iisc The Worm Lab

Publications / Recommended reading

Singh V & Aballay A. Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1. J Biol Chem 2012 287, 33191

Summary: Arrestins are adaptors for G protein-coupled receptors (GPCRs), and required for receptor desensitization. Arrestin-1, the sole arrestin in Caenorhabditis elegans, is active exclusively in the nervous system to suppress innate immunity to bacterial infections. Using a novel Arrestin-1transgene tool, we showed that Arrestin-1 activity in 4 subsets of neurons regulates innate immune responses.  This study shows for the first time that GPCR signaling in a network of sensory neurons is utilized to respond to an infection. In future studies, this tool can be utilized to study any neuronal GPCR dependent biological process including innate immunity.

Sun J, Singh V, Kajino-Sakamoto R & Aballay A. (2011). Neuronal GPCR    controls innate immunity by regulating non canonical unfolded protein response genes. Science332, 729

Summary: OCTR-1, a G protein-coupled catecholamine receptor in Caenorhabditis elegans, functions in sensory neurons designated ASH and ASI to actively suppress innate immune responses to the Gram- negative bacterial pathogen Pseudomonas aeruginosa. OCTR-1 down-regulates the expression of abu genes that are part of a non canonical stress response pathway in the ER called unfolded protein response (UPR). I contributed to this study by showing that non-canonical UPR genes are induced during infection and expressed in non- neuronal tissues.

Singh V & Aballay A. (2009). Regulation of DAF-16-mediated innate immunity in Caenorhabditis elegans. J Biol Chem284, 35580

Summary: Dauer formation abnormal (DAF)-16 is a stress inducible Forkhead family transcription factor in C. elegans and promotes innate immune responses. We showed that excessive DAF-16 can be deleterious during microbial infection leading to hyper-inflammation like condition and death. Heat-shock transcription factor (HSF)-1 through its transcriptional target Hsp70 can suppress excessive activity of DAF-16 by promoting its export from the nucleus. Thus, Hsp70 regulates DAF-16 mediated immune responses to prevent inflammatory conditions.

Styer KL, Singh V, Macosko E, Steele SE, Bargmann CI & Aballay A. (2008). Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science 322, 460

Summary: NPR-1, a G protein-coupled neuropeptide Y receptor in C. elegans, inhibits a neural circuit composed of AQR, PQR and URX sensory neurons that suppresses innate immune responses to Pseudomonas aeruginosa. I demonstrated that NPR-1 activity in this neural circuit controls the activation of p38 MAPK that promotes innate immune responses.  This is a seminal study linking a GPCR in a defined neural circuit to the regulation of anti-microbial innate immune responses.

Singh V & Aballay A. (2006). Heat shock and genetic activation of HSF-1 enhance immunity to bacteria. Cell Cycle 5, 2443 (review)

Singh V & Aballay A. (2006). Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci U S A 103, 13092

Summary: HSF-1 and heat shock proteins (HSPs) are required for resistance to bacterial pathogens. Thus, raising the levels of HSPs by mild heat-shock pretreatment or specific mutations enhances resistance. Heat shock pretreatment also increases the survival of immuno-compromised host lacking p38 MAPK. Leading from this study and others, small molecule inducers of HSF-1 can potentially be utilized as a component of anti-microbial therapeutics in immuno-compromised individuals.