Department of Biotechnology

Indian Institute of Technology Hyderabad (IITH) is a premier institute of science and technology established in 2008. IITH has been consistently ranked in the&nbsp;<a href="https://iith.ac.in/reports/" rel="noopener noreferrer">top 10 institutes</a>&nbsp;in India for Engineering&nbsp;<a href="https://www.nirfindia.org/2021/EngineeringRanking.html" rel="noopener noreferrer" target="_blank">according to NIRF</a>&nbsp;making it one of the most coveted schools for science and technology in the country.

IITH offers&nbsp;<a href="https://iith.ac.in/academics/under-graduate/">undergraduate programs</a>&nbsp;in all the classical engineering disciplines, applied sciences, design, as well as several modern interdisciplinary areas. Students are given a flexibility to explore a broad set of areas, and potentially pursue a minor or double major in a discipline that is not their own. Students who wish to seek a deeper understanding of their own discipline are strongly encouraged to get involved in cutting-edge research with the help of a faculty to mentor them, and earn an Honors in their own field.

The very foundation of IIT Hyderabad is based on&nbsp;<a href="https://iith.ac.in/research/">research and innovation</a>. The vibrant research culture is evident from the number of patents and publications that IITH produces consistently every year. IITH offers&nbsp;<a href="https://iith.ac.in/academics/programmes-offered/">graduate programs</a>&nbsp;at both a masters, and a doctoral level, in several diverse areas. There are separate programs for technology, design, science, and liberal arts. The&nbsp;<a href="https://iith.ac.in/academics/post-graduate/">MTech program</a>&nbsp;is offered in various modes and durations to cater to the ever-growing need of postgraduate level professionals in the country.

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IITH enjoys a very special relationship with Japanese universities and industries that goes beyond academic and research collaborations. In fact, some of the iconic buildings in IITH campus will carry the signature of Japanese architecture.

IITH creates a unique holistic ecosystem for education that offers interactive learning, a very flexible academic structure, cutting-edge research, strong industry collaboration, and entrepreneurship. This is an environment which enables students and faculty to translate their dreams into realities.

IIT Hyderabad

Meiosis is a specialized cell division process by which haploid gametes are produced from a diploid mother cell. Reductional chromosome segregation during meiosis I (MI) is achieved by two unique and conserved events: centromeric cohesin protection (CCP) and sister kinetochore mono-orientation (SKM). In Saccharomyces cerevisiae, a meiosis-specific protein Spo13 plays a role in both these centromere-specific events. Despite genome-wide association of Spo13, we failed to detect its function in global processes such as cohesin loading, cohesion establishment and homologs pairing. While Shugoshin (Sgo1) and protein phosphatase 2A (PP2ARts1) play a central role in CCP, it is not fully understood whether Spo13 functions in the process through a Sgo1- PP2ARts1-dependent or -independent mechanism. To delineate this and to find the relative contribution of each of these proteins in CCP and SKM, we meticulously observed the sister chromatid segregation pattern in the wild type, sgo1Δ, rts1Δ and spo13Δ single mutants and in their respective double mutants. We found that Spo13 protects centromeric cohesin through a Sgo1– PP2ARts1-independent mechanism. To our surprise, we observed a hitherto unknown role of Sgo1 in SKM. Further investigation revealed that Sgo1-mediated recruitment of aurora kinase Ipl1 to the centromere facilitates monopolin loading at the kinetochore during MI. Hence, this study uncovers the role of Sgo1 in SKM and demonstartes how the regulators (Sgo1, PP2ARts1, Spo13) work in a coordinated manner to achieve faithful chromosome segregation during meiosis, the failure of which leads to aneuploidy and birth defects. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

World University root node

Current Genetics

An interplay between Shugoshin and Spo13 for centromeric cohesin protection and sister kinetochore mono-orientation during meiosis I in Saccharomyces cerevisiae

UHRF1 is a multi-domain protein comprising of a tandem tudor (UHRF1 TTD), a PHD finger, and a SET and RING-associated domain. It is required for the maintenance of CG methylation, heterochromatin formation and DNA repair. Isothermal titration calorimetry binding studies of unmodified and methylated lysine histone peptides establish that the UHRF1 TTD binds dimethylated Lys9 on histone H3 (H3K9me2). Further, MD simulation and binding studies reveal that TTD-PHD of UHRF1 (UHRF1 TTD-PHD) preferentially recognizes dimethyl-lysine status. Importantly, we show that Asp145 in the binding pocket determines the preferential recognition of the dimethyl-ammonium group of H3K9me2. Interestingly, PHD finger of the UHRF1 TTD-PHD has a negligible contribution to the binding affinity for recognition of K9me2 by the UHRF1 TTD. Surprisingly, Lys4 methylation on H3 peptide has an insignificant effect on combinatorial recognition of R2 and K9me2 on H3 by the UHRF1 TTD-PHD. We propose that subtle variations of key residues at the binding pocket determine status specific recognition of histone methyl-lysines by the reader domains. © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)

