Current Research Opportunities
Our research group is a diverse
one with post-Doctoral fellows, graduate students and technicians
from around the world. Post-Doctoral fellows and graduate
students each have their own project focus [link], but also
frequently engage in joint projects with other lab members
[link]. We are currently pursuing several major directions.
We are particularly keen to attract individuals with an interest
in the areas outlined below, BUT there is always a place for
bright, intelligent, motivated individuals, no matter what
they would like to work on.
Structural basis of K channel activity
Our work on the structural basis of K channel activity has
developed over the last fifteen years, first with cloning
of constituent subunits, then structure-function analysis
by mutagenesis and sophisticated biophysical as well as biochemical
approaches. There is still much to learn about ligand-regulation
of Kir channels by these approaches, and we have multiple
potential projects studying nucleotide and lipid regulation
of K channel complexes.
We have also developed methods for assaying the activity
of bacterial Kir channel activity, and have generated diffraction-quality
crystals of Kir channels. We have ambitious plans for combining
structural and functional assays of Kir channels to take our
understanding of the molecular basis of channel activity to
a new level. We need to examine channel activity using both
Rb flux assays and bilayer voltage-clamp assays. We need to
perform extensive crystallization of recombinant protein,
and analysis of X-ray diffraction patterns for model generation.
These projects should appeal to anyone with experience or
interest in bilayer/patch-clamp, protein crystallography,
or computational modeling.
Pancreatic physiology/pathophysiology
Our work on manipulation of the pancreatic electrophysiological
substrate has generated several transgenic mouse lines with
features of direct relevance to human disease. There is still
much to be learned about the effects of altered electrical
substrate on the glucose-excitabiltiy relationships of ?-cells.
Individuals with experience or interest in mechanistic basis
of perforated patch-clamp recordings would be most welcome
for this project. Long-term alterations in insulin secretory
capacity as a consequence of altered electrical substrate
must reflect alterations in insulin processing, or cell proliferation/apoptosis.
This project should appeal to individuals with experience
or interest in these aspects of cell biology.
Cardiac physiology/pathophysiology
Our work on manipulation of the cardiac electrophysiological
substrate has also generated several transgenic mouse lines
with features of relevance to human disease, in particular to
the recently recognized short-QT syndrome. Despite being the
densest K-conductance in the heart there are still significant
gaps in out understanding of the role of this channel in cardiac
function. Multi-level analysis of our transgenic and knockout
models promises to advance our understanding of the role of
ion channels and remodeling in control of excitability. These
projects should appeal to individuals with experience or interest
in cardiac electrophysiology or protein chemistry.
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