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About CSIR-IMTech

Introduction to the Lab

Established in 1984, the CSIR-Institute of Microbial Technology (IMTech) is one among the chain of
38 national laboratories, 6 units and 39 outreach centres of the Council of Scientific & Industrial
Research. Set-up to be a fore-runner in the niche domain of microbial biotechnology, the Institute in
its initial years functioned from a start-up laboratory that provided a truly world-class R&D ambience
in an area of over 10,000 sq. ft. to its researchers. In September, 1989, upon completion of the
permanent campus, the Institute shifted to occupy an area of about 47 acres, of which the labs
covered 22 acres and the residential campus 25 acres. The Institute covering a built up area of
about 3.60 lakh sq. ft., is spread over four main buildings, namely, Main R&D block, Fermentation
block, Animal House, Workshop, Stores and Services area, several service building including a
guest house and Cafeteria. Recently another block of almost 50000 sq. ft. area (the G.N.
Ramachandran Protein Centre) has been added, to cater to R&D in all aspects of Protein science
and engineering. The Institute provides laboratories which are functionally modular and offer large,
air-conditioned, clean research areas to all the scientists.
The Institutes primary asset is a team of more than 55 highly motivated scientists, with a majority of
them having several years of training in world renowned laboratories. Supported by more than 300
well trained technical staff and graduate students, these scientists have built strong peer credibility
both in basic and application-oriented broad thematic areas of Molecular biology and microbial
genetics, Cell biology and immunology, Protein science and engineering, and Fermentation
technology and applied microbiology. These overarching focus areas required enabling research
facilities, structures and practices which IMTech has created over the years, recognized nationally to
be the best, and globally at par with the best. This required a visionary approach and objectives with
a long term mandate of scientific relevance.
CSIR-IMTechs team of scientists having cutting edge R&D expertise in the areas of: Cloning &
expression of recombinant / engineered proteins & their scale-up, Understanding / manipulating
proteins and their engineering, Protein structure determination through X-ray crystallography,
Molecular microbiology of pathogens especially with respect to drug resistance & vaccine
development, Immunology of infectious diseases, Yeast Genetics, Screening of microorganisms for
novel enzymatic activities and strain improvement, Bioinformatics & high end computational biology,
Microbial taxonomy and metagenomics, and allied areas like technology and business management
and intellectual property protection.
That IMTech could attract and gather a highly motivated and creative team of scientists speaks
volumes of the ambience, achievements and a defined focus which are associated with it. CSIR-
IMTech as it stands now, a symbol of a top biotechnology institute in the country.

Mandate of IMTECH
 To provide integrated research, development and design base for microbial technology.

 To undertake basic and applied research and development programmes in established and newly
emerging areas of relevant biotechnology including genetic engineering.
 To optimise the existing microbial processes currently available and in use in the country.

 To develop and maintain gene pool resources and genetic stocks of microbial cultures and other cell
lines. This could also serve as a reference centre to assist other centres.

 To establish facilities for biochemical engineering, instrumentation development including


microprocessor systems, a computer centre and development of mathematical models for process
parameters.

 To establish facilities for design of process equipment and bioreactors.

 To impart training in microbiology, microbial technology and biochemical engineering.

 To conduct training and refresher courses for research workers and technologists.

 To establish documentation and information retrieval and dissemination facilities and a data bank to
meet the needs of the Institute.

 To establish and maintain effective linkages with industry and educational institutions.

 To develop capabilities for producing design and engineering packages for industrial plants.

