The Collaborative Center for XDP invites applicants to submit letters of intent for the 2019 Research Funding Program.

Purpose

The Collaborative Center for X-Linked Dystonia-Parkinsonism (CCXDP) supports an international consortium of scientists, clinicians, and patient advocates working together to advance research and treatments for X-Linked Dystonia-Parkinsonism (XDP), a debilitating neurodegenerative disease. CCXDP is now seeking applications for its 2019 Research Funding Program.  Three grant mechanisms are offered:

  • Investigator Awards:                   2 years, up to $250,000/year in direct costs.
  • Exploratory Pilot Grants:            1 year, up to $100,000 in direct costs
  • Postdoctoral fellowships:           2 years, $75,000/year in direct cost.

In addition to the amounts listed above, awards will provide 10% indirect costs to recipient institutions. 

Background

XDP is a neurodegenerative disorder endemic to the Philippines. Recent CCXDP-funded research studies have shown that XDP is most likely caused by a disease-specific SINE-VNTR-Alu (SVA)-type retrotransposon insertion in an intron of the human TAF1 gene.  The SVA contains a hexameric sequence (CCCTCT)n, the length of which is polymorphic among patients and inversely correlated to age of disease onset.  The insertion results in aberrant TAF1 mRNA splicing and partial intron retention which decreases levels of the full-length transcript.  The neuropathology of XDP has not yet been fully defined, but previous studies have reported a progressive loss of striatal medium spiny neurons in the brains of individuals with XDP.

Available Resources

CCXDP has generated biospecimens and reagents which are available for research studies, including:

  • DNA from XDP patients and unaffected relatives
  • Fibroblasts, lymphoblasts, and induced pluripotent stem cells (iPSCs) from XDP patients and unaffected relatives
  • Post-mortem human brain tissue from XDP patients
  • Novel TAF1 antibodies 

For a complete list of available resources, please click here

Research Objectives for the 2019 Funding Program

CCXDP welcomes applications from investigators in all disciplines proposing bold and rigorous approaches to the study of XDP. We encourage proposals involving collaborative studies, which can include investigators at different institutions, as well as ones which leverage existing resources. Areas of particular interest include, but are not limited to:

  • Characterization of SVA retrotransposon dynamics in XDP cells/tissue
  • Splicing regulation, RNA processing and/or RNA structure in XDP cells/tissue
  • Proteomic profiling of XDP and control cells/tissue
  • Development of assays to screen for modifiers of XDP cellular phenotypes
  • Development of novel iPSC-based models, including cerebral organoids and/or human neural progenitors implanted into rodent brain.

For a complete list of ongoing and completed CCXDP projects, click here 

Application Instructions

Applicants must submit a letter of intent by 5 pm Monday, February 25, 2019.  Letters should not exceed one (1) page with no less than 0.5 inch margins and 11-point font.  The following information must be included:

  1. Grant mechanism (Investigator Award, Pilot Project, or Postdoctoral Fellowship)
  2. Descriptive title
  3. Concise summary of proposed research
  4. Any CCXDP resources to be requested (DNA, cell lines, tissue, antibodies)
  5. Names and affiliations of all key personnel

Application Timeline

February 25, 2019          Letters of intent due

March 25, 2019              Applicants invited to submit full proposals will be notified

May 13, 2019                  Full proposals due by 5 pm   

July, 2019                         Funding decisions announced

Address for Inquiries and Submission of Letters of Intent

Dr. Amy Alessi, CCXDP Science Officer, at aalessi@partners.org.