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(An Autonomous Institute of the Department of Biotechnology, Govt. of India)

NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Post Box No.- 04, Faridabad-121001

Admission Notice No. THS/RN/15/2015

Result of the interview held at THSTI, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, P.O. Box No. 04, Faridabad - 121001 on 23rd & 24th June 2015.

Selected candidates (in alphabetical order)

Sl. No. Name Reference ID

1. AARTI TRIPATHI 12219

2. ANZER KHAN 12669

3. AYUSHI CHAURASIYA 12432

4. BAKUL PIPLANI 12411

5. BUGGA PARAMESHA 12349

6. CHARU AGGARWAL 12240

7. INDU BISHT 12422

8. JYOTI VERMA 12247

9. KIRTIKA 12288

10. NEERAJ KUMAR 12697

11. RASHMI PRIYA 12549

12. RAVI JAIN 12668

13. SAIMAH RAZA 12483

14. SAMIKSHA KUKAL 12265

15. SAPNA JAIN 12535

16. SHAILENDRA CHAUHAN 12289

17. SUDESH 12442

Selected candidates may interact with potential supervisors. Please download the Rank Preference form given on next page. Please go through the instructions given therein carefully before submitting the rank preference form by 02:00 pm on 29th June, 2015.

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THSTI JNU PhD program-2015 Rank preferences of Potential Supervisors by Doctoral Candidates

Name E-mail ID Phone No. Rank-order

Dr. Amit Awasthi aawasthi@thsti.res.in 0129-2876482

Dr. Amit Kumar Pandey amitpandey@thsti.res.in 0129-2876322

Dr. Arup Banerjee banerjeea@thsti.res.in 0129-2876325

Dr. Bhabatosh Das bhabatosh@thsti.res.in 0129-2876471

Dr. Gaurav Batra gaurav.batra@thsti.res.in 0129-2876357

Dr. Guruprasad R. Medigeshi gmedigeshi@thsti.res.in 0129-2876311

Dr. Jonathan Pillai jonathan@thsti.res.in 0129-2876347

Dr. Manjula Kalia manjula@thsti.res.in 0129-2876323

Dr. Mohan Babu Appaiahgari mohan@thsti.res.in 0129-2876310

Dr. Nisheeth Agarwal nisheeth@thsti.res.in 0129-2876304

Dr. Ramandeep Singh ramandeep@thsti.res.in 0129-2876305

Dr. Ranjith Kumar C.T. ctrkumar@thsti.res.in 0129-2876333

Dr. Samrat Chatterjee samrat.chatterjee@thsti.res.in 011-26741358 Ext: 425

Dr. Sanjay Kumar Banerjee skbanerjee@thsti.res.in 011-26741358 Ext: 437

Dr. Sankar Bhattacharyya sankar@thsti.res.in 0129-2876324

Dr. Shailaja Sopory ssopory@thsti.res.in 0129-2876345

Dr. Shinjini Bhatnagar shinjini.bhatnagar@thsti.res.in 0129-2876362

Dr. Sudhanshu Vrati vrati@thsti.res.in 0129-2876301

Dr. Uma Chandra Mouli Natchu unatchu@thsti.res.in 0129-2876356

INSTRUCTIONS

1. Assign a rank from 1-19 for each supervisor. It is mandatory for the student to interact and rank all supervisors.

2. The assignment of Supervisor is based on matching according to the preferences given by the students and faculty. Students are advised to interact with supervisors through personal meetings/email/ Skype as may be the case at a mutually convenient time and location.

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3. The forms must reach Mr. J N Mishra by email to jnmishra@thsti.res.in by 2.00 pm on

29th June, 2015. No delays will be accepted. Non-receipt of the form will be considered as a decision to not accept the admission at THSTI.

4. The final student – faculty match list will be displayed on THSTI website and

communicated to the candidates by 06:00 pm on 29th June 2015 via e-mail.

5. Research interests of potential supervisors are also attached below.

6. Please address doubts in this matter before submitting forms to Mr. J.N. Mishra, Administrative Officer at 0129-2876441/442.

Date _______________________

Name of the candidate_______________________________________________

Signature of the Candidate____________________________________________

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RESEARCH INTERESTS OF POTENTIAL SUPERVISORS

Dr. Amit Awasthi

Auto-reactive T cells induced tissue inflammation in both Multiple Sclerosis (MS) and Inflammatory Bowl Disease (IBD). Recently discovered Th17 and Th9 cells play a major role in inducing tissue inflammation. Major focus of my work is to define the transcriptional landscape of effector Th17, Th9 cells and Type1 regulatory T cells (TR1). To understand the pathogenic functions of pathogenic Th17 cells, I have developed IL-23R reporter/KO mouse models to track Th17 cells in various target organs during inflammation. I have found that TGF-instead of TGF- 17 cells, and interestingly the expression of TGF- -23 exposure. I have generated TGF- -YFP and TGF- -DTR mice to delineate the role of TGF- In addition, we have also identified the Th9 cells, which is mainly involved in lung inflammation in Asthma. We are also studying the effector functions and regulation of Th9 cells in airway inflammation and other allergic inflammation. On the same line, we have identified new transcription factors for the development of Th9 cells, which are crucial effector T cells for inducing tissue inflammation in allergic inflammation in asthma. Since IL-10 plays an important role in inducing regulation of inflammation, I have also defined the differentiation factors for IL-10-producing Tr1 cells. I have shown that IL-27, an IL-12 family cytokines, is critical in generation of IL-10-producing Tr1 cells, and these cells are the major contributor for regulating tissue inflammation.

Funding agencies: DBT-Wellcome Trust IYBA, DBT, Govt of India. Selected Publication: Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, Backstrom BT, Sobel RA, Wucherpfenning KW, Strom TB, Oukka M, Kuchroo VK. Myelin-specific regulatory T cells accumulate in the central nervous system, but fail to suppress pathogenic effector T cells at the peak of autoimmune inflammation. Nature Medicine 2007; 13: 423-31. Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, Oukka M, Kuchroo VK. IL-21 initiates an alternate pathway to induce proinflammatory Th17 cells. Nature 2007; 448: 484-7. Cited 705 times. Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL. A dominant function for interleukin 27 in generating interleukin 10–producing anti-inflammatory T cells. Nature Immunology 2007; 12:1380-9. Awasthi A*, Dardalhon V*, Kwon H, Galileos G, Gao W, Strom TB, Oukka M, Kuchroo VK. IL-4 inhibits TGF-b-induced-Foxp3+T cells and generates a Foxp3- IL-10/IL-9 T cell population. Nature Immunology 2008; 9:1347-55 Lee Y*, Awasthi A*, Yosef N, Quintana F, Xiao S, Kunder S, Regev A, Sobel R, Kuchroo VK. Induction and molecular signature of pathogenic TH17 cells. Nature Immunology 2012; 13:991-9 [Shared first and Co-senior author]. Yosef N, Shalek AK, Gaublomme J, Jin H, Lee Y, Awasthi A, Wu C, Karwacz K, Park H, Kuchroo VK, Regev A. Reconstruction of the dynamic regulatory network that controls Th17 cell differentiation by systematic perturbation in primary cells. Nature 2013, 25;496:461-8.

