Important information for Ph.D. applicants interviewing at the Department of MRDG during May 23-27 2022.
We encourage you to explore the department webpage to know more about our research.
When visiting the department, feel free to visit our labs. Looking forward to meeting all the applicants soon!
The following faculty at MRDG are considering accepting PhD students.
Click on the names to open the faculty home page in a new tab.
The role of the gut in modulating almost all physiology in an organism is well recognized. This can be a result of an altered microbiome or misregulation of signaling pathways in the intestinal epithelial cell. Using transgenic and knockout mouse models, we propose to study the role of cGMP in the gut, which encompasses aspects of inflammation, infection, epithelial cell function and stem cell regulation. We will utilize organoid models to study the development of specific intestinal cell types and monitor responses using cellular, molecular and biochemical approaches.
1 Mishra V., Bose A., Kiran S., Banerjee S., A Shah I., Chaukimath P., M Reshi M., Srinivas S., Barman A., Visweswariah SS (2021). Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C. J. Exp. Med. e20210479. doi: 10.1084/jem.20210479.
2 Bose, A., Banerjee, S. and Visweswariah, S.S. (2020) Mutational landscape of receptor guanylyl cyclase C: functional analysis and disease-related mutations. IUBMB Life 2020; 1-20 https://doi.org/10.1002/iub.2283
3. Prasad, H., Shenoy, A.R. and Visweswariah, S.S. (2020) Cyclic nucleotides, gut physiology and inflammation. FEBS J 287: 1970-1981.
4. Bose A, Visweswariah SS. (2022) The pseudokinase domain in receptor guanylyl cyclases. Methods Enzymol. 2022;667:535-574. doi: 10.1016/bs.mie.2022.03.046. Epub 2022 Apr 18.
Position open to study TCS signaling in Mtb and implications of its crosstalk”
Two-Component Systems (TCS) are essential Mycobacterial signaling systems that aid in sensing and adapting the bacteria to their ever-changing environment. Mycobacteria have 12 pairs of TCSs, and several studies have been carried out to characterize each pair extensively. Towards understanding the network among these systems, we previously identified the presence of unsual and extensive crosstalk, which leads to the formation of various networks and generates hierarchy in these signaling systems.
Given that these systems also regulate critical cellular adaptive processes, the present opening allows the candidate to characterize the implications of cross talk on regulating specified cellular mechanisms such as virulence, cell wall integrity, growth, and adaptation to environmental changes using biochemical and biophysical approaches. In vivo analysis of crosstalk between and across different TCSs using knock-out strains and identification of regulons impinge on crosstalk and their role in virulence and infection will be examined. The long-term question is to understand the evolutionary design of crosstalk or its absence.
We utilize Caenorhabditis elegans, a nematode lacking traditional pattern recognition receptors (PRRs), to understand pathogen recognition via non-canonical PRRs. We utilize multidisciplinary approaches to identify microbe-associated molecular patterns from pneumonia pathogens and study their sensing by G protein-coupled receptors (GPCRs) of C. elegans. We focus on microbial odors as microbe associate molecular patterns (MAMPs).
We utilize Pseudomonas aeruginosa, a Gram-negative bacterium, to understand how it harnesses its large genomic repertoire of histidine kinase sensors to identify and compete with other microbes, in the context of respiratory infections including pneumonia.
The role of sugars in cell migration across evolution
Do cancer cells migrate using principles employed by unicellular eukaryotes? How do substrate geometries affect migration in normal and cancerous contexts? On how many mechanistic levels are sugars involved in such movement?
Time lapse, confocal, electron microscopy, cell and molecular biological assays, organoid and 3D culture, multiscale modeling, bioinformatics and omic approaches, field trips, lots of hard work and fun!
Ramray Bhat, Associate Professor, MRDG
Please visit our website: https://morphogenesisiisc.wixsite.com/home
Please also visit our laboratory @GA 07, MRDG to know more about our laboratory activities.
We are interested in understanding the protein synthesis and its regulation. Although translation initiation is a fundamental and indispensable process, many of its aspects are poorly understood. We employ biochemical, mutational and structural biology approaches to understand the molecular details of the initial steps of protein synthesis and to figure out how it is regulated. This understanding will be beneficial for treating many human disorders and cancers. Further, it may provide avenues to develop strategies for development of novel therapeutic strategies against bacterial, fungal and viral infection.
Phone: 08022932764 & 08022933676
Lab webpage: https://www.thethlab.comLaboratory: GB 04, B wing, MRDG
1. M Afsar, R Narayan, MN Akhtar, Das D, H Rahil, Nagaraj SK, SM Eswarappa, S Tripathi, Hussain T#. Drug targeting Nsp1-ribosomal complex shows antiviral activity against SARS-CoV-2. eLife (2022);11:e74877 doi: 10.7554/eLife.74877
2. Llácer JL#, Hussain T#, Dong J*, Villamayor L, Gordiyenko Y, Hinnebusch AG# (2021) Large-scale movement of eIF3 domains during translation initiation modulate start codon selection. Nucleic Acids Res. (2021): 49 (20): 11491-11511. doi: 10.1093/nar/gkab908.
