The impact of innate immune recognition of Staphylococcus ...

1 PI: Putnam, Nicole Title: The impact of innate immune recognition of Staphylococcus aureus on bone homeostasis and skeletal immunity Received: 12/08/2016 FOA: PA16-309 Council: 05/2017 Competition ID: FORMS-D FOA Title: RUTH L. KIRSCHSTEIN NATIONAL RESEARCH SERVICE AWARD (NRSA) INDIVIDUAL PREDOCTORAL FELLOWSHIP (PARENT F31) 1 F31 AI133926-01 Dual: AR Accession Number: 4000839 IPF: 8721001 Organization: VANDERBILT UNIVERSITY Former Number: Department: Pathology and Microbiology Edu IRG/SRG: ZRG1 F13-C (20)L AIDS: N Expedited: N Subtotal Direct Costs (excludes consortium F&A) Animals: Y Humans: N Clinical Trial: N Current HS Code: 10 HESC: N New Investigator: Early Stage Investigator: Senior/Key Personnel: Organization: Role Category: Nicole Putnam Vanderbilt University PD/PI James Cassat Vanderbilt University Medical Center Other (Specify)-Sponsor Julie Sterling Vanderbilt University Medical Center Other (Specify)-Co-Sponsor Always follow your funding opportunity's instructions for application format.

2 Although this application demonstrates good grantsmanship, time has passed since the grantee applied. The sample may not reflect the latest format or rules. NIAID posts new samples periodically: The text of the application is copyrighted. You may use it only for nonprofit educational purposes provided the document remains unchanged and the PI, the grantee organization, and NIAID are credited. Note on Section 508 conformance and accessibility: We have reformatted these samples to improve accessibility for people with disabilities and users of assistive technology. If you have trouble accessing the content, please contact the NIAID Office of Knowledge and Educational Resources at APPLICATION FOR FEDERAL ASSISTANCE SF 424 (R&R) 1. TYPE OF SUBMISSION* 0 MB Number 4040-0001 Expiration Date 06/30/2016 3. DATE RECEIVED BY STATE State Application Identifier TN: Tennessee Federal Identifier 0 Pre-application OApplication Changed/Corrected b.

3 Agency Routing Number Application 2. DATE SUBMITTED Application Identifier c . Previous Tracking Number 2016-12-08 U0044255 GRANT12302234 5. APPLICANT INFORMATION Organizational Legal Name : Vanderbilt University Department: Pathology and Microbiology Edu Division: School ofMedicine Street1 : Street2: City : County: State : Province: Country : Z IP / Postal Code : Person to be contacte d on matters involving this application DUNS*:-Prefix: First Name : Dorothy Middle Name: Janiece Last Name : Harrison Suffix: Position/Title: Director, Sponsored Programs Administration Street1 : Street2 : City : County: State : Province: Country : Z IP / Postal Code : Phone Number : Fax Number: 6. EMPLOYER IDENTIFICATION NUMBER (EIN) or (TIN)' 7. TYPE OF APPLICANT" O: Private Institution of Higher Education Other (Specify): Small Business Organizatio n Type 0 Women Owned 0 Socially and Economically Disadvantaged 8. TYPE OF APPLICATION* eNew 0 Resubmission ORenewal 0 Continuation ORevision Is this application being submitted to other agenc ies?

4 * 9. NAME OF FEDERAL AGENCY* National Institutes of Health/ Unknown 11. DESCRIPTIVE TITLE OF APPLICANT'S PROJECT" If Revision, mark appropriate box(es). O A. Increase Award OB. Decrease Award O C. Increase Duration OD. Decrease Duration O E. Other (specify) : OYes eNo What other Agencies? 10. CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER TITLE: Ruth L. Kirschste in National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F3 1) The impact of innate immune recognition of Staphylococcus aureus on bone homeostasis and skeletal immunity 12. PROPOSED PROJECT 13. CONGRESSIONAL DISTRICTS OF APPLICANT Start Date Ending Date TN-005 07/01/2017 06/30/2019 Funding Opportunity Number: PA-16-309. Received Date: Tracking Number: GRANT12302470 Page 1 2016-12-08T15:14 :00 Contact PD/Pl: Putnam, Nicole E SF 424 (R&R) A PPLICATION FOR FEDERAL ASSISTANCE Page 2 14. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATION Prefix: First Name : Nicole Middle Name: E Last Name : Putnam Suffix: Position/Title: Grad Stu Research Asst Monthly Organization Name : Vanderbilt University Department: Pathology and Microbiology Edu Division: School ofMedicine Street1 : -Street2 : City : County: State : Province: Country : Z IP / Postal Code : Phone Number : Fax Number: 15.

5 ESTIMATED PROJECT FUNDING a . Total Federal Funds Requested b. Total Non-Federal Funds c. Total Federal & Non-Federal Funds d. Estimated Program Income APPLICATION SUBJECT TO REVIEW BY STATE EXECUTIVE ORDER 12372 PROCESS?* a. YES O THIS PREAPPLICATION/APPLICATION WAS MADE AVAILABLE TO THE STATE EXECUT IVE ORDER 12372 PROCESS FOR REVIEW ON: DATE: $ b. NO PROGRAM IS NOT COVERED BY 12372; OR 0 PROGRAM HAS NOT BEEN SELECTED BY STATE FOR REVIEW 17. By signing this application, I certify (1) t o the statements contained in the list of certifications* and (2) that the statements herein are true, complete and accurate to the best of my knowledge. I also provide the required assurances * and agree to comply with any resulting terms if I accept an award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to criminal, civil, or administrative penalties. ( Code, Title 18, Section 1001) e I agree The list of certifications and assurances, or an Internet site Where you may obtain this l ist, is contained in the announcement or agency specific instrucoons.