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Carbon metabolism in Mycobacterium tuberculosis and its implications on mycobacterial persistence

PI: Dr. Amit Kumar Pandey

Dr. Pandey is a veterinarian by training. After his bachelors in Veterinary Sciences from Orissa Veterinary College, Bhubaneswar, he received Masters degree in Animal Biotechnology from National Dairy Research Institute (NDRI) Karnal, Haryana. He is a PhD from Indian Veterinary Research Institute (IVRI), Izatnagar, Bareilly, India. Dr Pandey’s postdoctoral stints were at University of Nebraska-Lincoln, Nebraska, USA and University of Massachusetts Medical School, Worcester, Massachusetts, USA. Dr. Pandey’s long-term research interests lie in contributing towards a better understanding of mycobacterial pathogenesis. Currently, his lab is engaged in understanding carbon metabolism in Mycobacterium tuberculosis and its implications on mycobacterial persistence. Cholesterol utilization and its implication on mycobacterial persistence Although Mtb ingests cholesterol throughout the infection process, cholesterol becomes essential only during the later stage of chronic infection. The proposal involves generation and characterization of Mtb strains lacking genes critical for cholesterol utilization. Genetic and molecular understanding of cholesterol utilization, its mechanism and relevance would contribute significantly in designing novel intervention strategies in the treatment of tuberculosis. The knowledge acquired on the genes involved in uptake and metabolism of cholesterol in Mtb is very likely to generate new and more efficient drug targets. The role of cholesterol metabolism in mycobacterial persistence would also be better understood. Information from the project on regulatory genes and the motifs of the related regulatory proteins would be very helpful in unraveling the complex regulatory network. The ultimate goal will be to generate an interactome map of the regulatory pathways of cholesterol utilization in Mtb. Cholesterol catabolic pathways as therapeutics target Current tuberculosis treatment regimen involves multiple drugs for a prolong period. The duration could be from three months to two years depending on the type of infection. Prolong treatment leads to non-compliance and emergence of newer drug resistance strains. Shortening the therapy would go a long way in alleviating this problem. It is widely perceived that the major culprits are the so-called non-replicating and metabolically inactive “persister” population. The importance of cholesterol metabolism during the persistence stage of Mtb infection and its potential role in generation of persisters is very intriguing. In light of the above facts and hypothesis the focus of the current proposal is to screen for chemical inhibitors that specifically target these pathways. The long-range goal would be identify novel anti-tubercular drugs that specifically targets “persisters”. These novel compounds in combination with the standard frontline anti-tubercular drugs would significantly enhance the success rate in tuberculosis therapy. Genetic essentiality study of Mycobacterium tuberculosis under various growth and stress conditions Advancement in new cost-effective high throughput sequencing techniques has led to the identification of complete genome of various pathogens. The volume of the data generated, failed in its objective of further understanding of microbial pathogenicity. Genetic essentiality study of a pathogen is one such technique where in a gene is functionally characterized and associated with a phenotype. In this laboratory the process of standardizing protocol to study genetic essentiality of Mtb under various growth and stress condition is in progress. To achieve the goal, the use of mariner based mycobacteriophage system for generating high-density transposon mutant library is planned. The library will passage through different growth and stress conditions and the genetic essentiality would be determined by comparing input and output libraries. Since it is demonstrated that cholesterol is required only during the late stages of Mtb infection, the hypothesis, that a genetic essentiality screen for the gene required for bacterial growth in cholesterol would be more relevant physiologically, if done under hypoxic conditions, is proposed. A better understanding on cholesterol metabolism at the molecular level under physiologically relevant conditions would definitely help in designing of effective therapeutic solutions for TB.

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Dr Arup Banerjee Virology Lab I

Research Focus: MicroRNAs (miRNAs) have been emerged as a powerful tool to regulate gene expression through the RNA interference pathway. They are highly conserved, endogenous, small noncoding RNAs. The human genome encodes more than 1,500 miRNAs (miRBase v.17) that play key roles in diverse regulatory pathways. It forms a complex network that is predicted to regulate more than 30% of protein coding gene. Based on the 2-7 nt seed sequence match, single miRNA can bind and regulate multiple mRNAs function. In addition to their regulatory roles in diverse biological pathways, cellular miRNAs play vital roles in virus–host interactions. Viral infections to the host are an active dynamics process. Several animal viruses have been demonstrated to cause dramatic changes in cellular miRNAs expression and influence the ability of a virus to replicate or spread. Therefore, simultaneous identification and characterization of miRNA-mRNA through profiling will provide a comprehensive view on host viral interaction and allow us to identify key factors associated with pathogenesis.

Currently, two projects are going on in our lab to identify key factors that are involved in Flaviviral pathogenesis; Project 1: Role of microRNAs in innate immune response and pathogenesis during Japanese Encephalitis virus (JEV) infection. In our lab, we are focusing to understand (1) How JEV infection modulates microRNA expression in infected microglia to control innate immune response; (2) Identification of host microRNAs that potentially target JEV genome and inhibit JEV replication; (3) Biological significance of JEV induced extracellular microRNAs and their impact on immune modulation

Project 2: Identification of novel biomarker for disease progression in Dengue patients; Our focus in this project is to study the early transcriptional signature in the peripheral blood mononuclear cells (PBMCs) in a large number of clinically and virologically well characterized patients with mild and severs dengue infection and establishes their correlation with disease progression.

This year, as continuation of these above mentioned projects, we are offering two potential projects to fresh PhD students.

