CENTRE FOR CELLULAR AND MOLECULAR BIOLOGY, HYDERABAD

Dr Pushpa Mittra Bhargava, widely regarded as the architect of modern biology in India, has conceived the idea of establishing the Centre for Cellular and Molecular Biology (CCMB) and saw to it that it was built, equipped and staffed to uncompromising standards.

It is his vision that - `a Centre for research in frontier areas of modern biology at par with those in Western countries can be built and maintained in India too' - led to what CCMB is today as acclaimed by many distinguished people. His vision of the establishment of CCMB fulfilled a long-felt need in the country for providing the necessary thrust in molecular and cellular biology. CCMB is the first institution in India devoted exclusively to research in frontier-areas of modern biology and it has played a key role in the development of Biotechnology programme in the country.

The results of the care and attention to detail that Dr Bhargava evinced at every step are visible - in the laboratories as well as in the beautiful green surroundings. His experiment in forging a novel framework for the sharing of all facilities, equipment and chemicals amongst the scientific groups is unique in Indian set-up. In effect, this means that the CCMB functions as one integrated laboratory; and so far this experiment has been successful. He is a firm believer in that science and art are the two facets of creative human activity and they go hand in hand. His penchant for aesthetics reflects at various places in the CCMB campus. Dr Bhargava's continued association and support to CCMB is a great help to maintain and improve these traditions.

The Centre, formally set up as an autonomous organisation in 1977, moved to its own modern building complex and was dedicated to the nation by the then Prime Minister, Mr Rajiv Gandhi, on 26th November 1987. The inaugural function was attended by a galaxy of distinguished scientists including few Nobel Laureates such as Dr F H C Crick, Dr C D Gajdusek, Dr B S Blumberg, Dr J C Kendrew, Dr Georges Kohler and Dr S O Choa.

The Centre for Cellular & Molecular Biology (CCMB) is a premier research organization in the frontier areas of modern biology. The objectives of the Centre are to aid the development of biotechnology in India on a sound basis, conduct training courses in advanced areas of biology, promote centralized national facilities for new and modern techniques in the inter-disciplinary areas of biology, interact with industry carrying out basic and applied work, and to collect, collate and disseminate information relevant to biological research. The Centre is ushering in the new millennium to continue its mission of conducting a high quality basic research in chosen areas of biology, socially relevant research and application-oriented work towards commercialization.

*The Genesis

CCMB was set up initially as a semi-autonomous Centre on April 1, 1977 with the Biochemistry Division of the then Regional Research Laboratory (presently, Indian Institute of Chemical Technology), Hyderabad forming its nucleus and Dr P M Bhargava heading the new Centre. Earlier, the Governing Board of the Council of Scientific and Industrial Research (CSIR) New Delhi, the apex body which constituted 44 research institutions in the country, approved the proposal in 1976 to establish such a Centre in view of the importance of research in the frontier and multi-disciplinary areas of modern biology. During 1981-82, the CCMB was accorded the status of a full-fledged national laboratory with its own Executive Committee and Scientific Advisory Council. With major expansion plans, it was decided to relocate the Centre to a spacious campus.

Research Output/Patents

Since its inception, CCMB has published about 1200 research papers mainly in reputed international journals. The Centre has the distinction of being one among the top 3 institutions in the country in terms of the impact factor - an index of the number of times a research paper is referred by others in their publications. CCMB has started filing patents way back in 1979 and has filed so far more than 14 patents, both Indian and international.

Science Dissemination

The CCMB publishes its Annual Report, containing the ongoing research activities, which are widely circulated nationally and internationally. Popularising science is yet another mission of taking science to the doorstep of the common man. Towards fulfilling this objective, the scientists make contributions to newspapers, magazines etc., and participate in science programmes on Television and Radio.Further, to reach a larger national audience, a popular science magazine in Hindi (Jigyasa - meaning curiosity) was brought out. The magazine which contains articles contributed by CCMB- Scientists is well received by the public.

Industry Collaboration

CCMB played a key role in the development of the country's first recombinant DNA-based Hepatitis-B vaccine for human use by Shantha Biotechnics (P) Ltd., Hyderabad. CCMB helped Dr Reddy's Research Foundation, Hyderabad through specific technology tie-ups.

A technology about RNasin - an enzyme-inhibitor - has been successfully transferred to M/s Bangalore Genei (P) Ltd., Bangalore.

CCMB scientists have helped M/s EID Parry Ltd., Chennai by developing a protocol for standardization of PCR-based markers to distinguish the parental and hybrid seed varieties of rice.

CCMB has undertaken a collaborative research project with M/s Dabur Research Foundation and the IICT to develop a new therapeutic agent for the treatment of cancer. A collaborative research programme is on the anvil with M/s Biological Evans Ltd., Hyderabad to provide rapid, accurate and reliable diagnostic service based on modern molecular methods to cancer patients.

