My group is currently working on the relationship between the molecular
and biophysical properties of voltage-dependent calcium channels and their
physiological roles.
We are using a number of different techniques to tackle these problems:
heterologous expression of siRNA in cell lines with or without endogenous
channels, biophysical studies of macroscopic currents, together with
site-directed mutagenesis and chimeric channel production. We have made a number of antibodies to
calcium channels which are being used for studies of the molecular epitopes
controlling the selective trafficking of different subtypes of calcium
channels.
We are also using fusion proteins and epitope-tagged proteins and
domains for the biochemical study of calcium channel domain interactions using
surface plasmon resonance studies. The
yeast two hybrid technique is being used to identify novel interactions
involved in trafficking and processing of different subtypes of calcium
channels.
Some
specific current projects
1. Sites of interaction between
alpha1 and beta subunits of calcium channels using tagged channels and loops.
2. Mechanism of action of
alpha2delta subunits to traffic calcium channels, and the mechanism of action
of the drug gabapentin on calcium channel trafficking both in vitro and in
vivo.
3. Consequences of the mutation
in the alpha-2 delta2 subunit in the mouse mutant Ducky that has
absence epilepsy and cerebellar ataxia.
4. Mechanism of dominant negative
suppression of expression by truncated calcium channel alpha1 subunits, and
relationship to episodic ataxia-2
5. Mechanisms of G protein
modulation of calcium channels
6. Consequences of novel neuronal
calcium channel stargazin-like (gamma7) subunit expression
Recent papers and
PDF files to download