Assistant Professor in Residence
Research in our lab seeks to understand the fundamentals of host-pathogen interactions in the context of the whole organism. We are interested in the mechanistic details of these interactions, but we are also considering the natural context in which these interactions have evolved and in which they occur. To this end, we are using the nematode Caenorhabditis elegans, a powerful model organism for genetic studies, as a host model. Consideration of the ‘real life’ context of host-pathogen interactions suggests exploring new dimensions that affect host-pathogen interactions. Thus, research in our lab includes three major directions: a) characterizing regulatory mechanisms of innate immune responses; b) characterizing age-dependent changes in the contribution of stress-activated signaling to infection resistance and to other types of stress; and c) studying the contribution of the natural gut microbiota to host resistance to pathogens and to its overall well-being.
Pathogen recognition Although C. elegans immune responses to various pathogens have been characterized, by our lab and by others, it is yet unknown how the worm can differentiate between different pathogens. C. elegans does not use any of the pattern recognition receptors known from other animals. This makes the identification of the mechanisms it uses for pathogen recognition doubly interesting as those may represent new recognition modules potentially functioning also in mammals.
The C. elegans microbiota C. elegans has been grown in the lab for several decades with E. coli as its sole source of food. While this greatly simplifies cultivating and working with C. elegans it left us with no knowledge about the worm natural interactions with microbes in its natural soil habitat. Several labs are now trying to bridge this gap. Our lab is using ‘deep sequencing’ to characterize the C. elegans gut microbiota, and follow its assembly from diverse soil microbiotas. In addition, isolation of individual gut residents allows us to interrogate their specific contributions to the host. We are particularly interested (but not exclusively) in mechanisms that affect the host’s ability to respond to pathogens and to resist them.
The KGB-1 age-dependent switch A spin-off of our host-pathogen studies has opened a new direction in the lab - the study of aging - for which C. elegans provides significant experimental advantages, thanks to its short lifespan and its plasticity. Studying a mechanism that provides protection from infection exposed a protein’s age-dependent contribution to stress resistance. Activation of this protein, a homolog of the mammalian JNK mitogen-activated protein kinase during development provided protection from environmental stress, but similar activation two days later in young adults caused increased stress resistance and shortened lifespan. This age-dependent functional reversal represents a mechanism of antagonistic pleiotropy, a principle that was proposed half a century ago to explain how aging has evolved. Through characterization of this mechanism we hope to learn about the evolution of aging and about the aging process itself.
Twumasi-Boateng, K., Berg, M., and Shapira, M. Automated separation of C. elegans variably colonized by a bacterial pathogen. (2014). J Vis Exp Mar 21;(85).
Montalvo-Katz, S., Huang, H. Appel, M.D., Berg, M. and Shapira, M. Association with soil bacteria enhances p38-dependent infection resistance in C. elegans (2013). Infection and Immunity 81(2):514-20.
Twumasi-Boateng, K., Wang, T., Tsai, L., Lee, K.L., Salehpour, A., Bhat, S., Tan, M.W. and Shapira, M. (2012) An age-dependent reversal in the protective capacities of JNK signaling shortens C. elegans lifespan. Aging Cell. 11(4):659-67
Twumasi-Boateng, K. and Shapira, M. (2012) Dissociation of immune responses from pathogen colonization supports pattern recognition in C. elegans. PLoS ONE, 7(4).
Tan, M.W. and Shapira, M. (2011) Genetic and molecular analysis of nematode-microbe interactions.Cell Microbiol 13(4):497-507.
Shapira, M. (2010) Stress effects on immunity in vertebrates and invertebrates. In Stress: from molecules to behavior. A comprehensive analysis of the neurobiology of stress responses. Wiley Publishing.
Shapira, M. and Tan, M-W. (2008) Genetic analysis of C. elegans innate immunity. Methods Mol. Biol. 415, 429-42.
Kurz, C.L., Shapira, M., Chen, K., Baillie, D.L. and Tan, M.W. (2007) C. elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 MAP kinase cascade. Biochem. Biophys. Res. Commun. 363(2): 438-43.
Shapira, M. Hamlin, B.J., Rong, J., Chen, K., Ronen, M. and Tan, M.W. (2006) A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc. Natl. Acad. Sci. USA103: 14086-14091.