Established in : 1977
 

MANDATE

• To conduct research in frontier and multidisciplinary areas of modern biology and to seek potential applications of this work.
• To carry out exploratory work for the development of modern biochemical and biological technologies in the country.
• To train people in advanced areas of biology, specially in the techniques for which adequate facilities may not exist elsewhere.
• To provide centralized facilities in the country for modern techniques in inter-disciplinary areas of biology.
• To collect, collate and dessimate information relevant to biological research.

MAIN FACILITIES

• Protein analysis, and peptide and DNA synthesis facilities.
• Cell culture facilities.
• Laboratory animal facilities.
• Modern analytical facilities including NMR spectrometer, electron microscope and a nanosecond fluorimeter, flow cytometry facility.
• Library and Bioinformatics - Distributed Information Centre with online access to international databases.

SIGNIFICANT ACHIEVEMENTS                          

1. Biomedicine and Biotechnology.
2. Genetics and Evolution.
3. Cell Biology and Developmental Biology.
4. Molecular Biology.
5. Biochemistry and Biophysics.
6. Applied Research.

Biomedicine and Biotechnology

• CCMB, in collaboration with Osmania General Hospital, has developed sensitive PCR methods, for detecting Hepatitis C Virus (HCV) which is a major cause of post transfusional hepatitis. Enriched preparations of the virus have been made and analysed for virus proteins.The antigenicity of the individual proteins has been determined by immublot using lgG from ELISA positive patients, and peptides, corresponding to conserved regions in the antigenic proteins, have been synthesized and used for sensitive ELISA assays for detecting HCV antibodies.The method developed is superior to commercially available test kits.
• The connection between smoke and increased vulnerability to cataract of the eye lens has been established. A molecular epidemiological study has revealed that the poly cyclic aromatics and trace materials present in the smoke condensate solutions are rich sources of reactive oxygen species which causes oxiditative damage to the eye lens cell membranes, cyctolic proteins and perhaps even DNA. Sustained assualt with smoke keads to accumulated damage resulting in lens opacity. In complimentary studies using lens organ culture, it has been shown that smoke constituents notably alter transmembranic uptake of material by damaging the transport pumps therein.
• The mechanism of spontaneous tumour regression and the role of cytokines in this process is a subject of continuing investigation.The mechanism has been found to involve gamma interferon and the interleukins IL-2 and IL-12.IL-12 appears to stimulate the natural killer cells and the involvement of gamma interferon has also been clarified. Tumour cell death occurs through both perforin-mediated necrosis and apoptosis. Inhibition of the latter by actinomycin and cycloheximide suggests the requirement of macromolecular synthesis in the apoptosis of the AK-5 tumor cells that have been chosen for the study.

Genetics and Evolution

• The Bkm derived DNA probe developed at the CCMB has found new uses, in addition to those in forensic medicine. The probe has been able to establish generic affinity among different crocodilian species.This pioneering observation establishes the utility of  this molecular technique in the study of plant and animal phylogenisis. A mouse Y chromosome specific repeat M34 isolated in another study has shown that this is distributed along the length of the Y chromosome but not in the sex determinimg region ( the Y short arm). Thirty two copies of the GATA repeats are concentrated on a 2.7 kb fragment.A 1.2 kb fragment of M34 containing GATA repeats, is seen to have scaffold attachement region (SAR) motifs which bind to nuclear matrices. Relevant studies has shown a conserved sex and tissue -specific  Bkm binding protein  associated with decondensation of the sex determining chromosomes in the germ cells.
• In ongoing research on the genetics of osmoregulation of evidence has been obtained that a decrease in polyamine synthesis is causally correlated with osmotolerance, and that glutamate systhesis and the anaerobic regulator protein FNR are also necessary for adaptation to growth in high osmolar environments. A model for regulation of the kdp operon ( encoding a transport system for K⁺ ions, which play an important role in maintenance of cell turgor) has been proposed which states that the signal which controls the kdp transcription is the rate of K⁺ -flux across the cytoplasmic membrane.
• In a continuing study on acquisition of resistance to phytoalexins by fungi and cellular slime moulds, erg3 gene of  Neurospora crassa has been cloned and sequenced. Surprisingly, the gene product (Sterol C-14 reductase) has been found to have a very high degree of homology to chicken lamin B-recepetor.

Cell Biology and Developmental Biology

• A study on the steroid effects on the reproductive tissues has shown that the response of the rat vaginal epithelium to the steroid hormone estradiol is developmentally regulated. This response seems to be an unusual post-transcriptional effect of estradoil. Anonst its complex effects estradiol also regulates the transcription of certain keratin polypeptides.