Institutional Highlights
The Institute's primary asset is a team of more than 55 highly motivated scientists, with a majority of
them having several years of training in world renowned laboratories. Supported by more than 300
well trained technical staff and graduate students, these scientists have built strong peer credibility
both in basic and application-oriented broad thematic areas of Molecular biology and microbial
genetics, Cell biology and immunology, Protein science and engineering, and Fermentation
technology and applied microbiology. These overarching focus areas required enabling research
facilities, structures and practices which IMTECH has created over the years, recognized nationally
to be the best, and globally at par with the best. This required a visionary approach and objectives
with a long term mandate of scientific relevance.
IMTECH's team of scientists having cutting edge R&D expertise in the areas of: Cloning &
expression of recombinant / engineered proteins & their scale-up, Understanding / manipulating
proteins and their engineering, Protein structure determination through X-ray crystallography,
Molecular microbiology of pathogens especially with respect to drug resistance & vaccine
development, Immunology of infectious diseases, Yeast Genetics, Screening of microorganisms for
novel enzymatic activities and strain improvement, Bioinformatics & high end computational biology,
Microbial taxonomy and metagenomics, and allied areas like technology and business management
and intellectual property protection.

CSIR-IMTECH opens up a High-Tech Skill Development Centre in


partnership with Merck
In a first-of-its-kind public-private partnership, CSIR-Institute of Microbial Technology(IMTECH) today in
collaboration with Merck
Read More
Dr. Tapan Chakrabarti, Consultant, NCCS Pune Visited CSIR-IMTECH
Dr. Tapan Chakrabarti, Consultant, NCCS Pune Visited CSIR-IMTECH

Prof. S. P. Gautam visited CSIR-IMTECH


Prof.S. P. Gautam, Former Chairman, Central Pollution Control Board, New Delhi visited CSIR-IMTECH
on 13 Oct 2019

Dr Shiv Sarin, ILBS visited CSIR-IMTECH


Dr Shiv Sarin, ILBS visited CSIR-IMTECH

Sh Jayant Sahasrabudhe, National Organising Secretary, VIBHA visited


CSIR-IMTECH
Sh Jayant Sahasrabudhe, National Organising Secretary, VIBHA visited CSIR-IMTECH on 16/10/2019
भारतीय
Read More

Dr. Vijay Chautaiwale, Healthcare-Biotech Consultant visited CSIR-


IMTECH
Dr. Vijay Chautaiwale, Healthcare-Biotech Consultant visited CSIR-IMTECH on 21 nov 2019 Dr. Vijay
Chauthaiwale who is a
Read More

Prof.(Dr.) Jagmohan Singh Rana, Member, Uttarakhand Public Service


Commission visited CSIR-IMTECH
Prof.(Dr.) Jagmohan Singh Rana, Member, Uttarakhand Public Service Commission and Prof. (Dr. ) Anita
RawatRegistrar, Uttarakhand
Read More

CSIR-IMTECH has signed an MoU with NABI Mohali


CSIR-Institute of Microbial Technology (IMTECH), Chandigarh hassigned anagreement withNational Agri-
Food Biotechnology Institute
Read More

About CSIR
The Council of Scientific & Industrial Research (CSIR), known for its cutting edge R&D
knowledgebase in diverse S&T areas, is a contemporary R&D organization. Having pan-India
presence, CSIR has a dynamic network of 38 national laboratories, 39 outreach centres, 3
Innovation Complexes and 5 units. CSIR’s R&D expertise and experience is embodied in about
4600 active scientists supported by about 8000 scientific and technical personnel.
CSIR covers a wide spectrum of science and technology – from radio and space physics,
oceanography, geophysics, chemicals, drugs, genomics, biotechnology and nanotechnology to
mining, aeronautics, instrumentation, environmental engineering and information technology. It
provides significant technological intervention in many areas with regard to societal efforts which
include environment, health, drinking water, food, housing, energy, farm and non-farm sectors.
Further, CSIR’s role in S&T human resource development is noteworthy.
Pioneer of India’s intellectual property movement, CSIR today is strengthening its patent portfolio to
carve out global niches for the country in select technology domains. CSIR is granted 90% of US
patents granted to any Indian publicly funded R&D organization. On an average CSIR files about
200 Indian patents and 250 foreign patents per year. About 13.86% of CSIR patents are licensed - a
number which is above the global average. Amongst its peers in publicly funded research
organizations in the world, CSIR is a leader in terms of filing and securing patents worldwide.
CSIR has pursued cutting edge science and advanced knowledge frontiers. The scientific staff of
CSIR only constitute about 3-4% of India’s scientific manpower but they contribute to 10% of India’s
scientific outputs. In 2012, CSIR published 5007 papers in SCI Journals with an average impact
factor per paper as 2.673. In 2013, CSIR published 5086 papers in SCI journals with an average
impact factor per paper as 2.868.
CSIR has operationalized desired mechanisms to boost entrepreneurship, which could lead to
enhanced creation and commercialization of radical and disruptive innovations, underpinning the
development of new economic sectors.
CSIR has put in place CSIR@80: Vision & Strategy 2022 – New CSIR for New India. CSIR’s mission
is “to build a new CSIR for a new India” and CSIR’s vision is to “Pursue science which strives for
global impact, technology that enables innovation-driven industry and nurture trans-disciplinary
leadership thereby catalysing inclusive economic development for the people of India”. CSIR is
ranked at 84th among 4851 institutions worldwide and is the only Indian organization among the top
100 global institutions, according to the Scimago Institutions Ranking World Report 2014. CSIR
holds the 17th rank in Asia and leads the country at the first position.
Research Areas
 Disease Area units
 Technology Area units
 Enabling Area units

