 Staff
Professor
Peter McIntyre
Head of Department
(+61 3) 8344 7843
Ms
Elizabeth Guida
Research Assistant
Postgraduate Students
Ms Merril
Curry
Ms Archana Bhaskaracharya
Honours Student
Ms Yu Ran
(Christina)
Collaborators
Professor Nigel
Bunnett
University of California San Francisco
Professor Stuart
Bevan
King's College London
Funding
Seed funding from
the Faculty of Medicine Dentistry and Health Sciences.
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The Molecular Pharmacology
Laboratory focuses on the molecular pharmacology of receptors and ion
channels involved in pain sensation. In particular, we study a group of
thermosensitive “Transient Receptor Potential” (TRP) ion channels
that sense heat, cold and painful stimuli.
Hot chilies spice-up our food but they can also cause excruciating pain
if they get into a cut or onto sensitive tissues. This pain is caused
by the opening of the TRPV1 ion channel on the affected sensory nerves
and initiating action potentials in them. TRPV1 is also activated by noxious
heat and by low pH solutions and it is a marker for pain-sensing or “nociceptive”
nerves. The “polymodal” activation of TRPV1 makes it a major
target for drug companies trying to make new types of pain-killing drugs.
While working for Novartis, Professor McIntyre's group was the first to
show that antagonists of TRPV1 are effective in reversing inflammatory
and neuropathic hyperalgesia in experimental models [1]. They have since
developed orally available TRPV1 antagonist which could prove to be effective
in humans [2]. The TRPV1 ion channel is regulated at multiple levels.
It expression on the surface of nerves is controlled by phosphorylation
and probably also by interacting proteins, it ability to open in response
to agonist is under feedback control by calcium-dependent mechanisms to
either sensitize or desensitize the channel to activators (also involving
phosphorylation). We are interested in understanding how this ion channel
and its close homologue TRPV4, is trafficked to the cell surface and how
phosphorylation acts as a molecular switch to sensitize and desensitize
these channels to agonists. We also use species differences to dissect
important functional regions of the channel [3].
Working together with
the group of Ardem Patapoutian in San Diego, we identified one novel and
two “orphan” TRP channels. This exercise revealed the existence
of the heat -activated TRPV3 [4] and the cold-activated TRPM8 [5] and
TRPA1 (formerly anktm1) [6].
We are currently particularly interested in two areas: 1) desensitization
and activation of the heat-activated ion channels, TRPV1 and TRPV4 and
the cold-activated ion channels TRPM8 and TRPA1. We are currently studying
the post-translational modification of TRPM8 and the molecular mechanisms
controlling sensitization of this ion channel to agonists and thermal
stimulation [7].
The laboratory also
has broad interests in ion channel expression in mammalian cell systems
for analysis of multi-subunit ion channel function.
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