International Collaboration

CCMB has collaborated with the international agencies such as the Imperial Cancer Research Fund (UK), the Volkswagen Foundation (Germany), The India Japan Science Council and the University of Ryukyus, Okinawa (Japan), The National Institutes of Health (USA) and the Centre Nationale de la Recherche Scientifique (CNRS) and the Pasteur Institute (France). CCMB gained the stature of a truly international Centre with short-term and long-term overseas visitors from US, UK, France, Germany, Japan, China, New Zealand, the Czech Republic, Mauritius, Cameroon, etc., for research assignments in various groups of the laboratory.

Visitors to the Centre

The Centre receives a large number of visitors throughout the year. CCMB organiszes a Open House on the 26 September every year, in Celebration of the Foundation Day of its parent body, CSIR and receives on an average nearly 5000 visitors on this day. The laboratory also receives professional visitors from India and abroad as well as students from various universities in the country. The laboratory is also visited by various international delegations, from time to time, sponsored by the Government and other science agencies.

A Learning Centre

CCMB imparts training to doctoral students in an academic programme linked with the Jawaharlal Nehru University, New Delhi, besides post-doctoral research fellows sponsored by the CSIR, the Department of Biotechnology (DBT), and the Department of Science and Technology (DST), Govt. of India, New Delhi. On an average, at any one time there are nearly 100 such researchers at the CCMB. The Centre also provides training in specific areas of modern biology, besides conducting courses and workshops, time to time.

Technology Awareness Program

At the request of the National Police Academy, the Andhra Pradesh Police Academy, the Andhra Pradesh Judicial Academy, Administrative Staff College of India, Hyderabad and the National Bureau of Crime Records, New Delhi, CCMB organises presentations on the DNA fingerprinting technology. The participants include Indian police officials, Judges, and also experts from forensic/criminal investigating agencies from India and abroad. Such half-day sessions are followed by visit to various laboratory facilities.

Information Technology

A Bioinformatics Centre (BIC) was started at CCMB in 1986, under the sponsorship of Dept. of Biotechnology, Govt. of India with the principal objective to serve as a part of national network providing biological information by accessing several scientific databases from India and abroad. It has an Internet facility through the National Informatics Centre (NIC), New Delhi. Since its inception, the BIC has been functioning round the clock contributing significantly to modern biological research.

National & International Awards/Honours

CCMB has been chosen as a Centre of Excellence, by UNESCO's Global Network of Molecular and Cell Biology. CCMB received the Third World Academy of Sciences (TWAS) Award, Italy and was designated as a South Centre of Excellence in Research & Training.

The probe developed at the CCMB for DNA fingerprinting won the CSIR Technology Award in Biological Sciences.

CCMB has been given the Federation of Indian Chambers of Commerce and Industry (FICCI) Award for Ourstanding

Achievement in Science & Technology.

CCMB is a Member of the ICICI Knowledge Park launched jointly by the Industrial Credit & Investment Corporation of India (ICICI) Ltd., and the Govt. of Andhra Pradesh, Hyderabad.

CCMB is a Member of APBioNet, an International Website for the advancement of Bioinformatics.

State-of-the-Art Facilities

Confocal Microscopy - a national facility funded by the DST and CSIR to cater to the needs of users in cell biology, material sciences and allied disciplines.

Automated DNA Sequencer - for applications in DNA sequencing and GeneScan analysis.

Digital Imaging - for use in the preparation of slide-show presentation by scientists and colour graphics used in their publications.

Interactive Graphics Molecular Modelling Facility - for macromolecular modelling, such as protein and nucleic acids as well as their interactions.

MAJOR BREAKTHROUGHS IN RESEARCH

Unique RNase from Cobra Snake Venom

RNase cutting enzyme, which has specificity towards cytidylic acid was isolated, purified and characterized from Cobra Venom. Such an enzyme was reported for the first time by the scientists at the CCMB. The enzyme has a potential to be used as a tool for sequencing RNAs and in their structural studies.

Gene Delivery System

CCMB, in collaboration with its sister Institute, the IICT, has successfully designed a formulation for efficient delivery of DNA into the cells. This patented formulation, based on the novel chemistry and DNA condensation process, has demonstrated higher transfection efficiency when compared to commercial formulation.

Microbes from Antarctica: Biodiversity and Cold Adaptation Scientists at the CCMB have identified a number of cold- loving bacteria and yeasts, hitherto unknown from Antarctica. The cold-loving bacteria adapt to low temperature by their ability to modulate membrane fluidity through the regulation of the synthesis of fatty acids. A few cold-active and heat-labile enzymes from these microorganisms have been characterized for the first time.

