daryl davies

Daryl Davies is a Research Associate Professor of Molecular Pharmacology and Toxicology.
[curriculum vitae] [webpage]

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 perform?

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 responsibility.

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. 

To find out more about Dr. Davies and his research, please visit his homepage.