Signaling in the gut : all disease begins in the gut!

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1 Prof. Sandhya S. Visweswariah Laboratory: GA09, Biological Sciences Building, Indian Institute of Science E mail: sandhya@mrdg.iisc.ernet.in Web page: Signaling in the gut : all disease begins in the gut! Receptor guanylyl cyclase C: a modulator of intestinal fluid and ion secretion; regulator of cell proliferation Identified the first mutations in humans that are the cause of familial secretory diarrheal syndrome We now wish to characterize mouse models that mimic human disease What are the changes that occur in the gut? Can we find ways to modulate GC- C function? Approaches: Transgenic mouse models; NGS to identify differentially regulated genes. mirnas Gut organoid cultures to identify the roles of GC-C in gut development: is there a cell non-autonomous regulation of intestinal stem cell function? A growing mouse organoid Differential expression of inflammatory genes and cytokines in the gut Representative publications Müller. T., et al (2015) Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C. Gut. doi: /gutjnl Fiskerstrand, Tet al (2012) Familial Diarrhea Syndrome caused by an activating GUCY2C activating mutation. N. Engl. J. Med.366: Basu et al (2014) Intestinal cell proliferation and senescence is regulated by receptor guanylyl cyclase C. J. Biol. Chem.. 289: Mishra et al (2017) Guanylyl Cyclase C in Encylopedia of Signaling Molecules (Springer)

2 Arun Kumar, PhD Professor Human Molecular Genetics & Cancer Biology Lab Lab: GE12 Tel: Current research interests: Role of micrornas in oral cancer with an aim to use them as therapeutic targets. Identification of transcriptional targets of the tumor suppressor TSC2 and their use in oral cancer therapeutics. Next generation sequencing based discovery of causative genes for primary microcephaly (small brain) & Anencephaly (no brain). Mock mir-125a mimic Mutation in Anencephaly gene TRIM36 disrupts microtubules PI3K-AKT-TSC1/TSC2-mTOR pathway Targeting ESRRA by a synthetic mir-125a mimic reduces oral cancer xenograft in nude mice Selected publications: 1.Singh N et al. (2017). A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family. Human Molecular Genetics, 26: Tiwari A et al. (2014). microrna-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor alpha: implications for cancer therapeutics. Journal of Biological Chemistry, 289: Pradhan SA et al. (2014). Evidence that TSC2 acts as transcription factor and binds to and represses the promoter of epiregulin. Nucleic Acids Research, 42:

3 Deepak K Saini MRDG/ BSSE, IISc deepak@mrdg.iisc.ernet.in Cellular signaling in aging, inflammation and infection Signals Mechanism Processing Identify Therapy Aging Inflammation Cross-talk Drug targeting Diagnostics Biosensors Targets Regulators Anti - inflammatory Senolytics Research interests Signal transduction in aging and inflammation Intervention strategies for inflammation triggered degenerative diseases including cancers Signaling and adaptation in tubercle bacilli Novel diagnostic processes based of microscopy and spectroscopy techniques Potential projects: 1. Modulation of crosstalk in Two component signal transduction systems in M. tuberculosis 2. Inflammodulation in aging through regulation of kinases and phosphatases

4 Ramray Bhat, MBBS, PhD Assistant Professor, MRDG, IISc GA07 Biological Sciences Building MRDG, IISc Research Focus: morphology and microenvironment Ovarian cancer metastasis An important focus of our group is the investigation of mechanisms by which ovarian cancer cells undergo metastasis. Whereas we are beginning to understand how spheroids, metastatic multicellular collectives form, an understanding of how they explode and attach upon reaching prospective sites of colonization remains ill-elucidated. The incoming student will have an opportunity to tackle this translational cancer-biological question in collaboration with clinicians and physical scientists.

5 Normal Cancer and Stem Cells Anu Rangarajan, MRDG Anoikis resistance EMT Stemness Cancer (Sundarraman et al., JBC, 2016) AMPK Notch Metastasis Drug Resistance (Balaji SA et al., PloS One, 2016) (Mittal et al, Mol Cancer Ther., 2014) Primary Cancer Tissue Cancer spheres Enriched in stem/progenitors In collaboration with hospitals: KMIO, NIMHANS, Bangalore Mechanisms of cancer stemness, drug resistance. Proteomics, Genomics, Cell culture, Animal models.

6 TANWEER HUSSAIN s Lab PROJECT: Understanding protein synthesis and its regulation The synthesis of proteins using genetic information encoded in mrna is tightly controlled and much of this regulation occurs during the initial steps of translation. In higher organisms the translation initiation is much more regulated than in prokaryotes. Although the regulation of translation initiation is critical for many life processes, the molecular mechanism(s) of its regulation is poorly understood. Understanding translation initiation and its regulation is essential because dysregulation of initiation is associated with several human metabolic disorders and cancer. We aim to understand the molecular mechanisms involved in the regulation of translation initiation using biochemical, mutational and structural approaches. Cryo-electron microscopy and X-ray crystallography will be used to determine 3D structures of the proteins and the macromolecular complexes involved. There are 2 PhD projects aiming to elucidate two separate mechanisms by which translation initiation is regulated. Steps involved in determination of 3D structure by cryo-electron microscopy

7 Developmental and Biomedical Genetics Laboratory ( GB03) Prof. Upendra Nongthomba s group Primarily our group is interested on understanding the molecular and genetic basis of myopathies and neurodegenerative disorders, using the genetically amenable model organisms, Drosophila Fruit fly and Danio rerio - Zebrafish. We also use both the model systems for dissecting muscle and neural related Immunity responses, Drug screening, Functional genomics and Biomechanics studies. Our long term goals include providing therapeutic solutions and developing new diagnostic tools for protein aggregate myopathies, Dystrophies, neurodegenerative diseases and age-related disorders. Selected Recent articles: Haddadi M., Jahromi S. R., Nongthomba U., Shivanandappa T. and Ramesh S. R., Hydroxyisophthalic Acid from Decalepis hamiltonii rescues the neurobehavioral deficit in transgenic Drosophila model of Taupathies. Neurochemistry International 100: doi: /j.neuint Chatterjee A., Roy D., Patnaik E. and Nongthomba U., Muscles are important immune responsive tissues. Disease Model Mechanisms 9: doi: /dmm Sinam Y. M., Chatterjee A., Ranjini M. S., Poojari A., Nagarajan A., Ramachandra N. B. and Nongthomba U., Adaptive response of long and short lived Cytoraces of Drosophila to pathogens. Infection, Genetics and Evolution 44: 1 7. doi: /j.meegid Firdaus H., Mohan J., Naz S., Arthi B. P., Ramesh S. R. and Nongthomba U., A cisregulatory mutation in Troponin-I of Drosophila reveals the importance of proper stoichiometry of structural proteins during muscle assembly. Genetics 200: Rai M., Katti P. and Nongthomba U., Drosophila erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opal-like gene. Journal of Cell Science 127: