Dissecting molecular mechanisms of high immune specificity in C. elegans

• Applicants: Dr. Katja Dierking; Professor Dr. Hinrich Schulenburg
• Subject Area: Immunology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 349742302

It is widely believed that only the adaptive immune system is capable of generating highly specific immune responses to infection with different strains of the same pathogen species. This dogma has been challenged in the past years by accumulating evidence of highly specific immune responses generated by the innate immune system in invertebrates. The exact molecular mechanisms underlying invertebrate high immune specificity are unknown. Our overall objective is to explore and test experimentally the molecular mechanisms underlying pathogen strain-specific immunity in the genetically amenable invertebrate model organism Caenorhabditis elegans. Our novel unpublished results show that C. elegans has a strain-specific inducible transcriptome response to infection with the B. thuringiensis strains MYBT18679 (BT679) and MYBT18247 (BT247), which differ in virulence and the number and type of nematicidal toxins. We found that the strain-specific response is mediated by the GATA transcription factor gene elt-2. The aim of this study is to further investigate how ELT-2 mediates this highly specific response. On the host side our specific objective is to identify elt-2 downstream target genes. For this purpose, we will 1st) identify elt-2 target candidate genes using a combination of transcriptomic and bioinformatics analysis and assess the involvement of known host defense components and host resistance factors, 2nd) confirm the role of the thus identified candidate genes in elt-2 dependent resistance and susceptibility using gene knockouts and/or knockdowns, and 3rd) characterize the exact function of a few selected elt-2 target genes in generating immune specificity based on several genetic manipulation approaches combined with phenotypic analyses using microscopic and molecular tools. On the pathogen side our specific objective is to identify the virulence factors triggering the specific response by analyzing the effect of single B. thuringiensis toxins on the elt-2 dependent response to infection. Overall, the proposed project assesses the molecular basis of the highly specific immune response of the invertebrate model C. elegans to different B. thuringiensis pathogen strains and the influence of the GATA transcription factor ELT-2 on this specific response. As immune mechanisms have often been conserved across evolution, the generated results may yield new general insights into innate immune defence in other taxa.

• DFG Programme: Research Grants