Repository of Theses and Dissertations of Indian Institute of Science, Bangalore, India. The repository has been developed to capture, disseminate and preserve research theses of Indian Institute of Science.
Molecular Reproduction, Development and Genetics (mrdg)
Rai, Mamta
Muscle development involves concerted action of a repertoire of mechanisms governing myoblast proliferation, migration, fusion and differentiation. Subsequently, there are cellular events administrating proper muscle function and maintenance of muscle integrity. Chapter 1 covers what is known about muscle development, building up of mass and maintenance in vertebrates and Drosophila, highlighting the myogenic programs and factors that play a role in them. The formation of vertebrate skeletal muscles can be recapitulated in Drosophila indirect flight muscles (IFMs), making IFMs an interesting model to dissect and understand the mechanisms of muscle development and maintenance. The cellular and developmental events that occur...
Sehgal, Priyanka
Insulin-like growth factor binding proteins (IGFBPs) modulate the bioavailability of IGFs in circulation. IGFBPs 1-6 bind IGFs with high affinity and can either potentiate or inhibit IGF signaling in a context dependent manner. IGFBP2 is a 36 kDa protein and the second most abundant IGFBP in serum.
Numerous studies in the recent past have implied a pro-tumorigenic role of IGFBP2. Elevated expression of IGFBP2 has been observed in multiple malignancies, including glioblastoma multiforme (GBM), ovarian, pancreatic, gastric, prostate, colon, breast, thyroid cancer and leukemia. In addition, increased expression of IGFBP2 in both tissues and serum of patients has been correlated with...
Khan, Imran
Oral Submucous Fibrosis (OSF) is a chronic inflammatory disease resulting in progressive fibrosis of the oral tissues that can cause difficulty in chewing, swallowing, speaking, and mouth opening. Epidemiological studies have shown that OSF is a precancerous condition and 2-8% of the OSF patients develop squamous cell carcinoma. This disease affects 0.5% of the population in the Indian subcontinent and is now a growing public health issue in many parts of the world. Habit of chewing betel quid has been proposed as an important etiological factor in the development of this disease and is coline, a principle alkaloid of areca...
Chib, Savita
Studies on stationary phase cultures of microorganisms in the laboratory have helped us understand the genetic and physiological basis of adaptation in their natural habitats. Stasis or decline in bacterial populations due to nutrient depletion during stationary phase has been shown to lead to the selection of mutants that are able to survive better than their parent. This phenomenon, where a mutant exhibits relatively better growth than its immediate parent, under the conditions that prevailed during its appearance, is termed as Growth Advantage in Stationary Phase (GASP) and constitutes a general strategy to survive prolonged stationary phase. A mutation conferring...
Abbey, Deepti
Pluripotent stem cells (PSCs) are specialized cells, which have remarkable ability to maintain in an undifferentiated state and are capable of undergoing differentiation to three germ-layer lineage cell types, under differentiation-enabling conditions. PSCs include embryonic stem (ES)-cells, embryonal carcinoma (EC)-cells and embryonic germ (EG)-cells. ES-cells are derived from the inner cell mass (ICM) of day 3.5 blastocysts (mouse). On the other hand, EC- and EG-cells have different source of origin and exhibit some differences in terms of their differentiation abilities and culture requirements. These PSCs act as an ideal in-vitro model system to study early mammalian development and cell differentiation...
Nambi, Subhalaxmi
Tuberculosis continues to be one of the major causes of morbidity and mortality worldwide. Several mycobacterial species such as M. tuberculosis and M. africanum are responsible for causing this disease in humans. Reports of high cAMP levels in mycobacterial species (as compared to other bacteria such as E. coli) suggested that this second messenger may play an important role in the biology of mycobacteria. Further, it was reported that infection with mycobacteria led to an increase in the cAMP levels within the host macrophage. More recent studies have shown that this cAMP increase may be due to bacterially derived cAMP,...
Arshad, Najla
The survival of the any living organism depends on its availability to communicate, and a breakdown of cellular signaling can have dire consequences such as uncontrolled cellular proliferations or even cell death. Environmental cues or ligands are perceived by cognate receptors, expressed primarily on the cell surface, and transmitted to the interior of the cell to elicit a response. This universal phenomenon is termed as signal transduction. During this process, second messengers such as cyclic nucleotides, cAMP and cGMP, are produced which serve to amplify the signal.
Cyclic GMP is emerging as a universal second messenger, and is found in both...
Roy, Shubhendu Sen
The zona-pellucida (zona, ZP) is an adhesion-refractory, acellular coat enclosing the rapidly growing, free-living mammalian preimplantation embryo which undergoes successive cleavage divisions to form the blastocyst, composed of ICM-cells surrounded by outer TE-cells. For further development, the blastocyst must ‘hatch’ or ‘escape’ out of the zona before it can implant into the endometrium for further development (Fig. 5.1A). Hence, the event of hatching or ‘zona escape’ assumes critical importance for the establishment of a successful pregnancy. The golden-hamster blastocyst offers a very unique paradigm to understand hatching, whereby upon attainment of a fully-expanded state, the blastocyst undergoes a dramatic (and...
