Mahadik, Kasturi Suryakant
Study of cell signalling pathways affected by pathogen entry comprises a fundamental aspect of understanding host-pathogen interactions. In this respect, the current study attempted to ascribe novel roles to Bone Morphogenesis Protein (BMP) signaling during infection. BMP pathway has been majorly studied in context of development where it plays an imperative role and its contribution to immunity has been poorly documented. Subsequent narrative talks about the perturbation of BMP signaling in context of specific signaling networks and its collaboration with other molecular players of host innate armamentarium.
There is a pressing need to develop effective chemotherapy against Mycobacterium tuberculosis, the...
Mu is a temperate bacteriophage which infects Escherichia coli and several other Gram negative enteric bacteria. It is an extraordinary phage in several respects and has carved a special niche for itself both as a genetic tool and a paradigm in phage biology, almost rivaling phage lambda. It is also a predator that has adapted its hunting skills well in order to have an extraordinarily wide host range. While phage Mu finds a mention in almost every genetics textbook for several of its unique and well-studied characteristics, there are a few aspects of its biology that are far from understood....
Thesis addresses the physiological role of formyl tetrahydrofolate synthetase (Fhs) and bifunctional folate dehydrogenase (FolD) in folate mediated one carbon metabolism in bacteria. Thesis consists of 5 chapters. First chapter provides the details of the literature on folate metabolism, enzymes involved the synthesis and physiological roles various folate co-factors. Second chapter discusses the study of Clostridium perfringens Fhs generation of folD deletion in the support of fhs. Third chapter explores the characterization of the folD deletion strain. Fourth chapter presents the characterization of monofunctional versions of FolD from Clostridium perfringens. Fifth chapters talks about anti-correlation existence of Fhs and PurT...
As a human fungal pathogen, Candida albicans can cause a wide variety of disease conditions ranging from superficial to systemic infections. Many of these infections are caused by an inherent ability of the pathogen to form biofilms on medical devices resulting in high mortality. Biofilms formed by C. albicans are a complex consortium of yeast and hyphal cells embedded in an extracellular matrix and are regulated by a network of transcription factors. Here, I report the role of a novel Zn(II)2-Cys6 binuclear cluster transcription factor, ZCF32, in the regulation of biofilm formation. Global transcriptome analysis reveals that biofilm development is...
Nagampalli, Vijay Krishna
Gene deletions are a powerful method to uncover the cellular functions of a given gene in living systems. A limitation to this methodology is that it is not applicable to essential genes. Even for non-essential genes, gene knockouts cause complete absence of gene product thereby limiting genetic analysis of the biological pathway. Alternatives to gene deletions are mutants that are conditional, for e.g, temperature sensitive (ts) mutants are robust tools to understand temporal and spatial functions of genes. By definition, products of such mutants have near normal activity at a lower temperature or near-optimal growth temperature which is called as...
The PhD thesis is on the studsy of the influence of the ftsZ antisense RNA and FtsH protease on the synthesis and function of the Escherichia coli cytokinetic protein, FtsZ, which mediates septation during cell division. Thus, it involves three molecules, FtsZ, ftsZ antisense RNA, and FtsH protease. While the E. coli ftsZ antisense RNA is being identified and structurally and functionally characterised for the first time, there has been some earlier studies in the laboratory in which the FtsH protease was found to have influence on the presence of the FtsZ rings at the mid-cell site.
The Chapter 1 is...
The genus Mycobacterium represents more than 120 species of bacteria including the pathogenic M. tuberculosis, the etiological agent of tuberculosis. The host mounts a robust inflammatory and cell-mediated response to contain the spread of pathogenic mycobacteria. While macrophages, dendritic cells (DCs) and neutrophils are known to facilitate early responses, the effector functions of CD4+ and CD8+ T cells are critical for containment of the mycobacteria. The type I T helper (Th1) subset of CD4+ T cell population orchestrates the protective immunity through cytokines like interferon (IFN)-γ, interleukin (IL)-12, IL-23 and tumor necrosis factor (TNF)-α However, it is known that despite...
