Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating the mycomembrane protein assembly pathway

Award Number: K99AI190054
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/03/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Investigating the mycomembrane protein assembly pathway - PROJECT SUMMARY The bacterial cell envelope functions as the cell’s primary defense against environmental threats, including antibiotics. Rising levels of resistance to antimicrobial treatments demand the development of new therapeutics that target this formidable barrier. Protein transport to the outer layers of the cell envelope is a high-priority candidate for further therapeutic development as proteins that reside within the outer layers of the cell envelope are critical in mediating interactions between the intra- and extracellular environment. The transport and assembly of proteins that reside within the outer layers of diderm bacterial species is highly regulated due to their importance for cell viability. Gram-positive microbial species in the Mycobacteriales order contain a protein- rich outer layer called the mycomembrane (MM) that is functionally analogous to the Gram-negative outer membrane. However, despite this diderm organization, the lipid composition and proteins that reside within the MM are structurally distinct from Gram-negative bacteria. Additionally, Gram-negative outer membrane protein transport pathways are not conserved and the mechanism through which mycolate outer membrane proteins (MOMPs) are transported to the MM is an outstanding question in the field. By cross-referencing my preliminary datasets from a FACS-based Tn-seq screen and immunoprecipitation for interaction partner with a surface- exposed MOMP, I hypothesize that a family of redundant enzymes called mycoloyltransferases are MOMP assembly factors. I will validate binding between mycoloyltransferases and MOMPs, characterize the binding interfaces, and utilize a spheroplast-based transport assay to test the hypothesis that MOMPs are transported across the cell envelope by mycoloyltransferases. Additionally, I have demonstrated through mass spectrometry and immunoblotting that, in addition to the previously described lipidation of these proteins, MOMPs undergo an additional post-translational modification that I propose is glycosylation. I will investigate the identity of the sugar modification, determine the residues that are glycosylated, and identify the responsible glycosyltransferase. Finally, I will investigate the dynamics of MOMPs within the MM using a surface exposed tag on a model MOMP in relation to other layers of the cell envelope by fluorescence microscopy. The results of this work will elucidate the essential process of MM biogenesis in the Mycobacteriales suborder, identifying novel targets for antibiotic development against pathogenic members such as Mycobacterium tuberculosis. The Specific Aims of this K99 application are: Aim 1: Investigate mycomembrane protein assembly factors Aim 2: Characterize mycomembrane protein post-translational modifications Aim 3: Analysis of in vivo global dynamics of proteins in the mycomembrane


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: 2026 ( Subtotal = $101,175 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	2	8/14/2026	NON-COMPETING CONTINUATION	$125,901
2026	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	4/24/2026	NEW	-$24,726
														Subtotal = $101,175

Issue Date FY: 2025 ( Subtotal = $125,901 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	9/3/2025	NEW	$125,901
														Subtotal = $125,901

Grand Total All Awards = $227,076

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the mycomembrane protein assembly pathway

Award Number: K99AI190054

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/03/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer