Molecular Biology Division is engaged in understanding the cellular and molecular basis of stress response in bacteria, plants and animals and use of fundamental knowledge generated herein for the development of products and technologies for bio-medical applications and societal benefits. Our research is focused on the following major objectives.
- Molecular mechanisms underlying DNA damage and repair, gamma radiation resistance and oxidative stress tolerance in bacteria
- Metal – microbes interaction and bioremediation
- Mechanisms underlying multipartite genome maintenance and cell division regulation in bacteria
- Identification of antioxidants and radioprotectors from radiation resistant bacterium, Deinococcus radiodurans
- CRISPR-cas technology in basic and applied research
- Guanine quadruplex (G4) DNA structure dynamics and radioresistance in bacteria and cancer cells
- Molecular basis of protein diversity and its significance in cancer and crop improvement
- Development of genetic constructs for metabolic engineering in plants
- Biomarker studies and development of tools for early detection of cancer mutation
- Understanding the cross-talk between transcriptional regulation, epigenetics, and genomic instability in mammalian system
Mapping of mid position in rod shaped objects are easily accomplished. However, the round shaped objects can have numerous longitudinal plane. Similar concept is extended in rod shaped and round shaped bacteria. Therefore, it is relatively easy to physically map mid position in rod shaped bacteria but very uncertain in cocci. What is known that bacteria divides through binary fission and they first decide mid cell position and then 2 daughter cells are produced. How this process is done in cocci is highly intriguing? We studied the mechanisms underlying polarity, plane and mid cell position determination in Deinococcus a cocci, and demonstrated that genome segregation and cell division are interdependently regulated through common macromolecular interactions. A protein DivIVA that interact with both these complexes play a pivotal role in determination of longitudinal axis that this bacterium uses for setting up plane of next cell division.
Historically, the bacterial genome is defined as a single circular chromosome (monopartite) in a limited copy per cell and multipartite genome with ploidy was known as unique feature for higher organisms. Recently, a large number of bacteria with multipartite genome system (MGS) and ploidy have been discovered. Incidentally, most of them are either parasite to some forms of life or highly stress tolerant. Deinococcus radiodurans is one amongst them, which has 2 chromosomes and 2 plasmids and each of these exist in 6-10 copies per cells. Understanding on mechanisms underlying faithful segregation of multipartite genome and its maintenance has been highly challenging. We first painted chromosome I, chromoosmeII and megaplasmid with fluorescent system and then studied the segregation in daughter cells. While characterizing the genome segregation machinery, we discovered many interesting facts including that the maintenance of primary chromosome and secondary genome elements are independently regulated in conjunctions with cell division.
Majority bacteria use LexA/RecA type canonical SOS response mechanisms for their cell cycle regulation in response to DNA damage. Deinococcus radiodurans that is highly resistant to DNA damage does not display SOS response. A new type of DNA damage response mechanism that involves Ser/Thr quinoprotein kinase (RqkA) has been discovered in this bacterium, which display all the features of cell cycle regulation as reported in higher organisms.
Majority bacteria use LexA/RecA type canonical SOS response mechanisms for their cell cycle regulation in response to DNA damage. Deinococcus radiodurans that is highly resistant to DNA damage does not display SOS response. A new type of DNA damage response mechanism that involves Ser/Thr quinoprotein kinase (RqkA) has been discovered in this bacterium, which display all the features of cell cycle regulation as reported in higher organisms.
The cyanobacterium Anabaena 7120 is a nitrogen fixing photosynthetic bacterium that has capability to withstand very high doses of gamma radiation and other environmental stressors. The molecular basis of oxidative stress tolerance was investigated, and a Mn catalase (KatB) with role in higher oxidative stress tolerance has been demonstrated. KatB has been characterized both structurally and biochemically and observed some notable features like thermostability and function at wide pH range. The possibility this enzyme to use in detoxification of H2O2 in textile industries is being explored.
The cyanobacterium Anabaena 7120 is a nitrogen fixing photosynthetic bacterium that has capability to withstand very high doses of gamma radiation and other environmental stressors. The molecular basis of oxidative stress tolerance was investigated, and a Mn catalase (KatB) with role in higher oxidative stress tolerance has been demonstrated. KatB has been characterized both structurally and biochemically and observed some notable features like thermostability and function at wide pH range. The possibility this enzyme to use in detoxification of H2O2 in textile industries is being explored.