1. To elucidate the role of Interferon Regulatory Factor 8 (IRF8) (key factors in microglia activation), in mounting innate immune response against Japanese encephalitis virus in infected brain Microglia are myeloid lineage cells and the principal resident immune cells of the CNS. In the normal brain, these cells have a surveillance function but following perturbation of the local environment this can result in rapid transformation of these cells to highly active effector cells. IRF8 (interferon-regulatory factor-8) plays a critical role in regulating myeloid cell differentiation. The absence of IRF8 is associated with specific morphological and functional changes in peripheral macrophages as well as CNS resident myeloid cells known as microglia. During JEV infection, Blood brain barrier gets disrupted, leading to inflammatory cell infiltration. These cells have been shown to be pivotal in the pathogenesis of JEV encephalitis in mice. IRF8 is also cross talk with NOTCH and TLR signalling pathway, which showed to be involved in inflammatory process in microglia cells. MicroRNA may be involved in fine tuning these processes. Our preliminary study suggested that JEV infection induces IRF8 & NOTCH expression in infected mice brain and in human microglial cells. Therefore, Using CRISPR technology, we will knock down IRF8 and will examine the role of IRF8 in mounting innate immune response against JEV and assess its impact on viral replication and pathogenesis in vivo and in vitro.

2. Understanding the role of Platelet derived microRNA in Dengue pathogenesis Dengue is the most common mosquito borne viral disease which affects more than 20 million people per year. According to WHO, up to 2.5 billion people globally live under the threat of dengue fever and its severe forms—dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). More than 75% of these people, or approximately 1.8 billion, live in the Asia-Pacific Region. Classical dengue represent acute phase with high fever, headache, which can be cured by the immunological response of the host against the virus. On the other hand, dengue hemorrhagic fever (DHF) is more severe where fever leads to plasma leakage, pleural effusions due to increased vascular permeability and can lead to dengue shock syndrome (DSS).

Although plasma leakage is the hallmark of severe dengue infections, the molecular factors that cause increased vascular permeability have not been identified. Normal Platelets express high levels of microRNAs. Emerging evidence suggests that platelet miRNAs are biologically and clinically relevant as potential regulators of platelet protein translation and expression. We hypothesize that Dengue infection may lead to enhance expression of specific set of microRNAs that may play a critical role in modulating vascular endothelial inflammatory responses. Identification of miRNAs and their target genes will help us to understand molecular mechanisms and will offer miRNA based strategies to protect vascular leakage in infected patients.

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Bhabatosh Das, M.Tech., Ph.D.

Assistant Professor Centre for Human Microbial Ecology

Translational Health Science and Technology Institute Contact: bhabatosh@thsti.res.in

On Going Research In My Laboratory The human body surfaces are home to trillions of microbes that play a fundamental role in the wellbeing of their host. This includes synthesis of essential amino acids and vitamins; processing components of otherwise indigestible diet, protection against pathogens, and development of immune system. The constituents of the human microbiota—bacteria, viruses, and eukaryotes interact with each other and with the host immune system through pathways that influence the development of disease.

The overarching objective of my lab is to determine the identify, community structure, dynamics and the factors/pathways that modulate the dynamics of human associated microbiota in healthy and various disease conditions. Currently, we are working on-

Profiling and cataloguing of human microbiota at different human body sites: We are catalogouing gut and vaginal microbiota of helathy and disease subjects using most advance Next Generation DNA sequencing.

Understand the role of intestinal microbiota in under-nourished children with the aim of developing

interventions like molecular probiotics that could modulate the intestinal microbiota.

Guanosine penta- and tetraphosphate metabolisms in bacteria and implications in gut microbiota homeostasis: Bacterial species inhabit in human intestine, sense analogous environmental signals with the help of their heterologous sensors and accordingly adjust intra-cellular level of (p)ppGpp, the utmost important secondary metabolites directly regulate the rate of bacterial multiplication by controlling DNA replication, transcription, translation, amino acid biosynthesis, glycolysis, gluconeogenesis, proteolysis, virulence factor production and biofilm formation. Our hypothesis, modulation of optimal level of (p)ppGpp, hence the multiplication rate of bacterial species in gut like complex environment could be feasible.

Role and impact of gut microbiota in emergance of multidrug resistance human pathogens. An

understanding of antibiotic resistance determinants circulating in bacterial pathogens will provide information not only about resistance frequencies but also about identify new mechanisms that may help to eradicate resistance determinants from the existing pathogens.

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Dr. Gaurav Batra gaurav.batra@thsti.res.in Assistant Professor 0129-2876357 Centre for Biodesign and Diagnostics Research Interests Knowing the cause responsible for a patient’s illness remains fundamental to evidence based treatment and care. Despite the fact that the reliable diagnostic tools affect health care decisions to a degree well out of proportion to their cost, in the developing world healthcare workers are forced to use empirical approaches of treatment which often result in inappropriate clinical outcomes because of lack of reliable, affordable and practical in vitro diagnostic solutions. Goal of my lab is to develop diagnostic solutions, which are reliable in local conditions, affordable and practical. Major focus of our work is on the development of high quality diagnostic assays for acute febrile illnesses e.g. dengue, malaria, typhoid and scrub typhus and leptospirosis. My lab is also going to start work on the development of a multiplex point-of-care test for the blood borne infections (HIV, HCV and HBV) for emergency settings in a large Wellcome trust funded project (project approved in-principle). To generate high quality diagnostic intermediates, my lab is using and constantly improving the following technology platforms:

• Yeast Pichia pastoris based expression toolbox for the production of recombinant antibodies and

antigens. Host cell engineering to improve the secretion of antibodies and other complex proteins.

• Phage display

Genome fragment libraries (for immune epitope mapping and biomarker discovery)

Random peptide libraries (for immune epitope mapping and biomarker discovery)

Synthetic antibody libraries (for the generation of human framework monoclonal antibodies and

biomarker discovery). Library access through University of Turku, Finland.

• Immunoassay development

Different formats (well based, lateral flow and all-in-one dry chemistry)

Different detection technologies (HRP/AP, Gold, TRF (Eu,TB chelate and nanopart.) and novel

upconverting phosphors.

Most of the work in my lab is being done in collaboration with academic and industrial partners from India and Finland like ICGEB, New Delhi, University of Turku, Finland, University of Helsinki, Finland, Kaivogen Oy, Finland, Designinnova, India. Major contribution I was involved in the development of diagnostic intermediates and assays for the detection of anti-dengue virus IgG, IgM antibodies and NS1 antigen. This “know-how” was transferred to a diagnostic company, which resulted in a very successful commercial product for detection of dengue NS1 antigen & differential detection of IgM & IgG antibodies in Human Serum/ Plasma. Projects that may be offered to the student

The project will be decided basis the student’s attitude and aptitude. Projects could be around the following topics:

Pichia pastoris host cell engineering for the enhanced secretion of recombinant antibodies.