HCV genome is a positive sense single-stranded RNA containing a single open reading frame (ORF) flanked by untranslated regions (UTRs), 5’UTR and 3’UTR.Initiation of HCV RNA translation is mediated by internal ribosome entry site (IRES) present in 5’ UTR and this process is independent of cap-structure and requires only a small subset of canonical initiation factors. Hence, HCV IRES-mediated translation initiation mechanism is quite different from canonical cellular mRNA translation initiation. The IRES is organized into highly structured domains, namely domain II, III and IV. High affinity interactions between structured RNA elements present in the IRES and 40S ribosomal proteins...
The Mycobacterium genus contains major human pathogens, like Mycobacterium tuberculosis and Mycobacterium leprae, which are the causative agents of Tuberculosis and Leprosy, respectively. They have evolved as successful human pathogens by adapting to the adverse conditions prevailing inside the host, which include host immune activation, nutrient depletion, hypoxia, and so on. During such adaptation for the survival and establishment of persistent infection inside the host, the pathogen, like M. tuberculosis, regulates its cell division. It is known that M. tuberculosis enters a state of non-replicating persistence (NRP) inside the host, to establish latent infection, which helps the survival of the...
In angiosperms, specialized reproductive structures are borne in flowers to ensure their reproductive success. After the vegetative growth, plants undergo reproductive phase change to produce flowers. Floral meristems (FMs) are generated on the flanks of inflorescence and groups of specialized stem cells in the FM differentiate into four whorls of organs of a flower. In dicots, floral meristem successively gives rise to sepals, petals, stamens and carpels; after which it terminates. The fate of organs formed on FM is under the control of genetic regulators, key among which are members of MADS box transcription factor family. Their individual and combined...
Two mechanisms, intrinsic and factor-dependent, have evolved for accomplishing the termination of transcription in eubacteria. In this thesis, the first chapter is an introduction to the topic that presents what is known about the mechanisms of termination. The properties of the primary and secondary ‘players’- intrinsic terminators, Rho protein, rho-dependent terminators, RNA polymerse and Nus factors - are presented and the known mechanisms by which termination functions are discussed. In Chapter 2, a detailed analysis of intrinsic terminators – their differential distribution, similarity and divergence - has been penned. The database, compiled using the program GeSTer (Genome Scanner for Terminators),...
Shukla, Sudhanshu Kumar
Glioblastoma (GBM) is the most common and malignant of the glial tumors. These tumors may develop from lower-grade astrocytomas (diffuse astrocytoma; grade II or anaplastic astrocytoma; grade III) through a progressive pathway, but, more frequently, they manifest de novo without any evidence of a pre-malignant lesion. The treatment of GBM includes surgery, radiotherapy, and chemotherapy with temozolomide. Despite improvements in treatment protocols, the median survival of GBM patients remains very low at 12-15 months.
The cause of glioma (either development or progression) can be genetic and epigenetic modification driven changes. In contrast to genetic modifications, where DNA sequence is changed,...
Mohan Kumar, D
Astrocytoma, the tumor of astrocytic origin, accounts for about 60 % of the primary
brain tumors. As per World Health Organization grading system, astrocytoma is classified as circumscribed astrocytoma (Grade I; pilocytic astrocytoma) and diffusely infiltrating astrocytoma. Grade I tumor is biologically benign and can be cured by surgical resection of
the tumor. The diffusely infiltrating astrocytoma is further subclassified into grade II/diffuse astrocytoma (DA), grade III/anaplastic astrocytoma (AA) and grade IV/glioblastoma (GBM). Aggressiveness of the disease increases as the tumor progresses from lower grade to higher grade. In particular, GBMs are the most malignant and aggressive human cancers.
For a newly diagnosed...