Disease Area units


Antimicrobial Research

WHO 2017 report had identified globally most important drug resistant pathogens, which urgently
requires development of new antibiotics. The Antimicrobial Research Team of CSIR-IMTech has
been working on these priority pathogens with unmet medical needs, namely,Mycobacterium
tuberculosis(Mtb) and gram-negatives, for over a decade and has established novel screens,
innovative models and robust platforms for understanding disease pathogenesis. CSIR-IMTECH is
building a translational platform for infectious diseases drug discovery and development with specific
focus on drug-resistant pathogens. Furthermore, CSIR-IMTECH has identified leads for further
development as pre-clinical candidates. The objective of the project is to apply cutting-edge
technologies to the discovery of high quality pre-clinical candidates in two verticals: (i) Tuberculosis
and (ii) Gram-negatives. We intend to build a robust drug discovery portfolio and drive the early
discovery projects into translational mode in collaboration with industry and clinical partners.

Virology
Development of antiviral therapeutics against dengue/flaviviruses and
exploring Indian virome

Emerging and re-emerging viruses are posing serious public health problem globally including India
with the huge economic loss. The World has witnessed several epidemics and outbreaks of many
viruses in the recent past e.g. Zika, Ebola, Influenza, dengue, chikungunya, Japanese encephalitis,
hepatitis and respiratory syncytial virus etc. It is important to decipher the Indian virome in the
clinical/other settings to better understand their different aspects. Importantly, dengue remains a
medical problem in India and tropical part of the world affecting 390 million people per annum
(http://www.who.int/mediacentre/factsheets/fs117/en/). There is an urgent medical need to develop
antiviral therapeutics against dengue for which no drug or effective vaccine is presently available. To
address these unmet medical needs, CSIR-IMTECH Virology Discovery Unit is planning to find a
solution in mission mode. We are focusing on the development of antiviral therapeutics against
dengue/flavivirus targeting host/viral factors. We are also exploring clinically or medically important
Indian virome using NGS metagenomics approach for better diagnostics.

Microbiome
Current research activities in the unit

Human microbiomes of healthy and diseased individuals carry diverse strains and species of
microbes (Eckburg et.al, Science 2005). Recently, a unique species of Staphylococcus lugdunensis
has been identified from Skin that produces a novel antibiotic that can kill pathogenic species like S.
aureus (Zipper et.al. Nature, 2016). Consequently, signifying the existence of microbes in the human
gut that has enough potential to prevent us from diseases. Keeping in view of the above facts. gut,
lung and skin samples will be collected from TB, IBD and acne patients, their house hold contacts
and healthy subjects. Bacterial consortia will be generated, which will mainly comprise of Clostridium
spp., Enterobacteriaceae, lactic acid bacteria, etc. Further, their efficacy will be tested in the
experimental model of TB, IBD and acne. The major objective of the current activities is towards
MiCure or Microbiome Based Consortia as Therapeutics.

