About Jayalaxmi shetty
PhD Project title : Development of Biofunctional inorganic nonoparticle for efficient Delivery of siRNA, therapeutic gene and drugsto breast cancer cells. Academic Unit and Campus: Faculty of Medicine, Nursing & Health Sciences Malaysia. Part of my work is has been presented in American Diabetes Association (ADA) Symposium 2011 and ADA number is 31-LB. Title: “CNX-011-67, a novel orally available GPR40 agonist enhances glucose stimulated insulin secretion and significantly reduces fasting and non fasting hyperglycemia-studies invitro and in a preclinical model of T2DM”. MR Jagannath, BP Somesh, MR Venkataranganna, O Anup, D Anilkumar, MK Verma, B Sangamitra, C Bawana, S Manojkmar, R Sowmya, S Jayalaxmi. Introduction about manuscript: We report the development of highly selective potent molecule of GPR40 agonist CNX-011- 67 which exhibit unique property to improve beta cell function under condition of metabolic stress. CNX-011-67 improves beta cell sensitivity to glucose and enhances GSIS and content in multiple species including human T2DM islets. In preclinical model of T2DM CNX-011-67 has demonstrated good antidiabetic activity. Worked as Scientist in Connexious LifeSciences, Bangalore, India Main activities and responsibilities Project Title: Screening of different synthetic molecules for glucose clearance activity and insulin secretion using mouse rat and human cell lines of beta, alpha, pancreatic, adipose and muscle cells. And Insulin secretion in hGPR40-transfected and untrasfected NIT-1 cells, the effect of chronic GPR40 agonist treatment on the level of docked insulin granules in pancreatic beta cells and the effect of free fatty acids and GPR40 agonist on GSIS. The fatty acids (FFAs) have an opposite effects on the GSIS in acute and chronic conditions. The acute exposure can potentiate the GSIS whereas the chronic reduces the same. It is believed that the acute potentiating effect is determined by the GPR40 (FFAR1) agonism by FFA. In contrast, the chronic effect is mainly determined by the metabolic effect of the FFA. Hence, the small molecule agonist of GPR40 can potentiate the GISS in its both acute and chronic exposures. Both saturated and unsaturated FFA have similar role in GSIS potentiation. It is reported that increasing length and decreasing saturation will have positive impact on GSIS potentiation. The increase in GSIS by FFA also depends on the concentration on the FFA used. However, saturated FFAs in chronic condition cause more deleterious effect on the beta cells than the unsaturated ones. Considering the above facts, this project is aimed to estimate the potentiation in GSIS caused by the GPR40 agonist in the background on acute/chronic treatment of various FFAs. Project Title: RXR transactivation assay. Problem statement: 1. To design an assay that can be used for the estimation of the RXR transactivation in response to its ligand. 2. To design an assay that can be used for the estimation of the RXR heterodimerization with its J.P Nagar, The nuclear receptor RXR can control key cellular functions like growth, differentiation, migration and metabolism. The RXR can be activated by the 9-cis-ratinoic acid and can be heterodimerized with many other nuclear receptors like RAR, PPAR and LXR. The heterodimerization of RXR with PPAR is an important step in the metabolism and hence got attention in metabolic disorders. Here we aim to design an assay which can be used for the quantitative estimation of the RXR transactivation and its choice of making heterodimerization with other nuclear receptor in response to its target molecule. Therefore, the assay can be used for the screening of the RXR molecules. Other responsibility successfully completed Primary hepatocyte isolation, Primary islets isolation and hypothalamus dissection and many more. Dates 01/08/2009 - 22/10/2012 Occupation or position held R&D Assistant In Jawaharlal Nehru centre for advanced scientific research Jakkur Bangalore (India). Main activities and responsibilities Project Title: Gene targeting of mouse rudhira locus to generate knockout mice for functional analysis. Background: Lab has characterised a novel conserved gene Rudhira, a murine gene involved in the specification and differentiation of blood and vessel precursors from the mesoderm and vascular blood islands. Rudhira is a novel WD40 protein involved in erythropoiesis, angiogenesis and tumors. This is a 1st analysis of rudhira, a developmentally regulated conserved gene that is also implicated in human tumor development. Rudhira is identified In a gene trap screen of mouse ES cells using a promoter less lacZ reporter to deduce the expression pattern of the endogenous gene, one of the clone identified showed β-gal activity restricted to blood islands in different embryoid bodies suggesting possible role in vasculogenesis or hematopoisis, hence lab undertook analysis of the trapped locus, and named as rudhira (Sanskrit : Rudhira =blood) The mechanistic details of how mesoderm cells commit to various lineages is not well understood, due to the lack of appropriate markers. Rudhira can now be used to track the differentiating blood island components to hematopoietic and angiogenic precursors, because it is expressed before Flk 1 is expressed. It remains to be seen whether rudhira is capable carrying out this function because Rudhira expression in both blood and vessel precursors suggesting that it is appropriately positioned to regulating their differentiation and also switch between quiescent and re-activating