Gene sind die Bausteine des Lebens. Sie ähneln Rezepten, aber anstatt einen Kuchen zu backen, kodieren Gene Proteine, die wichtige Funktionen im Körper haben. FOXP1 ist ein spezifisches Gen auf Chromosom 3, das die Produktion des Forkhead Box P1-Proteins steuert. Wenn das Gen eine Veränderung oder Mutation aufweist, funktioniert es nicht richtig und das „Rezept“ für die Herstellung des Kuchens wird geändert, was zu verschiedenen Entwicklungs- und medizinischen Problemen führen kann.
Die Sequenzierung des gesamten Exoms ist ein einzelner Test, mit dem Veränderungen oder Mutationen im gesamten Erbgut einer Person identifiziert werden können. Mit Paneltests können Veränderungen oder Mutationen in einer Untergruppe von Genen identifiziert werden, die mit einem bestimmten klinischen Merkmal verbunden sind (z. B. Panel für Autismus, Panel für geistige Behinderung, Panel für Epilepsie). Mutationen werden am häufigsten bei Paneltests zur neurologischen Entwicklung oder bei der Sequenzierung des gesamten Exoms erkannt. In den letzten Jahren sind sowohl Panels als auch die Sequenzierung des gesamten Exoms zugänglicher geworden, sodass Kinder mit Entwicklungs- und/oder medizinischen Symptomen bereits in jüngeren Jahren diagnostiziert werden.
In der überwiegenden Mehrheit der FOXP1-Fälle wird die Mutation im Gen als De-novo-Mutation bezeichnet, was bedeutet, dass kein Elternteil die Mutation aufweist; Diese De-novo-Mutation trat höchstwahrscheinlich spontan während der frühen fetalen Entwicklung auf. Dies kann durch Gentests der Eltern bestätigt werden. Bei einer De-novo-Mutation ist die Wahrscheinlichkeit, dass die Eltern ein weiteres Kind mit derselben Mutation bekommen, sehr gering, obwohl das betroffene Kind als Erwachsener die Mutation weitergeben könnte.
Im Alphabet können verschiedene Buchstaben kombiniert werden, um nützliche und aussagekräftige Wörter zu erhalten - aber nur, wenn die Buchstaben richtig zusammengesetzt sind. Das gleiche gilt für DNA. Bestimmte Nukleotide (die Basiseinheit der DNA), ob Adenin (A), Thymin (T), Cytosin (C) oder Guanin (G), können auf spezifische Weise angeordnet werden, um das FOXP1-Gen zu bilden, das wiederum a codiert spezifisches Protein. Eine Missense-Mutation liegt vor, wenn das Gen einen einzelnen DNA-Nukleotidschalter enthält. Manchmal ist eine solche Änderung still und hat keinen Einfluss auf das von der DNA kodierte Protein. Andere Veränderungen führen zu einer Aminosäureveränderung im Protein, für das das Gen kodiert, was manchmal die Funktionsweise des Proteins grundlegend verändern kann.
Eine Missense-Mutation liegt vor, wenn das Gen einen einzelnen DNA-Nukleotidschalter enthält. Manchmal ist eine solche Änderung still und hat keinen Einfluss auf das von der DNA kodierte Protein. Andere Veränderungen führen zu einer Aminosäureveränderung im Protein, für das das Gen kodiert, was manchmal die Funktionsweise des Proteins grundlegend verändern kann.
Eligibility:
● Applicants must hold PI status at a university/institution or an organization with 501(c)(3) status.
● Applicants must have an MD, PhD, or MD/PhD. Applicants with a master's degree in life sciences are also eligible if they are in a full-time academic position.
● Open to all stages of investigators post-graduate degree.
● Applicants working in all countries are welcome to apply.
● Co-Principal Investigators on the application are allowed.
Funding ranges, duration, and indirect costs:
Indirect costs will be paid at a rate of 10% of direct costs. Grants will typically be awarded up to a maximum of $75K including indirect costs for the first year. To complete a project requiring more than one year, PIs may submit a request to continue a research program in the following cycle. Funding for follow-on years will be contingent upon adequate progress achieved in the first year. Funding amounts for follow-on years can vary from initial requests. Our hope is to increase funding amounts in the future. If no additional funds are required, PIs can request a no-cost extension for up to 1 year.
