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)
Baksi, Arka
Spermatogenesis is a complex and coordinated process of formation of sperms from the precursor spermatogonia, occurring inside the unique environment existing in the seminiferous epithelium. This process of development, characterized by concomitant changes in the cellular morphology, metabolism and differential gene expression, can be divided into 3 distinct phases: i) proliferation of the spermatogonia through mitosis; ii) meiosis or reduction division, which commences with transformation of the type B spermatogonia into primary spermatocytes and their subsequent entry into the meiotic prophase I. These primary spermatocytes, divide to form secondary spermatocytes, and then divide again to form haploid round spermatids; (iii)...
Dhar, Neha
GPCRs, influencing myriads of cellular functions, are the members of the largest family of the membrane proteins. However, their structures and the signaling mechanisms still remain enigmatic. In case of the Glycoprotein Hormone Receptor (GpHR) family the structure-function relationship is less understood because of a large extra-cellular domain (ECD). This large ECD, consisting of Leucine Rich Repeats (LRRs) and membrane-proximal hinge region, is sufficient for specific binding to the hormone (Ascoli, Fanelli, & Segaloff, 2002), but for receptor activation, hormone binding is translated via a conformation wave starting at hinge region and relayed to the transmembrane domain. Several biochemical, immunological...
Madan, Aditi
Muscle contraction is a highly fine-tuned process that requires the precise and
timely construction of large protein sub-assemblies to form sarcomeres, the
individual contractile units. Mutations in many of the genes encoding constituent
proteins of this macromolecular machine result in defective functioning of the
muscle tissue, and in humans, often lead to myopathic conditions like cardiomyopathies and muscular dystrophies, which affect a considerable number of people the world over. As more information regarding causative mutations becomes available, it becomes imperative to explore mechanisms of muscle
development, maintenance and pathology.
In striated muscles, contraction is regulated by the thin filament-specific
tropomyosin (Tm) – troponin (Tn) complex (Ca2+-binding troponin-C,...
Agrawal, Ruchi
Mycobacterium tuberculosis, the causative organism of the disease tuberculosis (TB) in humans, leads to nearly two million deaths each year. This versatile pathogen can exist in highly distinct physiological states such as asymptomatic latent TB infection where bacilli lie dormant or as active TB disease in which the bacilli replicate in macrophages. The pathogenic lifestyle requires the tubercle bacillus to sense and respond to multiple environmental cues to ensure its survival. Such stimuli include hypoxia, nutrient limitation, presence of reactive oxygen and reactive nitrogen intermediates, pH alterations, and cell wall/ membrane stress. Two component systems (TCSs) form the primary apparatus...
Janardan, Vishnu
A large number of evolutionarily conserved genes have been identified by comparative genomics approaches. However, a considerable fraction of these genes lack functional characterization despite the availability of several bioinformatics approaches for prediction of protein function. Moreover, with the advent of genome sequencing efforts, numerous disease associated genes have been identified. While high throughput approaches aid in identification of genes, studying individual genes is important to understand their cellular roles.
During studies on cyclic AMP metabolism in mycobacteria conducted in the laboratory, a Class III cyclic nucleotide phosphodiesterase, Rv0805 was identified from Mycobacterium tuberculosis. Interestingly, additional bioinformatics analysis identified orthologs...
Sinha, Shakun
Contraception through a vaccine has been a very attractive proposition and several attempts were made in the past. To achieve contraception through immunological means, several points need to be considered. First, the targeted antigen should be an important component of reproduction and interference in its actions should lead to infertility. Second, the antigen must be highly immunogenic and the antibodies elicited should be able to block the functions of the antigen. Third, the antibody titres should be effective and must sustain for longer periods. Gonadotropins fulfill all the above criteria and therefore, have been attractive targets for developing human contraceptive...