Fulltext

Biochimie

Biochemical and dynamic basis for combinatorial recognition of H3R2K9me2 by dual domains of UHRF1

Engineering the synthetic nanopores through lipid bilayer membrane to access the interior of a cell is a long persisting challenge in biotechnology. Here, we demonstrate the stability and dynamics of a tile-based 6-helix DNA nanotube (DNT) embedded in POPC lipid bilayer using the analysis of 0.2 s long equilibrium MD simulation trajectories. We observe that the head groups of the lipid molecules close to the lumen cooperatively tilt towards the hydrophilic sugar-phosphate backbone of DNA and form a toroidal structure around the patch of DNT protruding in the membrane. Further, we explore the effect of ionic concentrations to the in-solution structure and stability of the lipid-DNT complex. Transmembrane ionic current measurements for the constant electric field MD simulation provide the I-V characteristics of the water filled DNT lumen in lipid membrane. With increasing salt concentrations, the measured values of transmembrane ionic conductance of the porous DNT lumen vary from 4.3 to 20.6 nS. Simulations of the DNTs with ssDNA and dsDNA overhangs at the mouth of the pore show gating effect with remarkable difference in the transmembrane ionic conductivities for open and close state nanopores. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Nucleic Acids Research

Structure and electrical properties of DNA nanotubes embedded in lipid bilayer membranes

Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H2S) production. H2S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production. Restricting dietary sulfur amino acids can trigger angiogenesis and improve vascular health. © 2018 Elsevier Inc.

Cell

Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production

Background/Purpose: Reoperation is being increasingly utilized as a metric for surgical care quality. The aim of this study was to identify the incidence of and risk factors for unplanned reoperation following index hepatectomy. Methods: Pre, intra- and post-operative information of patients who underwent partial hepatectomy in 435 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2013 were analyzed. Results: 343 (4%) of 9195 patients required reoperation within 30 days of index hepatectomy. The index procedures with the highest incidence of reoperation (%) were trisectionectomy (7%) and right hepatectomy (5%). Patients who underwent reoperation had increased index operative duration (323 ± 174 min versus 243 ± 125 min, p < 0.001), postoperative transfusion (57% versus 23%, p < 0.001), wound complications, cardiorespiratory, renal, thromboembolic, and infectious events. Hemorrhage was the most common indication for reoperation (10%). Male gender, ASA class 4, and right hepatectomy or trisectionectomy were independent predictors of reoperation (OR 1.4 [1.1–1.7], p = 0.007; 2.0 [1.3–3.1], p = 0.003; 1.6 [1.2–2.0], p = 0.001 and 2.5 [1.8–3.4], p < 0.001, respectively). All reoperations occurred during index hospitalization and resulted in longer mean length of stay (19 ± 17 days versus 7 ± 7 days, p < 0.001). Conclusion: Reoperation is associated with several patient characteristics and procedural factors in this national sample. Knowledge of these factors can increase awareness of patients at risk for reoperation. © 2018 International Hepato-Pancreato-Biliary Association Inc.

Unplanned reoperation after hepatectomy: an analysis of risk factors and outcomes

Type IV pili (T4P) are surface-exposed protein fibers that play key roles in the bacterial life cycle via surface attachment/adhesion, biofilm formation, motility, and development. The order Myxococcales (myxobacteria) are members of the class Deltaproteobacteria and known for their large genome size and complex social behaviors, including gliding motility, fruiting body formation, biofilm production, and prey hunting. Myxococcus xanthus, the best-characterized member of the order, relies on the appropriate expression of 17 type IVa (T4aP) genes organized in a single cluster plus additional genes (distributed throughout the genome) for social motility and development. Here, we compared T4aP genes organization within the myxobacteria to understand their evolutionary origins and diversity. We found that T4aP genes are organized as large clusters in suborder Cystobacterineae, whereas in other two suborders Sorangiineae and Nannocystineae, these genes are dispersed throughout the genome. Based on the genomic organization, the phylogeny of conserved proteins, and synteny studies among 28 myxobacterial and 66 Proteobacterial genomes, we propose an evolutionary model for the origin of myxobacterial T4aP genes independently from other orders in class Deltaproteobacteria. Considering a major role for T4P, this study further proposes the origins and evolution of social motility in myxobacteria and provides a foundation for understanding how complex-behavioral traits, such as gliding motility, multicellular development, etc., might have evolved in this diverse group of complex organisms. © 2018 Sharma, Burrows and Singer.