endothelium. Rudhira regulation which when perturbed could lead to pathological condition. Interestingly BCAS3 (breast cancer amplified seq 3), the human ortholog of rudhira is localized in a region of chromosomal breakpoints associated with the progression of breast cancer and hematological neoplasm. BCAS3 has recently been reported to be a target of metastasis associated protein which is regulated by c-myc. Expression of BCAS3 (rudhira) in high grade brain tumors but not in normal brain tissue suggests that it also be associated with tumor progression. To validate this we have ordered cre mice which has site specific recombinase enzyme which can excise the rudhira gene which is flanked between the lox site. Cre mice in which cre is expressed under tissue specific promoter example only expressed in heart cells, brain cells, breast cells etc to make a conditional knock out I am generating homozygous rudhira knockout mice defective only in wished tissues to validated the observations. Dates 01/07/2007 - 31/07/2008 Occupation or position held Junior Research Fellow Main activities and responsibilities Project Title: Standardizing protocol for cryopresevation of transgenic mouse embryos Background: ES-cell derived cell types can be very useful for cell based therapy for many diseases. But the homing, survival and integration of ES cell derived cells are not well understood at in vivo situation. Hence there is a need to have labeled ES-cell derived cells that can be used for studying homing, survival and integration of in vitro differentiated cells into host organism by experimental cell transplantation. In order to study this aspect, lab is trying to derive ES-cell lines from ubiquitously enhanced green fluorescent protein (EGFP) expressing transgenic mouse and understand their lineage specification into cardiac lineage. Specifically lab is looking at the role of FGF and Wnt signaling during cardiac differentiation, also preserve these transgenic mice embryo for future experiment I am standardizing protocol for cryopreservation of transgenic mouse embryos by slow freezing method which mainly depends on cryoprotectant used and its diffusion rate which can be calculated with the help of vant’hoff curve. Name and address of employer Molecular Reproduction Development and Genetics (MRDG), Indian Institute of Science (IISc), Address C.V. Raman Road, 560012 Bangalore (India) Type of business or sector Education Dates 01/11/2006 - 31/05/2007 Occupation or position held Trainee Main activities and responsibilities Project title: Screening fungal antagonism by pathogen assay and growth pattern checking of fungal culture. Background: India is facing various problems regarding food security. Pests and diseases are major problems. Therefore, efforts have been made to breed resistant cultivars and to develop biocontrol agent, for the control of various fungal plant pathogens. Trichoderma is a well known biocontrol agent against plant diseases. Therefore, isolation and characterization of Trichoderma different geographical locations is likely to provide an array of diverse isolates within desired biocontrol potential against plant diseases and for isolation of valuable genes and their transfer to target plants through novel transgenic approach. Showing strong inhibitory activity in vitroon germination and hyphal growth Lab carring out these objectives 1. Screening of Trichoderma chitinolytic activity. 2. Cloning of endochitinase genes from Trichoderma. 3. Expression of the cloned chitinase gene isolated from T. virens in yeast (Saccharomyces cerevisiae). I was involved in testing fourteen isolates of the Trichoderma (six of T. viride, six of T. harzianum, one of T. polysporum, one of T. pseudokoningii) against the pathogenic fungus Rhizoctonia solani. They used 5 mm discs, placed on PDA plate in opposite direction at 7 cm from each other, and incubated at 26°C. Trichoderma isolates demonstrated high antagonistic action over R. solani; the isolates of T. harzianum were the most aggressive. The isolates of Trichoderma overlapped the colony of R. solani within 120 hours, except for the three isolates (2596, 3086 and 2745). The three isolates (3302, 3601 and Tm,) start overlapped the colony of R. solani earlier than the other isolates. The isolate T. pseudokoningii T14, was not able to overlap the colony of R. solani, but inhibited its growth. Expressed an endochitinase-encoding gene from T. harzianum in tobacco and potato. High expression levels of the fungal gene were obtained in different plant tissues, the transformed plants showed increased resistance to sheath blight caused by R. solani and rice blast, endochitinase gene from T. harzianum was transferred through Agrobacterium mediated transformation. The presence of the gene was confirmed by southern analysis, for confirmation of Recombinant Clones. The confirmation of the presence of cloned fragment was done by PCR amplification of clones with respective primers. The total DNA and cloning vector were used as positive and negative controls in the PCR. Name and address of employer Department of Biotechnology, University of Agricultural Sciences, Krishinagar, Dharwad (India) Microbiology and Bio-technology. Taught rural children about hygiene and health as a part of “National Social Service”. A Campaign and study on “Cancer and isolation of microbial flora from oral cavity and characterization of Hemolytic micro-organisms at Karnatak Cancer Therapy and Research Institute, Navanagar, Hubli”. Under the guidance of Dr. A.C. Deka.