Biological Science Colloquium 2016

Biological Science Colloquium 2016

[ 2017 ]

Nov 8, 2016	Dr. Tapas Kundu, JNCSR, Bangaluru Venue & Time: C V Raman Hall, Nov 8, 2016 Fine Tuning Gene Expression in Physiology and Pathophysiology: Implications in Therapeutics Fine Tuning Gene Expression in Physiology and Pathophysiology: Implications in Therapeutics The highly ordered nucleoprotein structure in the eukaryotic nuclei is referred as chromatin. Though DNA sequence is the template for gene expression, the fine tuning of this process is mediated by the epigenetic machinery. Broadly, epigenetics refers to the modification of DNA, and the proteins that help organize the eukaryotic DNA. The protein component of chromatin undergoes several reversible post-translational modifications such as acetylation, methylation, phosphorylation etc., which occur on specific amino acid residues. We have found that lysine acetylation and arginine methylation of histones are essential for regulating the synthesis of mRNA as well as microRNA with functional consequences. The acetylation of proteins assisting transcription activation has also been found to be essential for the activation of gene expression. In pathophysiological conditions such as cancer, AIDS and in neurodegenerative disorders, homeostasis is affected, and the state of these modifications also undergoes alteration. Hence, enzymes responsible for these modifications could be target for new generation epigenetic therapeutics. We have discovered a few small molecules which specifically target these enzymes and eventually suppress tumor growth, viral multiplication in AIDS and enhance cognate brain function in a model of neurodegeneration. Besides therapeutic implications, these efforts significantly contribute to our understanding of fundamental disease biology.
Nov 7, 2016	Dr. Satyajit Rath, National Institute of Immunology, New Delhi, India Venue & Time: C V Raman Hall at 11:30 AM Source and consequences of biological diversity: lessons from the immune system Source and consequences of biological diversity: lessons from the immune system The immune system shows enormous variation, both between individual cells and between individual organisms. Within organisms, quantitative variation in cellular activation in the immune system can have diverse consequences, resulting in heterogeneity in activation and survival as well as in effector programming and function of cells. Between organisms, diversity in immune responses can provide species-survival advantages. I will use our data from a couple of different areas to explain our interest in the sources and consequences of immune heterogeneity. While examining relationships between lymphocyte heterogeneity and functionality, we have found that apparently unimodally distributed heterogeneity among T lymphocytes, which we simplistically expected to be due to intrinsic noise, is not only correlated with major functional variation but is modulated by extrinsic microenvironmental cues in vivo. Further, our results from related investigations suggest that heterogeneity in responding T cell populations is also likely to be a determinant of the familiar dose-response relationships in T cell responses. Finally, I will connect these mouse data-based ideas of heterogeneity to some field evidence in order to illustrate how measurement of heterogeneity can lead to interesting insights into both developmental and functional inter-individual variations in the human immune system.
Sept 19, 2016	Dr. Jyotsna Dhawan, CSIR Center for Cellular & Molecular Biology, Hyderabad, & Institute for Stem Cell Biology & Regenerative Medicine, Bangalore Local Host: Siddhartha S. Jana Venue & Time: C V Raman Hall, Sept 19, 2016 Quiescence and stem cell function-how does a dormant cell contribute to tissue repair? Quiescence and stem cell function-how does a dormant cell contribute to tissue repair? Abstract: Adult stem cells persist within tissues in a quiescent state (G0), and when activated by damage, contribute to regeneration. Growing evidence supports the view that G0 is a balanced or poised state where both the cell cycle and tissue-specific programs are held in check by active mechanisms. We have used a comparative approach to understanding quiescence, contrasting G0 to terminal differentiation, another mitotically inactive state, where distinct molecular mechanisms drive a tissue-specific program. Using skeletal muscle cells as a model, we find that in G0 myoblasts but not in differentiated myotubes, chromatin mechanisms ensure that repressed cell cycle genes are poised for activation. Genome-wide analysis of RNA polymerase II location and activity supports the emerging picture that polymerase stalling also contributes to maintenance of the poised state. Combined with analysis of gene activation in G1, our findings suggest that these transcriptional control mechanisms impact cell cycle exit and re-entry from quiescence. I will provide a brief introduction to stem cells and then discuss our interest in the quiescent or dormant state of the adult stem cell in tissues that are capable of robust regeneration such as skeletal muscle.