Past research activities / Achievements

IMTECH was the nodal laboratory of XII Five Year CSIR Network Project (2012-2017) titled "Man as
a Superorganism: the Human Microbiome (HUM). This project was one of the first dedicated
programs on Human Microbiome in the country and led to large number of high quality publications
in this field related to immunology, microbiology, genomics, and evolutionary aspects of human
microbiome of Indian origin.

Biotherapeutics and Metabolics


Current Research Highlights of:

Biotherapeutics Focus Area


The primary objective of our group is to perform a complete end-to-end research for bringing a select
number of protein-based biotherapeutics (biosimilar, biobetters and/or novel molecules) from a
laboratory set-up to the market. Based on the disease prevalence, both globally and in the Indian
context, our research will focus on developing biologics to treat cancer, rheumatoid arthritis, and
childhood bronchiolitis. Efforts are ongoing to develop biosimilars of (a) adalimumab (Humira, an
anti-TNF monoclonal antibody), used for treatment of rheumatoid arthritis, and (b) human
Granulocyte-Colony Stimulating Factor (hG-CSF), widely used to prevent and treat chemotherapy-
induced neutropenia. Our preliminary studies on the biosimilar of Humira produced by single cell
clone have indicated biosimilarity with the originator molecule. In the case of hG-CSF, we are in the
process of examining the biological activity and in vivo half-life of engineered versions of the G-CSF,
and securing the intellectual property rights for these inventions.
Metabolics Focus Area
Iron Deficiency Anemia Solutions via Microbial Engineering Technology [IDEAS MEET]
The activities of this unit are geared for achieving the national goals of Swast Nagrik, Swast Bharat,
and Saksham Bharat.
Iron deficiency is a major worldwide health problem and oral iron supplementation remains the
mainstay for its effective treatment. Unfortunately after almost five decades of this
approach India still tops the list of nations with most anemic women and children. The need of
the hour is to develop an arsenal of choices for providing low cost mass scale iron amelioration in
large segments of the population fully keeping in mind local social and cultural sensibilities. Besides
providing better iron supplementation products, efforts also have to focus on improving the
bioavailability of supplemented iron, as well as, iron trapped within the different tissue
compartments. To achieve this goal our group is focusing on the following strategies:
1. Development of organic/bio-molecules that would specifically increase sequestered iron release
from ferritin and to disrupt hepcidin-ferroprotin interaction and also explore for natural agents that
can enhance the expression of divalent metal transporter 1 (DMT1), erythropoietin and also improve
trafficking of iron containing molecular complexes across enterocytes. The goal is to enhance
effective enterocyte iron absorption and preventing loss of iron trapped in senescent enterocytes.
2. Mapping alterations in gut microflora that impact upon iron absorption capabilities utilizing next
generation sequencing technology with an ultimate goal of identifying putative bacterial species that
may be exploited as potential probiotic candidates for enhancing iron absorption and also countering
the side effects of conventional oral iron supplementation therapy.
3. Develop oral iron supplements utilizing GRAS compliant scaffolds that can be produced at low
cost via mass production by microbial technology/fermentation processes.
4. Screening Herbal/Microbial extracts as a source of heme iron [SatVik heme Nutraceuticals]

Past research activities / Achievements of Biotherapeutic Research Area

The major share of the biotherapeutic market belongs to the monoclonal antibodies (mAbs) and
recombinant proteins. In recent years, we have established a platform for therapeutic human mAbs
production using suspension CHO cells. Various steps, including cloning of genes, transfection
procedures, lab scale-up procedure to achieve high yielding single cell producers, and biophysical
characterization of purified mAbs for their biosimilarity, have been optimized. In addition, we have
also created polyethylene glycol (PEG) derivatives and novel variants of G-CSF using semi-rational
protein evolution approaches. By employing mRNA engineering, we have improved the yield of hG-
CSF production from E. coli.
The group already has considerable expertise in the area of cellular iron homeostasis, regulation of
biological effector molecules, gut microbiota analysis, sourcing of GRAS compliant complex
carbohydrates and heme like molecules from microbial sources.