Tiwari, Ankana
Sharma, Ankur
Notch receptors and ligands are single-pass transmembrane proteins which play important roles in cell-cell communication. Notch in ‘harmony’ with other signaling pathways regulate the entire diversity of metazoan life (Artavanis-Tsakonas & Muskavitch, 2010). These signaling pathways also play key roles in regulatingseveral developmental processes. Given the importance of Notch signaling in various developmental decisions, it is not surprising that aberrant gain or loss-of-function of Notch pathway leads to several human diseases including cancer (Ranganathan et al, 2011). Notch signaling has also been implicated in various human cancers, most notably in T-cell acute lymphoblastic leukemia (T-ALL) (Weng et al, 2004). In...
Matange, Nishad
All organisms must sense and respond to their environment in order to survive. The processes that allow a living cell to sense changes in its environment, and respond appropriately are collectively referred to as ‘signal transduction’. Cyclic AMP is a ubiquitously used second messenger molecule that plays diverse roles from hormone signalling in mammalian cells to catabolite repression in enteric bacteria. In several bacterial pathogens such as Pseudomonas aeruginosa, cAMP has also been found to mediate pathogenesis, usually by regulating the production of several virulence factors aiding in colonisation of the host. Cyclic AMP signalling has been suggested to regulate...
Rather, Mohammad Iqbal
CDC73, also known as HRPT2, is a tumour suppressor gene whose expression is lost or downregulated in parathyroid, renal, breast, uterine and gastric cancers. However, the reports regarding the role of CDC73 in oral squamous cell carcinoma (OSCC) are lacking. As part of the Paf1 complex, it remains associated with ribonucleic acid (RNA) polymerase II and is involved in transcript site selection, transcriptional elongation, histone H2B ubiquitination, histone H3 methylation, poly(A) length control and, coupling of transcriptional and posttranscriptional events. It has been reported to negatively regulate cellularproliferation by targeting oncogenes CCND1 (cyclin D1) and MYC (c-Myc). Moreover, it has...
Verma, Subhash Chandra
The genome of Escherichia coli harbors several catabolic operons involved in the utilization of a wide variety of natural compounds as carbon sources. The chitobiose (chu) operons of E.coli Is involved in the utilization of chitobiose(disaccharide of N-acety1-D-glucosamine) and cellbiose (disaccharide of glucose) derived from the two most abundant naturally occurring carbon sources on earth, chitin and cellulose respectively. The operon consists of the chbBCARFG genes coding for transport, regulation and hydrolysis functions required to utilize these compounds; the chuyBCA genes code for a multi-subuni PTS transporter ; the chuR codes for a dual function repressor/activator of the operon; the...
Avinash, Pradhan Shalmali
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, with a
worldwide incidence of 275,000 new cases annually (Warnakulasuriya, 2009). Globally, the head and neck carcinoma represents a major cause of morbidity and mortality and is the sixth most commonly occurring cancer (Warnakulasuriya, 2009). A majority (>90%) of the head and neck cancers are squamous in origin and thus are linguistically referred to as head and neck squamous cell carcinoma (HNSCC) (Warnakulasuriya, 2009). HNSCC includes cancers of the oral cavity, larynx and pharynx; oral cancer being the most common (Warnakulasuriya, 2009).
Although, HNSCC is the sixth most common...
Thejaswini, V
Autosomal recessive primary microcephaly (MCPH) is a congenital neurodevelopmental disorder characterised by a reduced occipital-frontal head circumference (OFC) of less than -3 SDs below the population mean for age and sex. It is a genetically heterogeneous disorder caused by mutations in one of the following 10 MCPH genes: MCPH1 (microcephalin 1), WDR62 (WD repeat domain 62), CDK5RAP2 (cyclin-dependent kinase 5 regulatory associated protein 2), CASC5 (cancer susceptibility candidate 5), CEP152 (centrosomal protein 152 kDa), ASPM (asp [abnormal spindle] homolog, microcephaly associated [Drosophila]), CENPJ (centromeric protein J), STIL (SCL/TAL1-interrupting locus), CEP135 (centrosomal protein 135 kDa) and CEP63 (centrosomal protein 135 kDa)....