April 04, 2016	Dr. Kaustuv Sanyal, Molecular Mycology Laboratory, Mol Biol & Gen Unit, JNCASR, Bangalore Local Host: Benu Brata Das Venue & Time: C V Raman Hall at 3:30 PM Genome indexing by histone H3 variants in a single-celled species Genome indexing by histone H3 variants in a single-celled species Each cell in a multi-cellular organism carries the same genomic content but not all genes are expressed in every cell of the same organism. Multiple mechanisms have been shown to be involved in converting a genome into several lineage-specific “epigenomes”. One of the provocative hypotheses is many similar forms of histone proteins, popularly known as variant histones, may play a crucial role in this process. Among the four core histones, histone H3 variants have been shown to be important in indexing mammalian genomes in transcriptionally active or silenced domains. A centromere-specific histone H3 variant, CENP-A, present in centromeres of most known organisms, is a classic example of how a specialized function can be defined on a eukaryotic chromosome by a histone H3 variant. Most unicellular organisms,such as popular model yeasts,Saccharomyces cerevisiae or Schizosaccharomycespombe,do not need to undergo cellular differentiation. Thus, these organisms have CENP-A but lack variants of canonical histone H3. Interestingly, we discovered presence of both CENP-A and variants of canonical histone H3 in the genomes of a group of single-celled organisms of the CTG clade. I will discuss our results on how CENP-A and other histone H3 variants bar code the genome of a dreaded human pathogen Candida albicans in functionally distinct domains.
March 17, 2016	Dr. Uday Bandyopadhyay, IICB Local Host: Siddhartha S. Jana Venue & Time: C V Raman Hall at 3:00 PM Mitochondria: A subcellular target to prevent non-steroidal anti-inflammatory drug (NSAID) -induced gastric ulcer Mitochondria: A subcellular target to prevent non-steroidal anti-inflammatory drug (NSAID) -induced gastric ulcer Non-steroidal anti-inflammatory drugs (NSAIDs) develop gastropathy, the cause for the induction of gastropathy is not yet clear. We have investigated the role of mitochondria on the development of indomethacin (a non-steroidal anti-inflammatory drug)-induced gastropathy in rat. Indomethacin, develops gastropathy by inducing mitochondrial pathology and reactive oxygen species (ROS) generation. Indomethacin damages mitochondrial ultrastructure and causes mitochondrial dysfunction as documented by transmission electron microscopic studies, decreased stage-3 respiration, dehydrogenase activity and transmembrane potential (Dym). Upregulation of proapoptotic Bax, Bak and downregulation of antiapoptotic Bcl-2, BclxL are found to occur in NSAID-induced gastric mucosal apoptosis, which favors mitochondrial translocation of Bax to open mitochondrial permeability transition pores (MPTP). Opening of MPTP releases apoptosis promoting factor, cytochrome c, which then activates caspase-9 and active caspase-9 further activates caspase-3. Mitochondrial pathology is associated with increased generation of intramitochondrial ROS, such as O2Â·-, H2O2 and Â·OH leading to oxidative stress. O2Â·- is the most effective to damage mitochondrial aconitase, leading to the release of iron from its iron-sulfur cluster. Immunoprecipitation of mitochondrial aconitase and subsequent westernimmunoblotting indicate carbonylation of aconitase along with the loss of activity in vivo after indomethacin treatment. The release of iron has been documented by fluorescence imaging of mucosal cells by using Phen Green SK, a specific probe for chelatable iron. Interestingly, intra-mitochondrial Â·OH generation is crucial for the development of mitochondrial pathology and activation of mitochondrial death pathway by indomethacin. Scavenging of Â·OH by dimethyl sulfoxide or α-phenyl-n-tert-butyl-nitrone, a spin-trap, prevents indomethacin-induced mitochondrial ultrastructural changes, oxidative stress, collapse of Dym, and mitochondrial dysfunction. Scavenging of Â·OH also prevents the activation of NSAID-induced gastric mucosal cell death and gastropathy.