Technology Area units


Microbial Type Culture Collection
Supporting Group Members
Microbial Type Culture Collection & Gene Bank (MTCC) : A National
Facility and an International Depositary Authority (IDA)

The Microbial Type Culture Collection and Gene Bank (MTCC) a National facility and an
International Depositary Authority (IDA) under World Intellectual Property Organization (WIPO) is
jointly funded by Council of Scientific and Industrial Research (CSIR) and Department of
Biotechnology (DBT). The main objective of MTCC are:

 ex-situ conservation of microbial resources of India

 to provide authentic microbial cultures to industries as well as academic and research institutes

 to provide identification, freeze drying and other microbiology related services

 to act as a depository of patent cultures

Additional objectives:
 Establish collection of clinically important microorganisms for supply and screening purposes.

 Exploration and bioprospecting of biodiversity hotspots of India, marine habitats and other ecological
niches using culturable and metagenomic approaches.

 Genome sequencing of industrially, economically and clinically important microorganisms.

 Provide support to other institutional and CSIR projects/programs.

Societal benefit from MTCC services:

MTCC has been in the forefront in providing quality services related to microbiology to its customers
and has occupied a unique position in the country. About 12,000 customers rely on the services
offered by MTCC. Most of the research organizations, academic institutes, pharmaceutical, biotech,
food companies involved in microbiology and biotechnology related work depend on MTCC for their
microbial cultures. During the last 5 years MTCC has supplied more than 35,000 microbial cultures
have been supplied to various customers from educational, research and commercial organizations.
More than 10,000 research publications cited the MTCC cultures in their publications in the last 5
years. Several patent, doctoral thesis, graduate and post-graduate theses cite the reference
microbial cultures procured from the MTCC.

Biochemical Engineering
Read on website https://www.imtech.res.in/focus-
area/biochemical-engineering
Diagnostics
Nitro-explosives - PETN, RDX, and TNT detection kit
The developed technology makes use of highly specific biorecognition molecules targeted against
explosive compounds. It addresses the key gap in current state of the art related to specificity and
overcomes this deficiency found in existing devices meant for explosives detection. The developed
method and device therein deals with a new and improved system for detecting nitrate containing
compounds that is highly sensitive and accurate, and is capable of quickly determining the presence
of nitrate containing explosive compounds in test samples with very high degree of selectivity. The
presently developed kit provides a new immunoassay format, and a hand-held optical detection
system that is capable of detecting the presence of nitrate containing explosives, mainly nitroamine
(RDX), nitrate ester (PETN) and nitro aromatic (TNT) explosives in test samples with high selectivity
up to a detection limit of 2.7, 1.2 and 2.3 ppm respectively. The detection system can facilitate real
time and on-field detection of nitrate containing explosive compounds. (2017-11031532)

Ammonium Nitrate Test kit


A dual test based on-spot colorimetry method was developed for the detection of ammonium nitrate
(NH4NO3) in samples. The method comprising optical sensing for the presence of ammonium (NH -3)
and nitrate (NO-3) ions simultaneously which are measured colorimetry by using modified Griess
diazotization reaction to detect nitrite and modified Ninhydrin reagent based method to use for
ammonium ions detection. The colorimetric apparatus comprising dual sources (LEDs) of specific
wavelengths coupled with individual detector unit, interfaced to digital signal processing module for
ammonium nitrate detection. The device is integrated with a heating means for reaction kinetics. The
developed hand-held system consists of two light sources (LEDs) of specific wavelengths (525 and
590 nm) for nitrite and ammonium ions respectively. The signals from detectors are coupled and
computed to determine the ammonium nitrate concentration in the samples which is displayed on
standard LCD screen in the form of ammonium nitrate concentration in PPM. (Patent Filing No.-
689/DEL/2015)

