Daryl Davies is a Research Associate Professor of Molecular
Pharmacology and Toxicology.
What kind of
research do you conduct?
My primary research interest is
in the area of neuropharmacology with an emphasis on identifying initial molecular
sites and mechanisms of alcohol actions on GABAA, glycine and P2X receptors.
GABAA and glycine receptors belong to a superfamily of LGICs, known as Cys-loop
receptors and are composed of five subunits arranged around a central ion-conducting
pore, with each subunit consisting of a large intracellular domain, four
transmembrane domains (TMDs) and a larger N-terminal extracellular domain.
Interestingly, the majority of molecular studies have focused on the TMDs
of the receptors as primary sites for the action of ethanol. P2X receptors
(P2XRs) constitute the most recently cloned family of LGICs and are not related
to the Cys-loop superfamily of LGICs. P2X channels possess 2-transmembrane
domains and are multimeric proteins. P2XRs are fast acting, cation-permeable
ion channels, that are gated by synaptically released extracellular adenosine
5’-triphosphate (ATP) and are widely distributed in the mammalian brain.
Although investigations are in the early stages, initial electrophysiological
evidence from our laboratory suggests that P2XR may also play a role in the
action of ethanol. My long term goals from this area of research is to identify
specific targets at which therapeutically relevant pharmacological agents
can be directed to reduce social problems, loss of lives and tremendous economic
costs resulting from the misuse and abuse of alcohol.
More recently, my research interests have expanded
to investigations focusing on the human intestinal dipeptide transporter (hPepT1).
The dipeptide transporter, hPepT1, is a 12-transmembrane domain protein that
is mainly expressed on the apical membrane of the intestinal epithelial cells.
It exhibits broad substrate specificity by facilitating the uptake of nutritional
di- and tripeptides and a variety of peptidomimetics and has received considerable
attention as a drug carrier system over the past several years. More importantly,
this transporter is an excellent target for developing dipeptide prodrugs
for compounds that show limited oral bioavailability. The goal of this project
is to increase knowledge regarding the structure-function relationships of
the hPepT1 in order to understand its substrate binding domain and mechanism
of transport. This will lead to a highly refined 3D computer model of the
substrate-binding domain which can be used for computational docking studies
and several other studies that can help us in rational drug design. It will
also help us to understand the substrate-protein interactions, thereby helping
us to identify genetic polymorphisms present in human populations that can
lead to disease (SNP's).
In a typical
semester, how many undergraduates do you work with? What
kind of research activities do the undergraduate students
In past years I normally only had 1 USC undergraduate
working in my laboratory per semester. However, the experiences have been
so positive for both me and the student, that I have begun accepting more
students into the laboratory. For example, I will have 5 - 6 USC undergraduate
students working in the laboratory during the Sping 2005 semester.
Roles of undergraduates
One of my personal goals is to actively participate in the training of potential
future scientists. To this end, I treat my students as if they were junior
colleagues working on the research project with me. Thus, the role of the
undergraduate researchers on the project incorporates an introduction to all
aspects of a career in research: Conceptualizing the project, designing and
performing well-controlled experiments, collecting and analyzing data, and
writing up the project. In addition, the students learn responsibility to
self and colleagues, problem-solving, proper laboratory technique, and ethical
Oversight and supervision
Students invited to join our laboratory will be given sufficient "hands-on"
support from me as well as from other senior level persons in the lab to ensure
that the students learn the techniques required to carry out the experiments
and understands the conceptual framework for the experiments. However, once
the students have gained a level of scientific competency (normally 2-3 weeks)
they will be placed in charge of their project and will be allowed to learn
from their mistakes (to some extent), and to develop self sufficiency both
in terms of learning how to conduct well controlled experiments, but more
importantly, to make a real intellectual contribution to the work. I have
found this to be successful in the past in exciting students about long-term
careers in research.
What are some
of your recent undergraduate projects?
Recent and on going projects involve
the student's characterizing the effects of alcohol on various membrane bound
receptors that are normally found in the central nervous system. The students
will be involved in all aspects of the project including 1) learning and performing
the molecular biological techniques necessary to produce the cDNA or cRNA
that we use in our projects; 2) isolation of the oocytes from Xenopus frogs;
3) injection of the cRNA into the oocytes; 4) learning and performing two-electrode
voltage clamp techniques to measure the effects of various drugs on the membrane
bound proteins expressed on the cell surface of the oocyte and 5) learning
data analysis and data presentation.
out more about Dr. Davies and his research, please