Chemical Genomics of Networks Controlling Vesicular Trafficking in Plant Development
Funded by the National Science Foundation, Arabidopsis 2010 grant 0520325
This project is to demonstrate that integration of an innovative and state-of-the-art chemical genomics approach with genomic tools is useful for elucidating networks of genes that control vesicular trafficking critical for Arabidopsis growth and development. Gene networks that are specific to plants, e.g., those that control plant cell division or polar transport of the plant hormone auxin, will be of particular interest in this pilot project. The chemical genomics approach is proposed because these networks have proven intractable to traditional genetic/genomics approaches alone. Chemical genomics is an emerging field, in which high-throughput technologies are employed to identify bioactive small molecules, which in turn are used to interrogate a complex biological process or its underlying network of genes. The following scientific goals will be achieved: 1) Discover a battery of small molecules that perturb the control of cell division that requires vesicular trafficking, 2) Initiate assigning the functions to a network of genes controlling cell division in Arabidopsis by integrating the chemical genomics approach with the genomics tools developed through previous 2010 projects (e.g., SIGNAL), and 3) Develop a web-based mechanism by which tools, materials, chemicals, and knowledge generated in this project can be easily disseminated to the public. The long-term goal of this project is to complement and enhance the existing functional genomics/genomics tools for the discovery of the functions of genes in Arabidopsis.
This project will have a broad impact on plant biology by proving the usefulness of chemical genomics in the research on gene function and regulatory networks. Tools and materials, developed in this project, e.g., high-throughput imaging-based chemical screen routines and novel genetics and molecular tools including mutants, transgenic lines, protein expression vectors, and sub-cellular markers will be made available to the public. An integrated database for compound mining, retrieval of screening data, phenotypes and downloadable open-source tools for compound analysis will be created and published through a centralized suite of Web services.
This project will integrate training of young scientists with the goal of providing them with a broad integrated experience within interdisciplinary chemical genomics research. The future scientists will be well trained and prepared for independent academic careers. Focused outreach efforts will be undertaken to stimulate interest in this leading edge of science among women and under-represented minority students. This training will produce a new generation of diverse scientists who can form complementary teams required for 21st century research careers.
Genes and Compounds Used and Identified by this Project
A list of the utilized compound libraries for this project is available on the compound source page under the section "UCR Screening Libraries". All compound structures and bioactivity information can be searched via the Annotation, Structure and Phenotype pages.
The generated compound bioactivity and phenotype data of this project are available in the corresponding entries of ChemMine's screening database:
- Screen #161: Trafficking Pathways in Root Tip
- Screen #235: Vesicular Trafficking in Root Tips
- Screen #242: Gravitropism and vesicular trafficking
- Screen #243: Identification of ROP/GAP interaction inhibitors
- Screen #244: Plasma membrane targeting and polar growth in pollen and seedlings
The pre-screening and phenotype data of this project are available on ChemMine's Screen and Bioactivity domain.
Generated Resources and Software Tools
The developed software of this project can be downloaded from this page:
- Chemmine.R: A compound similarity search and mining package for the statistical R environment
- Structural similarity search software written in C++
- HT Screening and microscopy protocols
Girke T, Cheng LC, Raikhel N (2005) ChemMine. A compound mining database for chemical genomics. Plant Physiol: 138: 573-577. PubMed
- Zhenbiao Yang (PI, CEPCEB, UC Riverside, firstname.lastname@example.org)
- Natasha Raikhel (Co-PI, CEPCEB, UC Riverside, email@example.com)
- Glenn Hicks (PI, CEPCEB, UC Riverside, firstname.lastname@example.org)
- David Carter (Co-PI, CEPCEB, UC Riverside, email@example.com)
- Thomas Girke (Co-PI, CEPCEB, UC Riverside, firstname.lastname@example.org)
- Jae-Ung Hwang (postdoc, CEPCEB, UC Riverside)
- Yong-Jik (postdoc, CEPCEB, UC Riverside)
- Stephanie Robert (postdoc, CEPCEB, UC Riverside)
- Eddie Cao (graduate student, CEPCEB, UC Riverside)
- Anna Charisi (graduate student, CEPCEB, UC Riverside)