Typhoid Test
Typhoid is a life threatening infection caused by the salmonella enterica serovar Typhi and
currently emerging as a major public health problem in developing countries. Diagnosis of
Salmonella Typhi is quite challenging because the symptoms of typhoid fever overlap with a wide
range of other diseases. The conventional methods which include the blood culture and Widal test
are considered to be a gold standard test for the diagnosis of typhoid fever. However, these methods
often give erroneous results. Therefore the need of an hour is to develop a fast, rapid and sensitive
immunoassay to detect the S. Typhi infection. By considering all these points our technology
focuses on the invention of hand-held optical system that employs three highly selective biomarkers
that include recombinant toxins and invention based peptides specific to S. Typhi. The developed
test is more specific and accurate since it is based on checking (IgM/IgG) response against three
biomarkers in typhoid infected patients. Thus the current technology can be use to provide a rapid,
sensitive and reliable immunoassay platform for detection of typhoid fever.

Bioinformatics and Big Data Analytics


The Government of India established the Biotechnology Information System Network in 1987, the
first of its kind in the world. Initially, nine Distributed Information Centres (DICs) were established all
over India with the objective of creating infrastructure for information dissemination in the field of
biotechnology. BIC at CSIR-IMTECH, Chandigarh is one of the DICs supported by DBT under the
BTIS programme. It has shown consistent growth in different areas of bioinformatics whether in
carrying out peer reviewed research or in providing services, data bases and software worldwide.
The centre also provides services in the fields of protein modelling, protein engineering,
biocomputing and networking. BIC staff has trained a large number of students and scientists over
the years by conducting national and international conferences/training workshops. They train
students of IMTECH and nearby universities. BIC provides education and research-related material
to public via its website and provides infrastructure for R&D in bioinformatics. BIC has developed
more than 200 webservers and data bases which are used by the public (with more than 125,000
hits per day) worldwide.

BIC is reputed for its research in bioinformatics, particularly in the field of computer-aided designing
of drugs and vaccines. In the last 15 years, more than 25 students successfully completed their
Ph.D. in bioinformatics. Presently, around 15 students are pursuing their Ph.D. in the field of
bioinformatics at BIC. Additionally, a few project fellows/research associates assist in the research
activities of BIC. The staff at BIC have published more than 250 research papers in reputed journals
(with an average of 15 publications per year), almost all of which are highly cited (with more than
8000 citations to date). The major research activities of BIC staff include Structure and function
characterization of proteins and peptides using in silico techniques, computer aided vaccine design,
annotation of genomes and proteomes, prediction of drug targets, cheminformatics, viral
bioinformatics and computational resources for drug discovery.

Bioinformatics Centre is equipped with state-of-art infrastructure that includes a 3D graphics facility
having immersive virtual reality system and graphics workstations. In India, this lab is the first of its
kind that fosters an atmosphere of active discussions in the area of structural biology and drug
design as it is used for high end visualization of protein structural data. Further, servers, storage
systems along with high performance computing provide necessary platform for the big data analysis
and predictive biology in the bioinformatics centre. We foresee the future of Bioinformatics Centre at
IMTECH having cloud based computing for solving the computational biology problems.

Thus, scientists at BIC at IMTECH shall continue to carry out research in different areas such i.
development of databases and web servers/analysis tools in the areas of genomics, proteomics,
immunology, system biology etc. ii. Prediction of protein structure-function relationship and beyond
iii. Understanding infectious and rare disease biology with systems based approaches for identifying
potential therapeutic interventions and diagnostic methods in addition to iv. Unraveling mechanistic
details of protein at molecular level with reference to its function and dynamics. Centre would also
like to experimentally validate predictions made using in silico methods. Staff of centre shall be
actively engaged in the research work in collaboration and otherwise.