6 18. SFLLL or OTHER EXPLANATORY DOCUMENTATION File Name: 19. AUTHORIZED REPRESENTATIVE Prefix: First Name : Dorothy Middle Name: Janiece Position/Title : Director, Sponsored Programs Administration Organization Name : Vanderbilt University Department: Sponsored ProgramsAdministrat Division: Street1 : Street2 : City : County: -State : Province: Country : Z IP / Postal Code : Phone Number :-Last Name : Harrison Suffix: Date -Signedt Funding Opportunity Number: PA-16-309 . Received Date: 2016-12-08T15:14 :00 Fax Number: Signature of Authorized Representative* Tracking Number: GRANT12302470 Page2 Contact PD/PI: Putnam, Nicole E 424 R&R and PHS-398 Specific Table Of Contents SF 424 R&R Cover Page.. 1 Table of Contents.. 3 Performance Sites.. 4 Research & Related Other Project Information.. 5 Project Summary/Abstract(Description).. 6 Project Narrative.. 7 Bibliography & References Cited.. 8 Facilities & Other Resources.. 12 Equipment.

7 16 Research & Related Senior/Key Person.. 17 PHS Fellowship Supplemental.. 34 Applicant's Background and Goals for Fellowship Training.. 38 Specific Aims.. 42 Research Strategy.. 43 Respective Contributions.. 49 Selection of Sponsor and Institution.. 50 Training in the Responsible Conduct of Research.. 51 Sponsor and Co-Sponsor Statements.. 52 Letters of Support from Collaborators, Contributors, and Consultants.. 58 Description of Institutional Environment and Commitment to Training.. 60 Vertebrate Animals.. 62 Resource Sharing Plan.. 64 TTaabbllee oof f CCoonntteennttss Page 3 Contact PD/PI: Putnam, Nicole E Project/Performance Site Location(s) OMB Number: 4040-0010 Expiration Date: 06/30/2016 Project/Performance Site Primary Location I am submitting an application as an individual, and not on behalf of a company, state, local or tribal government, academia, or other type of organization.

8 Organization Name: Vanderbilt University Duns Number: Street1*: Street2: City*: County: State*: Province: Country*: Zip / Postal Code*: Project/Performance Site Congressional District*: TN-005 Additional Location(s) File Name: Page 4 Tracking Number: GRANT12302470 Funding Opportunity Number: PA-16-309. Received Date: 2016-12-08T15:14 :00 Contact PD/PI: Putnam, Nicole E RESEARCH & RELATED Other Project Information OMB Number: 4040-0001 Expiration Date: 06/30/2016 1. Are Human Subjects Involved?* Yes No If YES to Human Subjects Is the Project Exempt from Federal regulations? Yes No If YES, check appropriate exemption number: 1 2 3 4 5 6 If NO, is the IRB review Pending? Yes No IRB Approval Date: Human Subject Assurance Number 2. Are Vertebrate Animals Used?* Yes No If YES to Vertebrate Animals Is the IACUC review Pending? Yes No IACUC Approval Date: Animal Welfare Assurance Number 3.

9 Is proprietary/privileged information included in the application?* Yes No Does this project have an actual or potential impact - positive or negative - on the environment?* Yes If yes, please explain: If this project has an actual or potential impact on the environment, has an exemption been authorized or an Yes environmental assessment (EA) or environmental impact statement (EIS) been performed? If yes, please explain: No No 5. Is the research performance site designated, or eligible to be designated, as a historic place?* Yes If yes, please explain: No 6. Does this project involve activities outside the United States or partnership with international Yes collaborators?* If yes, identify countries: Optional Explanation: No Filename 7. Project Summary/Abstract* 8. Project Narrative* 9. Bibliography & References Cited & Other Resources Page 5 Tracking Number: GRANT12302470 Funding Opportunity Number: PA-16-309.

10 Received Date: 2016-12-08T15:14 :00 Contact PD/PI: Putnam, Nicole E Page 6 Project Summary/Abstract PROJECT SUMMARY Staphylococcus aureus is a ubiquitous human pathogen, resulting in superficial, invasive, and disseminated infections. One of the most common invasive manifestations of S. aureus disease is osteomyelitis, a frequently occurring and debilitating infection of bone. Osteomyelitis triggers dramatic alterations in bone architecture, leading to severe complications such as bone destruction, pathologic fractures, and growth defects. An emerging body of literature suggests that both local and systemic inflammation trigger altered interactions between bone-forming osteoblasts and bone-resorbing osteoclasts to impact bone homeostasis. Skeletal cells are known to express innate pattern recognition receptors (PRRs), but the contribution of innate sensing towards bone homeostasis and antibacterial immunity during S.