Development of sensitive and specific point of care assay for Salmonella typhi and paratyphi A (no

reliable test available). This work may include new target discovery and generation of unique

monoclonal antibodies against specific targets using synthetic antibody libraries.

Development of novel upconverting phosphors based whole blood point of care assay for HCV

Development of all-in-one dry chemistry based immunoassay for different targets including dengue and

malaria.

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Dr. Guruprasad Medigeshi Associate Professor, VIDRC, THSTI

Ongoing projects/potential projects for the new PH.D. student Project 1: Identification the mechanism of action of dengue virus inhibitors identified in a high-throughput screen Background and objective: There are currently no vaccines or antivirals against dengue virus (DENV) and recent vaccine clinical trials have not yielded promising results. Although a number of inhibitors targeting the viral protease and polymerase have been discovered the safety and efficacy of these compounds are yet to be proven. Our approach is to repurpose drugs that are approved for other conditions to treat dengue infections. We have screened a library of pharmacologically active compounds by using a immunofluorescence-based high-throughput screening approach for DENV-2 infection in vitro. After two iterations and elimination of false-positive hits and cytotoxic compounds we have identified 6 inhibitors that completely inhibit production of DENV-2 virus in cell culture. Further characterization of the mechanism of action and identifying the drug target and the pathway/s involved is due. Project 2: Understanding the role of zinc homeostasis in endothelial dysfunction in dengue infection Background and objective: Zinc is an essential micronutrient which is involved in regulating the functions of about 10% of the human proteome. One of the most important functions of zinc is in maintaining the permeability barrier of epithelial and endothelial cells and therefore, infections that affect zinc homeostasis are likely to affect the functions of barrier forming cells. The objective of this project is to use dengue virus as a model for studying the functions of epithelial and endothelial barriers in the context of zinc homeostasis. The effect of dengue infection on zinc homeostasis, the viral and host factors involved in mediating this effect and strategies to prevent disruption of barriers are some of the research areas that are of interest to the lab. The project will involve interaction with clinicians and will provide opportunity to study dengue disease in a natural model of infection, that is, in human beings.

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Dr. Manjula Kalia

Research Interest: Host-Pathogen Interactions of Japanese Encephalitis Virus

Flaviviruses are important arthropod-borne viruses that cause human disease globally. Japanese Encephalitis

(JE) is the leading form of viral encephalitis in South-East Asia and India. Around 30,000-50,000 cases of JE and

up to 15,000 deaths are reported annually. Most cases of JE are asymptomatic however a minority will develop

severe encephalitis with a significant chance of permanent neurological damage or death. Studies on host-

pathogen interactions are crucial to understanding the viral life-cycle and identifying possible therapies and

vaccine candidates and for the development of future anti-viral drugs.

Pharmacological induction of autophagy as a therapeutic for JEV infection. Autophagy is an important

cellular process that maintains cellular homeostasis. The autophagy mechanism is constitutive, but is up-

regulated in response to stress, and pathogen infection. It is also an important component of the innate and

adaptive immune response against pathogens. Recent work from our laboratory has shown that autophagy is

primarily anti-viral and controls JEV induced cell death. We are currently exploring how autophagy modulates

the innate immune responses to JEV infection and its effect on virus replication and disease outcome. This

project plans to elucidate the mechanism of autophagy induction during JEV infection and examine the

potential of pharmacological induction of autophagy as a therapeutic in mouse model of JEV.

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Identification and characterization of Dengue viral proteins interaction with other viral proteins and

host proteins

Dr. Mohan B Appaiahgari

Origin of the proposal: Viral proteins through their interactions with other viral and host proteins play

important roles in viral life cylce and, hence, are important candidates for detailed investigation. Study of the

importance of these interactions is critical in the development of effective vaccines and specific antiviral

therapeutics. With respect to flaviviruses, capsid and the NS1 proteins, besides playing critical roles in

replication, are known to be central in pathogenesis (Amorim et.al., 2014; Netsawang et.al., 2010; Urbanowski

et.al., 2008; Agarwal et.al., 2013; Medigeshi et.al., 2009). While several interacting partners of DENV NS1 have

been identified, importance of these interactions have been largely unknown (Silva et.al., 2013). For DENV

capsid, such information is slowly expanding and recently a role in mediating apoptosis of hepatocytes has

been demonstrated (Netsawang et.al., 2010).

Objectives of the study: The study is aimed at identifying interactions of DENV capsid and NS1 proteins with

other viral and host factors in different target cell types. Further, based on the strength of these interactions

and on the predicted role of identified proteins, some of the interactions will be studied in detail to decipher

their role during DENV replication and pathogenesis.

Methodology and study design: Capsid/NS1 interacting partners playing critical roles during DENV infection

will be identified using three different approaches: (i) Plasmids expressing Capsid/NS1 proteins will be

transfected into different target cell types and the protein complexes immunoprecipitated from the DENV

infected cell lysates at different time points post infection will be analyzed by mass spectrometry, (ii) Using

Capsid/NS1 proteins as bait, cDNA libraries of mouse/human origin will be screened for their interacting

partners in a yeast 2-hybrid screen. Similarly, their interactions with other viral proteins will also be tested in a

2-hybrid screen, and (iii) siRNA library specific to human/mouse cell types will be used to identify the proteins

crucial for viral replication in the target cell. Importance of the short-listed candidate proteins will be

thoroughly established in knock-down experiments. Similarly, the extent of their influence on viral replication

will be quantitated by qPCR as well as by virus titration assays. Based on this data, at least 3 candidate proteins

having strong influence on viral replication will be selected for further investigation of their mechanism of

action. Mechanistic studies will be designed based on the predicted roles of the selected protein candidates and

the pathways that they are known to be involved in. The mechanistic roles will be deciphered by employing

siRNAs and/or specific inhibitor drugs against different key players in the predicted pathways. Finally, the

most promising candidate(s) will be tested in a suitable mouse model.

Outcome of the proposed study: The proposed project is expected to generate large amount of data pertaining to

the protein-protein interactions between DENV Capsid/NS1 and other viral and host proteins. Similarly,

siRNA-library based screen will identify different host proteins/pathways involved in up- or down-regulating

DENV replication. This information will form the basis for future studies. Besides, data from the mechanistic

roles proposed to be investigated in the proposed study will help us design therapeutically viable antiviral

molecules.

