Drury, Florence et al. (2021) International Worm Meeting "A novel pair of receptor tyrosine kinases are required for oomycete pathogen recognition by C. elegans and resistance to infection"

Martinez-Perez, Enrique, Montoya, Alex, Kramer, Holger, Grover, Manish, Pacheco, Sarai, Barkoulas, Michalis, Drury, Florence

[International Worm Meeting, 2021]

Over the past two decades, C. elegans has been used as a model to study innate immune responses to naturally infecting pathogens, such as viruses, bacteria, microsporidia and fungi. Studying natural C. elegans pathogens allows us to understand immune response pathways that have co-evolved alongside the pathogen, which may be pathogen-specific or more broadly conserved. We previously described a new natural oomycete infection of C. elegans by Myzocytiopsis humicola. Oomycetes are morphologically similar to fungi and cause disease in plants and animals, including humans. Phytophthora infestans is the most notorious oomycete, responsible for potato blight, which is thought to have resulted in the Irish Potato Famine. Animal oomycete infections are less well understood, leaving a niche that can be fulfilled by C. elegans as a tractable model host. We have found that C. elegans are able to detect an M. humicola extract and upregulate an immune response that appears to be unique to oomycete infection. Pathogen detection is likely to occur in sensory neurons, which in turn trigger a cross-tissue signalling cascade leading to upregulation of chitinase-like genes in the epidermis and structural changes in the cuticle that confer resistance to oomycete infection. Using a forward genetic approach, we have identified a pair of receptor tyrosine kinases expressed in the epidermis that are required for upregulation of chitinase-like genes. Loss of either of these RTKs leads to increased susceptibility to M. humicola infection, and overexpression of one results in constitutive activation of the downstream immune response pathway. Phosphoproteomic analysis upon extract treatment has identified RTK-dependent downstream phosphorylation events and highlighted genes that we are currently testing as to whether they play a role in mounting the immune response. By characterising the role and interactions of these RTKs, we can not only understand a novel pathogen recognition response pathway in C. elegans, but also potentially assess its relevance for other animal oomycete infections that are largely understudied.

Susan Carlson et al. (2008) C.elegans Aging, Stress, Pathogenesis, and Heterochrony Meeting "Iowa State University ADVANCE Program's Collaborative Transformation: Advancing Women Faculty in STEM Fields"

Susan Carlson, Jo Anne Powell-Coffman, Lisa Larson, Diane Debinski, Sharon Bird, Kristen Constant, Jan Thompson, Charles Glatz, Bonnie Bowen, Carla Fehr, Fred Janzen, Sandra Gahn, Florence Hamrick

[C.elegans Aging, Stress, Pathogenesis, and Heterochrony Meeting, 2008]

The goal of the NSF-funded ISU ADVANCE program is to investigate the effectiveness of a multilevel collaborative effort to produce institutional transformation that results in the full participation of women faculty in science, technology, engineering and math fields in the university. Our approach focuses on transforming departmental cultures, practices, and structures, as well as university policies. Here, we summarize the findings of the Collaborative Transformation Project with the 3 departments that participated in the first round (Departments of Genetics, Development, and Cell Biology; Ecology, Evolution, and Organismal Biology; and Material Science and Engineering) (Bird and Hamrick 2008). A 3-step process for departmental transformation includes (1) focus groups to discuss aspects of department culture, practice and structure, (2) needs assessment meetings tailored to meet the needs of individual departments, and (3) collaborative problem solving sessions involving department faculty and ADVANCE program leaders. The findings include 6 major issues common to all 3 departments. Some issues do not specifically address gender or race, but these issues can have a disproportionate effect on underrepresented groups. Each of the 3 focal departments has developed strategies for change that address the issues identified in their departments. Examples of these strategies will be presented. Bird, Sharon R. and Florence A. Hamrick. 2008. ISU ADVANCE Collaborative Transformation Project: First Round Focal Department Synthesis Report. Ames, IA: Iowa State University ADVANCE Program. http://www.advance.iastate.edu

Ingrid Masse et al. (2006) European Worm Meeting "Identification of a Novel Protein Kinase that Acts in the DAF-18/PTEN Pathway and Regulates Lifespan"

Florence Solari, Marc Billaud, INGRID MASSE, Laurent Molin

[European Worm Meeting, 2006]

Ingrid Masse, Laurent Molin, Marc Billaud and Florence Solari. In Caenorhabditis elegans, the insulin/IGF-1 DAF-2 receptor controls entry into dauer and longevity. DAF-2 activates the PI3 kinase homologue AGE-1 which results in phosphorylation and cytoplasmic sequestration of the DAF-16 transcription factor. Activation of the DAF-2 pathway is downregulated by DAF-18 which is encoded by the orthologue of the PTEN human tumor suppressor gene. We have previously shown that DAF-18 antagonizes the activity of the PI3 kinase/AGE-1 and that this function requires the DAF-18 lipid phosphatase activity. To better characterize the pathways involving DAF-18, we have initiated a RNAi screen aimed at identifying novel genes that regulate lifespan and that genetically interact with daf-18. We focused our initial screening on the C. elegans kinome that comprises 438 genes coding for protein kinases. Using this strategy, we have identified a new interactor of daf-18 that controls lifespan. We found that this kinase acts upstream of the daf-16/FOXO transcription factor but in parallel of the canonical daf-2/age-1 pathway. We further established that worms with an inactivation of this gene were resistant to oxidative stress. More information on the nature and the mode of action of this protein kinase will be presented at the meeting.