Exceptions to the funding limit and to the 1-year duration of the initial awards may be granted. PIs seeking multi-year funding should present a strong argument that guaranteed multi-year funding is critical to project feasibility and success. If granted, the funding cap stated above will apply for each year, and projects must be concluded within 3 years of the start date. Similarly, projects that may have a profound impact toward the Foundation’s mission and require funds in excess of $75K may be proposed. Proposals that combine funding from the IFF with other sources are welcome.
Preference will be given to projects that adhere to the 1-year time frame and demonstrate efficient use of the funding provided. For this reason, applicants may choose to submit proposals requiring less than the $75K maximum.
RARE-X Data Collection Site:
The IFF would like to make researchers aware of the RARE-X Data Collection program, which has caregiver-entered data for over 200 patients with FOXP1 Syndrome. Researchers may request access to the data at this site: https://forms.monday.com/forms/02fc5ad2b4b1a75e1d3520b913d73ecb
Researchers may request data regardless of whether a proposal is submitted to this RFP, and use of the data will not affect the evaluation of proposals.
Letter of Intent:
Applicants must submit a letter of intent by September 13, 2024 in the form of a scientific abstract (250 word limit) describing their project prior to full submission of an application. PIs will be notified by September 24, 2024 whether they have been selected to submit a full proposal. Full proposals are due by November 1, 2024. Early submission of letters of intent prior to the September 13 deadline is highly encouraged.
Review process:
After final submissions are received, proposals will be sent to external reviewers. External reviewers will evaluate proposals based on the criteria below and submit their evaluations to the IFF. The Board of Directors and Scientific Advisory Board of the IFF will make final funding decisions.
Submission process:
All required components should be sent as a combined PDF email attachment to research@foxp1.org and CC to Dr. Samit Dasgupta (sdasgupta@foxp1.org) with the subject line: “Letter of Intent–PI Full Name–Cycle 1” for the letter of intent and “Proposal Submission–PI Full Name–Cycle 1” for the full proposal. By submitting the LOI and application, the applicant provides IFF permission to provide the materials to external
reviewers, the IFF Board and Scientific Advisory Board for evaluation purposes.
Required Components:
By September 13, 2024:
● Letter of Intent – scientific abstract describing the proposed project (≤ 250words)
By November 1, 2024 (full application components):
The following information should be organized in this order within the PDF. Please use NIH formatting guidelines, particularly with respect to font and line spacing, as described here: https://grants.nih.gov/grants/how-to-apply-application-guide/format-and-write/format-attachments.htm.
● Project title
● Lay abstract (≤ 250 words)
● Scientific abstract (≤ 250 words) – can be the same as letter of intent or have minor updates.
● Specific Aims (≤ 1 page)
● Research strategy (≤ 3 pages not including references)
○ Should include background/significance, innovation, research approach including rationale, preliminary data (if applicable), methods, analysis plan, anticipated results/potential pitfalls/alternative approaches.
○ References should be included and do not count towards the page limit.
○ All graphs/charts must fit within the 3-page limit.
● Description of Translational Potential (≤ 1 page)
○ Explain why the proposal plays an important role in a specific path toward the development of a treatment for FOXP1 Syndrome.
○ This section should be written to be understandable by both scientific and layperson audiences.
● Data Management and Sharing Plan
○ Applicants may complete the NIH Data Management and Sharing Plan found
here: https://grants.nih.gov/grants/forms/data-management-and-sharing-plan-format-page
○ In lieu of completing the form above, applicants may provide a summary of ≤ 1 page explaining their data management and sharing plan, including how results will be released once the project is complete (publication, website article, etc.), the plan for sharing data and possible other products produced with other researchers, etc
○ By submitting a proposal, applicants agree to deliver a 1-hour live presentation over Zoom to the IFF describing project results following study completion.
● Budget - Exact budget allocations as line items.
● Budget justification - Short descriptions explaining budget line items.
● CV or NIH-format biosketch of PI and any Co-PIs (≤ 5 pages)
Review criteria:
● Impact to forward the Foundation’s research mission: To accelerate the development of effective treatments for FOXP1 Syndrome.
● Investigator background and track record, and likelihood of success of the proposal.
● Feasibility of experimental strategy and/or novelty of research question(s) posed, including likelihood of project goals to be met within stated time frame.
● Potential for the proposed project to make important strides towards an eventual therapeutic strategy.
● Is the budget appropriate, and is this an effective use of Foundation funds?
Successful applicants will be notified by the end of January 2025. Applicants not selected for an award will receive a summary of reviews in an anonymous fashion at this time.
For grant-related inquiries, please contact research@foxp1.org