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Dr Nisheeth Agarwal Every year millions of people die because of tuberculosis (TB). The TB causing human pathogen, Mycobacterium tuberculosis (Mtb) has an ability to undergo latency in the host cells where it persists for years. According to an estimate by the World Health Organization, 2 billion people carry the latent Mtb bacilli which may revert back to active bacteria under the immunocompromised state of the host. Despite the availability of multi-drug treatment option, number of TB cases remains daunting mainly due to the emergence of drug-resistant Mtb population. Although there are several recombination-based tools available to manipulate Mtb genome, but most of these are inefficient. Because of the lack of an efficient approach, identification of new drug targets has been severely impeded. Recently, our lab has developed a new approach based on CRISPR-interference to suppress the expression of any gene in any mycobacterial species by >90% (Choudhary et al, Nature Communications, 2015). The major objective of my lab is to implement the CRISPRi approach for identifying the core set of essential genes, to understand their function in mycobacteria and establish them as potential drug targets. With this objective, currently we are characterizing the role of P-loop GTPases, DNA gyrase, a pre-protein translocase and essential proteases. In parallel to characterizing the role of Mtb genes, we are also working on the effect of Mtb infection on post-translational modification of host proteins. The project is funded by Department of Biotechnology where we have proposed studying the effect of Mtb and BCG infection on host phosphoproteome. Some of the areas where a prospective student can work in my lab include:

1. Identification of a core essential gene of Mtb and an in-depth characterization of its function.

2. Further characterization of the role of YidC, a pre-protein translocase of Mtb (the work is persuaded by

a PhD student, Ms. Preeti Thakur)

3. Construction of a knockdown strain of Mtb targeting all 17 adenylate cyclases to better understand the

role of cAMP in Mtb physiology and pathogenesis.

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Title of the research theme: Understanding mechanisms of persistence of M. tuberculosis and validation of new drug target pathways to combat tuberculosis.

Principle Investigator: Dr. Ramandeep Singh,

Associate Professor

Theme of Research:

Tuberculosis kills annual 2 million people globally and an estimated one-third of world population is infected with latent tuberculosis, 10% of them have a risk for developing active TB disease. This situation has further aggravated due to HIV-TB nexus and emergence of various drug resistant strains of M. tuberculosis. Eradication of this dreaded disease requires understanding of the pathways that enables the bacteria to persist in the host and design of strategies aimed at targeting these non-replicating/latent bacteria residing in host tissues. The current focus of my research group is to identify metabolic pathways that enable M. tuberculosis to adapt to various conditions and to persist in the host. Another focus of the lab is to identify synthetic molecules that are active against non-replicative/persistent bacteria and to understand their mechanism of action.

Bacterial drug-tolerance is reported to result from lower metabolic requirements for processes that characterize actively growing cells such as transcription, translation, replication and cell wall synthesis. An attractive hypothesis for the origin of these persisters is that they arise from stochastic over expression of endogenous regulators of macromolecular synthesis in a subset of cells, toxin antitoxin modules or activation of stringent response pathways of M. tuberculosis. In our lab we have characterized enzymes involved in polyphosphate metabolism and showed that polyphosphate deficiency increases susceptibility of Mtb to various front line TB drugs (Singh et al., 2013). We have also biochemically characterized toxin-antitoxin systems of Mtb and observed that these TA systems are differentially regulated upon exposure to various stress conditions (Tiwari et al., 2015). In a recent paper published we show that these ribonucleases contribute cumulatively to the ability of Mtb to survive in oxidative, nutritional and in guinea pigs (Tiwari et al., 2015). Currently, experiments are in progress to identify the pathways regulated by these ribonucleases and polyphosphate in Mtb. We have also biochemically characterized phosphoserine phosphatase enzyme and identified novel scaffolds that specifically inhibit SerB2 enzyme from Mtb (Arora et al., 2014). In the drug screening activities of the group, we have identified various scaffolds that inhibit Mtb growth in vitro. We have also raised revertants for few of these scaffolds and are currently performing Next-gen sequencing to identify SNPs in these revertant strains (Unpublished data). In collaboration with various medicinal chemists we have identified few chemical entities that are active against Mtb in low micromolar range (Kumar et al., 2014a, b, Bansal et al., 2014, Beena et al., 2012, Unpublished data). In addition to this we have also initiated few projects such as (i) Understanding the role of rTCA enzymes in physiology and pathogenesis of Mtb, (ii) Modulation of host sumoylation pathways upon Mtb infection, (iii) Understanding the role of Nucleoid associated proteins and GntR transcription factors in physiology and pathogenesis of Mtb. iv) Validation of other amino acid metabolic enzymes as drug targets for Mtb. v) VapC toxins: Identification of their cellular targets and their role in drug tolerance and virulence of Mtb.

Projects on offer for new Ph.D. students.

1. Using proteomics and genomic approaches to identify metabolic pathways regulated by toxin-antitoxin systems and polyphosphate levels. Using RNA-seq approach to study cross-talk between these pathways.

2. Development of an assay system to identify inhibitors for essential transcription factors of Mtb. 3. We have developed various attenuated strains of Mtb, therefore, we would want to evaluate these

strains for their protective efficacy in various animal models. 4. Screening of libraries to identify novel inhibitors for Mtb and identify their drug targets using reverse

genetic approach. 5. Structure-activity relationship studies to improve the activity of already screened scaffolds (For

Students with preferably M.Sc (H) Chemistry).

References

1. Tiwari P, Arora G, Singh M, Kidwai S, Narayan O and Singh R*. MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs. Nature Communications Jan 22; 6:6059 doi 10.1038/ncomms 7059.

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2. Kumar D, Khare G, Beena, Kidwai S, Tyagi AK, Singh R and Rawat DS. Novel isoniazid-amidoether derivatives: synthesis, characterization and antimycobacterial activity evaluation. Med Chem Comm 2015 (6) 131-137.

3. Bansal S, Singh M, Kidwai S, Bhargava P, Singh A, Sreekanth V, Singh R* and Bajaj A*. Bile acid amphiphiles with tunable head groups as highly selective anti-tubercular agents. Med Chem Comm. * Co-corresponding author 2014 (5) 131-137.

