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Determining the molecular organization of TDP-43 in liquid spherical annuli and establishing a designer gene therapeutic strategy to degrade TDP-43 aggregates

Award Number: K99NS114162
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2021

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Determining the molecular organization of TDP-43 in liquid spherical annuli and establishing a designer gene therapeutic strategy to degrade TDP-43 aggregates - In this new Pathway to Independence Award (K99/R00) application the candidate proposes to determine the structure and composition of phase separated TAR DNA-binding protein 43 (TDP-43) as a means to understand the pathology behind TDP-43 aggregates and to investigate approaches to ameliorate these aggregates. The candidate will acquire training in Cryo-EM methods, protein purification, single molecule imaging, and RNA sequencing through a combination of collaborations and coursework. The candidate, Dr. Yu, was regarded as an extremely promising junior investigator, with good productivity (including middle authorship on three publications since submission of this proposal), excellent previous training, and outstanding letters of recommendation. Reviewers agreed that the mentor, Dr. Cleveland, was excellent and remarked that he has an outstanding track record of mentoring many trainees who successfully transitioned to independent careers. The mentor also clearly stated that the candidate can take this research with him to establish his own research program. Collaborators provided strong letters of support and additional training opportunities. The environment was regarded as excellent, with many career and scientific opportunities available and a clear demonstration of institutional support for the candidate. Reviewers considered the training plan to be well-structured, appropriate to the candidate’s research and career goals, and further strengthened by inclusion of a detailed and clear timeline. The proposed research was regarded as exciting and highly innovative, with the potential to substantially impact the field. The research plan includes the use of state-of-the art methods and technologies and will provide a solid foundation from which the candidate can launch an independent career. Reviewers noted a few minor limitations with the research plan, including that it was not clear what samples would be used in the experiments. The research plan was also regarded as somewhat risky and potentially overly ambitious, but reviewers noted this was a negligible to minor concern given the demonstrated productivity of the candidate. In summary, the panel considered this an exciting proposal from an excellent candidate with only negligible to minor weaknesses that slightly lowered enthusiasm for some reviewers. As reflected in the final scores, most reviewers considered this an excellent proposal while others rated it as either outstanding or very good.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = -$59,857 )
2022	2021	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/9/2022	NON-COMPETING CONTINUATION	-$59,857
														Subtotal = -$59,857

Issue Date FY: 2021 ( Subtotal = $124,794 )
2021	2021	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	3/11/2021	NON-COMPETING CONTINUATION	$124,794
2021	2020	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	2/10/2021	NEW	$0
2021	2020	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/4/2021	NEW	$0
														Subtotal = $124,794

Issue Date FY: 2020 ( Subtotal = $124,794 )
2020	2020	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/20/2019	NEW	$124,794
														Subtotal = $124,794

Grand Total All Awards = $189,731

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Determining the molecular organization of TDP-43 in liquid spherical annuli and establishing a designer gene therapeutic strategy to degrade TDP-43 aggregates

Award Number: K99NS114162

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2021

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