Frontiers in Microbiology

Diversity and evolution of myxobacterial type IV pilus systems

The sandfly midgut and the human macrophage phagolysosome provide antagonistic metabolic niches for the endoparasite Leishmania to survive and populate. Although these environments fluctuate across developmental stages, the relative changes in both these environments across parasite generations might remain gradual. Such environmental restrictions might endow parasite metabolism with a choice of specific genotypic and phenotypic factors that can constrain enzyme evolution for successful adaptation to the host. With respect to the available cellular information for Leishmania species, for the first time, we measure the relative contribution of eight inter-correlated predictors related to codon usage, GC content, gene expression, gene length, multi-functionality, and flux-coupling potential of an enzyme on the evolutionary rates of singleton metabolic genes and further compare their effects across three Leishmania species. Our analysis reveals that codon adaptation, multi-functionality, and flux-coupling potential of an enzyme are independent contributors of enzyme evolutionary rates, which can together explain a large variation in enzyme evolutionary rates across species. We also hypothesize that a species-specific occurrence of duplicated genes in novel subcellular locations can create new flux routes through certain singleton flux-coupled enzymes, thereby constraining their evolution. A cross-species comparison revealed both common and species-specific genes whose evolutionary divergence was constrained by multiple independent factors. Out of these, previously known pharmacological targets and virulence factors in Leishmania were identified, suggesting their evolutionary reasons for being important survival factors to the parasite. All these results provide a fundamental understanding of the factors underlying adaptive strategies of the parasite, which can be further targeted. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Journal of Molecular Evolution

Evolutionary Perspectives of Genotype–Phenotype Factors in Leishmania Metabolism

The hurdles in drug and vaccine development pipelines for leishmaniasis, a complex, multifaceted disease, are largely due to the digenetic lifecycle, differential clinical manifestations of the parasite, and the incomplete understanding of its adaptations within its hosts. Here, we discuss the distinct computational and experimental techniques employed to identify the species and stage-specific adaptive mechanisms at different levels of biological organization, the progress made so far, and limitations in comprehending leishmaniasis as a systems biology disease. Based on the available perspectives, we also provide suggestions and requirements to tackle the growing challenges for bridging the genotype with the phenotype. A systems perspective can be instrumental in understanding the complexities of the disease and can provide insights for targeted control. © 2018 Elsevier Ltd

Trends in Parasitology

Perspectives on Leishmania Species and Stage-specific Adaptive Mechanisms

Iron deprivation induces transcription of genes required for iron uptake, and transcription factor Aft1 and Aft2 mediate this by regulating transcriptional program in Saccharomyces cerevisiae. Iron-dependent Fe(II) and 2-oxoglutarate-dependent dioxygenase family proteins are involved in various cellular pathways including DNA alkylation damage repair. Whether Aft1/Aft2 are required for DNA alkylation repair is currently unknown. In this report, we have analyzed DNA alkylation repair under iron-deprived condition. Saccharomyces cerevisiae Tpa1 is a member of Fe(II) and 2-oxoglutarate-dependent dioxygenase family, and we show that deletion of AFT1 and AFT2 genes affects Tpa1 function resulting in sensitivity to alkylating agent methyl methane sulfonate (MMS). Deletion of AFT1 and AFT2 along with base excision repair pathway DNA glycosylase MAG1 renders the aft1Δaft2Δmag1Δ mutant highly sensitive to MMS. We have further studied effect of iron depletion by replacing S. cerevisiae Tpa1 with Escherichia coli AlkB and human AlkBH3. We observed that the activity of AlkB and AlkBH3 is also diminished similarly when present in aft1Δaft2Δ background as evident by sensitivity to MMS.

FEMS yeast research

DNA repair activity of Fe(II)/2OG-dependent dioxygenases affected by low iron level in Saccharomyces cerevisiae

A cryo-cooler based cryogenic test setup has been designed, fabricated, and tested. The setup incorporates two numbers of cryo-coolers, one for sample cooling and the other one for cooling the large magnet coil. The performance and versatility of the setup has been tested using large samples of high-temperature superconductor magnet coil as well as short samples with high current. Several un-calibrated temperature sensors have been calibrated using this system. This paper presents the details of the system along with results of different performance tests. © 2018 Author(s).