4. Arora G, Tiwari P, Mandal RS, Gupta A, Sharma D, Saha S and Singh R*. High through put screen identifies small molecule inhibitors specific for Mycobacterium tuberculosis phosphoserine phosphatase. J Biol Chem Sep 5 2014; 289(36): 25149-25165.

5. Gupta M, Sajid A, Sharma K, Ghosh S, Arora G, Singh R, Nagaraja V, Tandon V and Singh Y. HupB, a nucleoid associated protein of Mycobacterium tuberculosis is modified by Serine/Threonine protein kinases in vivo. J Bacteriol July 2014 (196)2646-2657.

6. Kumar D, Beena, Khare G, Kidwai S, Tyagi AK, Singh R and Rawat DS. Synthesis of 1,2,3 triazole derivatives of isoniazid and their in vitro and in vivo anti-mycobacterial activity evaluation. Euro J Med Chem June 2014, (81) 301 – 313.

7. Chauhan P, Reddy PV, Singh R, Jaisinghani N, Gandotra S and Tyagi AK. Secretory phosphatases deficient mutant of Mycobacterium tuberculosis imparts protection at the primary site of infection in guinea pigs. pLOS One Oct 2013 8 (10): e77930.

8. Kumar N, Kapoor E, Singh R, Kidwai S, Kumbukgolla W, Bhagat S and Rawat DS. Synthesis and antibacterial/antitubercular activity evaluation of symmetrical trans-cyclohexane-1,4-diamine derivatives. Ind J Chem Nov 2013 52B 1441 – 1450.

9. Singh R, Singh M, Arora G, Kumar S, Tiwari P, Kidwai S. Polyphosphate deficiency in mycobacterium tuberculosis is associated with enhanced drug susceptibility and impaired growth in guinea pigs. J Bacteriol May 2013 195 2839 – 51.

10. Beena, Joshi S, Kumar N, Kidwai S, Singh R, Rawat DS. Synthesis and antitubercular activity evaluation of novel unsymmetrical cyclohexane-1,2-diamine derivatives. Arch Phar Nov 2012 345 (11) 896-901.

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Principal Investigator: Dr. Ranjith Kumar

Co- Principal Investigator: Dr. Sudhanshu Vrati

Research theme: Viral replication and modulation of innate immune response by viral proteins.

Research area

How RNA viruses can establish successful infection in the face of the host innate response is important for

pathogenesis and will offer potential solutions to some of the most deadly diseases. My laboratory is interested

in studying the replication mechanisms of hepatotropic RNA viruses such as hepatitis C virus (HCV) and

hepatitis E virus (HEV) with the aim of developing better direct-acting antivirals. The study extends to

understanding the strategies used by viruses to evade host innate immunity responses with the goal of

developing attenuated vaccines.

On going Projects: Viral RNAs contain molecular signals known as pathogen associated molecular patterns

(PAMPs) that are detected by innate immunity receptors to activate a suite of cellular defense responses.

Viruses are known to have evolved strategies to interfere with the host responses either by blocking

recognition of molecular patterns or by cleaving adaptor proteins.

Our laboratory is currently characterizing biological role of the HEV proteins during viral infection with special

focus on their involvement in interfering with innate immunity response.

We are also developing and characterizing small molecule inhibitors of HCV and HEV

Proposed project: RNA dependent RNA polymerase (RdRp) is the catalytic subunit of the replicase complex

responsible for the replication of viral RNA. The RdRp is an essential enzyme found in all RNA viruses and

hence is a potential target for drug design and development.

In spite of the critical role of RdRp in the viral life cycle, the replication of HEV is poorly understood. This

project will involve the characterization of HEV RdRp and understanding its role in replication of viral genomic

and subgenomic RNA. Furthermore, the role of host proteins involved in viral replication will be elucidated.

Understanding HEV replication will be crucial for the development of more effective antivirals.

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Dr. Samrat Chatterjee My research area: Through mathematical modelling and data analysis, my lab’s research work is dedicated to understand biological problems. We use small conceptual models using different kinds of differential equations as well as large-scale models to understand relation between processes (variables) and the factors (parameters) driving those processes. We analyze these models both analytically using different mathematical tools and also numerically using computer softwares like Matlab, Maple, SPlus and XPP-AUTO. I also handle large volumes of high-throughput data using systems biology techniques (like network analysis) using softwares like cytoscape, Simca and other online packages like KEGG pathway, PANTHER and STRING data set. I am also developing tools (using Matlab with my own algorithm) that can be used to handle large volume of high-throughput data and to estimate parameters for the proposed model. Project (1) “Unraveling the architecture of biological networks to identify points of sensitivity under random perturbation”: Therapeutic strategies that target key molecules have not fulfilled expected promises for most common malignancies. Major difficulties include the incomplete understanding and validation of these targets in patients, and the uses of single-pathway targeted approaches that are proving to be not so effective therapies for human malignancies. Signaling pathways are not linear pathways but it includes molecular cross-talk. To understand this we need to consider and analyze the system as a complex network of interacting components. Such departure from the traditional paradigm of studying single pathway to more global approach will aid the design of novel therapeutics and will help to overcome the shortcomings of the existing therapeutic strategies. Here, we use mathematical models to dissect the network to understand the importance of motif structure in determining the cellular function in presence of noise and their distribution in a signaling network. This will help us to quantitatively measure the sensitivity of a motif in the signaling network under noise and thus enable us to develop a formula that will rank the nodes according to their presence in different motifs in a biological network. This ranking could then be used to identify potential drug candidates. Project (2)-“ Mathematical approaches to understand host-pathogen cross-talk in Mycobacterial pathogenesis”: Development of an effective vaccine or a small molecule formulation for therapeutic management of TB has been a major challenge owing to the complex nature of disease and emergence of multi-drug resistance (MDR). In such complex biological systems, mathematical models are emerging as important tools. The proposed study will help in expanding the current understanding of Mycobacterial pathogenesis to delineate the strategies adopted by pathogen to fight against drug regimen and concomitant disease establishment and progression at both cellular as well as population level. The current study is an attempt to draw a common thread through the survival strategies adopted by the pathogen to establish itself at both population and cellular level. Using the mathematical model the proposal seeks to understand the underlying process/mechanism(s) by which emerging trait is acquired by the pathogen, manifesting a new phenotype, leading to suppression of host antimicrobial responses and unresponsiveness to drug regimen. Project (3)- “Use of model trajectories to understand the regulatory mechanisms underlying metabolic diseases”: Obesity is not only itself a concern for decades, but also leads to other health problems like development of type 2 diabetes mellitus (T2D), coronary heart disease, certain form of cancer etc. Existing knowledge at this interface is still fragmentary and the present study is mainly focused in this area. The main objective of the present study is as follows-1) To study the temporal gene expression patterns and find the temporal changes in the functional class of obese and diabetic mice. 2) To understand disease progression in obese and diabetic mice using mathematical models. The solution trajectories of the models leading to different equilibrium points will mimic the disease progression and the parameter driving these trajectories will dissect the internal mechanism. Here by changing the parameters we can theoretically re-engineer the pathways and can get a possible conversion from one disease state to other and merging them all to the healthy state.