Genetics of Osmo-regulation

CCMB was the first to discover the gene ProU in E.coli, to decipher the genetic organisation, and to establish its role in osmo-regulation. Functions of several other similar genes have also been established. As an offshoot, this work has led to the development for the production of genetically engineered polypeptide products.

How does the protein fold

Protein folding is a major unsolved problem in biology. CCMB scientists have arrested the protein (RNase-A) under a certain set of conditions in a state of partially folded active protein - the state known as molten globule - for the first time.

Failure of protein folding is known to lead to diseases. It was established in that one of the eye lens proteins a - Crystalline is shown to assist in protein folding and assembling - an ability similar to molecular chaperones. These studies have relevance in the remedy of the eye disease, cataract.

Peptides to fight bacterial invasion

Nature uses peptides to combat bacterial invasions. Taking this as an example, CCMB scientists have designed peptides consisting of 11-15 amino acid residues, which possess selective antibacterial activity. Understanding of structure-function relationship in antibacterial and membrane-active peptide toxins could be used in therapies in such a way that resistance would not be developed against these molecules.

Protein from seminal plasma plays multi-functional role A protein - seminal plasmin - discovered at this Centre is a potent microbial agent as well as anti-HIV agent. It lyses dividing cells and shows inhibitory properties towards host of other biological functions, such as RNA-polymerases, reverse transcriptases, sperm motility and in vitro fertilising ability of spermatozoa.

Regulation of cell division

A new model explaining the non-phenomenology of regulation of cell division and malignant transformation was proposed by scientists from this Centre.

A new universal probe for DNA fingerprinting

CCMB developed a new probe derived from an Indian banded krait snake. This probe is being used for forensic investigations, paternity determination and seed stock verifications. Based on this probe, DNA fingerprinting evidence was presented in the Court of Law, for the first time in the annals of Indian history and was accepted as an infallible evidence. This indigenous probe was used in more than 600 cases such as paternity disputes, identification of missing children, identification of mutilated bodies, exchange of babies in maternity wards, cases of rape and murder, etc.

Molecular basis of sex determination Sex determination is one of the most important unsolved problems in modern biology. Isolation of highly conserved sex chromosome-specific satellite DNA, `Bkm' from the female Indian branded krait snake has paved the way to our understanding of the molecular basis of sex determination. The contrbution from the CCMB is considered to be a major breakthrough in this field and has become the basis of our understanding of sex reversal in humans as well.

Can sex be reversed ?

CCMB studies on sex determination revealed a unique case of sex reversal of XXY female. An individual having the chromosomal constitution 47 XXY but a female phenotype has been reported for the first time. This is an interesting case for identification and characterisation of the new gene(s) involved in the complex pathway of sex determination.

How the limbs grow in fruit-fly

It has been shown for the first time in CCMB that organising centres of limbs are subjected to the regulation by the genes, which are involved in the positioning of the organs in the body of the fruit-fly. CCMB scientists also cloned a new gene, which regulates growth during the wing and limb development.

The Centre for DNA Fingerprinting and Diagnostics (CDFD) Based on the development of new Bkm probes for DNA fingerprinting technology developed at the CCMB, a separate autonomous laboratory, called the "Centre for DNA Fingerprinting and Diagnostics (CDFD)" has been set-up by the DBT, Govt. of India. This is a major effort on the part of CCMB and an important achievement for the CCMB and the CSIR. The ultimate aim of the CDFD is to develop, acquire and standardize the protocols for carrier detection, prenatal diagnosis and genetic counselling for all genetic disorders prevalent in the country.

The Future Focus

CCMB has taken steps towards research in new areas such as gene therapy and drug delivery system and the human genome using the advanced DNA technologies. It has plans to acquire the "DNA Chip Technology" and an advanced version of NMR Imaging facility to study the images of experimental animals without having to kill them.The laboratory is abreast of the fast changing R & D scenario, as advances in Biotechnology are bound to have a far-reaching impact. The mapping of human genome, for example, would enable us define normal and abnormal human biology, and utilise this knowledge in detecting, predicting, preventing, counseling and possibly treating human diseases through the application of DNA technology by gene therapy. Yet another exciting area in the new millennium, the "Gene Chip" Technology would make it possible to look for subtle changes in any gene at a reasonable cost; and subject any defective gene to therapeutic regimes to circumvent its limitation. This preventive mode would enable majority of individuals to live a normal and healthy life without any diseases.

CCMB has the responsibility to adopt, modify and develop these areas for the benefit of the country at large and

Biotechnology in particular.

Contact

Dr Lalji Singh,
Director,
Centre for Cellular & Molecular Biology,
(Council of Scientific & Industrial Research),
Uppal Road,
Hyderabad-500007,
A.P., INDIA.
Phone: 040-7172241-50/7170130-39,
FAX: 040-7171195,
E-Mail : lalji@ccmb.ap.nic.in