Enabling Area Units


Screening Platforms
In last two decades, antimicrobial resistance (AMR) has emerged as a global threat to public health
systems in the world. The constant misuse and abuse of antimicrobials in veterinary and human
medicine have been contributing alarmingly on the growing burden of AMR worldwide. The situation
is further aggravated as there is a serious lack of new antibiotics to combat with AMR crisis.
Therefore, it is the need to hour to discover and explore novel anti-infectives by exploiting small
chemical libraries and natural extracts. In this regard, CSIR-IMTECH is giving conscious effort to
develop bio-assay strains, targeting cellular pathways which are sine quo non for pathogens’ survival
and disease establishment in host. Presently, the group is concentrating on WHO categorized
important pathogens including Mycobacterium tuberculosis, Gram-negatives and fungi. In addition to
microbial pathogen, model systems targeting human diseases are also in screening pipeline. CSIR-
IMTECH has state of art robotic screening platform “Freedom Evo”. We have already set up linkage
with academia and industry partners and intend to come up with a robust drug discovery program.
Genomics and Structural Biology
Current research activities
Riboflavin (vitamin B2) is a universal precursor for flavin mononucleotide (FMN) and flavin adenine
dinucleotide (FAD) which are essential cofactors for many flavoenzymes that carry out great
diversity of redox reactions. These flavoenzymes participate in a wide range of biological processes,
including carbohydrate, amino acid, and fatty acid metabolisms. While yeast and other higher
animals obtain riboflavin from their diet, bacteria and some plants synthesize these cofactors by de-
novo method. In bacteria, seven enzymes (ribA, ribB, ribC, ribD, ribE, ribF and ribH) are involved in
the biosynthesis of these cofactors (riboflavin, FMN and FAD) using GTP and ribulose-5-phosphate
as initial substrates. Since these enzymes are shown to be essential for the bacterial growth and not
present in human, they are considered as potential targets for the development of anti-bacterial
drugs. Our lab is interested in establishing the structure-function relationship of these bacterial
enzymes by X-ray crystallography. The three-dimensional structure available from these studies will
provide a platform for rational structure based drug design to identify potential lead molecules which
can kill pathogenic bacteria specifically. Some of the representative structures from riboflavin
biosynthesis pathway is shown here.

.
A key focus of our laboratory is on studying new types of "molecular recognition" mechanism(s) with
an aim to establish a novel framework for the design of intelligent drugs which will exhibit more
selectivity and potency towards their targets, as compared to their conventional counter parts,
orthosteric and allosteric drugs. Our approach involves a combination of structural, computational,
and analytical methods, with hypothetical models to test and validate yet undiscovered molecular
recognition principles. By using above approaches, we recently discovered a competitive-allosteric
mechanism by which a low-affinity ligand can displace a high-affinity lignd bound to the target by not
only compete for the same site but also by inducing specific allsoteric structural changes to the
target which accelerates the dissociation of the high-affinity competitor. Currently, our efforts towards
establishing a experimental framework for rapid identification of "competitive-alosteric" ligands and
validating their relevance for pharmaceutical industry.
High-affinity inhibitor is shown as magenta sticks and enzyme, marine blue. a) Free enzyme in the
open-state, ready to bind inhibitor. b) OASS·inhibitor complex in open-state. c) Binding of low-affinity
substrate to enzyme·inhibitor complex. d) Translocation of substrate to reaction center and
dissociation of inhibitor from S1 site. e) Reaction of the substrate, and exit of the inhibitor. f) Inhibitor
is expelled and OASS is trapped in enzyme·reaction-intermediate complex in the final closed state,
ready to react with incoming sulfide to form cysteine. After cysteine release, OASS switches back to
open-state (a) to start the cycle again

