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Molecular mechanisms of Gram-negative outer membrane organization

Award Number: F32GM139232
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 09/30/2022

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Molecular mechanisms of Gram-negative outer membrane organization - The rising frequency of drug-resistant bacterial infections pose an imminent threat to human health. Attempts to generate novel antibiotics to address this problem often fail because the outer membrane (OM) of gram-negative bacteria acts as a barrier that blocks the entry of many small molecules. This OM barrier is densely packed with lipopolysaccharides (LPS) and outer membrane proteins (OMPs) that organize heterogeneously within the OM. Specifically, it has been demonstrated that OMPs form higher-order assemblies in the membrane termed “islands”. The OM porins are trimeric and highly abundant OMPs but it is unknown how this oligomerization state influences their function, insertion into the OM, or the assembly of OMP islands. I hypothesize that OMP trimerization is critical for OMP function and fundamentally underlies the heterogenous organization of the OM. Using the model OMP, LamB, I have developed a set of tools that will allow me to examine this hypothesis. First, I will use bacterial genetic techniques to determine how OMP oligomeric state influences OMP function and partitioning of LPS. Second, I will use fluorescence microscopy techniques to characterize the role of OMP oligomerization in the OMP island assembly. Finally, I will determine how local secretion of OMPs affect OM organization. Together, my proposed work will define the molecular mechanisms that govern the organization of the OM. Importantly, this will inform strategies for disrupting the OM and in designing OM permeable antibiotics. The training goal of this fellowship is to continue to grow my scientific knowledge while further developing skills as a leader and mentor in order to fulfill my career goal of becoming a research group leader. Being a member of the Silhavy lab at Princeton University will allow me to develop a teaching philosophy and participate in the teaching and mentoring of undergraduate and graduate students. I will perfect my communication skills through ample opportunities to present my work at meetings and conferences. Additionally, the Molecular Biology Department at Princeton University is collaborative, interdisciplinary environment that promotes that development of ideas and sharing of expertise. Together, I believe that the completion of this training plan in the research environment of the Silhavy lab at Princeton University will allow me to develop the necessary skills to run my own research group.


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: 2023 ( Subtotal = -$17,508 )
2023	2022	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	001	2	7/21/2023	NON-COMPETING CONTINUATION	-$3,600
2023	2022	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	2	11/15/2022	NON-COMPETING CONTINUATION	-$13,908
														Subtotal = -$17,508

Issue Date FY: 2022 ( Subtotal = $67,582 )
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	2	12/20/2021	NON-COMPETING CONTINUATION	$66,390
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	001	2	5/23/2022	NON-COMPETING CONTINUATION	$1,192
														Subtotal = $67,582

Issue Date FY: 2020 ( Subtotal = $64,926 )
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	1	8/21/2020	NEW	$64,926
														Subtotal = $64,926

Grand Total All Awards = $115,000

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Molecular mechanisms of Gram-negative outer membrane organization

Award Number: F32GM139232

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 09/30/2022

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