February 29, 2016	Dr. Arabinda Chaudhuri, IICT Local Host: Prof. P. K. Das Fighting Cancer with Fatty Bubbles Fighting Cancer with Fatty Bubbles Liposomes, the fatty bubbles containing an aqueous interior, are finding widespread uses in directing potent anti-cancer drugs selectively to tumor vasculature in anti-angiogenic cancer therapy. To this end, recently we have developed efficient integrin receptor selective liposomal systems for delivering potent anti-cancer drugs/genes to tumor vasculature and have demonstrated their significant tumor growth inhibition properties in syngeneic mouse tumor model. In the emerging field of dendritic cell (DC) based genetic immunization, previously we showed that immunization with autologous DCs ex-vivo pre-transfected with electrostatic complexes (lipoplexes) of a plasmid DNA encoding melanoma tumor associated antigen (DNA vaccine) and liposomes of cationic amphiphiles with mannose-mimicking quinoyl- & shikimoyl head-groups induces long-lasting immune responses against melanoma tumor. However, there are a number of time-consuming and cost-ineffective steps to be followed in such ex-vivo DC-transfection based cancer immunotherapy. One needs to painstakingly isolate the autologous DCs from the recipients. The isolated DCs then need to be ex vivo pre-transfected with DNA vaccines of interest and finally the ex-vivo transfected DCs needs to be re-implanted back into recipient’s body. Stated differently, the currently practiced ex vivo DC-transfection based genetic immunization procedures are labor-intensive and are likely to be prohibitively costly for large scale applications. We have now succeeded in designing efficient liposomal DNA vaccine carriers for direct in vivo targeting of tumor antigen encoded DNA vaccines to dendritic cells. Importantly, this newly developed liposomal DNA vaccine carriers are capable of inducing long-lasting immune response including strong memory response against melanoma tumors in a syngeneic mouse tumor model. Most recently, we have succeeded in developing a platform technology for eradicating/regressing established tumors through a combination of in vivo DC-transfection based cancer immunotherapy and targeted chemotherapy. My presentation will be centered around discussing these translationally important recent findings from our laboratory.
January 18, 2016	Dr. Roop Mallik, TIFR Local Host: Dr. Deepak Sinha Lipid Rafts as Force Generating Platforms for Motor Proteins Lipid Rafts as Force Generating Platforms for Motor Proteins Liposomes, the fatty bubbles containing an aqueous interior, are finding widespread uses in directing potent anti-cancer drugs selectively to tumor vasculature in anti-angiogenic cancer therapy. To this end, recently we have developed efficient integrin receptor selective liposomal systems for delivering potent anti-cancer drugs/genes to tumor vasculature and have demonstrated their significant tumor growth inhibition properties in syngeneic mouse tumor model. In the emerging field of dendritic cell (DC) based genetic immunization, previously we showed that immunization with autologous DCs ex-vivo pre-transfected with electrostatic complexes (lipoplexes) of a plasmid DNA encoding melanoma tumor associated antigen (DNA vaccine) and liposomes of cationic amphiphiles with mannose-mimicking quinoyl- & shikimoyl head-groups induces long-lasting immune responses against melanoma tumor. However, there are a number of time-consuming and cost-ineffective steps to be followed in such ex-vivo DC-transfection based cancer immunotherapy. One needs to painstakingly isolate the autologous DCs from the recipients. The isolated DCs then need to be ex vivo pre-transfected with DNA vaccines of interest and finally the ex-vivo transfected DCs needs to be re-implanted back into recipient’s body. Stated differently, the currently practiced ex vivo DC-transfection based genetic immunization procedures are labor-intensive and are likely to be prohibitively costly for large scale applications. We have now succeeded in designing efficient liposomal DNA vaccine carriers for direct in vivo targeting of tumor antigen encoded DNA vaccines to dendritic cells. Importantly, this newly developed liposomal DNA vaccine carriers are capable of inducing long-lasting immune response including strong memory response against melanoma tumors in a syngeneic mouse tumor model. Most recently, we have succeeded in developing a platform technology for eradicating/regressing established tumors through a combination of in vivo DC-transfection based cancer immunotherapy and targeted chemotherapy. My presentation will be centered around discussing these translationally important recent findings from our laboratory.

biological-science-colloquium-2016