Institute of Membrane & Systems Biology - Faculty of Biological ...

Group
Research
Integrative
Membrane Biology
The membranes that surround cells
and the compartments within them
play critical roles in almost all aspects
of biology, ranging from the uptake
of nutrients and perception of the
environment to the transmission of
information from one part of the body
to another.
The importance of membranes
is highlighted by the finding that
membrane proteins account for more
than 20% of the human genome.
Membrane dysfunction is involved in
a panoply of common diseases and
membrane proteins represent the
targets of more than 50% of currently
used therapeutic drugs. Our research
in Integrative Membrane Biology aims
at a fundamental understanding of
the molecular mechanisms underlying
these roles of membranes at the levels
of cells, tissues and whole organisms.
Importantly, we are trying to integrate
the study of individual genes and
membrane proteins with investigations
of information flow within and
between cells, in order to understand,
for example, how the neural
networks involved in brain function
operate. To enable such a systems
biology approach, we have strong,
multidisciplinary research programmes
in multiple areas, many involving
collaborations with researchers not only
within other Institutes and Faculties at
Leeds, but worldwide. For example, at
the molecular level, our researchers are
collaborating with other groups in the
UK and Europe to solve the structures,
and thus understand the mechanisms,
of membrane transporters, ion channels
and hormone receptors (Figure 1).
Figure 1: Model of the human membrane protein GLUT1,
which transports glucose across the blood-brain barrier
Work on these experimentallychallenging
molecules has recently
been enhanced by establishment
of cutting-edge facilities for highthroughput
protein production and
crystallisation using robotic techniques.
The detailed examination of the
ligand binding sites of membrane
proteins necessary to inform drug
design has been made possible by the
development of novel solid-state NMR
techniques. In parallel, automated
high-throughput electrophysiological
and fluorescence approaches are being
used to assay membrane function. At
the cellular level, researchers studying
the trafficking of membranes between
cellular compartments, a process which
plays critical roles in neurotransmission
and in the response to hormones such
as insulin, are using our state-of-the-art
bioimaging facilities (Figure. 2).
These include confocal, deconvolution
and TIRF microscopes which can
be used for real-time investigations
on living cells. Current research on
the role of membranes in tissue and
whole organism function includes
electrophysiology on complex neuronal
networks and use of transgenic
organisms. These investigations of
normal physiology are complemented
by studies on the role of membranes
in disease, including Alzheimer’s
disease, hypertension, cardiovascular
disease, neuropathic pain, epilepsy
and diabetes. Via such an integrative
approach to membrane biology, we
hope not only to gain an understanding
of these key components of living
organisms, but also to address some
of the major healthcare problems in
the UK.
Figure 2: Surface location in a cultured human cell
of a green fluorescent protein-labelled component of
the exocyst complex, which plays a critical role in the
secretory pathway of eukaryotes