Abstract: Animals possess pattern-recognition mechanisms to detect pathogens and to improve survival by altering their behaviour and physiology. We utilize Caenorhabditis elegans as a model host to ask whether bacterial volatiles constitute microbe-associated molecular patterns (MAMPs). Using gas chromatography-mass spectrometry, we identified six prominent volatiles released by the bacterium Pseudomonas aeruginosa. A specific volatile, 1-undecene, activates nematode odour sensory neurons inducing both flight and fight responses in worms. In behavioural assays, worms are repelled by 1-undecene, and this aversion response is driven by the detection of this volatile through AWB odour sensory neurons. Furthermore, 1-undecene oduor can induce immune effectors specific to P. aeruginosa via AWB neurons and brief pre-exposure of worms to the odour enhances their survival upon subsequent bacterial infection. These results show that 1-undecene derived from P. aeruginosa serves as a pathogen-associated molecular pattern for the induction of protective responses in C. elegans. This study opens a new and exciting area of research into the use of odours as molecular patterns to enhance immune responses in animals. Can we harness volatile molecular patterns from various pathogens and gut microbiota to modulate the immune response of animals? I will discuss strategies to delve into this exciting area of research.

Biography: Varsha Singh obtained her Bachelor's in Science degree from Banaras Hindu University, Varanasi, India in 1997. During her undergraduate training, she developed an interest in host-pathogen interactions. She went on to do her Masters in Science at the Indian Institute of Science in Bangalore and studied virulence factors of Mycobacterium tuberculosis. She earned her PhD degree from the Department of Biochemistry, Indian Institute of Science for her thesis work on the role of heat shock protein (Hsp) 70 in the pathogenesis of human malarial parasite Plasmodium falciparum. While malaria parasite provided an interesting problem of cell biology, it was not genetically tractable at that time. It prompted Dr. Singh to seek a genetically tractable system to study host-microbe interactions. She joined the laboratory of Dr. Alejandro Aballay at Duke University Medical Center as a postdoc. She authored a profusely cited study in PNAS to show that host stress response machinery composed of heat shock proteins is required for the adequate response of worms to both Gram –ve and Gram +ve bacteria. This finding may explain why fever and heat shock response generated during a fever episode may be beneficial to mammalian hosts as well. She has also shown that G protein-coupled receptors (GPCRs) and GPCR adaptor Arrestin in the nervous system of C. elegans regulate core immune signaling pathways. Her studies underscore the importance of the nervous system as the master regulator of systemic immune responses in multicellular organisms.

Dr. Singh’s laboratory, at the Indian Institute of Science, utilizes C. elegans to understand how sensory neurons regulate behavioral as well as physiological responses to P. aeruginosa. Her lab utilizes a multi-disciplinary approach to understanding the role of specific odour sensory neurons. Her lab has contributed to the understanding of bacterial secondary metabolites specifically volatiles as microbe associate molecular patterns for C. elegans. Another interest of her lab is to study interspecies interaction amongst respiratory pathogens such as P. aeruginosa, Klebsiella pneumoniae, and Cryptococcus neoformans.

Dr. Singh is a fellow of the Wellcome Trust-Department of Biotechnology Alliance for her research program ‘Neural Regulation of Immune Responses and Longevity in Caenorhabditis elegans.’ She also has funding from Indo-French Center for Advanced Scientific Research (CEFIPRA).