Soumya, A M
Glioma, the tumor of glial cells, is one of the common types of primary central nervous system (CNS) neoplasms. Astrocytoma is the most common of all gliomas and originates from astrocytic glial cells. Astrocytoma tumors belong to two main categories: benign tumors, comprising of grade I Pilocytic astrocytoma and malignant tumors which diffusely infiltrate throughout the brain parenchyma. Diffusely infiltrating astrocytomas are graded into diffuse astrocytoma (DA; grade II), anaplastic astrocytoma (AA; grade III) and glioblastoma (GBM; grade IV) in the order of increasing malignancy. Patients with grade II astrocytoma have a median survival time of 6 to 8 years...
Deshpande, Gauravi M
Poaceae (or Gramineae) belong to the grass family and is one of the largest families among flowering plants on land. They include some of the most important cereal crops such as rice (Oryza sativa), barley (Hordeum vulgare), wheat (Triticum aestivum), maize (Zea mays), and sorghum (Sorghum bicolor). The characteristic bushy appearance of grass plants, including cereal crops, is formed by the activities of axillary meristems (AMs) generated in the leaf axil. These give rise to tillers from the basal nodes which recapitulate secondary growth axis and AMs are formed during vegetative development. On transition to flowering the apical meristem transforming...
Sang, Pau Biak
DNA repair proteins in mycobacteria and their physiological importance
Mycobacterium tuberculosis, the causative organism of tuberculosis, resides in the host macrophages where it is subjected to a plethora of stresses like reactive oxygen species (ROS) and reactive nitrogen intermediate(RNI) which are generated as a part of the host’s primary immune response. These stresses can damage the cellular components of the pathogen including DNA and its precursors. Two common damages to DNA and its precursors caused by ROS and RNI are oxidation of guanine to 8-oxo-guanine and deamination of cytosine to uracil. Mycobacteria, which are known to have high G+C content, must...
The eubacterial genome is maintained in a negatively supercoiled state which facilitates its compaction and storage in a small cellular space. Genome supercoiling can potentially influence various DNA transaction processes such as DNA replication, transcription, recombination, chromosome segregation and gene expression. Alterations in the genome supercoiling have global impact on the gene expression and cell growth. Inside the cell, the genome supercoiling is maintained judiciously by DNA topoisomerases to optimize DNA transaction processes. These enzymes solve the problems associated with the DNA topology by cutting and rejoining the DNA. Due to their essential cellular functions and global regulatory roles, DNA...
Hepatitis C virus (HCV), a blood-borne pathogen, is a small enveloped RNA virus belonging to the Hepacivirus genus of the Flaviviridae family. HCV infection represents one of the major health concerns affecting approximately 170 million people globally. Patients with chronic HCV infection are at risk of developing hepatic fibrosis, cirrhosis and hepatocellular carcinoma. No protective anti-HCV vaccine is available yet. Until recently, standard therapy based on pegylated interferon plus ribavirin, was inadequate in treating all the patients as it results in a sustained virological response in only 40 to 50 percent of patients infected with the most common genotype (gt...
Arandkar, Sharath Chandra
p53 is a nodal tumor suppressor protein that acts as a major defense against cancers. Approximately 50% of human tumours have mutations in p53 gene. Among its myriad features, the most distinctive is the ability to elicit both apoptotic death and cell cycle arrest. p53 has several isoforms. Most of them are produced by either internal promoter activity of the gene or alternate splicing of the pre-mRNA. Apart from these mechanisms, p53 mRNA has also been shown to be translated into two isoforms, the full-length p53 (FL-p53) and a truncated isoform ΔN-p53, which acts as a dominant-negative inhibitor of FL-p53....
Gupta, Mainak Das
Growth polarity in leaves – a final discussion
Insights into the growth processes of leaf lamina have come from studies on several species including Arabidopsis, Antirrhinum, tobacco and maize. A feature common to the growth of leaf in these distantly related species is the existence of a pronounced growth gradient in the proximo-distal axis -growth at the tip (distal part) is arrested at an early stage while the basal region (proximal part) continues to grow for the longest duration. This is because the cell division is arrested first at the tip at an early stage of development and the arrest...