Mechanistic roles of DNA polymerase delta subunit 1 in resistance to DNA geminiviruses

Information

  • NSF Award
  • 2323058
Owner
  • Award Id
    2323058
  • Award Effective Date
    9/1/2023 - a year ago
  • Award Expiration Date
    8/31/2026 - a year from now
  • Award Amount
    $ 1,094,620.00
  • Award Instrument
    Standard Grant

Mechanistic roles of DNA polymerase delta subunit 1 in resistance to DNA geminiviruses

Cassava is an important crop for small, medium, and large-scale farmers. It is a hardy plant that can be grown without irrigation, fertilizer or pesticides and is highly productive even when grown on marginal land. As such, it is likely to become an even more important crop in the face of global climate change. Cassava Mosaic Disease (CMD) is a devastating disease of cassava across the African continent and has recently spread to Asia. Some varieties of cassava have natural genetic resistance to CMD and the gene responsible for this resistance was recently identified. However, it is not yet understood how the resistance works. With hundreds of millions of people depending on this one source of resistance to a devastating pathogen, a deeper understanding of the mechanism behind the resistance is desired. This research will reveal the molecular mechanisms of resistance and test whether this type of resistance can protect diverse and important crops from other virus pathogens. If successful, this research will lead to sustainable and effective disease control strategies for many important crops such as tomato and cotton. Throughout the research, training will be provided for undergraduate and graduate students and the importance of this research will be shared with society through a variety of public lectures, outreach events and YouTube videos explaining the importance of this specific project targeted at non-scientist audiences.<br/><br/>CMD is caused by species of DNA geminiviruses. The CMD resistance was tracked to specific amino acid changes within the DNA polymerase delta subunit 1 (POLD1) protein. Viruses are fantastically effective at overcoming host resistance mechanisms and yet this resistance trait has been stable for decades. Further, several resistant cultivars of cassava are periclinal chimeras with the resistance allele present in only specific cell layers. Why this resistance is so stable and how it can function in the context of a periclinal chimera, is not yet clear. While some of the identified POLD1 mutations are novel, others have been observed in yeast and result in decreased DNA replication fidelity, pointing towards a possible functional mechanism. Transient assays will be used to test this and other candidate mechanistic hypotheses. These include characterizing viral replication rates and fidelity of the different POLD1 alleles, interaction with candidate viral and host co-factors and protein crystallography. Beyond cassava, this research may yield new resistance strategies for other important crops. A resistant POLD1 allele will be transformed into the model system Arabidopsis, to directly test if this resistance mechanism is effective in a distinct pathosystem. In addition, exploration of publicly available genomic data suggests that similar alleles exist in germplasm collections from tomato, cotton, and several other important crops. The relevant germplasm has been obtained and will be challenged with the respective viral pathogens<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

  • Program Officer
    Courtney Jahncjahn@nsf.gov7032927746
  • Min Amd Letter Date
    8/8/2023 - a year ago
  • Max Amd Letter Date
    8/8/2023 - a year ago
  • ARRA Amount

Institutions

  • Name
    Donald Danforth Plant Science Center
  • City
    SAINT LOUIS
  • State
    MO
  • Country
    United States
  • Address
    975 N WARSON RD
  • Postal Code
    631322918
  • Phone Number
    3145871285

Investigators

  • First Name
    Nigel
  • Last Name
    Taylor
  • Email Address
    ntaylor@danforthcenter.org
  • Start Date
    8/8/2023 12:00:00 AM
  • First Name
    Tessa
  • Last Name
    Burch-Smith
  • Email Address
    tburch-smith@danforthcenter.org
  • Start Date
    8/8/2023 12:00:00 AM
  • First Name
    Rebecca
  • Last Name
    Bart
  • Email Address
    rbart@danforthcenter.org
  • Start Date
    8/8/2023 12:00:00 AM

Program Element

  • Text
    Plant-Biotic Interactions

Program Reference

  • Text
    MINORITY INVOLVEMENT -- BIO
  • Code
    1228
  • Text
    UNDERGRADUATE EDUCATION
  • Code
    9178
  • Text
    GRADUATE INVOLVEMENT
  • Code
    9179
  • Text
    REU SUPP-Res Exp for Ugrd Supp
  • Code
    9251