Molecular Biology

• A pyrimidine specific initiation site in E.coli. RNA polymerase has been identified, which is distinct from the classical purine-specific initiation site 'i'. Such a pyramidine specific site can explain transcription initiation at pyramidine residue as is observed for certain promoters. This site has been mapped with respec tto both the rifampicin binding site and the purine-specific 'i' site.
• Site specific mutagenesis of the E.coli. sigma subunit has provided further clues to it's mode of action. While the replacement of the tryptophans in the 2.3 and 2.4 regions by glycine residues abolishes the activity, mutation to phenylalanine is tolerated. Likewhise mutations of a valine residue to glycine in the C-terminal region 4.2 ( involved in the recognition of -35 sequence elements of the promoter) results in loss of function while the structure appears unchanged. These results support the model that the hudrophobic regions of domain 1 mask the specific DNA binding domains in the free sigma molecule.Binding of the core enzyme to sigma cuases a conformational change and exposes the DNA binding regions 2.4 and 4.2.
• Biochemical and molecular biological studies of Antartic microbes have indicated that psychrotropic bacteria sense temperature through the phosphoorylation of some proteins. Transcription in these bacteria is functional even in the cold, suggesting the presence of an RNA polynerease with a modified cold specific sigma subunit. In addition, these bacteria possess some other enzyme which are active at low temperature but labile upon warming.
• Studies on the details of transport of macromolecules across the nuclear membrane have established that protein phosphorylation at the nuclear port apparatus is obligatory to elicit transport of substrates across the pore. Dephosphorylation abolishes this transport which can be restored through treatment by protein kinase. Two constituent proteins have been identified as possible candidates for this phosphorylation.
• Investigations on the role of protein phosphorylation and dephosphorylation as signal transduction aspects in the events of the cell cycle suggests that the DNA binding PTP-S may play a role during the Go to S transition event of the cell cycle. An altered form of PTP-S appears only during g mitosis indicating a role for PTP-S in the signal transduction asn cell differntial events.

Biochemistry and Biophysics

• Investigation on acylations of fatty acids, such as myristic or palmitic acids indicate that while the primary role of myristoylation for palmitoylation is generally not to anchor and ensure membrane attachment as has been assumed, palmitoylation in proteins containing transmembrane segments serves to realign these segments in their orientation in the membrane.
• Red edge excitation shift (REES) has been used as a tool for probing the environments of the four tryptophans in the channel forming peptide gramicidin A, when it is embedded in a model membrane. Although all the four tryptophans are motionally restricted, it is possible to group them into two classes experiencing different microenviroments.
• Certain biopolymers acts as "chaperones" in aiding the solubility and proper folding of proteins in the cell. The ability of the eye lens cortical protein a-crystallin as a chaperone has been evaluated in a study which is a point of revealence to the maintenance of eye-lens transparency. a-Crystallin has been found to prevent the aggregation of non-native structures of other lens proteins by providing appropriately placed hydrophobic surfaces. A structural transition in a-crystallin above 30^oC enhances its protective ability much like what happens with other chaperone protein GroEL. Whether a structural switch is involved in modulating chaperone activity is being investigated.
• Bovine pancreatic ribonuclease A (RNase A) has long been thought of as the gold standard of globular proteins that display the two state (native and unfolded) structural transition, with no intermediate states. However,  this appears no longer true. Treating RNase A with trichloroacetic acid (TCA) results  in denaturation, but this process appears to involve intermediate states. The molecule dissolved in 15-20 % TCA has no confirmational features that answer all the specifications of a molten globule.

Applied Research

• A study on the genetics of osmoregulation has led to successfull construction of a salt sensitive expression vector system and its use to express several proteins of biochemical and commercial interest. In a collaborative project with the National Environmental Engineering Research Institute (NEERI), Nagpur, genes have been cloned for the proU system from E.coli. into oil-degrading Pseudomonas species that NEERI wishes to utilize for handling oil spills, with a view to engineering salt tolerance in these microbes. The engineered bacteria are being treied out for oil-spill management.
• CCMB has succesfully demonstrated the large scale production ( over 1 kg ) of L-Asparatic acid from ammonium funmarate using E.coli. cells immobalized in cells with a shelf life of several months. Also pure RNAsin from human placenta has been produced and the material passed on to Banglore Geneil for marketing.
• Work on the fish-feed has gone on large-scale field trials in Nizamabad district, on five acres of fresh water ponds, and the results have established the distince superiority and cost-effectiveness of the feed developed at CCMB. Negotitations are in progress to sell this technology to interested parties.
• CCMB has tied up with Defence Research and Development Orgranisation (DRDO) to develop psychrtrophic microbes for human waste management in cold environments.
• The DNA typing technology developed at CCMB has been findind increasingly diverse applications. This technology has been transferred to plant scientists at the Indian Council of Agricultural Research. The Central Silk Board of India has expressed interest in utilizing this genetic fingerprinting technology to identify silkworm races.

 DIRECTOR
 Prof. D. Balasubramainan,
 M.Sc., Ph.D.
 

CONTACT ADDRESS
 Uppal Road, Hyderabad. 500 007.
 Telephone: (091)40 672241-50; 670130-39; 
 Telegram : BIOCENTRE, HYDERABAD.
 Telex   : 0425-7046 CCMB IN.
           0425-7061 IICT IN.
 Fax     : (091)40 671195
 E-mail  : dbla@ccmb.uunet.in.