The cyanobacterium Anabaena 7120 is a nitrogen fixing photosynthetic bacterium that has capability to withstand very high doses of gamma radiation and other environmental stressors. The molecular basis of oxidative stress tolerance was investigated, and a Mn catalase (KatB) with role in higher oxidative stress tolerance has been demonstrated. KatB has been characterized both structurally and biochemically and observed some notable features like thermostability and function at wide pH range. The possibility this enzyme to use in detoxification of H2O2 in textile industries is being explored.
A very high density of guanine repeats (G motifs) have been observed in the genome of all the organisms. Structural studies showed that these G motifs can forms non Watson-Crick type secondary structure in dsDNA. G4DNA is shown to regulate various molecular events needed for survival in any organism. We observed that the arrest of G4 DNA structure dynamics has direct impact on the radioresistance of Deinococcus radiodurans. Later on, this effect was found to be by suppressing the DNA damage responsive expression of very important DNA repair genes in this bacterium. G4 DNA structure stability is regulated by topoisomerases and RecQ enzyme in this bacterium.
A very high density of guanine repeats (G motifs) have been observed in the genome of all the organisms. Structural studies showed that these G motifs can forms non Watson-Crick type secondary structure in dsDNA. G4DNA is shown to regulate various molecular events needed for survival in any organism. We observed that the arrest of G4 DNA structure dynamics has direct impact on the radioresistance of Deinococcus radiodurans. Later on, this effect was found to be by suppressing the DNA damage responsive expression of very important DNA repair genes in this bacterium. G4 DNA structure stability is regulated by topoisomerases and RecQ enzyme in this bacterium.
BRD4 is an epigenetic regulator and a transcription factor, belongs to the BET (Bromodomain and extra terminal domain) family. BET inhibitors are being tested in FDA approved Phase I/II clinical trials for cancer therapeutics. We have found that BRD4 regulates alternative splicing by interacting with spliceosome machinery during transcription elongation. In view of these findings, it becomes important to change the way we define BRD4-specific transcriptome, specifically for the purposes of cancer diagnostics and therapeutics.
The molecular basis of salinity tolerance in rice was investigated. It was found that salt tolerant cultivars of rice produces greater diversity of superoxide dismutases (SOD), an enzyme responsible for detoxification of reactive oxygen species. Comparative studies with salt sensitive cultivars suggested functional significance of SODs in salt tolerance of rice. The SOD diversity was found to be due to the presence of multiple splice variants isoforms. All these variants have been biochemically and biophysically characterized. Molecular basis of SOD diversity generation and the factor that controls alternate splicing in rice is being investigated.
CRISPR-Cas mediated genome editing technology has been one of the finest inventions of this century and is the best example of translation of fundamental knowledge into application. We have developed our capabilities of creating CRISPR –cas based technologies for their used in both fundamental research and bio-medical applications. We made CRISPR vector with advanced features and used them for generating constructs for creating gene knockouts in mouse model.
For monitoring DNA damage and repair
For studying macromolecular interactions and particle size estimations
Animal cell culture experiments
Protein purification
For GFP and chlorophyll expression in cells
2D analysis
For analysis of biomolecular interactions
For analysis of secondary structure of biomolecules
Microarray analysis
For analysis of cell surface and nanoparticles
For confocal microscopy of biological sample
For high resolution imaging of the biological samples/materials in their native states and dehydrated states along with elemental analysis
For imaging of biological and non-biological specimens within and out of Bioscience Group
Escherichia coli cell factory for producing recombinant phosphopeptides for bio-medical applications (Application No. India Patent No. 202021008606 dt 28.02.2019)
Cold Plasma based Electroporator for Biological transformation or Electroporation (AB22MBD)
Molecular Biology Division
Molecular Biology Research Directed to Applications
Salient Technology Corner
SBYR Green-based Gel-free DNA marker detection approaches
Understanding Impact of Alternative Splicing in Stress Response in Plants
Metal-microbe interactive mechanisms important for metal/uranium bioremediation
Oxidative stress in Cyanobacteria: From fundamental concepts to applications
DNA Double strand break repair in the cyanobacterium Anabaena/Nostoc PCC7120
BRD4 regulates alternative splicing in normal cells and in cancer cells
How longitudinal axis is determined in round shaped bacteria (cocci)?
G4 DNA role in molecular mechanisms underlying radioresistance in Deinococcus radiodurans
A new type of DNA damage response and cell cycle regulation in Deinococcus radiodurans
Cyanobacteria in the Perspective of Fundamental Research
Glimpses of Fundamental Research at Molecular Levels