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Dr. Sanjay K Banerjee

Cardio‐metabolic Laboratory Drug Discovery Research Center, THSTI, Faridabad Research interest of Dr. Banerjee’s laboratory is to investigate the molecular and genetic mechanisms of cardiovascular and metabolic disorders (diabetes), and drug discovery through screening of small molecules. Cardiomyopathy, disease of heart muscle, deteriorates cardiac function as the disease progress. Dr. Banerjee’s group mostly work on hypertrophic and diabetic cardiomyopathy. If untreated, both cardiomyopathies stated above may progress to heart failure. The pathophysiology of cardiomyopathy is complex and still not completely understood. Cardiac metabolism especially glucose and fatty acid oxidation, mitochondrial dynamics and oxidative stress play together to deteriorates cardiac function. At the molecular level our focus is to understand how HDACs, particularly classIII HDACs (Sirtuins) regulate cellular function under different pathophysiological conditions. Sirtuins are NADdependent deacetylases. They are implicated in regulation of myriad of biological functions, spanning from cell growth and metabolism to senescence. We are using cells, animals and human tissues to determine the signaling pathways contributing to pathologic cellular growth and metabolism, and then to understand how sirtuins modify these pathways and protect cells from various insults. Using system biology approach, we have also identified several novel genes which are perturbed in metabolic disease state. We are looking the functional role of unknown genes and searching novel targets for cardiac diseases and metabolic disorder. At the same time, we are also elucidating the role of human gene mutation in cardiac function and identifying genetic, biochemical, cellular and biophysical pathways that lead from mutation to disease. Overall goal is to bridge the gap between observations in the basic research laboratory and the clinical bedside. My studies will be an integral part in ‘‘translating’’ new discoveries into therapeutic initiatives.

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Dr. Sankar Bhattacharyya Introduction The virus group of flaviviruses consist of aetiological agents for many infectious diseases relevant for the Indian subcontinent. These include the mosquito borne viruses responsible for causing encephalitis (Japanese encephalitis virus or JEV) and dengue (Dengue virus or DENV). Viruses do not possess the cellular machinery for either translation of viral proteins or replication of the viral genome. Therefore, they are dependent on the host cell for providing all components that are necessary for the above functions. However, host cells have also evolved elaborate pathways to counter virus infection and prevent the virus from usurping cellular machinery. An understanding of these host-virus interactions is important to devise prophylactic and/or therapeutic methods which can protect the hosts i.e. humans from the harmful effects of virus infection. Specific objectives We are interested in studying host-pathogen interactions, with respect to the influence of RNA-binding proteins on the replication efficiency of two flaviviruses, JEV and DENV. The genome of flaviviruses is a plus-sense single-stranded RNA which is directly translated to produce the viral proteins. Following this, the genome is replicated by the virus-encoded polymerase with the help of different virus-encoded and host-encoded factors. As part of their role in viral replication, these protein factors interact with the viral RNA and a disruption of this interaction(s) might lead to inhibition of viral replication. Therefore, the specific objectives towards such an achievement are:

1. Explore viral-RNA interacting partner proteins, with potential role in viral replication, using in vitro and

in vivo methods

2. Decipher the specific role in viral replication for known interacting protein partners

3. Devise strategies to disrupt interaction between viral RNA and critical host factors for therapeutic

purposes

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Dr. Shailaja Sopory Scientist-D

Pediatric Biology Center Research Interest: My laboratory works in collaboration with the laboratory of Dr. Uma Chandra Mouli Natchu. We are interested in looking at the development of the neonatal immune system at the immunophenotypic and functional level. We are trying to understand the role of nutrition, intestinal inflammation and microbial exposures to linear growth in children during the initial stages of their life. Another aspect of the research involves looking at specific childhood diseases, like minimal change nephrotic syndrome in children, which is associated with proteinuria (loss of protein in the urine) due to disruption of the podocyte slit diaphragm (a modified tight junction specific to the podocyte). This forms part of a larger picture of finally looking at loss of barrier function in other epithelial cells during infection and inflammation.

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Dr. Shinjini Bhatnagar

Pediatric Biology Centre

It is essential that innovative and sustainable intervention strategies for child health in the country are built on a sound, more rigorous understanding of underlying biology. The Pediatric Biology Centre (PBC) was established at the Translational Health Science and Technology Institute (THSTI), serves as an interdisciplinary research center where research on the biological basis of childhood health and disease leads to the creation of knowledge-driven interventions and technologies that can be sustainably implemented.

We have initiated an inter-institutional program on maternal and infant sciences as a multidisciplinary research effort to predict & diagnose Preterm Birth (PTB) by increasing the understanding of the underlying pathophysiological mechanisms, which would facilitate use of existing or novel therapeutic agents & appropriate timing of clinical intervention. It is envisaged that the clinically relevant research outputs from the study will be appropriate characterization of biological, clinical and epidemiological risk factors to achieve appropriate risk stratification of mothers who may deliver before term.

As part of this study we will follow 8000 pregnant women in a districy hospital at Gurgaon, from early pregnancy, before 20 completed weeks of gestation (POG), until delivery to capture their exposure to important environmental, clinical and biological factors and to assess associations of these factors with PTB. We will collect bio specimens like blood, saliva, high vaginal swab from all 8000 women at < 20 weeks POG, 18-22 weeks POG, 26-28 weeks POG of pregnancy and maternal blood and cord blood at delivery. These bio-specimens are further being analyzed by global “omics” approaches including genomics, epigenomics, proteomics and for microbiomic alterations. This is being done in order (i) to identify and study mechanistic pathways for better targets that could be used for prediction & therapeutic interventions and (ii) identify potential biomarkers that can be used for risk stratification and early diagnosis of PTB and/or intervention modalities. Serial ultrasound imaging is done at similar time points to document accurate “dating” of pregnancy and period of gestation, congenital anamolies and fetal growth.

