# BIOCHEMISTRY OF BACTERIAL CELL MEMBRANES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 1988 · $231,069

## Abstract

The fundamental functions of biological membranes are to serve as general
permeation barriers and at the same time allow the selective permeation of
certain types of molecules.  The structural basis of these functions will
be studied at the molecular level by using three different membrane
systems.  (1) The outer membrane, located outside the cytoplasmic membrane
and peptidoglycan layer of Gram-negative bacteria, is an ideal model
membrane for the study of this type, because its functions are very simple
in that it allows only passive and facilitated diffusion processes.  The
diffusion of hydrophilic molecules is mediated by porin and other channels,
and it is proposed to characterize the properties of these channels in
detail.  Furthermore, the lipid domains of the outer membrane show an
unusually high resistance tothe diffusion of hydrophobic molecules.  By
studying the molecular basis of this resistance by the use of mutants,
agents that increase the permeability of this domain, and various
biophysical techniques, we hope to gain insight on the molecular basis of
the barrier property of this unusual lipid bilayer.  The results of these
two lines of work will be of potential medical significance, because the
most effective weapon of many gram-negative opportunistic pathogens that
are currently causing problems in hospital-related infections is the
generalized antibiotic resistance caused by the low permeability of the
outer membrane.  Thus the outcome of this study will be able to provide
methods for increasing the permeability of chemotherapeutic agents through
the outer membrane, either via the modification of their structures so that
they can pass through the porin channel more rapidly, or by interfering
with the organization of the lipid domains so that their permeability to
all agents are increased.  (2) The molecular mechanism of active transport
of maltose will be studied by characterizing the protein components and
eventually by attempting reconstitution.  "Binding-protein-dependent"
transport systems such as this one are not understood at all in terms of
their mode of action, and this study is hoped to serve as a model for many
such systems that operate in various Gram-negative bacteria.  (3) Finally,
the properties of the gap junction channel, which connects the cytoplasms
of the neighboring animal cells, will be studied by reconstitution
approach.  This study has implications in the study of cellular
differentiation and of the process of development of tumors, as the
disappearance of gap junction channel is one of the earliest events in the
development of solid tumor.

## Key facts

- **NIH application ID:** 3124592
- **Project number:** 5R01AI009644-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **SAM.gov UEI:** GS3YEVSS12N6
- **Principal Investigator:** HIROSHI NIKAIDO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $231,069
- **Award type:** 5
- **Project period:** 1976-03-01 → 1991-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124592

## Citation

> US National Institutes of Health, RePORTER application 3124592, BIOCHEMISTRY OF BACTERIAL CELL MEMBRANES (5R01AI009644-19). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124592. Licensed CC0.

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