Using C. elegans to integrate a fundamental cellular stress response into a tissue system at the interface with the environment
Very little is known about how extracellular matrix barriers and inducible cytoprotective transcription factors function together to detect environmental stress and promote homeostasis. Caenorhabditis elegans has a single antioxidant/detoxification response transcription factor named SKN-1 and a collagen-rich extracellular barrier called the cuticle. Progress has been made in understanding how SKN-1 responds to chemical stress within cells, but nothing is known about how it interacts with extracellular matrices or responds to mechanical stress. We have made the surprising discovery that high external osmotic pressure or genetic distortion of the cuticle activate several SKN-1 dependent cytoprotective genes and that SKN-1 influences cuticle structure and expression of cuticle remodeling genes.
The central hypothesis for this project is that SKN-1 is activated by a cuticle associated damage sensor and that SKN-1, in turn, protects against toxic insults and directs or modifies cuticle synthesis or remodeling during stress. Objectives are to leverage molecular and genetic approaches in C. elegans to identify signaling from the cuticle to SKN-1 and investigate why and how SKN-1 modifies the cuticle.
Supported by NSF CAREER Grant IOS 1452948
The central hypothesis for this project is that SKN-1 is activated by a cuticle associated damage sensor and that SKN-1, in turn, protects against toxic insults and directs or modifies cuticle synthesis or remodeling during stress. Objectives are to leverage molecular and genetic approaches in C. elegans to identify signaling from the cuticle to SKN-1 and investigate why and how SKN-1 modifies the cuticle.
Supported by NSF CAREER Grant IOS 1452948
Improving scientific collaboration, training, and education
Caenorhabditis elegans is used by over 15 research groups in Florida, but as of 2015, there was no organized effort to connect these groups. To foster scientific collaboration and provide students opportunities to present and share their research, we are collaborating with researchers at Florida Institute of Technology and the University of South Florida to organize annual Florida Worm Meetings (http://floridawormmeeting.weebly.com/).
Genetic model systems are emerging as models for education, but they are far from reaching their potential in K-12 schools. To help implement genetic models into K-12 curriculum and science fair projects, we are conducting workshops for teachers and students in collaboration with the University of Florida Center for Precollegiate Education and Research (http://www.cpet.ufl.edu/).
Supported by NSF Grant IOS 1452948
Genetic model systems are emerging as models for education, but they are far from reaching their potential in K-12 schools. To help implement genetic models into K-12 curriculum and science fair projects, we are conducting workshops for teachers and students in collaboration with the University of Florida Center for Precollegiate Education and Research (http://www.cpet.ufl.edu/).
Supported by NSF Grant IOS 1452948
Understanding drug detoxification and resistance in nematodes
Nematode parasitize domesticated animals, crop plants, and ~30% of humans costing over $100 billion annually and causing debilitating and potentially fatal diseases. Nematicides and helminth targeting drugs, or anthelmintics, have been used to control parasitic nematodes for decades. However, many parasitic nematodes are evolving resistance. Multidrug resistant strains are especially problematic because they are insensitive to many compounds. The role of detoxification in drug resistance is poorly understood for nematodes.
We are using molecular genetics to study the role of transcription factors such as SKN-1 and DAF-16, because they regulate the expression of hundreds of potential drug detoxification genes. Understanding the fundamental pathways that mediate resistance is an important first step toward being able to monitor and eventually prevent resistance with the potential to improve US agriculture and the lives of hundreds of millions of people worldwide.
Supported by NIH grant 1R21NS067678-01 and NSF grants IOS 1120130 and IOS 1452948 (CAREER)
We are using molecular genetics to study the role of transcription factors such as SKN-1 and DAF-16, because they regulate the expression of hundreds of potential drug detoxification genes. Understanding the fundamental pathways that mediate resistance is an important first step toward being able to monitor and eventually prevent resistance with the potential to improve US agriculture and the lives of hundreds of millions of people worldwide.
Supported by NIH grant 1R21NS067678-01 and NSF grants IOS 1120130 and IOS 1452948 (CAREER)