# The Structures of hVDAC-1 and hVDAC-2 by High Frequency Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $67,582

## Abstract

PROJECT SUMMARY/ABSTRACT
Research
 In the Griffin lab, I will use solid state NMR techniques to study the transport mechanisms of hVDAC1
and hVDAC2, highly efficient gating proteins in the mitochondrial outer membrane (MOM). They are associated
with many diseases including neurodegenerative diseases, cardiac diseases, and cancer. We hypothesize that
the gating mechanism of hVDAC1 involves a conformational change of the β-barrel, movement of the N-
terminus within the β-barrel, or both. I will use cell free labeling strategies that allow for 13C, 15N, and 2H labels
to be incorporated into hVDAC1, hVDAC2, and other proteins. They will be placed in 2D crystals of
phospholipid bilayers to collect high resolution, 1H detected NMR spectra. These experiments will be used to
assign resonances and obtain structural constraints to allow for the determination of completed structures of
hVDAC1, hVDAC2, and small molecules that bind to them. I will use 1.3 mm and 0.7 mm rotors to spin the
sample at frequencies higher than 100 kHz to remove strong 1H-1H dipolar couplings. Such spinning
frequencies improve spectral resolution and lengthen homogenous relaxation times. The former is important
for resonance assignments, and the latter for maintaining a usably high level of sensitivity in multidimensional
experiments. Cryogenic NMR will be used to freeze molecules that only weakly bind to hVDAC1 and
hVDAC2, such as ATP and NADH, in their bound states so that detailed structural information can be obtained.
Freezing the sample will also facilitate the implementation of dynamic nuclear polarization (DNP).
Training Plan
 I have a considerable amount of previous research experience performing DNP, which the Griffin lab is
renowned for. In the Griffin lab, I will gain experience applying my DNP knowledge to biological systems to
determine their structure and dynamics. In order to disseminate my findings, I will write multiple scientific
papers and present my original research at national and international conferences. Furthermore, I will aid in
the preparation of grant proposals to help prepare me for this aspect of starting my own, independent lab.
Environment
 MIT is a top tier institution with a long history of successfully training postdoctoral fellows. Prof. Griffin
has himself trained ~75 postdocs and many of these have gone on to begin successful careers as independent
researchers that are leaders in their fields. Furthermore, MIT has a strong magnetic resonance presence
besides just Prof. Griffin’s lab. Prof. Mei Hong is a leading member of the structural biology community, and
Prof. John Waugh helped to lay the groundwork for solid state NMR. The proposed research, training plan, and
institutional environment make the Griffin lab at MIT the perfect place for me to receive postdoctoral training.

## Key facts

- **NIH application ID:** 10460626
- **Project number:** 5F32GM139304-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Edward Paul Saliba
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460626

## Citation

> US National Institutes of Health, RePORTER application 10460626, The Structures of hVDAC-1 and hVDAC-2 by High Frequency Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy (5F32GM139304-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460626. Licensed CC0.

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