We study ligand-gated ion channels that mediate neuron-neuron and nerve-muscle
transmission. Transmitter molecules coax these receptors to change from
a closed- to an open-channel conformation. A major goal of our lab is
to understand the molecular details of this 'gating' reaction, as well
as the other reactions that drive the synaptic response, for example transmitter
binding and desensitization. We measure single-channel kinetics to probe
the energy landscapes of these reactions (using wild-type and mutant receptors),
and relate these results regarding reaction mechanism to the physiological
response of the synapse.
Our group's research focuses on developing and utilizing statistical
mechanics theories, bioinformatic, and simulation methods to explain
and predict the behavior of biologically interesting macromolecules.
The current research program aimed at the understanding of the molecular
mechanisms and bioinformatic studies of protein folding, stability,
and binding. The long-term goal of the proposed research is to elucidate
the relations between the sequence, structure, and function of proteins
and to uncover the molecular mechanism associated with solute-assisted
protein denaturation and stabilization. This will be accomplished by
designing simple (yet realistic) models and by developing statistical
Noxious stimuli such as protons (H+), temperature (temp) etc. applied
to endorgans activate nociceptors. Injury leads to the release of prostaglandins
such as prostaglandin E2 (PGE2), serotonin (5-HT), nerve growth factor
(NGF) etc. from damaged cells, Bradykinin (BK) from blood vessels and
substance P (sP) from nociceptors. These agents either activate nociceptors
directly or senstitize them to subsequent stimuli by parallel activation
of intracellular kinases by G-protein coupled receptors and tyrosine
kinase receptors. Primary nociceptive afferents (C-fibers, Ad-fibers)
of dorsal root ganglion (DRG) neurons synapse on second order neurons
(S) in the spinal dorsal horn (magnified in inset). Here, glutamate
(Glu) and sP released from primary afferent terminals (A) activate glutamate
receptors (NMDA R, AMPA R, mGluRs) and neurokinin-1 (NK-1) receptors,
respectively, located post-synaptically on spinal neurons. These synapses
are negatively modulated by spinal inhibitory interneurons (I), which
employ enkephalins (Enk) or gamma-amino-butyric acid (GABA) as neurotransmitters.
Spinal neurons convey nociceptive information to the brain and brainstem.
Activation of descending noradrenergic and/or serotonergic systems,
which originate in the brain and brainstem, leads to the activation
of spinal inhibitory interneurons (I) thereby resulting in antinociception.
The work in my laboratory focuses on DNA motor protein complexes or DNA
nano-machines. These machines are frequently coupled to, or powered by,
DNA helicases. DNA helicases are ubiquitous enzymes whose primary function
is to unwind DNA duplexes into their component single strands, a process
that is coupled to the hydrolysis of nucleoside 5'-triphosphates. Our
work is aimed at understanding DNA helicase mechanism(s) and how these
mechanisms contribute to and are adapted to the processes of replication,
recombination, DNA repair and transcription.