Majumdar, Ritankar
The glycoprotein hormones, Luteinizing Hormone (LH), human Chorionic Gonadotropin (hCG), Follicle Stimulating Hormone (FSH) and Thyroid Stimulating Hormone (TSH) are heterodimeric proteins with an identical α-subunit associated non-covalently with the hormone specific β-subunit and play important roles in reproduction and overall physiology of the organism [1]. The receptors of these hormones belong to the family of G-protein coupled receptors (GPCR) and have a large extracellular domain (ECD) comprising of 9-10 leucine rich repeats (LRR) followed by a flexible hinge region, a seven helical transmembrane domain (TMD) and a C terminal cytoplasmic tail [2]. Despite significant sequence and structural homologies observed...
Mattoo, Rohini
Pathogenic bacteria such as M.tuberculosis have evolved several mechanisms to aid their intracellular survival and subvert host defenses. One of the contributing factors is thought to be the production and secretion of large amount of cAMP, Mycobacterial genomes encode a large number of adenylyl cyclases distinct in their structure and regulatory mechanisms. The roles of these enzymes in the physiology and pathogenesis of virulent mycobacteria are only now being elucidated. The roles of phosphodiesterases (PDEs), which serve to lower cAMP levels through degradation are, however, relatively unexplored.
The Rv0805 gene was previously shown to code for an active phosphodiesterase from...
Dasari, Santosh Kumar
In mammals, freshly ejaculated spermatozoa do not possess the ability to fertilize a mature oocyte. They acquire fertilization competence upon residing for a period of time in the female reproductive tract. The physiological changes that bring about these time-dependent changes in motility pattern and acquisition of fertilizing ability of spermatozoa are collectively referred to as capacitation, culminating in sperm hyperactivation. Capacitation-associated increase in sperm protein tyrosine phosphorylation (PYP), exhibited by mammalian sperm, is one of the major downstream events, regulating hyperactivated motility. However, it is still unclear which are the tyrosine kinases and phosphatases involved in modulating the capacitation-associated increase...
Kumar, Hindupur Sravanth
Rapidly growing tumor cells outgrow their blood supply resulting in a microenvironment with reduced oxygen and nutrients. Using an in vitro transformation model we found that cancer cells expressing the SV40 ST antigen (+ST cells) are more resistant to glucose deprivation-induced cell death than cells lacking the SV40 ST antigen (−ST cells). Mechanistically, we found that the ST antigen mediates this effect by activating a nutrient-sensing kinase, AMP-activated protein kinase (AMPK). We further show that AMPK mediates its effects, at least in part, by inhibiting mTOR (mammalian target of rapamycin), thereby shutting down protein translation, and by inducing autophagy as...
Salvi, Sheetal S
Myofibrillogenesis is a complex process, which involves assembly of hundreds of structural proteins in a highly ordered manner to form the contractile structural unit of muscle, the sarcomere. Several myopathic conditions reported in humans are caused due to abnormal myofibrillogenesis owing to mutations in the genes coding for many of these structural proteins. These myopathies have highly variable clinical features and time of onset. Since their aetiology is poorly understood, it becomes imperative to have a model system to study the muscle defects. Present study proposes to employ the Indirect Flight Muscle (IFM) system in Drosophila melanogaster as a model...
Singh, Gurbind
Genesis of life begins with the fusion of female and male haploid gametes through a process of fertilization leading to the formation of a diploid cell, the zygote. This undergoes successive cleavage divisions forming 2-, 4- and 8- cell embryos and their individual cells (blastomeres) are totipotent. As development proceeds, there is a gradual restriction in their totipotency, resulting in the generation of two distinct cell lineages i.e., the differentiated trophectoderm (TE) cells and the undifferentiated, inner cell mass (ICM) during blastocyst morphogenesis (Rossant and Tam 2009). During the course of development, the ICM cells can give rise to all...
Singhmar, Pooja
Autosomal recessive primary microcephaly (MCPH) is defined by congenital microcephaly and associated mental retardation with head circumference of the affected individual at least 3 standard deviations below age- and sex-means. It is a disorder of abnormal fetal brain growth which is a consequence of impaired neurogenesis. It is genetically heterogeneous with seven known loci and genes for all the seven loci have been identified: MCPH-1-MCPH1, MCPH2-WDR62, MCPH3-CDK5RAP2, MCPH4-CEP152, MCPH5-ASPM, MCPH6-CENPJ, and MCPH7-STIL. All the seven MCPH proteins localize at the centrosome. Apart from MCPH, many other proteins associated with the phenotype microcephaly have been localized to the centrosome or linked...
Biswas, Kabir Hassan
Sharma, Ritu
The discovery of cyclic AMP (cAMP), nearly 50 years ago by Sutherland radically altered the appreciation of metabolic regulation. Since then the presence of cAMP and its tremendous physiological impact has been demonstrated in many prokaryotic systems. In fact, virulence mechanisms of several pathogens known today exploit cAMP dependent pathways. Interestingly the genome of Mycobacterium tuberculosis H37Rv, the causative agent of tuberculosis, encodes as many as 16 adenylyl cyclases (enzymes that convert ATP to 3’, 5’-cAMP) and 10 cyclic-nucleotide binding proteins. Recent reports show that bacterial-derived cAMP manipulates host signaling for bacterial survival, suggesting an important role for cAMP in...
Venkatesh, N
Desai, Kartiki
Saha, Saikat