protein tyrosine phosphatases that are involved in human diseases in a global scale using substrate trapping mutants of protein tyrosine phosphatases in order to evaluate their functional aspects that will result in the identification of lead molecules for therapeutic interventions.