Check diagrams if needed on website


Instrumentation & Core Facilities

The Instrumentation Services Division (ISD) of CSIR-IMTECH is a strong and supportive group
which takes care of testing, maintenance and repairs of Instruments. Most of the repairs are carried
out in-house and minimum maintenance contracts are given. All the small & medium-level
instruments of the institute are repaired and maintained without much downtime due to the support
and services provided by the group. Many of the major facilities of the institute for research work are
also operated by the members of the group.
The instruments are maintained and repaired without much downtime with the aid of various
manuals and only the state-of-the-art, high-end and sophisticated instruments are given on
maintenance contracts. A full-fledged test and measuring facility has been set up to help in the repair
which has sophisticated instruments like Digital Storage Oscilloscope, Variable power supply,
multimeters, function generator, SMD soldering workstation, etc.
The Instrumentation Services Division (ISD) also maintains the Modular Instrumentation Lab (MIL)
facility of the Institute. The Modular Instruments Lab (MIL) facility at the Institute offers round-the-
clock instrumentation service to users for carrying out routine experiments. Eight such MILs have
been set up spread across the CSIR-IMTECH campus which provide the researchers access to the
state-of-the-art instruments. The facility offers normal spectrophotometric techniques such as
UV/visible spectrophotometers, spectrofluorometers, ELISA readers, centrifuges, gel-doc systems,
phosphoimagers, high end purification systems, etc.

Medicinal Chemistry
Our lab is well equipped with basic facilities for organic synthesis, chromatography techniques,
protein purification, chemoinformatics, modeling and simulation software.
The major focus of our group is to generate therapeutics towards various diseases and infectious
agents using a combined approach of medicinal chemistry, drug discovery, chemical biology,
chemoinformatics, and biochemistry. Current research topics include:
Venoms derived drugs for TB: Of particular interest to us is the development of therapeutics
against M. tuberculosis by exploring venoms from different species.
Targeting DprE1 enzyme: DprE1 and DprE1-DprE2 enzyme complex is a potential drug target for
pharmacological intervention against M. tuberculosis. We are exploring small molecule for targeting
these important cell wall enzymes.
DNA encoded libraries to discover Sirtuin agonists as pan antivirals: We are interested in
developing antiviral therapeutics using DNA encoded and peptoid libraries.
SIRT activators and inhibitors of high affinity and specificity: Our interest is to develop
therapeutics by selectively targeting SIRT proteins.

Recently, we identified six inhibitors against both SIRT2 and SIRT3, out of which four are selective
to SIRT3. The screening library was selected by employing EpiDBase. EpiDBase was developed by
our group and it consists of ligands against epigenetic proteins with information such as
experimental IC50 value, structural data, toxicological and chemoinformatics profile etc. Similarly, we
also developed SMMRNA database targeting RNA molecules. We also investigated the missing
structural information about the two disordered regions of Mtb DprE1 enzyme. We used
computational modeling and MD simulations and determined that these regions are involved in
DprE1-DprE2 complex formation.

iCARE
The state-of-the-art barrier-maintained iCARE is designed to conduct experiments using rodents,
rabbits and chicken. The facility has been constructed with clean and dirty corridor concept. The
facility has been built in compliance with the guidelines of Committee for the Purpose of Control and
Supervision of Experiments on Animals (CPCSEA) with a total built up area of about 30, 000 square
feet spread over three floors. Registration number of the facility is
55/GO/Re/Rc/Bi/Bt/S/99/CPCSEA.
The Facility is a core service department of the Institute with an objective to procure, breed, supply
and raise experimental animals of high quality and provide husbandry, veterinary care and technical
and professional support to the scientific community of the Institute to facilitate research on animals.
Defined barrier practices are followed strictly. The facility is under electronic surveillance (CCTV
system) and access to facility is through access cards only, with access only to authorized persons
to minimize the risk of infection to the animals.
Accredition

iCARE Facility of IMTECH has been accredited by Committee for the Purpose of Control and
Supervision of Experiments on Animals (CPCSEA), Ministry of Environment & Forests, Govt. of India
to breed and experiment on animals. Our Registration Number is 55/GO/Re/Rc/Bi/Bt/S/99/CPCSEA.
Animals

The facility maintains following species and strains of various laboratory animals for breeding as well as experiment
as per the standards of CPCSEA:
Mice : BALB/c, C57BL/6J, DBA/1, DBA/2, C3H/HeJ, NOD & Knockout mice.
Rat: Sprague Dawley
Hamster: Syrian
Rabbit: New Zealand White
Chicken: Egg laying hens only for experimentation

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