We will also conduct sub-studies within the larger cohort to understand (i) the nutritonal and metabolic factors that can influence pregnancy outcomes such as preterm birth, growth retardation and still birth, (ii) the presence of infection in early pregnancy and its etiological role in preterm birth/still birth; its association with changes in the cervical morphology and the placenta, (iv) potential non invasive imaging markers that can predict pregnancy outcomes, (v) environmental fatcors (such as environmental toxins, social factors, mental health) that influence fetal growth and early birth.

PBC has also initiated distinct research programs to create new insights in the neonatal and infant immune systems and early child health. There has been a void in the understanding of immunology and infectious diseases in neonates and infants because of a lack of a clear characterization of their developing immune systems and their maturation. An in-depth knowledge of the neonatal immune system, its maturation over infancy, and how it responds to antenatal, perinatal and early childhood stressors will help in understanding the increased susceptibility to infections in neonatal period and in infancy. This would lay the background for developing critical, time-point specific interventions that can partially or completely reverse the adverse effects. We have examined the differences in the immune status between small for gestational (SGA) and appropriate for age (AGA) babies that may underlie the susceptibility of SGA neonates to infections using a cross-sectional design. We have found differences in diverse cellular lineages of the immune system and believe that these are likely to reflect altered maturation of the immune system due to the intrauterine conditions causing growth retardation rather than simply retarded immune system maturation. Our findings open new avenues for examining both the molecular-cellular genesis and the functional-clinical consequences of immune dysfunction in underweight neonates.

Dr. Satyajit Rath & Dr. Vineeta Bal (Senior Scientists at NII) who are adjunct Faculty at PBC mentor the biology program at the center. We collaborate extensively with Prof. Dinkar Salunke and his team, Prof. Partha Majumdar and his team & Prof. G B Nair and his team for genomics, proteomics and microbiome work. We work very closely with the paediatricians and gynaecologists at the Gurgaon District Hospital and the faculty at AIIMS, MAMC and Safdarjung Hospital.

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Biology of Japanese encephalitis virus replication

Dr. Sudhanshu Vrati

Dean-THSTI and Head-VIDRC http://www.thsti.res.in/profile.php

Ongoing research in the lab Japanese Encephalitis virus (JEV) is a member of the Flaviviridae family of animal viruses that contains several other medically important viruses such as Dengue and Yellow fever. JEV is a major cause of human encephalitis and is responsible for considerable mortality and morbidity in India. Frequent epidemics of Japanese encephalitis (JE) are being reported from various parts of India and JEV has become endemic in several parts of the country. We are studying the replication of JEV and investigating the role of the cellular proteins in virus replication. We are also examining the potential of small nucleic acid molecules such as siRNA and DNAzymes for inhibiting JEV replication. Our group also focuses on key aspects of the JEV life-cycle like receptor-binding and entry mechanisms, molecular mechanisms of virus replication, assembly and egress. The virus infectious-cycle involves a complex interaction between virus and host proteins. We are employing JEV- recombinant proteins and infectious viruses as exploratory systems in combination with molecular biology, cell biology and proteomic approaches. These studies provide insight into JEV pathogenesis, and have the potential to offer therapeutic interventions. Japanese encephalitis virus receptor system JEV is a major cause of human encephalitis and is responsible for considerable morbidity and mortality in India. No drug is presently available to specifically treat JEV infection. Considering the extent of infection and its consequences, there is urgent need to develop molecules that can inhibit JEV infection. Virus interaction with attachment factors and receptors on the cell membrane is the first step towards the establishment of infection. This interaction is often a multistep process, involving a wide range of host cell surface molecules which facilitate virus recognition, attachment, binding and entry into the host cell. Identification of membrane proteins interacting with JEV envelope protein will allow us to decipher the virus receptor system and help us understand the molecular events involved in JEV entry into permissive cells. The proposed doctoral study would identify host cell membrane proteins that bind JEV envelope protein using the yeast-2-hybrid system. This information would be very useful to design novel molecules that interfere with JEV binding with cells, and thus the virus infection process, and may have great prophylactic and therapeutic potential.

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Dr Uma Chandra Mouli Natchu The Immunity, Nutrition and Child Health Laboratory (INCH)

The laboratory houses the combined groups of Dr Shailaja Sopory and Dr Uma Chandra Mouli Natchu of the Pediatric Biology Centre. My group explores issues of nutrition and immune function in pregnancy and childhood with a multidisciplinary approach that involves fundamental biology, clinical research and public health perspectives and methods. The group currently focuses on Vitamin D, as a nutrient that plays a major role in susceptibility to infectious morbidity and mortality. Our focus is to look at relationships between nutritional status and immune function in pregnant women, the fetus and infants. This includes associations between components of the 'immune cytome' (cellular profiles of the immune system determined by flowcytometry) and serum Vitamin D concentrations in the umbilical cord and a clinical trial to assess if daily Vitamin D supplementation to newborns for 6 months affects immune responses to vaccines administered at birth and early in infancy. We are also studying inflammation and linear growth in infancy. The group links clinical research exercises with fundamental biological experiments by efficiently nesting efforts to understand human biology within well-executed clinical trials and cohort studies. We often incorporate questions of biological mechanisms with collaborators early in the process of designing and structuring clinical research projects. We collaborate extensively for a number of these approaches internally across the Pediatric Biology Centre and THSTI; with Dr Nitya Wadhwa & Prof Shinjini Bhatnagar for clinical research and Drs Shailaja Sopory, Anna George, Vineeta Bal, Satyajit Rath and Guruprasad Medigeshi for research involving biological mechanisms. The bulk of our clinical research is conducted at the General Hospital, Gurgaon in collaboration with the departments of Pediatrics and Gynecology. In addition, we work with Dr Jeremy Goldhaber-Fiebert at Stanford University for modeling based research on health policy and economics and with Professors Halvor Sommerfelt and Tor A Strand at the Centre for International Health, Bergen for clinical and community health research. Chosen students are likely to work on ongoing projects on Vitamin D immunology, neutrophil dynamics in infancy and linear growth. Dissertation activities can range from clinical research and data analyses to understanding of immunological mechanisms in infants using biological methods (human and animal experiments). Dr Natchu can be contacted at unatchu@thsti.res.in or ext. 356 or 0129-2876356.