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Chemical tools to reveal the sterol lipid interactome in the syphilis agent Treponema pallidum

Award Number: F32AI200231
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Chemical tools to reveal the sterol lipid interactome in the syphilis agent Treponema pallidum - Project Summary/Abstract Syphilis is a sexually transmitted bacterial infection of the spirochete Treponema pallidum and has plagued humanity for centuries, yet little is known about the biology of T. pallidum. With the number of cases rising globally in tandem with the increased burden of antimicrobial resistance, the expansion of the knowledge surrounding T. pallidum biology is critical for the development of effective therapies. The goal of this project is to deduce the mechanisms through which T. pallidum procures lipids, including sterols, from its host. Identifying the routes used by the pathogen to obtain essential metabolites will provide a better understanding of its pathogenicity and reveal potential avenues for strategic therapeutic design. Despite lacking the machinery necessary for the biosynthesis of most lipids, the cellular envelope of T. pallidum is rich with neutral lipids, phospholipids, and cholesterol. How it acquires these is poorly understood and is hypothesized to assist the spirochete in its immune evasion mechanisms. Because in vitro culture of T. pallidum has only recently been established, very few techniques have been used to study gene and protein function in the cell. The reliance of T. pallidum on its host presents a unique avenue for investigating the pathogenicity of the spirochete. To identify proteins critical to the maintenance of lipid homeostasis in T. pallidum, we will combine sequence- and structure-bioinformatics, protein biochemistry, chemical biology, and genetic manipulation to reveal the lipid interactome of the T. pallidum. These proposed approaches for studying the pathogen will expand the set of techniques available for continued study of the bacterium and other spirochetes. With the focus on broadening our understanding of the lipid interactome of T. pallidum, novel aspects of this proposal include 1) characterization of lipid-interacting proteins expressed in T. pallidum, 2) quantification of the lipidome of T. pallidum relative to its rabbit epithelial cell host, 3) development of targeted and chemoproteomic methods in T. pallidum for identification of sterol binding proteins, and 4) development of a gene silencing technique for in vitro cultures of T. pallidum. This goals of this project will expand on my PhD training in organic chemistry and mammalian cell biology and allow me to practice more complex models of mammalian and bacterial cell culture as well as protein biochemistry and structural biology, which will be especially useful for my transition into future protein-based therapeutic research.


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 = $76,300 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	1	5/27/2026	NEW	$0
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	1	5/27/2026	NEW	$76,300
														Subtotal = $76,300

Grand Total All Awards = $76,300

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Chemical tools to reveal the sterol lipid interactome in the syphilis agent Treponema pallidum

Award Number: F32AI200231

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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