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2023 Request for Proposals

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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 caused by a transposable element. CCXDP is now seeking applications, and 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 costs

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. 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

For a complete list of available resources and details about acquiring reagents, please see:

https://www.massgeneral.org/neurology/xdp-center/resources/

Research Objectives

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:

Functional analyses of TAF1 protein, including but not limited to mechanisms of gene regulation and/or interactions with partner proteins, with specific emphasis on how these functions may be affected in XDP
Studies of the potential role of glial cells in XDP
Screening projects that develop models and/or assays to seek compounds that modulate XDP-related phenotypes, with emphasis on opportunities for drug repurposing.
Projects that leverage machine learning/artificial intelligence (AI) to identify and analyze phenotypes in XDP model systems.
Molecular studies of the XDP-specific SVA element, including but not limited to potential regulation by host cell factors, RNA transcription, and/or DNA replication dynamics.
Comparative analyses to identify cellular mechanisms that may be shared by XDP and other neurodegenerative diseases.

Application Timeline

September 15, 2023: Letters of intent due by 5 pm EST
November 15, 2023: Full applications due by 5 pm EST
April 2024: Funding decisions announced
July 2024: Anticipated project start

For additional information, contact Dr. Amy Alessi, CCXDP Program Director, at aalessi@mgb.org

Application Instructions

Step 1: Complete the initial inquiry form below. Once submitted, you will be sent a unique survey link to fill out your LOI, or you may complete it here as well if ready.

Step 2: Submit Letter of intent (LOI) using your emailed survey link by Sept 15th.

Submission of an LOI is required. Each will be reviewed and an invitation to apply will be sent if approved.

Step 3: Should your LOI be approved, you will receive a second link to fill out the application form. Submit full grant applications portal by November 15th.

To preview application instructions and required documents, see linked PDF below.

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