Sonowal, Robert
Bacteria are ubiquitous in all ecosystems and are often challenged by multiple stresses such as extreme temperatures, high salt concentrations, nutrient limitation, pH variations, radiation, predation and the presence of antibiotics/toxins. The most challenging among them is predation pressure which is one of the major causes of their mortality in different niches. Bacteria have evolved different adaptive measures to counter predation. Some of them include change in shape, size, motility, and unpalatable aggregate formation.
Aromatic β-glucosides such as salicin, produced by plants as secondary metabolites, play a significant role in protecting them from herbivores. Members of the family Enterobaceriaceae primarily...
Singh, Nivedita
Wilson disease (WD) is an autosomal recessive disorder characterized by deposition of copper in the body, mainly in the liver and brain. WD patients present with hepatic, neurological, and psychiatric problems. The diagnosis of WD is very challenging, and is performed by taking
into account both clinical and biochemical parameters. The treatment of WD exists, which aims at initial chelation therapy followed by maintenance therapy. WD is caused by mutations in the ATP7B gene. Till date, more than 600 mutations in ATP7B have already been described from many countries, including India. However, there are a very few large cohort studies which...
Rasool, Insha
Guanylyl cyclase C (GC-C) is a member of particulate guanylyl cyclases, discovered primarily as the target of a family of heat stable enterotoxins (ST), produced by enterotoxigenic Escherichia coli (ETEC). ST is acknowledged as a prime cause of traveller’s diarrhea and the leading cause of child mortality under the age of 5 years in developing nations. The bacterial expression of ST peptides represents molecular mimicry where the pathogen has exploited a gastrointestinal tract-signaling pathway to disperse and propagate. GC-C is primarily expressed on the apical or the brush border membranes of intestinal epithelial cells. GC-C agonists elaborated in the gastrointestinal...
Zaveri, Anisha
Mycobacterium tuberculosis is one of the most successful human pathogens, estimated to have infected close to one-third of the global human population. In order to survive within its host, M. tuberculosis utilises multiple signalling strategies, one of them being synthesis and secretion of universal second messenger cAMP. This process is enabled by the presence of sixteen predicted adenylyl cyclases in the genome of M. tuberculosis H37Rv, ten of which have been characterised in vitro. The synthesized cAMP is recognised by ten putative cAMP-binding proteins in which the cyclic AMP-binding domain is associated with a variety of enzymatic domains. The cAMP...
Pandey, Aparamita
Energy homeostasis is an important physiological mechanism essential for balancingenergy flow through the living systems by managing overall metabolism in the body.
Thus, energy homeostasis is under a tight control by means of extremely well-regulated energy metabolism. One of the most common metabolic disorders that occur following disruption in energy homeostasis mechanisms is obesity. Obese individuals develop insulin resistance in the peripheral tissues (fat and muscle) and may also include non-alcoholic fatty liver disease. Insulin resistance is the primary factor responsible for the development of type 2 diabetes mellitus (T2D). Towards control and management of T2D condition, insulin, drugs that regulate...
Sundararaman, Ananthalakshmy
AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis in cells. It has been implicated as a therapeutic target for various metabolic diseases like type II diabetes and obesity. However, its role in cancer is context-dependent and therefore warrants further studies to explore its possible use as a therapeutic target. AMPK can either promote or retard the growth of cancer cells depending on other cues and stresses in the milieu of the cancer cells. This study aims to understand AMPK signalling in response to extracellular cues of matrix deprivation and matrix stiffness that are important determinants of metastasis....
Sundararaman, Ananthalakshmy
AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis in cells. It has been implicated as a therapeutic target for various metabolic diseases like type II diabetes and obesity. However, its role in cancer is context-dependent and therefore warrants further studies to explore its possible use as a therapeutic target. AMPK can either promote or retard the growth of cancer cells depending on other cues and stresses in the milieu of the cancer cells. This study aims to understand AMPK signalling in response to extracellular cues of matrix deprivation and matrix stiffness that are important determinants of metastasis....