3. Kumar R, Afsar M, Khandelwal N, Chander Y, Riyesh T, Dedar RK, Gulati BR, Pal Y, Barua S, Tripathi BN#, Hussain T#, Kumar N#. Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E. Antiviral Res. (2021):189,105056. doi: 10.1016/j.antiviral.2021.105056.
4. Mishra RK, Datey A, Hussain T#. mRNA recruiting eIF4 factors involved in protein synthesis and its regulation. Biochemistry (2020): 59: 34-46. doi: 10.1021/acs.biochem.9b00788.
Epigenetic regulation of gene expression during early mammalian development and disease
Keywords: Epigenetics, X-chromosome inactivation, Naïve and primed pluripotency, Pre-gastrulation, Primordial germ cells, iPSC, Long non-coding RNAs, enhancer RNAs, RNA methylation, Transcriptional bursting and heterogeneity in Cancer
Emerging evidence implicates that epigenetics plays an essential role in gene regulation in development and diseases. However, much about the mechanistic aspects of epigenetic regulation remains to be understood. Our research strives to further the understanding of the mechanism of epigenetic regulation through the study of X-chromosome inactivation/reactivation, X-chromosome upregulation, Genomic imprinting and Random monoallelic gene expression, transcriptional bursting using mouse/human embryo and stem cells. We use regular molecular biology tools, single cell genomics, RNA-FISH and computational methods.
Incoming students can frame their future research in any of the following ongoing projects in the lab.
1. Transcriptional bursting and heterogeneity in cancer.
2. Allelic co-ordination of transcriptional bursting in cell fate specification
3. Enhancer RNAs (eRNAs) in gene regulation
4. X-chromosome states in human embryos and pluripotent stem cells
5. Mechanism of X-chromosome upregulation in mouse and human pluripotent stem cells.
6. Identification of factors responsible for maintenance of X-chromosome inactivation
The research program in my laboratory focuses on key transcription factors and lipid molecules that regulate adipose tissue function and maintenance of pre-adipose stem cells. To address our research hypothesis, we employ several cutting-edge approaches, including CRISPR-Cas9 mediated gene editing, transcriptomics, lipidomics, and transgenic mouse models.
Divakaran SJ, Srivastava S, Jahagirdar A, Rajendran R, Sukhdeo SV, Rajakumari S. (2020) Sesaminol induces brown and beige adipocyte formation through suppression of myogenic program. FASEB J. 34(5):6854-6870.
Shapira SN, Lim HW, Rajakumari S, Sakers AP, Ishibashi J, Harms MJ, Won KJ, Seale P. (2017). EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex. Genes Dev. 31(7):660-673.
Rajakumari S, Wu J, Ishibashi J, Lim HW, Giang AH, Won KJ, Reed RR, and Seale P. (2013) EBF2 Determines and Maintains Brown Adipocyte Identity. Cell Metab. 17(4):562-574.
The research group is interested in understanding the role of the microbiome in host nutritional physiology and the emerging consequences on host dietary adaptation.
Currently, we are interested in characterising the microbiome of economically important insects to elucidate the molecular pathways involved in digestion and supplementation of essential nutrients. The projects will provide possibilities to acquire a broad set of skills combining analyses at the molecular, cellular and organismal level, quantitative and statistical methodologies, and provide opportunities for collaborations.
For more information visit the lab page at https://shantanu-shukla.com
Can looking at pancreatic cells with high-resolution microscopic techniques give us answers about diabetes?
Pancreas has exocrine and endocrine regions which is responsible for secretion of exocrine and endocrine hormones – these play a major role in metabolism and health.
The specialized cells in islets of Langerhans in the endocrine pancreas makes up only a small portion of the pancreas, but their function is of profound importance. The β-type islet cells produce insulin, the hormone needed to assimilate blood glucose after a meal and maintain glucose homeostasis. Other types of islet cells in the pancreas perform other functions related to glucose balance, and a large portion of the pancreas is related to entirely different functions altogether with major influence on nutrient metabolism and well-being.
Our interest is in looking at signalling pathways leading to secretion of islet hormones. We depend on high-resolution optical imaging, ELISA based assays, cell culture, molecular biology, etc for this purpose. The overall idea is to understand how these signalling pathways in islet cells are dysregulated in diabetic islet cells and hopefully discover novel treatment targets, diagnostic tools to help people suffering from these ailments.
1) NR Gandasi, P Yin, M Omar-Hmeadi, EO Laakso, P Vikman, S Barg. Glucose dependent granule docking limits insulin secretion and is decreased in human type-2 diabetes (2018) Cell Metabolism 27(2): 470-4785.
2) NR Gandasi, P Yin, M Riz, G Cortese, M Chibalina, P Rorsman, A Sherman, MG Pedersen and S Barg. Ca2+ channel clustering with insulin containing granules is disturbed in type 2 diabetes (2017) Journal of Clinical Investigation 127(6):2353-2364.
More details in – https://nikhilgandasi.com